Beta-Carboline → N,3-Dimethyl-1-butanamine
Reaction equation
[CH:1]1[C:13]2NC3[C:6](=CC=CC=3)[C:5]=2[CH:4]=[CH:3][N:2]=1.[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25]([OH:27])=O)[C:19]1[CH2:28][N:29]([CH3:32])[CH2:30][CH2:31][C:18]2=1>>[CH3:3][NH:2][CH2:1][CH2:13][CH:5]([CH3:6])[CH3:4].[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25]([N:2]([CH2:1][CH2:13][CH:5]([CH3:6])[CH3:4])[CH3:3])=[O:27])[C:19]1[CH2:28][N:29]([CH3:32])[CH2:30][CH2:31][C:18]2=1Participants
Procedure
Method for the preparation of compound 14[2-(6-chloro-2-methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9(2H)-yl)-N-isopentyl-N-methylacetamide]: (4-chlorophenyl)hydrazine is alkylated with ethyl 2-bromoacetate to give the substituted phenylhydrazine ethyl 2-(1-(4-chlorophenyl)hydrazinyl)acetate (III). The reaction of III with 4,4-dimethoxy-N-methylbutan-1-amine gives the indole derivative ethyl 2-(5-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)acetate (V). Effecting the indole to standard Pictet Spingler conditions with formaldehyde gives the β-carboline intermediate (VI) ethyl 2-(6-chloro-2-methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9(2H)-yl)acetate. Following treatment of VI with base the acid (VIII) 2-(6-chloro-2-methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9(2H)-yl)acetic acid is obtained. The treatment of this acid under standard peptide coupling conditions with N,3-dimethylbutan-1-amine gives compound 15 2-(6-chloro-2-methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9(2H)-yl)-N-isopentyl-N-methylacetamide. After the successful synthesis of the compound, purification can be achieved using standard normal phase or reverse phase methods.
Workup
- customis obtained
Sources & evidence
- ORD record
- ord-7146f29ffe45491a92d490869f461c42
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09260429B2
Reaction notes
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