Acetic Acid → 3-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazole

HRID 1946977Notes

Reaction equation

HRID 1946977 reaction equation
C(OC(=O)[NH:7][NH2:8])(C)(C)C.C(O)(=O)C.F[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]([C:23]1[CH:28]=[CH:27][N:26]=[C:25]([S:29][CH3:30])[N:24]=1)=O.C1CCN2C(=NCCC2)CC1>CO.C1COCC1>[CH3:30][S:29][C:25]1[N:24]=[C:23]([C:21]2[C:16]3[C:15](=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:8][N:7]=2)[CH:28]=[CH:27][N:26]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 70091tert-Butyl carbazateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59743427(2-Fluoro-phenyl)-(2-methylsulfanyl-pyrimidin-4-yl)-methanone

Product 1

HCID 597433513-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazoleYield 63.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butylcarbazate (899 mg, 6.8 mmol) and acetic acid (0.5 mL) were added to a mixture of (2-fluoro-phenyl)-(2-methylsulfanyl-pyrimidin-4-yl)-methanone (840 mg, 3.4 mmol) in MeOH. The resulting mixture was heated at reflux for 16 h; it was then cooled to RT and partitioned between EtOAc and aqueous sodium bicarbonate. The organic layer was separated and dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was placed in a sealed tube with DBU (0.79 mL, 5.3 mmol) and THF. The resulting mixture was heated to 150° C. in a microwave reactor for 30 minutes. The reaction mixture was then evaporated under reduced pressure and the crude residue was purified by flash chromatography (hexane/EtOAc, 4/1) to afford 525 mg of 3-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazole.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 16 h
  3. custompartitioned between EtOAc and aqueous sodium bicarbonate
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. temperatureThe resulting mixture was heated to 150° C. in a microwave reactor for 30 minutes
  9. customThe reaction mixture was then evaporated under reduced pressure
  10. customthe crude residue was purified by flash chromatography (hexane/EtOAc, 4/1)

Sources & evidence

ORD record
ord-996d2bc7868c4cff9db18c33dfecf9f4
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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