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Trifluoroacetic acid → (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one

HRID 538986
Notes
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Reaction equation

HRID 538986 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:14][O:13][C:12]3=[O:22])=[N:7][C:6]=12.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][C:34]([C:37]3[N:38](COCC[Si](C)(C)C)[CH:39]=[CH:40][N:41]=3)=[CH:33][CH:32]=2)O1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.FC(F)(F)C(O)=O>O1CCOCC1.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:38]1[CH:39]=[CH:40][N:41]=[C:37]1[C:34]1[CH:35]=[CH:36][C:31]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@@H:15]([C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=5)[CH2:14][O:13][C:12]4=[O:22])=[N:7][C:6]=23)=[CH:32][CH:33]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034277(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-oneHCID 670343202-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

Product 1

HCID 50997721(S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution containing (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one (0.100 g, 0.278 mmol), 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (0.334 g, 0.835 mmol) and 2M Na2CO3 (0.418 mL, 0.835 mmol) in dioxane (10 mL) was degassed with argon. Dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (13.3 mg, 0.0278 mmol) and Pd2(dba)3 (6.5 mg, 0.028 mmol), were added and the solution was degassed again with argon. The reaction vessel was sealed and heated to 80° C. for 18 hours. The cooled reaction mixture was partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Purification of the crude material by column chromatography, eluting with 1-5% MeOH/dichloromethane afforded the protected intermediate which was taken up in dichloromethane (2 mL). Trifluoroacetic acid (2 mL) was added and the mixture stirred at ambient temperature for 12 hours. The reaction mixture was concentrated, washed with saturated aqueous NaHCO3, extracted into ethyl acetate, dried over sodium sulfate, filtered and concentrated. Purification of the crude material by column chromatography, eluting with 2-4% MeOH/dichloromethane, afforded (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one as a light yellow solid, 14 mg (12%). LCMS (APCI+) m/z 423 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 9.10 (d, J=7.8 Hz, 1H), 8.65 (s, 1H), 7.93 (d, J=7.8 Hz, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.78 (d, J=8.6 Hz, 2H), 7.44-7.50 (m, 5H), 7.22 (s, 2H), 5.94-5.98 (m, 1H), 4.93 (t, J=8.6 Hz, 1H), 4.23-4.27 (m, 1H).

Workup

  1. customwas degassed with argon
  2. customthe solution was degassed again with argon
  3. customThe reaction vessel was sealed
  4. customThe cooled reaction mixture
  5. customwas partitioned between ethyl acetate and brine
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by column chromatography
  10. washeluting with 1-5% MeOH/dichloromethane
  11. customafforded the protected intermediate which
  12. concentrationThe reaction mixture was concentrated
  13. washwashed with saturated aqueous NaHCO3
  14. extractionextracted into ethyl acetate
  15. dry with materialdried over sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customPurification of the crude material by column chromatography
  19. washeluting with 2-4% MeOH/dichloromethane

Sources & evidence

ORD record
ord-f9f81816ee43496fa680bfa9a1b8017d
Source dataset
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08865726B2

Reaction notes

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