Methyl chloroformate → 6-[(cyclopropylmethyl)(propyl)amino]-N-[3-(1H-1,2,4-triazol-1-yl)phenyl]pyrimidine-4-carboxamide

HRID 1746801Notes

Reaction equation

[CH:1]1([CH2:4][N:5]([CH2:15][CH2:16][CH3:17])[C:6]2[N:11]=[CH:10][N:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=2)[CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.ClC(OC)=O.[N:32]1([C:37]2[CH:38]=[C:39]([CH:41]=[CH:42][CH:43]=2)[NH2:40])[CH:36]=[N:35][CH:34]=[N:33]1>C(Cl)Cl>[CH:1]1([CH2:4][N:5]([CH2:15][CH2:16][CH3:17])[C:6]2[N:11]=[CH:10][N:9]=[C:8]([C:12]([NH:40][C:39]3[CH:41]=[CH:42][CH:43]=[C:37]([N:32]4[CH:36]=[N:35][CH:34]=[N:33]4)[CH:38]=3)=[O:14])[CH:7]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 0 °C

Procedure

A cooled (0° C.) solution of 6-(cyclopropylmethyl(propyl)amino)pyrimidine-4-carboxylic acid (Intermediate 21, 112 mg; 0.45 mmol) in DCM was treated with diisopropylethylamine (78.4 mL; 0.52 mmol) and methyl chloroformate (36.2 mL; 0.47 mmol). After stirring at 0° C. for 15 minutes, 3-(1H-1,2,4-triazol-1-yl)aniline (Maybridge, 108 mg; 0.67 mmol) was added and the mixture stirred for 72 hours. The solvent was evaporated and the compound purified by preparative HPLC to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 10.16 (1H, s), 8.60 (2H, d, J=18.1 Hz), 8.37 (1H, s), 8.11 (1H, s), 7.68-7.64 (1H, m), 7.53-7.48 (2H, m), 7.36 (1H, s), 3.54 (4H, s), 1.75-1.65 (2H, m), 1.10 (1H, s), 0.97 (3H, t, J=7.3 Hz), 0.58 (2H, d, J=7.7 Hz), 0.36-0.30 (2H, m). MS (ESI+) 387. HPLC (Condition C) Rt 3.77 min (HPLC purity 99.9%).

Workup

stirringthe mixture stirred for 72 hours
customThe solvent was evaporated
customthe compound purified by preparative HPLC

Sources & evidence

ORD record: ord-bfc20e7a0ed545e7834ad3b43195044a
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150519B2

Reaction notes

Loading…