Methanol → 6-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinamide

HRID 1424101Notes

Reaction equation

HRID 1424101 reaction equation
[OH:1][CH2:2][C:3]1([CH3:30])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][N:23]=5)=[CH:18][CH:17]=4)[CH2:15][CH2:14]3)=[N:11][N:12]=[C:5]2[CH2:4]1.CO.C(=O)([O-])[OH:34].[Na+]>Cl.O1CCOCC1>[OH:1][CH2:2][C:3]1([CH3:30])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:29]=[CH:28][C:25]([C:26]([NH2:27])=[O:34])=[CH:24][N:23]=5)=[CH:18][CH:17]=4)[CH2:15][CH2:14]3)=[N:11][N:12]=[C:5]2[CH2:4]1

Participants

5

Reactant 3

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 867129426-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinonitrile

Product 1

HCID 867129506-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinamideYield 38%

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

A solution of the compound (9.14 g, 17.2 mmol) obtained in Example 60-5) in 2 N hydrochloric acid-1,4-dioxane (200 mL) was stirred at 50° C. for 2 h. The reaction mixture was cooled to room temperature, methanol (40 mL) was added to the reaction mixture, and insoluble substances were dissolved by sonication. Saturated aqueous sodium hydrogencarbonate (400 mL) was added to the reaction mixture, and the mixture was extracted with dichloromethane and purified by silica gel column chromatography (ethyl acetate:methanol=3:2) to obtain the title compound (2.74 g, 38%) as a white solid.

Workup

  1. dissolutionwere dissolved by sonication
  2. extractionthe mixture was extracted with dichloromethane
  3. custompurified by silica gel column chromatography (ethyl acetate:methanol=3:2)

Sources & evidence

ORD record
ord-f7a24605308548a3b50fa929da2a7a01
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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