Diisopropylethylamine → N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxamide

HRID 2374077Notes

Reaction equation

HRID 2374077 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[C:9]2=[O:16])=[CH:4][CH:3]=1.C(OC1C=[CH:29][C:28]([NH:31][C:32]2[N:37]=CN=[C:34]([O:38][C:39]3[CH:44]=[CH:43][C:42]([NH:45]C(=O)CC(NC4C=CC(F)=CC=4)=O)=[CH:41][C:40]=3[F:59])[CH:33]=2)=CC=1)C1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[NH2:37][C:32]1[CH:33]=[C:34]([O:38][C:39]2[CH:44]=[CH:43][C:42]([NH:45][C:13]([CH:10]3[CH2:11][CH2:12][N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:9]3=[O:16])=[O:15])=[CH:41][C:40]=2[F:59])[CH:29]=[CH:28][N:31]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 41820071-(4-Fluorophenyl)-2-oxo-3-pyrrolidinecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide2×

Product 1

HCID 11495542N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxamideYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxylic acid (0.3 mol), 4-(4-amino-2-fluorophenoxy)pyridin-2-amine (Compound B of Example 24, 21.9 mg, 0.1 mmol) in DMF (0.5 ml), was added HATU (76 mg, 0.2 mmol) and followed by diisopropylethylamine (0.1 mL, 0.57 mmol). The reaction mixture was stirred at room temperature overnight and was then quenched with 2 mL of methanol. The reaction mixture was purified by prep HPLC. The desired fractions were combined, neutralized with sat. aq. NaHCO3 solution, and concentrated in vacuo to afford the title compound (18 mg, 43%) as a white solid. 1H NMR (DMSO-d6) δ 10.76 (br s, 1H), 7.95 (d, 1H, J=7.2 Hz), 7.91 (m, 1H), 7.68 (m, 2H), 7.50 (m, 1H), 7.44 (t, 1H, J=10.0 Hz), 7.24 (m, 2H), 6.70 (m, 1H), 6.11 (d, 1H, J=2.8 Hz), 3.91 (m, 2H), 3.78 (t, 1H, J=5.0 Hz), 2.41 (m, 2H); MS(ESI+) m/z 425.15 (M+H)+.

Workup

  1. customwas then quenched with 2 mL of methanol
  2. customThe reaction mixture was purified by prep HPLC
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-896db2d2e2e94e289844ff8d6781b6d6
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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