1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea → N-((4-((2-aminopyridin-4-yl)oxy)-3-fluorophenyl)carbamoyl)-2-(4-fluorophenyl)acetamide

HRID 2237196Notes

Reaction equation

HRID 2237196 reaction equation
COC1C=C[C:6]([CH2:7][NH:8][C:9]2[N:14]=CN=[C:11]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26](=[O:35])[CH2:27][C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)=[O:24])=[CH:18][C:17]=3[F:36])[CH:10]=2)=CC=1.NC1C=CC(OC2C=CN=C(N)C=2)=C(F)C=1>C(Cl)Cl>[NH2:14][C:9]1[CH:10]=[C:11]([O:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26](=[O:35])[CH2:27][C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)=[O:24])=[CH:18][C:17]=2[F:36])[CH:6]=[CH:7][N:8]=1

Participants

4

Reactant 2

HCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea2×HCID 231533352-Amino-4-(4-amino-2-fluorophenoxy)pyridine

Product 1

HCID 17748441N-((4-((2-aminopyridin-4-yl)oxy)-3-fluorophenyl)carbamoyl)-2-(4-fluorophenyl)acetamideYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(4-Fluorophenyl)acetyl isocyanate (Compound D of Example 11, 0.362 M, 0.351 mL, 0.127 mmol, 1.3 eq) was added to a solution of 4-(4-amino-2-fluorophenoxy)pyridin-2-amine (0.022 g, 0.100 mmol, 1.0 eq) in CH2Cl2 (2.0 mL) at room temperature. The reaction mixture was stirred for 13 h at room temperature and then concentrated in vacuo. The residue was purified by silica gel flash chromatography (Merck gel 40-63 μM, 230-240 mesh, 1:1 ethyl acetate/hexane) to afford the title compound (0.025 g, 64%) as a solid. 1H NMR (CD3OD) δ 7.62-7.67 (m, 2H), 7.23-7.29 (m, 2H), 7.07-7.12 (m, 2H), 6.95-6.99 (m, 2H), 6.12-6.14 (m, 1H), 5.86-5.87 (m, 1H), 3.61 (s, 2H); MS(ESI+) m/z 399 (M+H)+; HRMS(ESI+) calcd.: 399.1269, found: 399.1269.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by silica gel flash chromatography (Merck gel 40-63 μM, 230-240 mesh, 1:1 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f8e45e2f89994086bc7ed44e2229ac70
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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