4-Methylmorpholine → N1-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

HRID 347481Notes

Reaction equation

HRID 347481 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:30])[CH2:20][C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:22])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[CH:15][CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.[F:51][P-](F)(F)(F)(F)F.CN1CCOCC1.FC1C=CC(N)=CC=1>CN(C)C=O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:30])[CH2:20][C:21]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([F:51])=[CH:28][CH:29]=2)=[O:22])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[CH:15][CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 97314-FluoroanilineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11668583N1-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-phenylmalonamide2×

Product 1

HCID 11690357N1-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenylamino)-3-oxopropanoic acid (18 mg, 0.55 mmol, Compound B of Example 23), BOP reagent (36 mg, 0.082 mmol), 4-methylmorpholine (30 μL, 0.27 mmol), and 4-fluoroaniline (5.2 μL, 0.055 mmol) in dimethylformamide (0.5 mL) was stirred at room temperature for 16 h. The reaction was diluted with EtOAc (4 mL) and washed with water, 10% aq LiCl solution, and brine (1×3 mL each). The organic solution was dried over anhydrous Na2SO4 and then concentrated in vacuo. Purification by flash chromatography on silica gel (SiO2, EtOAc/Hexane 7:3) gave the desired compound as a white solid. The product was lyophilized with acetonitrile/water to give the title compound (14 mg, 61%) as a white powder. 1H NMR (CDCl3) δ 9.28 (br s, 1H), 8.64 (br s, 1H), 7.89 (s, 1H), 7.73 (dd, 1H, J=2.5, 1.5 Hz), 7.69 (dd, 1H, J=11.6, 1.9 Hz), 7.42 (m, 3H), 7.21 (m, 1H), 6.97 (m, 3H), 6.80 (dd, 1H, J=4.5, 2.6 Hz), 3.49 (s, 2H); MS(ESI+) m/z 424.1 (M+H)+.

Workup

  1. washwashed with water, 10% aq LiCl solution, and brine (1×3 mL each)
  2. dry with materialThe organic solution was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customPurification by flash chromatography on silica gel (SiO2, EtOAc/Hexane 7:3)

Sources & evidence

ORD record
ord-3731dfd55c7448af89dbb8a225a26213
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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