Acrylonitrile → 2-(Hydroxy(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)methyl)acrylamide
Reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[N:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]3[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=3)[CH:25]=[O:26])[CH:16]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30](#[N:33])[CH:31]=[CH2:32].C1N2CCN(CC2)C1.[O:42]1CCOCC1.O>>[OH:26][CH:25]([C:24]1[CH:27]=[CH:28][CH:29]=[C:22]([NH:21][C:17]2[CH:16]=[C:15]([NH:14][C:11]3[CH:10]=[CH:9][C:8]([O:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:13][CH:12]=3)[N:20]=[CH:19][N:18]=2)[CH:23]=1)[C:31](=[CH2:32])[C:30]([NH2:33])=[O:42]Participants
Procedure
To a stirred solution of 3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)benzaldehyde (100 mg, 0.26 mmol) and acrylonitrile (36 mg, 0.52 mmol) in 1,4-dioxane/H2O (0.5 mL/0.5 mL) was added DABCO (29 mg, 0.26 mmol) at rt. Stirring was continued at room temperature for 48 h after which time the reaction mixture was concentrated under reduced pressure. The residue obtained was further purified by column chromatography (SiO2, 60-120, pet ether/ethyl acetate, 6/4) to give 2-(hydroxy(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)methyl)acrylamide (I-84) as a white solid. 1H NMR (DMSO-d6) δ ppm: 5.33 (s, 1H), 6.06 (s, 1H), 6.20 (s, 1H), 6.25 (s, 1H), 6.80 (s, 1H), 6.88 (s, 1H), 6.95-7.05 (m, 4H), 7.09-7.13 (m, 2H), 7.16 (bd, J=7.92 Hz, 1H), 7.32-7.39 (m, 5H), 7.47 (s, 1H), 8.31 (s, 1H); LCMS: m/e 436 (M+1).
Workup
- concentrationafter which time the reaction mixture was concentrated under reduced pressure
- customThe residue obtained
- customwas further purified by column chromatography (SiO2, 60-120, pet ether/ethyl acetate, 6/4)
Sources & evidence
- ORD record
- ord-ff7b4912fa7c4acdb5b133205045266c
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09040541B2
Reaction notes
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