HCID 66783290, compound → HCID 24955779, compound

HRID 1095562Notes

Reaction equation

HRID 1095562 reaction equation
Cl.[CH3:2][N:3]([CH3:29])[C:4]1([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:9][CH2:8][C:7]([C:10]2[NH:11][C:12]3[C:17]([C:18]=2[CH:19]2[CH2:21][CH2:20]2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:6][CH2:5]1>CO.[Pd]>[CH2:22]([C:4]1([N:3]([CH3:2])[CH3:29])[CH2:5][CH2:6][CH:7]([C:10]2[NH:11][C:12]3[C:17]([C:18]=2[CH:19]2[CH2:21][CH2:20]2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:8][CH2:9]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

4

Reactant 1

HCID 66783290HCID 66783290, compound

Product 1

HCID 24955779HCID 24955779, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The free base from Example 33 (210 mg, 0.567 mmol) was dissolved in methanol (35 ml), and palladium on charcoal (5 per cent strength; 90 mg) was added. The reaction mixture was hydrogenated under 3 bar for 5 h. The catalyst was separated off over Celite and the filtrate was concentrated. The solid residue (185 mg) was separated by chromatography [silica gel 60 (40 g); ethyl acetate/methanol 10:1 (250 ml), ethyl acetate/methanol 4:1 (250 ml)]. 1-Benzyl-4-(3-cyclopropyl-1H-indol-2-yl)-N,N-dimethylcyclohexanamin (more polar diastereoisomer) was obtained in a yield of 50% (105 mg) with a melting point of 65-70° C. The less polar diastereoisomer was isolated in a yield of 26% (54 mg) together with by-products. This fraction was purified again by chromatography [silica gel 60 (20 g); trichloromethane/methanol 40:1 (250 ml)]. The less polar diastereoisomer was obtained by this procedure in a yield of 43 mg (20%) with traces of an impurity and was employed in this form for the citrate preparation.

Workup

  1. customThe catalyst was separated off over Celite
  2. concentrationthe filtrate was concentrated
  3. customThe solid residue (185 mg) was separated by chromatography [silica gel 60 (40 g); ethyl acetate/methanol 10:1 (250 ml), ethyl acetate/methanol 4:1 (250 ml)]

Sources & evidence

ORD record
ord-580e8f5120b342c58e972bddcdd521bf
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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