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

HRID 1670207Notes

Reaction equation

HRID 1670207 reaction equation
NC1C=CC(OC2N=CN=C(N)C=2)=C(F)C=1.FC1C=CC(CC(N=C=O)=O)=CC=1.COC1C=CC(C[NH:37][C:38]2[N:43]=[CH:42][N:41]=[C:40]([O:44][C:45]3[CH:50]=[CH:49][C:48]([NH:51][C:52]([NH:54][C:55](=[O:64])[CH2:56][C:57]4[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=4)=[O:53])=[CH:47][C:46]=3[F:65])[CH:39]=2)=CC=1>C1COCC1>[NH2:37][C:38]1[N:43]=[CH:42][N:41]=[C:40]([O:44][C:45]2[CH:50]=[CH:49][C:48]([NH:51][C:52]([NH:54][C:55](=[O:64])[CH2:56][C:57]3[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=3)=[O:53])=[CH:47][C:46]=2[F:65])[CH:39]=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 598528916-(4-Amino-2-fluorophenoxy)pyrimidin-4-amine

Product 1

HCID 116469711-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)ureaYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared from 6-(4-amino-2-fluorophenoxy)pyrimidin-4-amine (92 mg, 0.42 mmol) and 0.36 M 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 1.3 mL, 0.45 mmol) in THF as described above for Example 11. The crude product was purified by trituration using 1:1 EtOH/H2O followed by absolute EtOH. The product was vacuum dried to give the title compound (100 mg, 60%). A second, slightly less pure crop of the product (45 mg, 27%) was obtained by extracting the combined filtrates and washing with EtOAc. 1H NMR (DMSO-d6) δ 10.99 (s, 1H), 10.50 (s, 1H), 8.01 (s, 1H), 7.65 (dd, 1H, J=12.6, 2.1 Hz), 7.33 (dd, 2H, J=8.1, 6.0 Hz), 7.28 (dd, 1H, J=8.6, 2.0 Hz), 7.22 (dd, 1H, J=8.8, 8.8 Hz), 7.17-7.12 (m, 2H), 6.89 (br s, 2H), 5.80 (s, 1H), 3.71 (s, 2H); MS (ESI+) m/z 400.09 (M+H)+.

Workup

  1. customThe crude product was purified by trituration
  2. customdried

Sources & evidence

ORD record
ord-62b7c9762fde42229cdaa8e332c48a79
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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