Tetrafluoro-m-phenylenediamine dihydrochloride → 1-[6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-{4-[2-(dimethylamino)ethyl]phenylamino}-1,5-naphthyridin-3-yl)ethanone dihydrochloride
Reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])=[CH:18][CH:17]=1.[Cl:27][C:28]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[C:30]([F:43])[C:29]=1[OH:44].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>>[ClH:1].[ClH:27].[Cl:27][C:28]1[CH:33]=[C:32]([C:2]2[N:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]3[NH:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][N:24]([CH3:25])[CH3:26])=[CH:20][CH:21]=2)[CH:31]=[C:30]([F:43])[C:29]=1[OH:44]Participants
4
Reactant 3
Product 1
Procedure
Following general procedure II, 1-(6-chloro-4-{4-[2-(dimethylamino)ethyl]phenylamino}-1,5-naphthyridin-3-yl)ethanone (40 mg, 0.11 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (41 mg, 0.15 mmol) followed by formation of the dihydrochloride salt to afford the desired product (13 mg, 22%) as an orange solid: 1H NMR (500 MHz, CD3OD) δ 9.29 (s, 1H), 8.42 (d, J=9.1 Hz, 1H), 8.32 (d, J=9.0 Hz, 1H), 7.44 (d, J=8.5 Hz, 2H), 7.41-7.35 (m, 3H), 7.11 (br s, 1H), 3.43-3.36 (m, 2H), 3.23-3.13 (m, 2H), 2.98 (s, 6H), 2.80 (s, 3H); ESI MS m/z 479 [M+H]+; HPLC>99% (AUC), tR=9.67 min.
Sources & evidence
- ORD record
- ord-844a7815d89b4a91902295e0e59795ee
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09345709B2
Reaction notes
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