Diisopropylethylamine → N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

HRID 2237207Notes

Reaction equation

HRID 2237207 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:16][CH:15]=3)[CH:8]=2)=[C:4]([F:30])[CH:3]=1.FC1C=C(N[C:55](=[O:67])[CH2:56][C:57]([NH:59][C:60]2[CH:65]=[CH:64][C:63]([F:66])=[CH:62][CH:61]=2)=[O:58])C=CC=1OC1C=CN=C(NCCN2CCOCC2)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.COC1C=CC(CNC2N=C(OC3C=CC(NC(=O)CC(NC4C=CC(F)=CC=4)=O)=CC=3F)C=CN=2)=CC=1>CN(C=O)C>[CH2:21]([O:20][C:17]1[CH:16]=[CH:15][C:14]([NH:13][C:9]2[N:10]=[CH:11][N:12]=[C:7]([O:6][C:5]3[CH:28]=[CH:29][C:2]([NH:1][C:55](=[O:67])[CH2:56][C:57]([NH:59][C:60]4[CH:65]=[CH:64][C:63]([F:66])=[CH:62][CH:61]=4)=[O:58])=[CH:3][C:4]=3[F:30])[CH:8]=2)=[CH:19][CH:18]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59852883N1-(4-(2-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideHCID 59852917N1-(3-Fluoro-4-(2-(2-morpholinoethylamino)pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide2×HCID 598530036-(4-Amino-2-fluorophenoxy)-N-(4-(benzyloxy)phenyl)pyrimidin-4-amine

Product 1

HCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared from a mixture 6-(4-amino-2-fluorophenoxy)-N-(4-(benzyloxy)phenyl)pyrimidin-4-amine (45 mg, 0.11 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (Compound B of Example 1, 24 mg, 0.12 mmol), TBTU (48 mg, 0.15 mmol), DIPEA (0.26 mL, 0.15 mmol), and DMF (1 mL) using a similar procedure described for the preparation of Compound C of Example 1. The crude product was triturated with isopropyl ether to give the title compound (56 mg, 88%) as a pink solid. 1H NMR (DMSO-d6) δ 10.47 (s, 1H), 10.27 (s, 1H), 9.45 (s, 1H), 8.25 (s, 1H), 7.77 (dd, 1H, J=12.7, 2.0 Hz), 7.65-7.62 (m, 2H), 7.46 (d, 4H, J=7.3 Hz), 7.40 (dd, 2H, J=7.6, 7.3 Hz), 7.37-7.29 (m, 3H), 7.17 (dd, 2H, J=9.0, 8.3 Hz), 7.00 (d, 2H, J=9.0 Hz) 6.09 (s, 1H), 5.09 (s, 2H) 3.49 (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-4a15a611bdef426f8ecbb4eca6d6f84d
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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