1-(4-Chlorophenyl)cyclopropanecarbohydrazide → 8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-[1-(4-chlorophenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1423971Notes

Reaction equation

HRID 1423971 reaction equation
[Cl: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)=[CH:4][CH:3]=1.[Si:15]([O:22][CH2:23][C:24]1([CH3:33])[S:30][CH2:29][CH2:28][N:27]=[C:26](SC)[CH2:25]1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>C(O)CCC>[Si:15]([O:22][CH2:23][C:24]1([CH3:33])[S:30][CH2:29][CH2:28][N:27]2[C:11]([C:8]3([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[CH2:10][CH2:9]3)=[N:13][N:14]=[C:26]2[CH2:25]1)([C:18]([CH3:21])([CH3:19])[CH3:20])([CH3:16])[CH3:17]

Participants

4

Reactant 2

HCID 227221341-(4-Chlorophenyl)cyclopropanecarbohydrazideHCID 685222157-({[t-Butyl(dimethyl)silyl]oxy}methyl)-7-methyl-5-methylthio-2,3,6,7-tetrahydro-1,4-thiazepine

Product 1

HCID 867128348-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-[1-(4-chlorophenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepineYield 49%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of the compound (2.03 g, 10 mmol) obtained in Example 1-1) and 7-({[tert-butyl(dimethyl)silyl]oxy}methyl)-7-methyl-5-(methylthio)-2,3,6,7-tetrahydro-1,4-thiazepine (WO2008078725) (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 (2.27 g, 49%) as a light yellow oily substance.

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-cb4f4691c5e544b698e687c4bfe3df1b
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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