Dimethylformamide → N-[4-(4-amino-6-cyano-7-formylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

HRID 73694Notes

Reaction equation

HRID 73694 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]4[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=4[F:34])=[O:22])=[CH:16][CH:15]=3)[C:9]([C:12]#[N:13])=[C:10](Br)[N:6]2[N:5]=[CH:4][N:3]=1.[Li]CCCC.CN([CH:43]=[O:44])C>C1COCC1>[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]4[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=4[F:34])=[O:22])=[CH:16][CH:15]=3)[C:9]([C:12]#[N:13])=[C:10]([CH:43]=[O:44])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 66641333HCID 66641333, compoundHCID 178418339Butyllithium

Product 1

HCID 86635784N-[4-(4-amino-6-cyano-7-formylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]ureaYield 99.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of THF (20 mL) was added N-[4-(4-amino-7-bromo-6-cyanopyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea (230 mg, 0.430 mmol) which was cooled to −77° C. n-BuLi (2.5 M in hexanes, 0.86 mL, 2.15 mmol) was slowly added to the solution via syringe. The solution was stirred for 10 min and then DMF (0.20 mL, 2.58 mmol) was added. The cooling bath was removed and the reaction was allowed to warm to ambient temperature over the following 17 h. EtOAc (20 mL) and water (20 mL) were added to the reaction which was then transferred to a separatory funnel. The organic layer was washed with aq 1 N NaOH (20 mL) followed by water (20 mL). The organic was isolated, dried (MgSO4), filtered, and concentrated to dryness yielding 207 mg (0.428 mmol, yield 99%) of product. 1H-NMR (DMSO-d6) δ 10.38 (s, 1H), 9.43 (s, 1H), 8.99 (d, J=2.7 Hz, 1H), 8.68 (br s, 1H), 8.61 (dd, J=6.8, 1.8 Hz, 1H), 8.27 (s, 1H), 7.66 (d, J=8.6 Hz, 2H), 7.52 (m, 1H), 7.47 (d, J=8.6 Hz, 2H), 7.40 (m, 1H), 6.06 (br s, 1H); MS [M+H]+=484.1; LCMS RT=3.34.

Workup

  1. additionwas slowly added to the solution via syringe
  2. customThe cooling bath was removed
  3. additionEtOAc (20 mL) and water (20 mL) were added to the reaction which
  4. customwas then transferred to a separatory funnel
  5. washThe organic layer was washed with aq 1 N NaOH (20 mL)
  6. customThe organic was isolated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-2ae8fa9877f84a8fae6bfd6cddb7a39c
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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