1,1'-Carbonyldiimidazole → 4-[3-fluoro-4-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]-N-methylpyridine-2-carboxamide

HRID 658492

Reaction equation

HRID 658492 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1[CH:7]=[CH:6]N=C1)=[O:2].NC1C=[CH:29][C:17]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([C:25]([NH:27][CH3:28])=[O:26])[CH:20]=2)=[CH:16][C:15]=1[F:31].[CH3:32][N:33]1[C:41]2[C:36](=CC(N)=[CH:39][CH:40]=2)[CH:35]=[N:34]1>C1C=CC=CC=1.C(Cl)Cl>[F:31][C:15]1[CH:16]=[C:17]([CH:29]=[CH:11][C:12]=1[NH:8][C:1]([NH:3][C:7]1[CH:6]=[C:36]2[C:41](=[CH:40][CH:39]=1)[N:33]([CH3:32])[N:34]=[CH:35]2)=[O:2])[O:18][C:19]1[CH:24]=[CH:23][N:22]=[C:21]([C:25]([NH:27][CH3:28])=[O:26])[CH:20]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27680321-methyl-1H-indazol-5-amineHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

Product 1

HCID 104555834-[3-fluoro-4-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]-N-methylpyridine-2-carboxamideYield 27%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1′-carbonyldiimidazole (62 mg, 0.38 mmol) in benzene (2 mL) and CH2Cl2 (1 mL) was added 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide (100 mg, 0.38 mmol). The resulting solution was stirred at room temperature for 16 h, then was treated with 1-methyl-5-aminoindazole (56 mg, 0.38 mmol). The reaction continued to stir at room temperature for 18 h. The mixture was concentrated under reduced pressure and the residue was triturated with Et2O. The solid was collected by filtration, and then purified by preparative HPLC to afford 44 mg (27%) of the title product. 1H-NMR (DMSO-d6) δ 2.78 (d, J=4.8, 3H), 4.01 (s, 3H), 7.02-7.07 (m, 1H), 7.14-7.18 (m, 1H), 7.28-7.36 (m, 2H), 7.39 (d, J=2.9, 1H), 7.52-7.59 (m, 1H), 7.89-7.96 (m, 2H), 8.23 (t, J=9.0, 1H), 8.49 (d, J=4.9, 1H), 8.57-8.63 (m, 1H), 8.71-8.81 (m, 1H), 9.06 (s, 1H); MS LC-MS [M+H]+=435.1; mp 231-234° C.

Workup

  1. stirringto stir at room temperature for 18 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was triturated with Et2O
  4. filtrationThe solid was collected by filtration
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-42cb988f1dd64c1da18e768779d9d0bc
Source dataset
uspto-grants-2011_12
Patent number
US08076488B2

Linked notes

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