Hydrochloric Acid → (8-Methyl-3-{1-[4-(1H-pyrazol-5-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl)methanol

HRID 1424129Notes

Reaction equation

HRID 1424129 reaction equation
[Si]([O:8][CH2:9][C:10]1([CH3:34])[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[NH:33][N:32]=[CH:31][CH:30]=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>[CH3:34][C:10]1([CH2:9][OH:8])[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[NH:33][N:32]=[CH:31][CH:30]=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 867129748-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1H-pyrazol-5-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Product 1

HCID 86712973(8-Methyl-3-{1-[4-(1H-pyrazol-5-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl)methanolYield 66.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of the compound (295 mg, 0.60 mmol) obtained in Example 83-1) and 4 M hydrochloric acid (1,4-dioxane solution, 3 mL) in methanol (6 mL) was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, a 5 M aqueous sodium hydroxide solution (10 mL) was added to the residue, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate:methanol=20:80) to obtain the title compound (152 mg, 66%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiona 5 M aqueous sodium hydroxide solution (10 mL) was added to the residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous sodium sulfate
  6. concentrationAfter concentration under reduced pressure
  7. customthe residue was purified by silica gel chromatography (ethyl acetate:methanol=20:80)

Sources & evidence

ORD record
ord-278e54cc38f646ae8548bb747511ecaf
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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