Hydrochloric Acid → 1-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclobutanecarboxylic acid

HRID 1930132Notes

Reaction equation

[OH-].[K+].[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([C:28]([O:30]C)=[O:29])[CH2:27][CH2:26][CH2:25]4)=[CH:20][C:19]=3[Cl:32])=[CH:14][CH:13]=2)[C:9]([CH3:33])=[N:8][C:7]=1[CH3:34])(=[O:5])[NH2:4].Cl>C(O)(C)(C)C.C(O)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([C:28]([OH:30])=[O:29])[CH2:25][CH2:26][CH2:27]4)=[CH:20][C:19]=3[Cl:32])=[CH:16][CH:17]=2)[C:9]([CH3:33])=[N:8][C:7]=1[CH3:34])(=[O:5])[NH2:4]

Participants

Conditions

Temperature: 40 °C

Procedure

Powdered potassium hydroxide (56.9 mg, 1.01 mmol) was added in one portion to methyl 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclobutanecarboxylate (Intermediate 7-1; 152 mg, 0.34 mmol)/in tert-butanol (10 mL) at 40° C. under nitrogen. The resulting suspension was stirred at 40° C. for 1 hour LCMS showed the reaction was complete. The reaction mixture was quenched with HCl (2.027 mL, 2.03 mmol) in ethanol (10 mL) and the resulting solution stirred for a further 20 minutes before being evaporated to dryness. The resulting solid was washed with water (50 mL) and dried in a dessicator to afford 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclobutanecarboxylic acid (68.0 mg, 46.2%) as a cream solid.

Workup

customat 40° C.
stirringthe resulting solution stirred for a further 20 minutes
custombefore being evaporated to dryness
washThe resulting solid was washed with water (50 mL)
customdried in a dessicator

Sources & evidence

ORD record: ord-dc6db0987bd746f29e76203e79d59113
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188092B2

Reaction notes

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