Trifluoroacetic acid → HCID 54597088, compound

HRID 2174651Notes

Reaction equation

HRID 2174651 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9]1[C:10]([N:27]2[CH2:31][CH2:30][CH:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28]2)=[N:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])=[CH:17][CH:16]=2)=[CH:13][N:14]=1>C(Cl)Cl>[NH2:32][CH:29]1[CH2:30][CH2:31][N:27]([C:10]2[C:9]([NH2:8])=[N:14][CH:13]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]([S:21]([CH:24]([CH3:25])[CH3:26])(=[O:23])=[O:22])=[CH:19][CH:20]=3)[N:11]=2)[CH2:28]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 58084368HCID 58084368, compound

Product 1

HCID 54597088HCID 54597088, compoundYield 47.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (200 μL, 2.596 mmol) was added to a stirred solution of tert-butyl 1-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)pyrrolidin-3-ylcarbamate (46 mg, 0.09966 mmol) in DCM (5 mL) at ambient temperature. The reaction was stirred at this temperature for 17 hours. A further portion of TFA (200 μL, 2.596 mmol) was added and the reaction stirred at ambient temperature for a further 2 hours. The solvent was removed in vacuo and the residue was azeotroped with DCM/ether (×3). The residue was passed through a 2 g SCX-2 cartridge and washed with MeOH. The product was eluted by washing the cartridge with 2M NH3 in MeOH. The residue was purified by column chromatography (ISCO Companion™, 12 g column, elueting with 0 to 10% MeOH+10% NH4OH/DCM) to give the title product as a yellow solid (17.2 mg, 45% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.17 (d, 6H), 1.61-1.70 (m, 1H), 1.97-2.06 (m, 1H), 3.01 (br s, 2H), 3.22 (dd, 1H), 3.38 (quin, 1H), 3.48-3.57 (m, 2H), 3.65-3.74 (m, 2H), 6.12 (br s, 2H), 7.84 (d, 2H), 8.13 (s, 1H) and 8.17 (d, 2H) ppm; (ES+) 362.3.

Workup

  1. stirringthe reaction stirred at ambient temperature for a further 2 hours
  2. customThe solvent was removed in vacuo
  3. customthe residue was azeotroped with DCM/ether (×3)
  4. washwashed with MeOH
  5. washThe product was eluted
  6. washby washing the cartridge with 2M NH3 in MeOH
  7. customThe residue was purified by column chromatography (ISCO Companion™, 12 g column, elueting with 0 to 10% MeOH+10% NH4OH/DCM)

Sources & evidence

ORD record
ord-e34fdc00c9114b7993fa036b5dda3009
Source dataset
uspto-grants-2015_06
Patent number
US09062008B2

Reaction notes

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