Water → HCID 66997065, 화합물

HRID 18472

반응식

HRID 18472 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:17]3[CH2:16][CH:15]([OH:18])[CH2:14][CH2:13][C:12]=3[N:11]([C:19]([NH:21][C@@H:22]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:23]([NH:25][CH3:26])=[O:24])=[O:20])[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].FC1C=C(C2C3CC4(OCCO4)CCC=3N(C(N[C@@H](C(C)(C)C)C(NC)=O)=O)N=2)C=CC=1F.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:19]([NH:21][C@@H:22]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:23]([NH:25][CH3:26])=[O:24])=[O:20])[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

참가 물질

6

반응물 4

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)-carboxamideHCID 46863563HCID 46863563, 화합물

생성물 1

HCID 66997065HCID 66997065, 화합물수율 91%

시약·촉매·용매 1

HCID 180Acetone용매

실험 절차

Preparation of 3-(3,4-difluorophenyl)-N—((S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-5-hydroxy-4,5,6,7-tetrahydro-1H-indazole-1-carboxamide (67) 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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-728e1c0d78d54310a6b3e1121a47319a
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741350B1

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