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

HRID 2373986Notes

Reaction equation

HRID 2373986 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[N:21]=[CH:20][N:19]=[C:18]([O:22]C3C=CC(NC(=O)CC(NC4C=CC(F)=CC=4)=O)=CC=3F)[CH:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC1C=CC(CC(N=C=O)=O)=CC=1.COC1C=CC(CNC2N=CN=C(O[C:72]3[CH:77]=[CH:76][C:75]([NH:78][C:79]([NH:81][C:82](=[O:91])[CH2:83][C:84]4[CH:89]=[CH:88][C:87]([F:90])=[CH:86][CH:85]=4)=[O:80])=[CH:74][C:73]=3[F:92])C=2)=CC=1>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[N:21]=[CH:20][N:19]=[C:18]([O:22][C:72]3[CH:77]=[CH:76][C:75]([NH:78][C:79]([NH:81][C:82](=[O:91])[CH2:83][C:84]4[CH:89]=[CH:88][C:87]([F:90])=[CH:86][CH:85]=4)=[O:80])=[CH:74][C:73]=3[F:92])[CH:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea3×HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide2×

Product 1

HCID 598529601-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)ureaYield 90.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared from 6-(4-amino-2-fluorophenoxy)-N-(4-(benzyloxy)phenyl)pyrimidin-4-amine (Compound B of Example 29, 45 mg, 0.11 mmol) and a solution of 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 0.13 mmol) in THF using a similar procedure described for the preparation of Compound E of Example 11. The crude product was triturated with isopropyl ether to give the title compound (58 mg, 90%) as a pink solid. 1H NMR (DMSO-d6) δ 11.02 (s, 1H), 10.54 (s, 1H), 9.46 (s, 1H), 8.24 (s, 1H), 7.70 (dd, 1H, J=12.7, 2.4 Hz), 7.46-7.26 (m, 9H), 7.18 (dd, 2H, J=9.6, 8.3 Hz), 7.00 (d, 2H, J=9.6 Hz), 6.11 (s, 1H), 5.09 (s, 2H), 3.75 (s, 2H); MS(ESI+) m/z 582.3 (M+H)+.

Workup

  1. customThe crude product was triturated with isopropyl ether

Sources & evidence

ORD record
ord-4abcd363029b430f864b530e072a627a
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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