Hydrochloric Acid → 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)nicotinic acid

HRID 1424102Notes

Reaction equation

HRID 1424102 reaction equation
[OH:1][CH2:2][C:3]1([CH3:31])[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:30]=[CH:29][C:25]([C:26](N)=[O: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.[OH-:32].[K+].Cl>C(O)C.O>[OH:1][CH2:2][C:3]1([CH3:31])[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:30]=[CH:29][C:25]([C:26]([OH:27])=[O:32])=[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

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 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)nicotinamide

Product 1

HCID 867129516-(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)nicotinic acidYield 83%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixed solution of the compound (200 mg, 0.458 mmol) obtained in Example 65 and potassium hydroxide (129 mg) in ethanol (5.00 mL) and water (1.50 mL) was stirred at 100° C. for 9 h. The reaction mixture was cooled to room temperature, poured into 0.05 N hydrochloric acid (50.0 mL) with ice cooling, extracted with dichloromethane/2-propanol (4/1), and dried with anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the residue, and the white precipitate was collected by filtration and dried under reduced pressure to obtain the title compound (166 mg, 83%) as a white solid.

Workup

  1. extractionextracted with dichloromethane/2-propanol (4/1)
  2. dry with materialdried with anhydrous sodium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionDiisopropyl ether was added to the residue
  5. filtrationthe white precipitate was collected by filtration
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-d1233f2b327043178456020ca1b5903f
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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