N-甲基-1,4-二噁螺[4.5]-8-癸胺(弗洛中间体)

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: N6-Methyl-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine dihydrobromide (3B) is prepared from 3A as described for 1B.

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

实验步骤: A solution of (1,4-dioxa-spiro[4.5]dec-8-yl)-methyl-amine (1.5 g, 9 mmol), CH2Cl2 (50 mL), and Et3N (1.7 mL, 12 mmol) was stirred with 4-fluorobenzene sulfonyl chloride (1.7 g, 9 mmol) at room temperature. After 1 hour, the reaction mixture was concentrated and the residue purified by flash chromatography on silica gel to afford 2.1 g of N-(1,4-dioxa-spiro[4.5]dec-8-yl)-4-fluoro-N-methyl-benzenesulfonamide. Mass spectrometric data [M+H]+=330. the reaction mixture was concentrated the residue purified by flash chromatography on silica gel

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

实验步骤: A solution of 1,4-dioxa-spiro[4.5]decan-8-one (3.1 g, 20 mmol) and CH2Cl2 (50 mL) was stirred with methylamine (15 mL, 30 mmol, 2.0M solution in THF), sodium cyanoborohydride (1.3 g, 20 mmol), and acetic acid (0.1 mL) at room temperature. After 8 hours, the reaction mixture was washed with water (50 mL) and concentrated. The residue was purified by flash chromatography to afford 1.5 g of (1,4-dioxa-spiro[4.5]dec-8-yl)-methyl-amine as an oil. the reaction mixture was washed with water (50 mL) concentrated The residue was purified by flash chromatography

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

实验步骤: N-Methyl-1,4-dioxaspiro[4.5]decan-8-amine (4.0 g, 23.39 mmol, 1.0 eq.) was dissolved in DCM (70 ml); benzaldehyde (2.83 g, 28.07 mmol, 1.2 eq.) and AcOH (0.2 ml) were added and the mixture was stirred for 30 minutes at RT. NaBH(OAc)3 (14.8 g, 70.17 mmol, 3.0 eq.) was added at 0° C. and the reaction mixture was stirred for a further 14 hours at RT. After monitoring by TLC, water (100 ml) was added to the reaction and the phases were separated. The aqueous phase was extracted with 10% MeOH in DCM (2×100 ml). The combined org. phases were washed in succession with water (100 ml) and sat. NaCl solution (100 ml), dried over sodium sulfate, concentrated under reduced pressure and purified by column chromatography (silica gel, 4% MeOH in DCM). Yield: 49% (3.0 g, 11.49 mmol) the reaction mixture was stirred for a further 14 hours at RT was added to the reaction the phases were separated The aqueous phase was extracted with 10% MeOH in DCM (2×100 ml) phases were washed in succession with water (100 ml) and sat. NaCl solution (100 ml) dried over sodium sulfate concentrated under reduced pressure purified by column chromatography (silica gel, 4% MeOH in DCM)

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

实验步骤: 1,4-Dioxaspiro[4.5]decan-8-one (10.0 g, 64.10 mmol, 1.0 eq.) was dissolved in MeOH (100 ml); AcOH (0.1 ml) and CH3NH2.HCl (8.65 g, 128.21 mmol, 2.0 eq.) were added and stirring was carried out for 2 hours at RT. NaCNBH3 (10.0 g, 160.256 mmol, 2.5 eq.) was added in portions at 0° C. and the mixture was then stirred for 16 hours at RT. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography (Alox, 5% MeOH in DCM). Yield: 54% (6.0 g, 35.08 mmol) the mixture was then stirred for 16 hours at RT The reaction mixture was concentrated under reduced pressure the residue was purified by column chromatography (Alox, 5% MeOH in DCM)