4-(5-chloro-[1H]-indol-3-yl)-piperidine → HCID 10327255、化合物

HRID 2357449ノート

反応式

HRID 2357449 の反応式
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

参加物

4

反応物 2

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

生成物 1

HCID 10327255HCID 10327255、化合物収率 11%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-f9a0608ba0714007a0897363324e071d
出典データセット
uspto-grants-2010_07
特許番号
US07759385B2

反応ノート

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