Ammonia → HCID 178448163, compound

HRID 538995Notes

Reaction equation

HRID 538995 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]([CH:35]([CH3:37])[CH3:36])[CH2:33][O:32][C:31]4=[O:38])=[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.FC1C=C(C2C=NN3C=CC(N4[C@@H](C(C)C)COC4=O)=NC=23)C=CC=1C1N(COCC[Si](C)(C)C)N=CN=1.FC(F)(F)C(O)=O.N>ClCCl.C(#N)C>[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]([CH:35]([CH3:36])[CH3:37])[CH2:33][O:32][C:31]4=[O:38])=[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

7

Reactant 4

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 67033116HCID 67033116, compoundHCID 67034105HCID 67034105, compound

Product 1

HCID 178448163HCID 178448163, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-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)-4-isopropyloxazolidin-2-one and (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-5-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (0.137 g, 0.255 mmol) was dissolved in dichloromethane (0.55 mL). Trifluoroacetic acid (1.1 mL) was added and the mixture allowed to stir at ambient temperature for 18 hours. The reaction mixture was concentrated with multiple dichloromethane additions to give a crude residue. Acetonitrile (5 mL) and 28% aqueous ammonia (3 mL, 44 mmol) were added and the mixture concentrated with multiple acetonitrile additions to a yellow solid. Purification by normal phase chromatography, eluting with 50-100% EtOAc/dichloromethane, provided (S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (0.032 g, 31%) as a yellow solid. LCMS (APCI+) m/z 408.5 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ 11.24 (broad s, 1H), 8.61 (d, J=7.8 Hz, 1H), 8.43 (s, 1H), 8.26 (t, J=8.2 Hz, 1H), 8.09 (m, 2H), 8.00 (d×d, J=13.8, 1.0 Hz, 1H), 7.87 (d×d, J=8.4, 1.2 Hz, 1H), 4.99-4.96 (m, 1H), 4.50-4.41 (m, 2H), 2.94-2.86 (m, 1H), 1.10 (d, J=7.0 Hz, 3H), 0.94 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated with multiple dichloromethane additions
  2. customto give a crude residue
  3. concentrationthe mixture concentrated with multiple acetonitrile additions to a yellow solid
  4. customPurification by normal phase chromatography
  5. washeluting with 50-100% EtOAc/dichloromethane

Sources & evidence

ORD record
ord-c448f4dfd88f4d638be8d0a354e0e4b5
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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