Propargylamine → 2-[4-(3-amino-1-propynyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide
Reaction equation
[CH2:1]([NH2:4])[C:2]#[CH:3].[F:5][C:6]1[C:7]([NH:20][C:21]2[CH:26]=[CH:25][C:24](I)=[CH:23][C:22]=2[F:28])=[C:8]([CH:16]=[CH:17][C:18]=1[F:19])[C:9]([NH:11][O:12][CH2:13][CH2:14][OH:15])=[O:10]>>[NH2:4][CH2:1][C:2]#[C:3][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:7]2[C:6]([F:5])=[C:18]([F:19])[CH:17]=[CH:16][C:8]=2[C:9]([NH:11][O:12][CH2:13][CH2:14][OH:15])=[O:10])=[C:22]([F:28])[CH:23]=1Participants
Procedure
The title compound was prepared by Sonogashira reaction of propargyl amine and 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide by the general procedure of Example 1, Step A. The orange oil resulting from workup was purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant), to give 2-[4-(3-amino-1-propynyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide as a pale orange solid (100%); m.p. (Et2O) 72–76° C. 1H NMR [400 MHz, (CD3)2SO] δ 9.14 (v br s, 1 H), 7.49–7.44 (m, 1 H), 7.21 (dd, J=12.3, 1.7 Hz, 1 H), 7.24–7.14 (m, 1 H), 7.08 (dd, J=8.4, 1.6 Hz, 1 H), 6.77 (ddd, J=8.8, 8.8, 5.1 Hz, 1 H), 5.45 (br s, 2 H), 3.83 (t, J=4.8 Hz, 2 H), 3.55 (t, J=5.0 Hz, 2H), 3.41–3.32 (m, 2H, obscured by H2O). Not all exchangeable protons observed. CRL10671. Await HRMS. Anal. calcd. for C28H16F3N3O3: C, 57.0; H, 4.3; N, 11.1. Await Found. HRMS (EI+) calcd for C18H16F3N3O3 379.1144 (M+), found 379.1140.
Workup
- customThe orange oil resulting from workup
- customwas purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant)
Sources & evidence
- ORD record
- ord-1d409171efd4418290188d6fe86a4dd7
- Source dataset
- uspto-grants-2006_07
- Patent number
- US07078438B2
Reaction notes
Loading…