HCID 59232009, compound → HCID 59232216, compound

HRID 1099297Notes

Reaction equation

HRID 1099297 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]([NH:22][C:23]4[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=4[F:33])=[O:21])=[C:15]([F:34])[CH:14]=3)[CH:9]=[C:10]([CH:11]=[O:12])[N:6]2[N:5]=[CH:4][N:3]=1.[CH:35]([Mg]Br)=[CH2:36]>C1COCC1>[NH2:1][C:2]1[C:7]2=[C:8]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]([NH:22][C:23]4[CH:28]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:26]=[CH:25][C:24]=4[F:33])=[O:21])=[C:15]([F:34])[CH:14]=3)[CH:9]=[C:10]([CH:11]([OH:12])[CH:35]=[CH2:36])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 59232009HCID 59232009, compoundHCID 178418507HCID 178418507, compound

Product 1

HCID 59232216HCID 59232216, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-[4-(4-amino-7-formylpyrrolo[2,1-f][1,2,4]triazin-5-yl) -2-fluorophenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea (450 mg, 0.95 mmol) dissolved in THF (10 mL), was added vinyl magnesium bromide (9.45 mL, 9.45 mmol, 1.0 M in THF) at rt. The reaction was allowed to stir for 1 hr and then quenched with MeOH (1 mL). The mixture was partitioned between EtOAc (250 mL) and saturated aq. Na2CO3 (100 mL). The organic phase was washed with brine (100 mL), dried (Na2SO4), and concentrated to dryness. Trituration with Et2O afforded 300 mg (63%) of the desired product. 1H-NMR (DMSO-d6) δ 8.65 (d, J=7.8 Hz, 1H), 8.27 (t, J=8.4 Hz, 1H), 7.85 (s, 1H), 7.36-7.27 (m, 5H), 7.13-7.07 (m, 1H), 6.90 (s, 1H), 6.70-6.60 (m, 1H), 4.29 (dd, J=1.5, 5.7 Hz, 1H); MS [M+H]+=505.2; LCMS RT=2.85 min.

Workup

  1. customquenched with MeOH (1 mL)
  2. customThe mixture was partitioned between EtOAc (250 mL) and saturated aq. Na2CO3 (100 mL)
  3. washThe organic phase was washed with brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-5e4a4d79327441a7aa8e1c4913f568cb
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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