Trifluoroacetic acid → HCID 178519206, compound

HRID 539121Notes

Reaction equation

HRID 539121 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@H:34]5[C:35]6[CH:36]=[CH:37][CH:38]=[CH:39][C:40]=6[CH2:41][C@H:33]5[O:32][C:31]4=[O:42])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][N:10](COCC[Si](C)(C)C)[N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@H:34]5[C:35]6[CH:36]=[CH:37][CH:38]=[CH:39][C:40]=6[CH2:41][C@H:33]5[O:32][C:31]4=[O:42])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][NH:10][N:9]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67034771(3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one

Product 1

HCID 178519206HCID 178519206, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (45 mg, 0.077 mmol) in DCM (5 mL) was added TFA (1 mL) and the reaction was stirred at ambient temperature for 6 hours. The reaction was concentrated to dryness and the residue dissolved in MeOH and added to 2N HCl in ether. After concentration, the residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 100:0 to 0:100, 20 column volumes) to yield (3aS,8aR)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (3.5 mg, 10% yield) as a pale yellow solid. LCMS (APCI+) m/z 454.2 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. dissolutionthe residue dissolved in MeOH
  3. additionadded to 2N HCl in ether
  4. concentrationAfter concentration
  5. customthe residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 100:0 to 0:100, 20 column volumes)

Sources & evidence

ORD record
ord-77320265c97f486089e45c9e81a28f2b
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

Loading…