Acetic Acid → 1-Ethyl-3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrile

HRID 992081Notes

Reaction equation

HRID 992081 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]2[CH:14]1[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1)#[N:2].[NH:21]1[C:29]2[C:24](=[C:25]([N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[CH3:13][CH2:12][N:8]1[C:9]2[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[C:6]([CH:14]2[CH2:19][CH2:18][CH:17]([N:33]3[CH2:34][CH2:35][N:30]([C:25]4[C:24]5[CH:23]=[CH:22][NH:21][C:29]=5[CH:28]=[CH:27][CH:26]=4)[CH2:31][CH2:32]3)[CH2:16][CH2:15]2)=[CH:7]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5945904-(piperazin-1-yl)-1H-indoleHCID 5049666Sodium triacetoxyborohydrideHCID 184140804-(5-Cyano-1-ethyl-3-indolyl)-cyclohexanone

Product 1

HCID 102757671-Ethyl-3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrileYield 39%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 4-(5-cyano-1-ethyl-indol-3-yl)-cyclohexanone (1.5 g, 5.6 mmol), 1-(indol-4-yl)piperazine (1.19 g, 5.9 mmol), sodium triacetoxyborohydride (1.73 g, 8.2 mmol) and acetic acid (0.9 ml, 15 mmol) in 1,2-dichloroethane (30 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3×80 ml), and washed with brine (3×80 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (2.5% methanol-ethyl acetate) afforded 0.98 g (39%) of product as a white solid: mp 226° C. (dec.).

Workup

  1. customThe reaction was quenched with 1N sodium hydroxide (10 ml)
  2. extractionextracted with methylene chloride (3×80 ml)
  3. washwashed with brine (3×80 ml)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered

Sources & evidence

ORD record
ord-30c03fe42fb74ab88c2fab335a01357c
Source dataset
uspto-grants-2002_10
Patent number
US06465482B2

Reaction notes

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