Water → HCID 66997065, compound

HRID 242473Notes

Reaction equation

HRID 242473 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:17]3[CH2:16][C:15]4(OCC[O:18]4)[CH2:14][CH2:13][C:12]=3[N:11]([C:22]([NH:24][C@@H:25]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:26]([NH:28][CH3:29])=[O:27])=[O:23])[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:17]3[CH2:16][C:15](=[O:18])[CH2:14][CH2:13][C:12]=3[N:11]([C:22]([NH:24][C@@H:25]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:26]([NH:28][CH3:29])=[O:27])=[O:23])[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 46863561(S)-3'-(3,4-difluorophenyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-6',7'-dihydrospiro[[1,3]dioxolane-2,5'-indazole]-1'(4'H)-carboxamide

Product 1

HCID 66997065HCID 66997065, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of compound 63 (0.91 g) and p-toluenesulfonic acid (1.3 g) was heated in acetone and water at 50° C. until starting material was consumed. After evaporation of acetone, the residue was extracted between EtOAc and saturated sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated to dryness. The crude product was purified by column chromatography with 70% to 80% EtOAc/Hex to give (S)-3-(3,4-difluorophenyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-5-oxo-4,5,6,7-tetrahydro-1H-indazole-1-carboxamide (0.75 g, 91% yield), which was reduced with sodium borohydride (1.0 equiv.) in MeOH to give compound 67 as a mixture of two diastereomers after purification with a preparative LC-MS. LCMS (+ESI) m/z=421.2 [M+H]+.

Workup

  1. customat 50° C.
  2. customwas consumed
  3. customAfter evaporation of acetone
  4. extractionthe residue was extracted between EtOAc and saturated sodium bicarbonate
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. customevaporated to dryness
  7. customThe crude product was purified by column chromatography with 70% to 80% EtOAc/Hex

Sources & evidence

ORD record
ord-57f2c460100a43a5992d495078a3fad0
Source dataset
uspto-grants-2014_02
Patent number
US08653127B2

Reaction notes

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