Diisopropylethylamine → N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide

HRID 1409280Notes

Reaction equation

HRID 1409280 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:25])[C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=2)[CH:3]=1.Cl.[NH:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:34](=[O:36])[CH3:35])[CH2:29][CH2:28]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CS(C)=O.CO>[C:34]([NH:33][CH:30]1[CH2:31][CH2:32][N:27]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:25])[C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:28][CH2:29]1)(=[O:36])[CH3:35]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 114011054-Acetamidopiperidine dihydrochlorideHCID 86652271HCID 86652271, compound

Product 1

HCID 67064218N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamideYield 35.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

An orange solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide (14A, 69 mg, 0.186 mmol), N-(piperidin-4-yl)acetamide hydrochloride (40 mg, 0.279 mmol), and N,N-diisopropylethylamine (96 mg, 0.745 mmol) in DMF (1.8 mL) was stirred at 100° C. for 2 h, cooled to 80° C., and stirred overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, filtered, and then purified by preparatory HPLC (50-70% (1:1 MeOH/MeCN)/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (31.3 mg, 35%). 1H NMR (DMSO-d6) δ: 10.99 (s, 1H), 8.05-8.12 (m, 2H), 7.85 (d, J=7.6 Hz, 1H), 7.44 (dd, J=9.1, 1.0 Hz, 2H), 7.26 (s, 1H), 6.09 (d, J=0.5 Hz, 1H), 4.28 (d, J=12.4 Hz, 2H), 3.72-3.94 (m, 1H), 3.14 (t, J=11.0 Hz, 2H), 2.31 (s, 3H), 1.84 (dd, J=13.1, 3.0 Hz, 2H), 1.75 (s, 3H), 1.41-1.58 (m, 2H); ESI-MS: m/z 477.3 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered
  3. custompurified by preparatory HPLC (50-70% (1:1 MeOH/MeCN)/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-f1a67a3f38b14d6e9b5fa2d24109e4f8
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

Loading…