1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea → HCID 59852854, compound

HRID 2374016Notes

Reaction equation

HRID 2374016 reaction equation
[NH2:1][C:2]1[CH:32]=[CH:31][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2/[CH:13]=[CH:14]/[C:15]([N:17]2[CH2:22][CH2:21][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]2)=[O:16])=[C:4]([F:33])[CH:3]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42]([N:44]=[C:45]=[O:46])=[O:43])=[CH:37][CH:36]=1.COC1C=CC(CNC2N=CN=C(OC3C=CC(NC(NC(=O)CC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1>>[F:33][C:4]1[CH:3]=[C:2]([NH:1][C:45]([NH:44][C:42](=[O:43])[CH2:41][C:38]2[CH:39]=[CH:40][C:35]([F:34])=[CH:36][CH:37]=2)=[O:46])[CH:32]=[CH:31][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[CH:9][C:8]=1/[CH:13]=[CH:14]/[C:15]([N:17]1[CH2:18][CH2:19][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:21][CH2:22]1)=[O:16]

Participants

4

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 59852847HCID 59852847, compound

Product 1

HCID 59852854HCID 59852854, compound

Procedure

The title compound was prepared from (E)-tert-butyl 1-(3-(4-(4-amino-2-fluorophenoxy)pyridin-3-yl)acryloyl)piperidin-4-ylcarbamate (42 mg, 0.092 mmol) and 0.3 M solution of 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 0.50 mL, 0.15 mmol) in a manner similar to that of Step D of Example 33. The crude product was adsorbed onto silica gel and purified by flash chromatography eluting with 0-5% MeOH/EtOAc to give the product (20 mg, 33%) as a white solid. 1H NMR (DMSO-d6) δ 11.05 (s, 1H), 10.59 (s, 1H), 9.03 (s, 1H), 8.37 (d, 1H, J=5.6 Hz), 7.82-7.74 (m, 2H), 7.47 (d, 1H, J=15.8 Hz), 7.42-7.33 (m, 4H), 7.20-7.13 (m, 2H), 6.89 (d, 1H, J=8.1 Hz), 6.63 (d, 1H, J=5.6 Hz), 4.31 (d, 1H, J=13.7 Hz), 4.19 (d, 1H, J=12.7 Hz), 3.74 (s, 2H), 3.56-3.47 (m, 1H), 3.22-3.13 (m, 1H), 2.84-2.76 (m, 1H), 1.76 (s, 2H), 1.37 (s, 9H), 1.32-1.20 (m, 2H); MS(ESI+): m/z 636.23 (M+H)+.

Workup

  1. custompurified by flash chromatography
  2. washeluting with 0-5% MeOH/EtOAc

Sources & evidence

ORD record
ord-85681c232bce4a8e9c319250307f4f1d
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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