Trifluoroacetic acid → 4-(3-Amino-6-(4-(benzoyloxy)-3,3-difluorocyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acid

HRID 596122Notes

Reaction equation

HRID 596122 reaction equation
[C:1]([O:9][CH:10]1[CH2:15][CH2:14][CH:13]([C:16]2[N:21]=[C:20]([C:22]3[CH:34]=[CH:33][C:25]([C:26]([O:28]C(C)(C)C)=[O:27])=[C:24]([F:35])[CH:23]=3)[C:19]([N:36](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:18][CH:17]=2)[CH2:12][C:11]1([F:52])[F:51])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:36][C:19]1[C:20]([C:22]2[CH:34]=[CH:33][C:25]([C:26]([OH:28])=[O:27])=[C:24]([F:35])[CH:23]=2)=[N:21][C:16]([CH:13]2[CH2:14][CH2:15][CH:10]([O:9][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:11]([F:51])([F:52])[CH2:12]2)=[CH:17][N:18]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118045245HCID 118045245, compound

Product 1

HCID 1180457824-(3-Amino-6-(4-(benzoyloxy)-3,3-difluorocyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acidYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(6-(4-(benzoyloxy)-3,3-difluorocyclohexyl)-3-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl)-2-fluorobenzoate (670 mg, 0.921 mmol) in DCM (12 mL) at RT was added TFA (4.96 mL, 64.4 mmol). The resultant mixture was stirred at RT for 2 hours. The mixture was concentrated, diluted with EtOAc, neutralized with NaHCO3 twice, then brine, the organic layer was separated, dried and concentrated to afford the crude product, which was used at the next step directly. (434 mg, 0.921 mmol, 100% yield). LC-MS (m/z): (MH+) 472.1, at 0.942 min. 1H NMR (400 MHz, DMSO) 6 ppm: 1.07 (t, J=7.04 Hz, 2H) 1.83 (t, J=10.17 Hz, 2H) 2.16 (d, J=5.09 Hz, 1H) 2.29-2.45 (m, 2H) 3.02 (br. s., 1H) 3.16-3.44 (m, 9H) 5.22-5.52 (m, 1H) 5.73 (s, 1H) 6.24 (s, 2H) 7.44-7.75 (m, 5H) 7.89 (t, J=7.83 Hz, 1H) 7.94-8.07 (m, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with EtOAc
  3. custombrine, the organic layer was separated
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-08f777e7bb8844c080cc43d639994ef1
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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