5-Methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole → HCID 10009749, compound

HRID 2357446Notes

Reaction equation

HRID 2357446 reaction equation
C1(O[C:8](=[O:26])[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.[CH3:27][O:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][CH:33]=[C:32]2[C:38]1[CH2:39][CH2:40][NH:41][CH2:42][CH:43]=1>O1CCOCC1>[CH3:25][N:23]([CH3:24])[C:14]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:15][CH2:16][CH:11]([CH2:10][NH:9][C:8]([N:41]2[CH2:42][CH:43]=[C:38]([C:32]3[C:31]4[C:35](=[CH:36][CH:37]=[C:29]([O:28][CH3:27])[CH:30]=4)[NH:34][CH:33]=3)[CH2:39][CH2:40]2)=[O:26])[CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 1080295-Methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indoleHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

Product 1

HCID 10009749HCID 10009749, compoundYield 32.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(4-dimethylamino-4-phenylcyclohexyl-methyl)-carbamic acid phenyl ester (528.7 mg, 1.5 mmole) was added to a solution of 5-methoxy-3-(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (317.9 mg, 1.5 mmole) in dioxane (10 ml). The reaction mixture was then boiled for 20 hours under reflux. The reaction mixture was a suspension at RT. The solid was filtered off, washed with cold dioxane (3×1 ml) and dried. The solid was part of the polar diastereomer of 4-(5-methoxy-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl-methyl)-amide (99 mg, m.p. 120°-125° C., 14%). The reaction solution (filtrate and wash phases) was concentrated by evaporation. The residue contained phenol as well as the non-polar product and the remainder of the polar product. The diastereoisomers were separated and purified by flash chromatography on silica gel (75 g). Methanol (900 ml) was used as eluent. The non-polar diastereoisomer of 4-(5-methoxy-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (234 mg, m.p. 98°-104° C., 32%) and a further part of the polar diastereoisomer (120 mg, m.p. 108°-111° C., 16%) were thereby obtained in pure form.

Workup

  1. temperatureunder reflux
  2. customat RT
  3. filtrationThe solid was filtered off
  4. washwashed with cold dioxane (3×1 ml)
  5. customdried
  6. washThe reaction solution (filtrate and wash phases)
  7. concentrationwas concentrated by evaporation
  8. customThe diastereoisomers were separated
  9. custompurified by flash chromatography on silica gel (75 g)

Sources & evidence

ORD record
ord-d7d23d8f63a64a3fbb11762c92580f03
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

Loading…