3-amino-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid isopropyl ester → 3-[5-Chloro-4-(2-fluoro-6-prop-2-ynylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid isopropyl ester
Reaction equation
[CH:1]([O:4][C:5]([N:7]1[C:13]2[CH:14]=[CH:15][C:16]([NH2:18])=[CH:17][C:12]=2[O:11][CH2:10][CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].Cl[C:20]1[N:25]=[C:24]([NH:26][C:27]2[C:38]([F:39])=[CH:37][CH:36]=[CH:35][C:28]=2[C:29]([NH:31][CH2:32][C:33]#[CH:34])=[O:30])[C:23]([Cl:40])=[CH:22][N:21]=1>>[CH:1]([O:4][C:5]([N:7]1[C:13]2[CH:14]=[CH:15][C:16]([NH:18][C:20]3[N:25]=[C:24]([NH:26][C:27]4[C:28]([C:29](=[O:30])[NH:31][CH2:32][C:33]#[CH:34])=[CH:35][CH:36]=[CH:37][C:38]=4[F:39])[C:23]([Cl:40])=[CH:22][N:21]=3)=[CH:17][C:12]=2[O:11][CH2:10][CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]Participants
Reactant 2
Product 1
Procedure
3-[5-Chloro-4-(2-fluoro-6-prop-2-ynylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid isopropyl ester was prepared from 3-amino-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid isopropyl ester and 2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-N-prop-2-ynyl-benzamide in an analogous manner to Example 1410. Product isolated as a pale yellow solid (99 mg, 53%). m.p.=242-244° C.; LCMS (m/e) 553 (M+H); 1H-NMR (d6-DMSO, 400 MHz) δ 9.47-9.35 (m, 1H), 9.25-9.15 (m, 1H), 9.04-8.95 (m, 1H), 8.19 (s, 1H), 7.57-7.40 (m, 3H), 7.26 (s, 1H), 7.13-7.04 (m, 1H), 6.98-6.87 (m, 1H), 4.87-4.71 (m, 1H), 4.06-3.82 (m, 4H), 3.68-3.41 (m, 2H), 3.11 (s, 1H), 1.97-1.79 (m, 2H), 1.33-0.98 (m, 6H).
Sources & evidence
- ORD record
- ord-96d34ef0a3674860a7829d8a622fce0e
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08552186B2
Reaction notes
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