4-(5-chloro-[1H]-indol-3-yl)-piperidine → HCID 10327255, 화합물

HRID 2357449노트

반응식

HRID 2357449 반응식
C1([O:7][C:8](=O)[NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([N:23]([CH3:25])[CH3:24])([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)C=CC=CC=1.[Cl:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>O1CCOCC1>[CH3:24][N:23]([CH3:25])[C:14]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:15][CH2:16][CH:11]([CH2:10][NH:9][C:8]([N:40]2[CH2:41][CH2:42][CH:37]([C:31]3[C:30]4[C:34](=[CH:35][CH:36]=[C:28]([Cl:27])[CH:29]=4)[NH:33][CH:32]=3)[CH2:38][CH2:39]2)=[O:7])[CH2:12][CH2:13]1

참가 물질

4

반응물 2

HCID 128313754-(5-chloro-[1H]-indol-3-yl)-piperidineHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

생성물 1

HCID 10327255HCID 10327255, 화합물수율 11%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (774 mg, 2.2 mmole) was added to the suspension of 5-chloro-3-piperidine-4-yl-1H-indole (516 mg, 2.2 mmole) in dioxane (20 ml). The reaction mixture was a suspension also at 100° C., and was boiled under reflux for 40 hours. To work up the suspension the existing precipitate was filtered off, washed with dioxane (1×1 ml) and diethyl ether (3×2 ml) and dried in vacuo. The isolated solid (183 mg, 17%, m.p. 140°-150° C.) was a still unpurified part of the polar diastereoisomer of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide, which was purified by flash chromatography on silica gel [20 g, eluent: methanol (500 ml)]. The mother liquor and the wash phases were concentrated by evaporation in vacuo. The residue contained in addition to phenol, also the two diastereoisomers of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide. The diastereoisomers were separated and purified by flash chromatography on silica gel (75 g). Methanol/EE (1:1; 900 ml) was used as eluent. The non-polar diastereoisomer (335 mg, m.p. 205°-207° C., 31%) and the polar diastereoisomer of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (115 mg, m.p. 140°-143° C., 11%) were thereby obtained as pale yellow solids.

후처리

  1. customalso at 100° C.
  2. temperatureunder reflux for 40 hours
  3. filtrationwas filtered off
  4. washwashed with dioxane (1×1 ml) and diethyl ether (3×2 ml)
  5. customdried in vacuo
  6. customwas purified by flash chromatography on silica gel [20 g, eluent: methanol (500 ml)]
  7. concentrationThe mother liquor and the wash phases were concentrated by evaporation in vacuo
  8. additionThe residue contained in addition to phenol
  9. customThe diastereoisomers were separated
  10. custompurified by flash chromatography on silica gel (75 g)

출처 및 근거

ORD 기록
ord-f9a0608ba0714007a0897363324e071d
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07759385B2

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