Diisopropylethylamine → N-(2-methyl-7-(4-oxo-3,4,7,8-tetrahydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-6-(trifluoromethyl)nicotinamide

HRID 1256340Notes

Reaction equation

HRID 1256340 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:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[N:16][CH:15]=2)[CH:3]=1.Cl.[N:26]1[C:31]2[CH2:32][CH2:33][NH:34][CH2:35][C:30]=2[C:29](=[O:36])[NH:28][CH:27]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:11][C:9]1[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[N:16][CH:15]=3)[CH:3]=[C:2]([N:34]3[CH2:33][CH2:32][C:31]4[N:26]=[CH:27][NH:28][C:29](=[O:36])[C:30]=4[CH2:35]3)[N:7]2[N:8]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86652270N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-6-(trifluoromethyl)nicotinamideHCID 1357416165,6,7,8-Tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one hydrochloride

Product 1

HCID 136374279N-(2-methyl-7-(4-oxo-3,4,7,8-tetrahydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-6-(trifluoromethyl)nicotinamideYield 64.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-6-(trifluoromethyl)nicotinamide (12A, 90 mg, 0.253 mmol), 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one hydrochloride (134 mg, 0.633 mmol), and N,N-diisopropylethylamine (98 mg, 0.757 mmol) in DMF (1.012 mL) was stirred at 100° C. for 90 min, then cooled to rt and maintained overnight. The mixture was filtered and the crude material recrystallized from hot methanol, providing the titled compound as a yellow solid (76.6 mg, 64%). 1H NMR (DMSO-d6) δ: 12.63 (br. s., 1H), 11.45 (s, 1H), 9.29 (s, 1H), 8.53-8.69 (m, 1H), 8.13 (s, 1H), 8.09 (dd, J=8.3, 0.8 Hz, 1H), 7.40 (s, 1H), 6.21 (s, 1H), 4.51 (s, 2H), 4.13 (t, J=5.7 Hz, 2H), 2.73 (s, 2H), 2.41 (s, 3H); ESI-MS: m/z 471.1 (M+H)+.

Workup

  1. temperaturemaintained overnight
  2. filtrationThe mixture was filtered
  3. customthe crude material recrystallized from hot methanol

Sources & evidence

ORD record
ord-87122f22d89f432f99ab1ca62e69e693
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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