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

HRID 1670210Notes

Reaction equation

HRID 1670210 reaction equation
[CH3:1][O:2][C:3]1[CH:38]=[CH:37][C:6]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([O:15]C3C=CC(NC(=O)CC(NC4C=CC(F)=CC=4)=O)=CC=3F)[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.FC1C=CC(CC(N=C=O)=O)=CC=1.COC1C=CC(CNC2N=CN=C(O[C:67]3[CH:72]=[CH:71][C:70]([NH:73][C:74]([NH:76][C:77](=[O:86])[CH2:78][C:79]4[CH:84]=[CH:83][C:82]([F:85])=[CH:81][CH:80]=4)=[O:75])=[CH:69][C:68]=3[F:87])C=2)=CC=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([O:15][C:67]3[CH:72]=[CH:71][C:70]([NH:73][C:74]([NH:76][C:77](=[O:86])[CH2:78][C:79]4[CH:84]=[CH:83][C:82]([F:85])=[CH:81][CH:80]=4)=[O:75])=[CH:69][C:68]=3[F:87])[CH:12]=[CH:11][N:10]=2)=[CH:37][CH:38]=1

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 59852883N1-(4-(2-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide2×

Product 1

HCID 115698941-(4-(2-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)ureaYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)pyrimidin-2-amine (Compound C of Example 14, 34 mg, 0.10 mmol) in THF (1 ml) was treated with 0.36 M 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 0.31 mL, 0.11 mmol) and the mixture stirred at RT for 1 h. The mixture was concentrated in vacuo and the solid obtained was triturated first with 3:1 isopropyl ether/EtOAc and then CH2Cl2 to give the title compound (32 mg, 62%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.47 (s, 1H), 10.26 (s, 1H), 8.15 (s, 1H), 7.76 (d, 1H, J=12.6 Hz), 7.61 (dd, 3H, J=9.1, 5.0 Hz), 7.29 (s, 2H), 7.31-7.21 (m, 3H), 6.81 (s, 3H), 6.24 (s, 1H), 4.32 (s, 1H), 3.96 (s, 1H), 3.68 (s, 3H), 3.48 (s, 2H); MS (ESI+) m/z 520.14 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe solid obtained
  3. customwas triturated first with 3:1 isopropyl ether/EtOAc

Sources & evidence

ORD record
ord-5a5944c4e64c42df920689524c247b17
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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