1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea → 1-(3-Fluoro-4-(3-nitropyridin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)urea

HRID 1670281Notes

Reaction equation

HRID 1670281 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:18])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16].[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([N:29]=[C:30]=[O:31])=[O:28])=[CH:22][CH:21]=1.COC1C=CC(CNC2N=CN=C(OC3C=CC(NC(NC(=O)CC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:30]([NH:29][C:27](=[O:28])[CH2:26][C:23]2[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=2)=[O:31])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16]

Participants

5

Reactant 3

HCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea2×HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 442030423-Fluoro-4-(3-nitropyridin-4-yloxy)benzenamine

Product 1

HCID 598530011-(3-Fluoro-4-(3-nitropyridin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)ureaYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-fluoro-4-(3-nitropyridin-4-yloxy)benzenamine (158 mg, 0.63 mmol) in THF (3 mL) was treated with a solution of solution of 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 1.3 mmol) and stirred at room temperature for 2 h then at 50° C. for 5 min. The mixture was concentrated and the residue treated with DMF (15 mL) and SiO2 (150 mg) and the mixture concentrated to dryness under vacuum and applied to a SiO2 column. The column was eluted with 20-60% EtOAc/hexanes to give the product, which was further purified by trituration with isopropyl ether to give a pale yellow solid (120 mg, 25%). 1H NMR (DMSO-d6) δ 11.07 (s, 1H), 10.63 (s, 1H), 9.19 (s, 1H), 8.67 (d, 1H, J=5.6 Hz), 7.85 (d, 1H, J=11.7 Hz), 7.46-7.45 (m, 2H), 7.39-7.35 (m, 2H), 7.18 (dd, 2H, J=8.6, 8.6 Hz), 7.01 (d, 1H, J=6.1 Hz), 3.76 (s, 2H).

Workup

  1. waitat 50° C. for 5 min
  2. concentrationThe mixture was concentrated
  3. additionthe residue treated with DMF (15 mL) and SiO2 (150 mg)
  4. concentrationthe mixture concentrated to dryness under vacuum
  5. washThe column was eluted with 20-60% EtOAc/hexanes
  6. customto give the product, which
  7. customwas further purified by trituration with isopropyl ether

Sources & evidence

ORD record
ord-9ad197f7bb514c6f8de04c2d49bd6f41
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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