Hydrochloric Acid → 6-chloro-4'-[5-chloro-2-(3-methanesulfonylamino-2,2-dimethyl-3-oxo-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504576ノート

反応式

HRID 504576 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH2:24][C:25]([C:28]([OH:30])=O)([CH3:27])[CH3:26])[CH2:14][C:13](=[O:31])[NH:12][CH:11]3[C:32]3[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=3[CH3:39])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:53][S:54]([NH2:57])(=[O:56])=[O:55].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH2:24][C:25]([CH3:27])([CH3:26])[C:28]([NH:57][S:54]([CH3:53])(=[O:56])=[O:55])=[O:30])[CH2:14][C:13](=[O:31])[NH:12][CH:11]3[C:32]3[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=3[CH3:39])[C:5]2=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 765678616-chloro-4'-[5-chloro-2-(2-hydroxycarbonyl-2-methyl-propoxy)-phenyl]-2'-(5-fluoro-2-methylphenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

生成物 1

HCID 866320956-chloro-4'-[5-chloro-2-(3-methanesulfonylamino-2,2-dimethyl-3-oxo-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione収率 21.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A solution of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(2-hydroxycarbonyl-2-methyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (300 mg, 0.5 mmol) prepared in Example 20f and CDI (160 mg, 1 mmol) in DMF (2 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of methanesulfonamide (285 mg, 3 mmol) and NaH (120 mg, 60%, 3 mmol) in DMF (1 mL), which had been mixed and stirred at room temperature for 2 h. After the resulting mixture was stirred at room temperature for 1 h, it was poured into water and the aqueous solution was acidified to “pH” 1-2 by addition of concentrated HCl. After the aqueous phase was extracted with EtOAc twice, the combined organic layers were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column to give the title compound as a white solid (70 mg).

後処理

  1. additionThen to this solution was added
  2. additionhad been mixed
  3. stirringAfter the resulting mixture was stirred at room temperature for 1 h
  4. extractionAfter the aqueous phase was extracted with EtOAc twice
  5. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customthe residue was purified by flash column

出典と根拠

ORDレコード
ord-3eb31fdcc9704d8cb6fc3d2bd7e0a875
出典データセット
uspto-grants-2010_08
特許番号
US07776875B2

反応ノート

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