Phthalic Anhydride → 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}pyrazolo[1,5-a]pyrimidine-5,7(4H,6H)-dione

HRID 510406Notes

Reaction equation

[NH2:1][C:2]1[C:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:15]=2[CH3:24])=[C:5]2[NH:6][C:7](=[O:11])[CH2:8][C:9](=[O:10])[N:4]2[N:3]=1.[C:25]1(=O)[O:30][C:28](=[O:29])[C:27]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]12>C(#N)C>[O:29]=[C:28]1[C:27]2[C:26](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:25](=[O:30])[N:1]1[C:2]1[C:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[C:15]=2[CH3:24])=[C:5]2[NH:6][C:7](=[O:11])[CH2:8][C:9](=[O:10])[N:4]2[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To the solution of 2-amino-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}pyrazolo[1,5-a]pyrimidine-5,7(4H,6H)-dione (1.5 g, 4.43 mmol) in acetonitrile (100 mL) was added phthalic anhydride (1.511 g, 10.20 mmol). The reaction mixture was stirred at 80° C. for 4 days. The reaction was concentrated. To the crude was added DCM (20 mL). The insoluble solid was filtered which is the pure product. The filtrate was purified on a silica column (eluting with 20-60% EtOAc/Hexane) which was combined with the solid from filtration to give the product (1.0 g, 48%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.20 (s, 3H) 3.93 (br. s., 2H) 6.89 (t, J=7.83 Hz, 1H) 7.10 (m, 1H) 7.22 (m, 1H) 7.49-7.62 (m, 1H) 7.62-7.70 (m, 1H) 7.79-7.94 (m, 4H); LC/MS: MS (ES+) m/e 469.1 [M+H]+.

Workup

concentrationThe reaction was concentrated
additionTo the crude was added DCM (20 mL)
filtrationThe insoluble solid was filtered which
customThe filtrate was purified on a silica column (eluting with 20-60% EtOAc/Hexane) which
filtrationwas combined with the solid from filtration

Sources & evidence

ORD record: ord-64a856ba82f148c6926444c029e234d7
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096605B2

Reaction notes

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