2-[4-(3-amino-1-propynyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide → 2-[4-(3-aminopropyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide
Reaction equation
[NH2:1][CH2:2][C:3]#[C:4][C:5]1[CH:26]=[CH:25][C:8]([NH:9][C:10]2[C:22]([F:23])=[C:21]([F:24])[CH:20]=[CH:19][C:11]=2[C:12]([NH:14][O:15][CH2:16][CH2:17][OH:18])=[O:13])=[C:7]([F:27])[CH:6]=1>CCO.[Pd]>[NH2:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:26]=[CH:25][C:8]([NH:9][C:10]2[C:22]([F:23])=[C:21]([F:24])[CH:20]=[CH:19][C:11]=2[C:12]([NH:14][O:15][CH2:16][CH2:17][OH:18])=[O:13])=[C:7]([F:27])[CH:6]=1Participants
Procedure
The product of Example 9, 2-[4-(3-amino-1-propynyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide was dissolved in absolute EtOH and hydrogenated in the presence of 5% Pd/C by the general procedure of Example 1, Step D. Purification of the resulting oil was carried out by column chromatography on silica gel (1% NH4OH in 25% MeOH/CH2Cl2 as eluant) to give 2-[4-(3-aminopropyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide as a cream solid (46%); m.p. (MeOH/CH2Cl2) 178–181° C. 1H NMR [400 MHz, (CD3)2SO] δ 7.61–7.53 (m, 1 H), 6.97–6.87 (m, 2 H), 6.78 (dd, J=8.2, 1.3 Hz, 1 H), 6.60 (dd, J=15.1, 8.6 Hz, 1 H), 4.10 (br s, 1 H), 3.77 (t, J=5.0 Hz, 2 H), 3.56 (t, J=5.0 Hz, 2 H), 2.70 (t, J=7.3 Hz, 2 H), 2.53 (t, J=8.0 Hz, 2 H), 1.75 (pentet, J=7.5 Hz, 2 H). Not all exchangeable protons observed. Anal. calcd. for C18H20F3N3O3: C, 56.4; H, 5.3; N, 11.0. Await Found.
Workup
- customPurification of the resulting oil
Sources & evidence
- ORD record
- ord-703e0c7bf0ba48d2916d2a4a288c816a
- Source dataset
- uspto-grants-2006_07
- Patent number
- US07078438B2
Reaction notes
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