Diisopropylethylamine → N1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

HRID 2373951Notes

Reaction equation

HRID 2373951 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=3[F:23])[N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.COC1C=CC(CNC2N=CN=C(OC3C=CC(NC(NC(=O)CC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1.NC1N=CN=C(OC2C=CC(NC(NC(=O)CC3C=CC(F)=CC=3)=S)=CC=2F)C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[F:124][C:125]1[CH:130]=[CH:129][C:128]([N:131](C2C=CC(OC3C=CN=CC=3)=CC=2)[C:132](=[O:137])[CH2:133][C:134](N)=[O:135])=[CH:127][CH:126]=1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[N:10]=[CH:11][N:12]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:134](=[O:135])[CH2:133][C:132]([NH:131][C:128]4[CH:129]=[CH:130][C:125]([F:124])=[CH:126][CH:127]=4)=[O:137])=[CH:18][C:17]=3[F:23])[CH:14]=2)=[CH:24][CH:25]=1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 115389121-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea2×HCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)ureaHCID 11610278N-(4-Fluorophenyl)-N-(4-(pyridin-4-yloxy)phenyl)malonamideHCID 59301603N-(4-Methoxybenzyl)-6-(4-amino-2-fluorophenoxy)pyrimidin-4-amine

Product 1

HCID 59301604N1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared from N-(4-methoxybenzyl)-6-(4-amino-2-fluorophenoxy)pyrimidin-4-amine. (Compound C of Example 11, 200 mg, 0.59 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (Compound B of Example 1, 128 mg, 0.65 mmol), TBTU (228 mg, 0.71 mmol), and DIPEA (123 μL, 0.71 mmol) in DMF using a similar procedure described for the preparation of Compound C of Example 1. The crude product was purified by trituration with isopropyl ether to give the title compound (250 mg, 82%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.43 (s, 1H), 10.25 (s, 1H), 8.09 (s, 1H), 7.85 (s, 1H), 7.72 (dd, 1H, J=9.1, 5.0 Hz), 7.62 (dd, 2H, J=8.8, 5.0 Hz), 7.31-7.21 (m, 4H), 7.15 (dd, 2H, J=8.8, 8.8 Hz), 6.88 (m, 2H), 5.90 (s, 1H), 4.42 (br s, 2H), 3.71 (s, 3H), 3.46 (s, 2H); MS(ESI+) m/z 520.14 (M+H)+.

Workup

  1. customThe crude product was purified by trituration with isopropyl ether

Sources & evidence

ORD record
ord-48747d8a37b344a8877c83d00ca3eec4
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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