Trifluoroacetic acid → HCID 68563994, compound

HRID 1517339Notes

Reaction equation

HRID 1517339 reaction equation
FC(F)(F)C(O)=O.[CH3:8][S:9]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([C:21]1[N:26]=[CH:25][N:24]=[C:23]([O:27][CH:28]3[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]3)[CH:22]=1)[CH2:16][CH2:15]2)(=[O:11])=[O:10].C(N(C(C)C)CC)(C)C.[CH2:50]([S:54](Cl)(=[O:56])=[O:55])[CH2:51][CH2:52][CH3:53]>ClCCl>[CH2:50]([S:54]([N:31]1[CH2:32][CH2:33][CH:28]([O:27][C:23]2[N:24]=[CH:25][N:26]=[C:21]([N:17]3[C:18]4[C:14](=[CH:13][C:12]([S:9]([CH3:8])(=[O:10])=[O:11])=[CH:20][CH:19]=4)[CH2:15][CH2:16]3)[CH:22]=2)[CH2:29][CH2:30]1)(=[O:56])=[O:55])[CH2:51][CH2:52][CH3:53]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 754301-Butanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 25242414Tert-butyl 4-((6-(5-(methylsulfonyl)indolin-1-yl)pyrimidin-4-yl)oxy)piperidine-1-carboxylate

Product 1

HCID 68563994HCID 68563994, compoundYield 82.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Trifluoroacetic acid (727 μL) was added at 0° C. to a dichloromethane (2.90 mL) solution of the tert-butyl 4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate (145 mg, 0.306 mmol) produced in Example 1, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure. To a dichloromethane (3.70 mL) solution of the obtained residue and diisopropylethylamine (1.07 mL, 6.14 mmol), a dichloromethane (1.85 mL) solution of 1-butanesulfonyl chloride (72.0 mg, 0.461 mmol) was added at 0° C., and the mixture was stirred at 0° C. for 1 hour and then at 80° C. for 3 hours. The solvent was distilled off under reduced pressure. To the residue, methanol was added, and the deposit was collected by filtration. The obtained crude product was washed with methanol to obtain the title compound as white powder (125 mg, yield: 82%).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. stirringthe mixture was stirred at 0° C. for 1 hour
  3. waitat 80° C. for 3 hours
  4. distillationThe solvent was distilled off under reduced pressure
  5. additionTo the residue, methanol was added
  6. filtrationthe deposit was collected by filtration
  7. customThe obtained crude product
  8. washwas washed with methanol

Sources & evidence

ORD record
ord-f152089bfd404ca29f64fd4f744630b7
Source dataset
uspto-grants-2012_07
Patent number
US08232287B2

Reaction notes

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