Trifluoroacetic acid → HCID 71293608, compound

HRID 1402569Notes

Reaction equation

HRID 1402569 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[NH:35][C:36]([NH:38][C:39]1[CH:44]=[C:43]([CH3:45])[CH:42]=[CH:41][C:40]=1[F:46])=[O:37])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17]([N:19]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[O:18])[CH:13]=2)[CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:46][C:40]1[CH:41]=[CH:42][C:43]([CH3:45])=[CH:44][C:39]=1[NH:38][C:36]([NH:35][C:34]1[CH:33]=[CH:32][C:4]([O:5][C:6]2[CH:11]=[CH:10][N:9]=[C:8]([C:12]3[NH:16][CH:15]=[C:14]([C:17]([N:19]4[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]4)=[O:18])[CH:13]=3)[CH:7]=2)=[CH:3][C:2]=1[F:1])=[O:37]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71293521HCID 71293521, compound

Product 1

HCID 71293608HCID 71293608, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 4-[(5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]piperazine-1-carboxylate (200 mg, 0.32 mmol) in 10 ml of methylene chloride was added 3 ml of TFA. The mixture was stirred at room temperature for 30 minutes, and evaporated to dryness under reduced pressure. The residue was re-dissolved in 5 ml of methanol and poured into 100 ml of water with vigorous stirring. Saturated NaHCO3 solution was added until pH=9. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 12% methanol in chloroform to give 1-(2-fluoro-5-methylphenyl)-3-[2-fluoro-4-({2-[4-(piperazin-1-ylcarbonyl)-1H-pyrrol-2-yl]pyridin-4-yl}oxy)phenyl]urea as white solid. Yield: 145 mg, 86%

Workup

  1. customevaporated to dryness under reduced pressure
  2. dissolutionThe residue was re-dissolved in 5 ml of methanol
  3. additionpoured into 100 ml of water with vigorous stirring
  4. additionSaturated NaHCO3 solution was added until pH=9
  5. filtrationThe precipitates were filtered
  6. washwashed with water
  7. customdried in vacuo
  8. customto give the crude, which
  9. customwas purified by silica gel chromatography
  10. washeluting with 12% methanol in chloroform

Sources & evidence

ORD record
ord-ada92260b5d54849b8a33b731962ad8d
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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