7-({[t-Butyl(dimethyl)silyl]oxy}methyl)-7-methyl-5-methylthio-2,3,6,7-tetrahydro-1,4-thiazepine → 3-[1-(4-Bromo-2-fluorophenyl)cyclopropyl]-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1423999Notes

Reaction equation

HRID 1423999 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([NH:13][NH2:14])=O)[CH2:10][CH2:9]2)=[C:4]([F:15])[CH:3]=1.[Si:16]([O:23][CH2:24][C:25]1([CH3:34])[S:31][CH2:30][CH2:29][N:28]=[C:27](SC)[CH2:26]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>C(O)CCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:28]4[CH2:29][CH2:30][S:31][C:25]([CH2:24][O:23][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])([CH3:34])[CH2:26][C:27]4=[N:14][N:13]=3)[CH2:10][CH2:9]2)=[C:4]([F:15])[CH:3]=1

Participants

4

Reactant 2

HCID 685222157-({[t-Butyl(dimethyl)silyl]oxy}methyl)-7-methyl-5-methylthio-2,3,6,7-tetrahydro-1,4-thiazepineHCID 867128521-(4-Bromo-2-fluorophenyl)cyclopropanecarbohydrazide

Product 1

HCID 867128533-[1-(4-Bromo-2-fluorophenyl)cyclopropyl]-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepineYield 40%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of the compound (2.73 g, 10 mmol) obtained in Example 14-4) and 7-({[tert-butyl(dimethyl)silyl]oxy}methyl)-7-methyl-5-(methylthio)-2,3,6,7-tetrahydro-1,4-thiazepine (3.2 g, 10 mmol) in n-butanol (50 mL) was stirred at 140° C. for 7 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Isco Combiflash, 40 g, hexane:ethyl acetate=0:100 to 100:0, gradient) to obtain the title compound (2.09 g, 40%) as a colorless solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by silica gel column chromatography (Isco Combiflash, 40 g, hexane:ethyl acetate=0:100 to 100:0, gradient)

Sources & evidence

ORD record
ord-34fe8a791c4b48d3b5e8321c5aeb49e2
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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