Methanol → (4'S,5'R)-6''-chloro-4'-(2-chloro-3-fluoropyridin-4-yl)-1'-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-N-[(3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]-4,4-dimethyl-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indole]-5'-carboxamide

HRID 470670노트

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HRID 470670 반응식
C([N:3]([CH2:6][CH3:7])CC)C.[Cl:8][C:9]1[CH:17]=[C:16]2[C:12]([C@@:13]3([C:26]4([CH2:31][CH2:30][C:29]([CH3:33])([CH3:32])[CH2:28][CH2:27]4)[N:25]4[C@@H:20]([C:21](=[O:46])[O:22][C@@H:23]([C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)[C@H:24]4C4C=CC=CC=4)[C@@H:19]3[C:47]3[CH:52]=[CH:51][N:50]=[C:49]([Cl:53])[C:48]=3[F:54])[C:14](=[O:18])[NH:15]2)=[CH:11][CH:10]=1.[Cl-].[NH4+].[CH3:57][OH:58]>>[Cl:8][C:9]1[CH:17]=[C:16]2[C:12]([C:13]3([C@@H:19]([C:47]4[CH:52]=[CH:51][N:50]=[C:49]([Cl:53])[C:48]=4[F:54])[C@H:20]([C:21]([NH:3][C@@H:6]4[CH2:7][CH2:12][C@@H:13]([CH2:14][OH:18])[O:58][CH2:57]4)=[O:46])[N:25]([C@H:24]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C@@H:23]([OH:22])[C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)[C:26]43[CH2:31][CH2:30][C:29]([CH3:33])([CH3:32])[CH2:28][CH2:27]4)[C:14](=[O:18])[NH:15]2)=[CH:11][CH:10]=1

참가 물질

5

반응물 4

HCID 887MethanolHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 86672587(3'S,4'R,7'S,8'S,8a'R)-6''-chloro-8'-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-3',4'-diphenyl-3',4',8',8a'-tetrahydro-1'H-dispiro[cyclohexane-1,6'-pyrrolo[2,1-c][1,4]oxazine-7',3''-indole]-1',2''(1''H)-dione

생성물 1

HCID 86672589(4'S,5'R)-6''-chloro-4'-(2-chloro-3-fluoropyridin-4-yl)-1'-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-N-[(3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]-4,4-dimethyl-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indole]-5'-carboxamide수율 89%

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온도
50 °C

실험 절차

The compound (131 mg, 1.00 mmol) obtained in Step 3 of Reference Example 2 and triethylamine (0.14 ml, 1.00 mmol) were added to a methanol (4 ml) solution of the compound (268 mg, 0.40 mmol) obtained in Step 1 of Example 16 and the resulting mixture was stirred at 50° C. for 5 days. After cooling, saturated ammonium chloride solution was added, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [chloroform:methanol=100:0→30:1 (v/v)] to give 288 mg (89%) of the title compound as a colorless amorphous solid.

후처리

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography [chloroform:methanol=100:0→30:1 (v/v)]

출처 및 근거

ORD 기록
ord-3040c5c8517843c19f75c09f90fdf5df
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629133B2

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