Hydrochloric Acid → 5-(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)-N,N-dimethylpyridine-2-carboxamide

HRID 1423988Notes

Reaction equation

HRID 1423988 reaction equation
[Si]([O:8][CH2:9][C:10]1([CH3:40])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26]([C:29]5[CH:30]=[CH:31][C:32]([C:35]([N:37]([CH3:39])[CH3:38])=[O:36])=[N:33][CH:34]=5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)(C(C)(C)C)(C)C.Cl>CO>[OH:8][CH2:9][C:10]1([CH3:40])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:24]=[CH:25][C:26]([C:29]5[CH:30]=[CH:31][C:32]([C:35]([N:37]([CH3:39])[CH3:38])=[O:36])=[N:33][CH:34]=5)=[CH:27][CH:28]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867128455-(4-{1-[8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine-3-yl]cyclopropyl}phenyl)-N,N-dimethylpyridine-2-carboxamide

Product 1

HCID 867128465-(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)-N,N-dimethylpyridine-2-carboxamideYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of the compound (120 mg, 0.21 mmol) obtained in Example 8-1) and 4 M hydrochloric acid (1,4-dioxane solution, 0.26 mL) in methanol (2 mL) was stirred at room temperature for 21 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (63 mg, 65%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with dichloromethane
  4. washthe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient)

Sources & evidence

ORD record
ord-7df24d6152f846178923e14eeba51326
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

Loading…