Oxalyl chloride → HCID 71294318, compound

HRID 469800Notes

Reaction equation

[CH:1]1([C:7]2[C:8]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:9][CH:10]=[C:11]([CH:15]=2)[C:12]([OH:14])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C.[N:37]1[CH:42]=[CH:41][N:40]=[CH:39][C:38]=1[NH2:43]>ClCCl>[CH:1]1([C:7]2[C:8]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:9][CH:10]=[C:11]([CH:15]=2)[C:12]([NH:43][C:38]2[CH:39]=[N:40][CH:41]=[CH:42][N:37]=2)=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 5-cyclohexyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (Example 4b) (50 mg, 0.16 mmol) in dichloromethane (5 mL) was added oxalylchloride (0.02 mL, 0.25 mmol) at 0° C. and the reaction mixture was stirred at 25° C. for 3 h. Solvent was removed in vacuo and the residue was dissolved in dry dichloromethane. To this was added DIPEA (0.2 mL, 0.99 mmol) followed by 2-pyrazinamine (CAN 5049-61-6, 19 mg, 0.21 mmol) at 25° C. and the reaction mixture was stirred for 12 hours at that temperature. The solvent was removed in vacuo and the crude residue was purified by prep-HPLC to give 5-cyclohexyl-N-pyrazin-2-yl-6-(2,2,2-trifluoro-ethoxy)-nicotinamide as off white solid (10 mg, 15.9%); MS (ESI): 381.4 [M+H]+.

Workup

customSolvent was removed in vacuo
dissolutionthe residue was dissolved in dry dichloromethane
stirringthe reaction mixture was stirred for 12 hours at that temperature
customThe solvent was removed in vacuo
customthe crude residue was purified by prep-HPLC

Sources & evidence

ORD record: ord-e87c63a2661640e5acd83445459e13b2
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629166B2

Reaction notes

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