3-(Trifluoromethyl)aniline → 7-Chloro-5-(3-(trifluoromethyl)phenylamino)pyrido[4,3-d]pyrimidin-4(3H)-one

HRID 1805753Notes

Reaction equation

[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].Cl[C:13]1[C:22]2[C:21](=[O:23])[NH:20][CH:19]=[N:18][C:17]=2[CH:16]=[C:15]([Cl:24])[N:14]=1>C1COCC1>[Cl:24][C:15]1[N:14]=[C:13]([NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=2)[C:22]2[C:21](=[O:23])[NH:20][CH:19]=[N:18][C:17]=2[CH:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-(trifluoromethyl)aniline (225.6 mg, 1.4 mmol) in THF (6 mL) cooled to 0° C. under dry N2 was added a solution of sodium bis(trimethylsill)amide in THF (1.0 M, 2 mL, 2 mmol) with a syringe resulting a mixture which was stirred at 0° C. for 20 min A solution of 5,7-dichloropyrido[4,3-d]pyrimidin-4(3H)-one (216 mg, 1.0 mmol) in THF (4 mL) was added and the reaction mixture was stirred at 0° C. for 30 minutes and at the room temperature for 5 hours and concentrated to a residue. Chromatography of the residue with gradient mixed solvents from DCM/MeOH/28% aqueous NH4OH (320:10:1) to (160:10:1) afforded the title compound. 1H NMR (DMSO-d6) δ 6.99 (s, 1H), 7.42 (d, J=9 Hz, 1H), 7.59 (m, 1H), 7.86 (d, J=9 Hz, 1H), 7.72 (s, 1H), 8.30 (s, 1H), 8.38 (s, 1H); ESI-MS m/z 341.1 (MH+).

Workup

customresulting a mixture which
additionwas added
concentrationconcentrated to a residue
additionChromatography of the residue with gradient mixed solvents from DCM/MeOH/28% aqueous NH4OH (320:10:1) to (160:10:1)

Sources & evidence

ORD record: ord-a0f3528b83f34ab68e4f5e1227b79a32
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354526B2

Reaction notes

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