Trifluoroacetic acid → HCID 73295468, compound

HRID 592485Notes

Reaction equation

HRID 592485 reaction equation
[C:1]([C:4]1([C:7]2[CH:43]=[CH:42][CH:41]=[CH:40][C:8]=2[CH2:9][CH2:10][C:11]2[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][N:14]=[C:13]([NH:21][C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]4)[CH:26]=3)[N:12]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:30]1[CH2:29][CH2:28][CH:27]([N:25]2[CH:26]=[C:22]([NH:21][C:13]3[N:12]=[C:11]([CH2:10][CH2:9][C:8]4[CH:40]=[CH:41][CH:42]=[CH:43][C:7]=4[C:4]4([C:1]([NH2:2])=[O:3])[CH2:5][CH2:6]4)[C:16]([C:17]([F:18])([F:20])[F:19])=[CH:15][N:14]=3)[CH:23]=[N:24]2)[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712346HCID 86712346, compound

Product 1

HCID 73295468HCID 73295468, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of tert-butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate A77 (0.213 g, 0.355 mmol) in DCM (10 mL) was treated with TFA (1.09 mL, 14.2 mmol) and stirred for 16 hours at room temperature. The volatiles were evaporated in vacuo before aq. HCl (2 M, 25 mL) was added to the residue. The aqueous phase was extracted with EtOAc (3×25 mL) and the combined organics were washed with brine and dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by column chromatography (Biotage Isolera, 12 g C18 cartridge, 0-100% MeOH in H2O) to give a yellow oil. This oil was taken up in a minimum amount of DCM and the desired product was precipitated by the addition of petroleum spirits. The solid was isolated by filtration to give the title compound 66 as a yellow solid (0.114 g, 64%). LCMS-D: rt 3.07 min; m/z 500 [M+H]+.

Workup

  1. customThe volatiles were evaporated in vacuo before aq. HCl (2 M, 25 mL)
  2. additionwas added to the residue
  3. extractionThe aqueous phase was extracted with EtOAc (3×25 mL)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customthe crude product was purified by column chromatography (Biotage Isolera, 12 g C18 cartridge, 0-100% MeOH in H2O)
  8. customto give a yellow oil
  9. customthe desired product was precipitated by the addition of petroleum spirits
  10. customThe solid was isolated by filtration

Sources & evidence

ORD record
ord-de0a0a9fc58e49a7b53796d096f6bd16
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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