Acetic Acid → (R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl benzoate

HRID 2378686Notes

Reaction equation

HRID 2378686 reaction equation
[C:1]([O:9][C@H:10]([CH2:15][C:16]1[C:17]([CH2:26][NH:27][CH2:28][C:29]([F:32])([F:31])[F:30])=[C:18]2[C:22](=[C:23]([Cl:25])[CH:24]=1)[NH:21][N:20]=[CH:19]2)[C:11]([O:13]C)=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.C(O)(=O)C>>[C:1]([O:9][C@H:10]1[C:11](=[O:13])[N:27]([CH2:28][C:29]([F:31])([F:32])[F:30])[CH2:26][C:17]2[C:18]3[CH:19]=[N:20][NH:21][C:22]=3[C:23]([Cl:25])=[CH:24][C:16]=2[CH2:15]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 1140TolueneHCID 59732084(R)-3-(7-chloro-4-((2,2,2-trifluoroethylamino)methyl)-1H-indazol-5-yl)-1-methoxy-1-oxopropan-2-yl benzoate

Product 1

HCID 59732073(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl benzoateYield 74%

Procedure

(R)-3-(7-chloro-4-((2,2,2-trifluoroethylamino)methyl)-1H-indazol-5-yl)-1-methoxy-1-oxopropan-2-yl benzoate (7.75 g, 16.5 mmol) in toluene (70.00 ml, 657 mmol) was added acetic acid (1.2 ml, 20.96 mmol) and refluxed for 12 h. The solvent was evaporated and the crude product was dissolved in EtOAc, washed with aqueous NaHCO3. The solvent was removed and the crude product was purified by flash chromatography using 50% EtOAc in hexane to give (R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl benzoate in 74% yield. MS (ESI) 438 (M+H); Rf=2.60.

Workup

  1. temperaturerefluxed for 12 h
  2. customThe solvent was evaporated
  3. dissolutionthe crude product was dissolved in EtOAc
  4. washwashed with aqueous NaHCO3
  5. customThe solvent was removed
  6. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-3fab6a3c21bd4de5b4da048f2a154cb6
Source dataset
uspto-grants-2008_12
Patent number
US07470679B2

Reaction notes

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