3,4-Difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)benzamide → 3,4-difluoro-2-[2-fluoro-4-(3-hydroxypropyl)anilino]-N-(2-hydroxyethoxy)benzamide
Reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][OH:26])=[CH:19][C:18]=2[F:27])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]>CCO.[Pd]>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][OH:26])=[CH:19][C:18]=2[F:27])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]Participants
Procedure
The product of Example 10, Step D, 3,4-Difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-benzamide was hydrogenated in absolute EtOH in the presence of 5% Pd/C by the procedure of Example 1, Step D. An off-white solid was isolated which was purified by filtration through a plug of silica gel (EtOAc as eluant). 3,4-Difluoro-2-[2-fluoro-4-(3-hydroxypropyl)anilino]-N-(2-hydroxyethoxy)benzamide was isolated as a crystalline cream solid (52 mg, 73%); m.p. (EtOAc/Et2O) 115–116° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.85 (br s, 1 H), 8.83 (br s, 1 H), 7.44–7.37 (m, 1 H), 7.13–7.05 (m, 1 H), 7.03 (dd, J=12.6, 1.6 Hz, 1H), 6.88 (dd, J=8.2, 1.6 Hz, 1 H), 6.81 (ddd, J=8.7, 8.7, 4.5 Hz, 1 H), 4.76 (br s, 1H), 4.46 (t, J=5.1 Hz, 1 H), 3.86 (t, J=4.8 Hz, 2 H), 3.57 (t, J=5.0 Hz, 2 H), 3.43–3.35 (m, 2 H), 2.58–2.52 (m, 2 H), 1.72–1.64 (m, 2 H). Anal. calcd. for C18H19F3N2O4.0.5Et2O: C, 57.0; H, 5.7; N, 6.7. Found C, 56.6; H, 5.5; N, 6.8.
Workup
- customAn off-white solid was isolated which
- filtrationwas purified by filtration through a plug of silica gel (EtOAc as eluant)
Sources & evidence
- ORD record
- ord-ac5dfe3769464fd4a6214661ea172ebc
- Source dataset
- uspto-grants-2006_07
- Patent number
- US07078438B2
Reaction notes
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