4-Bromo-1,3-thiazole-2-carboxylic acid → 4-bromo-N-(5-((6-methoxy-7-(piperidin-4-ylmethoxy)quinolin-4-yl)oxy)pyridin-2-yl)thiazole-2-carboxamide
Reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]4[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[Br:36][C:37]1[N:38]=[C:39]([C:42](Cl)=[O:43])[S:40][CH:41]=1.BrC1N=C(C(O)=O)SC=1>>[Br:36][C:37]1[N:38]=[C:39]([C:42]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:8][C:9]3[C:18]4[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]5[CH2:24][CH2:25][NH:26][CH2:27][CH2:28]5)=[C:16]([O:19][CH3:20])[CH:17]=4)[N:12]=[CH:11][CH:10]=3)=[CH:6][N:7]=2)=[O:43])[S:40][CH:41]=1Participants
Reactant 3
Product 1
Procedure
Following the general procedure reported in Preparative Example 16 Step 5 X15 was prepared from tert-butyl 4-(((4-((6-aminopyridin-3-yl)oxy)-6-methoxyquinolin-7-yl)oxy)methyl)piperidine-1-carboxylate and 4-bromothiazole-2-carbonyl chloride, which was prepared similar to Preparative Example 16 step 4 from commercially available 4-bromothiazole-2-carboxylic acid. 1H NMR (400 MHz, d6-DMSO, 300K) δ 1.53 (m, 2H), 1.98 (d, J=12.5 Hz, 2H), 2.18 (m, 1H), 2.95 (m, 2H), 3.33 (m, 2H), 3.94 (s, 3H), 4.08 (d, J=6.3 Hz, 2H), 6.58 (d, J=5.2 Hz, 1H), 7.45 (s, 1H), 7.54 (m, 1H), 7.87 (dd, J=2.9 Hz, J=9.0 Hz, 1H), 8.19 (d, J=9.0 Hz, 1H), 8.31 (s, 1H), 8.45 (d, J=2.9 Hz, 1H), 8.50 (d, J=5.2 Hz, 1H), 10.61 (br s, 1H). MS (ES) C25H24BrN5O4S requires: 570. Found: 570/572 (M−1-H)+.
Workup
- customwas prepared similar
Sources & evidence
- ORD record
- ord-5f4f77acd6254228825680da964e84c0
- Source dataset
- uspto-grants-2015_04
- Patent number
- US08999982B2
Reaction notes
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