Aniline → N1-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-phenylmalonamide

HRID 347480Notes

Reaction equation

HRID 347480 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:24])[CH2:20][C:21]([OH:23])=O)[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+](O[N:36]1N=N[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.NC1C=CC=CC=1>CN(C)C=O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:24])[CH2:20][C:21]([NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:23])[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 6115AnilineHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 210815903-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenylamino)-3-oxopropanoic acid

Product 1

HCID 11668583N1-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-phenylmalonamide

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 (17 mg, 0.052 mmol), BOP reagent (34 mg, 0.077 mmol), 4-methylmorpholine (28 μL, 0.26 mmol), and aniline (4.7 μL, 0.052 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 (12 mg, 57%) as a white powder. 1H NMR (CDCl3) δ 9.23 (br s, 1H), 8.22 (br s, 1H), 7.90 (s, 1H), 7.72 (m, 1H), 7.46 (d, 1H, J=8.2 Hz), 7.20 (m, 7H), 6.95 (m, 1H), 6.78 (m, 1H), 3.47 (s, 2H); MS(ESI+) m/z 406.1 (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-68bb5eea2baf4933b5d93b3931f7d685
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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