Tetrafluoro-m-phenylenediamine dihydrochloride → 1-[6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-{3 [2-(pyrrolidin-1-yl)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][CH:19]=[C:18]([CH2:22][CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:17]=1.[Cl:29][C:30]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[C:32]([F:45])[C:31]=1[OH:46].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>>[ClH:1].[ClH:29].[Cl:29][C:30]1[CH:35]=[C:34]([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:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH2:23][N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:17]=2)[CH:33]=[C:32]([F:45])[C:31]=1[OH:46]Participants
4
Reactant 3
Product 1
Procedure
Following general procedure II, 1-(6-chloro-4-{3-[2-(pyrrolidin-1-yl)ethyl]phenylamino}-1,5-naphthyridin-3-yl)ethanone (59 mg, 0.15 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (61 mg, 0.23 mmol) followed by formation of the dihydrochloride salt to afford the desired product (63 mg, 72%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 9.30 (s, 1H), 8.43 (d, J=9.0 Hz, 1H), 8.34 (d, J=8.9 Hz, 1H), 7.54-7.30 (m, 4H), 7.23 (br s, 1H), 7.13 (br s, 1H), 3.68-3.60 (m, 2H), 3.35-3.23 (m, 2H), 3.11-2.99 (m, 4H), 2.80 (br s, 3H), 2.19-2.07 (m, 2H), 2.05-1.96 (m, 2H); ESI MS m/z 505 [M+H]+; HPLC>99% (AUC), tR=10.17 min.
Sources & evidence
- ORD record
- ord-0721d07f639c4eb498252e5dc2f85edd
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09345709B2
Reaction notes
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