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 470670ノート

反応式

HRID 470670 の反応式
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

参加物

5

反応物 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

生成物 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'-carboxamide収率 89%

反応条件

温度
50 °C

実験手順

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.

後処理

  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)]

出典と根拠

ORDレコード
ord-3040c5c8517843c19f75c09f90fdf5df
出典データセット
uspto-grants-2014_01
特許番号
US08629133B2

反応ノート

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