Trifluoroacetic acid → HCID 50902337, compound

HRID 2281861Notes

Reaction equation

HRID 2281861 reaction equation
FC(F)(F)C(O)=O.[F:8][CH:9]([F:50])[C:10]1[N:11]=[CH:12][C:13]([C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([F:49])=[C:23]([C@:25]34[CH2:33][O:32][C@H:31]([C:34]([F:37])([F:36])[F:35])[C@H:30]3[C:29](=[O:38])[N:28]([CH2:39][CH3:40])[C:27]([NH:41]C(=O)OC(C)(C)C)=[N:26]4)[CH:24]=2)=[O:17])=[N:14][CH:15]=1>C(Cl)Cl>[NH2:41][C:27]1[N:28]([CH2:39][CH3:40])[C:29](=[O:38])[C@@H:30]2[C@@H:31]([C:34]([F:37])([F:36])[F:35])[O:32][CH2:33][C@:25]2([C:23]2[CH:24]=[C:19]([NH:18][C:16]([C:13]3[CH:12]=[N:11][C:10]([CH:9]([F:50])[F:8])=[CH:15][N:14]=3)=[O:17])[CH:20]=[CH:21][C:22]=2[F:49])[N:26]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86668926HCID 86668926, compound

Product 1

HCID 50902337HCID 50902337, compoundYield 86.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1 mL) was added to a stirred solution of tert-butyl ((4aS,5S,7aS)-7a-(5-(5-(difluoromethyl)pyrazine-2-carboxamido)-2-fluorophenyl)-3-ethyl-4-oxo-5-(trifluoromethyl)-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate (115 mg, 0.19 mmol) in DCM (1 mL) at RT. The volatiles were removed in vacuo and the residue was azeotroped with toluene (×1). The free base was isolated by loading this material on to a SCX cartridge (5 g) and eluting with MeOH (2×20 mL) and then 2M NH3 in MeOH (1×20 mL). The ammonia-methanol fraction was evaporated and the residue was treated with Et2O-hexanes to give a solid which was isolated by filtration and dried in vacuo to give the title compound (85 mg, cream solid). 1H NMR (400 MHz, MeOH-d4) δ ppm 1.12 (t, J=7.07 Hz, 3H) 3.65-3.81 (m, 2H) 3.94-4.03 (m, 1H) 4.29-4.35 (m, 1H) 4.36-4.41 (m, 1H) 4.56-4.66 (m, 1H) 6.95 (t, J=55.30 Hz, 1H) 7.19 (dd, J=11.49, 8.97 Hz, 1H) 7.74-7.81 (m, 1H) 7.97 (dd, J=6.95, 2.40 Hz, 1H) 9.02 (s, 1H) 9.40 (s, 1H).

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was azeotroped with toluene (×1)
  3. customThe free base was isolated
  4. washeluting with MeOH (2×20 mL)
  5. customThe ammonia-methanol fraction was evaporated
  6. additionthe residue was treated with Et2O-hexanes
  7. customto give a solid which
  8. customwas isolated by filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-bb1a66a9a358454f9dcd805c99172517
Source dataset
uspto-grants-2015_09
Patent number
US09139594B2

Reaction notes

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