Dimethyl malonate → 2-amino-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}pyrazolo[1,5-a]pyrimidine-5,7(4H,6H)-dione

HRID 510405Notes

Reaction equation

[CH3:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:12][C:13]1[C:14]([NH2:19])=[N:15][NH:16][C:17]=1[NH2:18].[C:20](OC)(=[O:26])[CH2:21][C:22](OC)=[O:23].C[O-].[Na+]>CO>[NH2:18][C:17]1[C:13]([CH2:12][C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:9])([F:10])[F:11])[C:2]=2[CH3:1])=[C:14]2[NH:19][C:20](=[O:26])[CH2:21][C:22](=[O:23])[N:15]2[N:16]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 4-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-1H-pyrazole-3,5-diamine (1 g, 3.70 mmol), dimethyl propanedioate (1.467 g, 11.10 mmol) in methanol (30 mL) was added sodium methoxide (0.680 g, 12.58 mmol). The reaction mixture was stirred at 65° C. for 18 h. After the reaction mixture was cooled to room temperature, the solvent was evaporated. Water (10 mL) was added in. The mixture was neutralized with 1 N HCl. Filtration gave the product (1.2 g, 96%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.41 (s, 3H) 3.59-3.67 (s, 2H) 3.73 (s, 2H) 5.64 (br. s., 2H) 7.14 (d, J=7.83 Hz, 1H) 7.30 (m, 1H) 7.54 (d, J=7.83 Hz, 1H) 11.26 (s, 1H); LC/MS: MS (ES+) m/e 339.1 [M+H]+

Workup

temperatureAfter the reaction mixture was cooled to room temperature
customthe solvent was evaporated
additionWater (10 mL) was added in
filtrationFiltration

Sources & evidence

ORD record: ord-b6610bc19617477c8734a34d279889c5
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096605B2

Reaction notes

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