1,4-二噁烷-2-甲醛

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-prop-2-ynyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-prop-2-ynyl-benzamide as a lyophylate (18%); 1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 9.19 (d, J=8.44 Hz, 1H), 8.97 (m, 1H), 8.17 (s, 1H), 7.52-7.45 (m, 3H), 7.25 (s, 1H), 7.15 (m, 1H), 6.87 (m, 1H), 4.38 (m, 1H), 4.01 (m, 2H), 3.84-3.3 (bm, H2O+11H), 3.11 (s, 1H), 2.81 (m, 1H), 2.67 (m, 2H); MS (m/e) 579.16 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide as a lyophylate (31%); 1H NMR (400 MHz, DMSO-d6) δ 9.39 (d, J=9.23 Hz, 1H), 9.33 (s, 1H), 8.55 (m, 1H), 8.18 (s, 1H), 7.51-7.43 (m, 3H), 7.26 (s, 1H), 7.17 (m, 1H), 6.89 (m, 1H), 4.39 (m, 1H), 3.74-3.4 (bm, H2O+11H), 2.81 (m, 1H), 2.74 (d, J=4.55 Hz, 3H), 2.67 (m, 2H); MS (m/e) 555.14 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide as a lyophylate (31%); 1H NMR (400 MHz, DMSO-d6) δ 9.39 (d, J=9.23 Hz, 1H), 9.33 (s, 1H), 8.55 (m, 1H), 8.18 (s, 1H), 7.51-7.43 (m, 3H), 7.26 (s, 1H), 7.17 (m, 1H), 6.89 (m, 1H), 4.39 (m, 1H), 3.74-3.4 (bm, H2O+11H), 2.81 (m, 1H), 2.74 (d, J=4.55 Hz, 3H), 2.67 (m, 2H); MS (m/e) 555.14 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide as a lyophylate (25%); 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.33 (s, 1H), 8.49 (bs, 1H), 8.29 (s, 1H), 7.84 (d, J=7.97 Hz, 1H), 7.71 (m, 1H), 7.41-7.32 (m, 3H), 7.07-7.01 (m, 1H), 4.39 (m, 1H), 3.78-3.49 (m, 10H), 2.87-2.77 (m, 2H), 2.65 (s, 6H); MS (m/e) 587.15 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-prop-2-ynyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-prop-2-ynyl-benzamide as a lyophylate (18%); 1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 9.19 (d, J=8.44 Hz, 1H), 8.97 (m, 1H), 8.17 (s, 1H), 7.52-7.45 (m, 3H), 7.25 (s, 1H), 7.15 (m, 1H), 6.87 (m, 1H), 4.38 (m, 1H), 4.01 (m, 2H), 3.84-3.3 (bm, H2O+11H), 3.11 (s, 1H), 2.81 (m, 1H), 2.67 (m, 2H); MS (m/e) 579.16 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide as a lyophylate (31%); 1H NMR (400 MHz, DMSO-d6) δ 9.39 (d, J=9.23 Hz, 1H), 9.33 (s, 1H), 8.55 (m, 1H), 8.18 (s, 1H), 7.51-7.43 (m, 3H), 7.26 (s, 1H), 7.17 (m, 1H), 6.89 (m, 1H), 4.39 (m, 1H), 3.74-3.4 (bm, H2O+11H), 2.81 (m, 1H), 2.74 (d, J=4.55 Hz, 3H), 2.67 (m, 2H); MS (m/e) 555.14 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide as a lyophylate (25%); 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.33 (s, 1H), 8.49 (bs, 1H), 8.29 (s, 1H), 7.84 (d, J=7.97 Hz, 1H), 7.71 (m, 1H), 7.41-7.32 (m, 3H), 7.07-7.01 (m, 1H), 4.39 (m, 1H), 3.78-3.49 (m, 10H), 2.87-2.77 (m, 2H), 2.65 (s, 6H); MS (m/e) 587.15 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-prop-2-ynyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-prop-2-ynyl-benzamide as a lyophylate (18%); 1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 9.19 (d, J=8.44 Hz, 1H), 8.97 (m, 1H), 8.17 (s, 1H), 7.52-7.45 (m, 3H), 7.25 (s, 1H), 7.15 (m, 1H), 6.87 (m, 1H), 4.38 (m, 1H), 4.01 (m, 2H), 3.84-3.3 (bm, H2O+11H), 3.11 (s, 1H), 2.81 (m, 1H), 2.67 (m, 2H); MS (m/e) 579.16 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide as a lyophylate (31%); 1H NMR (400 MHz, DMSO-d6) δ 9.39 (d, J=9.23 Hz, 1H), 9.33 (s, 1H), 8.55 (m, 1H), 8.18 (s, 1H), 7.51-7.43 (m, 3H), 7.26 (s, 1H), 7.17 (m, 1H), 6.89 (m, 1H), 4.39 (m, 1H), 3.74-3.4 (bm, H2O+11H), 2.81 (m, 1H), 2.74 (d, J=4.55 Hz, 3H), 2.67 (m, 2H); MS (m/e) 555.14 (M+H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (7-Amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone, prepared in a similar manner as 7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1,4-dioxinan-2-yl-methanone of Example 633b, was reacted with 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamide, in a similar manner as Example 601b, to yield desired product 2-{5-Chloro-2-[3-([1,4]dioxane-2-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide as a lyophylate (25%); 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.33 (s, 1H), 8.49 (bs, 1H), 8.29 (s, 1H), 7.84 (d, J=7.97 Hz, 1H), 7.71 (m, 1H), 7.41-7.32 (m, 3H), 7.07-7.01 (m, 1H), 4.39 (m, 1H), 3.78-3.49 (m, 10H), 2.87-2.77 (m, 2H), 2.65 (s, 6H); MS (m/e) 587.15 (M+H).