Trifluoroacetic acid → HCID 178448158, compound

HRID 538991Notes

Reaction equation

HRID 538991 reaction equation
[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4[N:29]=[CH:28][N:27](COCC[Si](C)(C)C)[N:26]=4)=[CH:21][CH:20]=3)=[C:12]2[N:11]=1)([CH3:3])[CH3:2].C([C@H]1COC(=O)N1C1C=CN2N=CC(C3C=CC(C4N(COCC[Si](C)(C)C)N=CN=4)=CC=3)=C2N=1)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH:27]1[CH:28]=[N:29][C:25]([C:22]2[CH:21]=[CH:20][C:19]([C:18]3[CH:17]=[N:16][N:13]4[CH:14]=[CH:15][C:10]([N:5]5[C@@H:4]([CH:1]([CH3:2])[CH3:3])[CH2:8][O:7][C:6]5=[O:9])=[N:11][C:12]=34)=[CH:24][CH:23]=2)=[N:26]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 67034476HCID 67034476, compoundHCID 67034578HCID 67034578, compound

Product 1

HCID 178448158HCID 178448158, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one and (S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-5-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (2.37 g, 4.25 mmol) was dissolved in dichloromethane (12 mL) and trifluoroacetic acid (22.5 mL) was added and the mixture allowed to stir at ambient temperature for 6 hours. The reaction mixture was concentrated and the residue partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL). The aqueous layer was washed with EtOAc (2×100 mL). The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to give a golden yellow solid. Purification of the crude material by column chromatography, eluting with a gradient of Hexanes to 50% EtOAc/Hexanes to 0-2% (9:1 MeOH/NH4OH)/EtOAc provided (S)-3-(3-(4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (1.30 g, 78%) as a yellow crystalline solid. LCMS (APCI+) m/z 390 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J=7.8 Hz, 1H), 8.77 (s, 1H), 8.37 (bs, 1H), 8.22 (d, J=8.6 Hz, 2H), 8.05 (d, J=8.6 Hz, 2H), 7.89 (d, J=7.4 Hz, 1H), 4.95-4.99 (m, 1H), 4.52 (d, J=6.2 Hz, 2H), 2.74-2.82 (m, 1H), 1.07 (d, J=7.0 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL)
  3. washThe aqueous layer was washed with EtOAc (2×100 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a golden yellow solid
  9. customPurification of the crude material by column chromatography
  10. washeluting with a gradient of Hexanes to 50% EtOAc/Hexanes to 0-2% (9:1 MeOH/NH4OH)/EtOAc

Sources & evidence

ORD record
ord-04c2d9e66b2348d5b7c9726ef12601be
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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