Ethanol → HCID 59160664, compound

HRID 1500048Notes

Reaction equation

[CH2:1]([O:8][C:9]1[N:14]=[C:13](Cl)[C:12]([F:16])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:17][C:18]([F:28])([F:27])[C:19]1[CH:20]=[C:21]([NH:25][NH2:26])[CH:22]=[CH:23][CH:24]=1.C(O)C.C(N(CC)CC)C>CCOCC>[CH2:1]([O:8][C:9]1[N:14]=[C:13]([NH:26][NH:25][C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([C:18]([F:17])([F:28])[F:27])[CH:20]=2)[C:12]([F:16])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A 25 mL vial was charged with 2-(benzyloxy)-4-chloro-5-fluoropyrimidine (153 mg, 0.639 mmol), (3-(trifluoromethyl)phenyl)hydrazine (338 mg, 1.92 mmol), ethanol (8 mL), and triethylamine (140 μL, 1.00 mmol). The resulting yellow solution was heated at 50° C. on an orbital shaker for 16 h. The crude material was then diluted with Et2O (100 mL) and washed with 1.0 M aqueous NaH2PO4 (50 mL) and then water (50 mL). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (EtOAc/hexane gradient) to afford 2-(benzyloxy)-5-fluoro-4-(2-(3-(trifluoromethyl)phenyl)hydrazinyl)pyrimidine (186 mg, 77%) as a brown oil: 1H NMR (300 MHz, DMSO-d6) δ 9.74 (bs, 1H), 8.38 (s, 1H), 8.07 (s, 1H), 7.36 (m, 1H), 7.26 (bs, 5H), 7.01 (m, 3H), 5.14 (s, 2H); MS (ESI) m/z 379 (M+H)+, 377 (M−H)−.

Workup

washwashed with 1.0 M aqueous NaH2PO4 (50 mL)
dry with materialThe organic phase was dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude material was purified by flash column chromatography (EtOAc/hexane gradient)

Sources & evidence

ORD record: ord-2fa7dadc8ba84fe2b52ad8d5a495b983
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09204653B2

Reaction notes

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