Morpholine → N-cyclohexyl-4-methyl-6-(2-morpholinoethoxy)-1H-indole-2-carboxamide

HRID 62664Notes

Reaction equation

HRID 62664 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[C:10]([C:14]([NH:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)=[O:15])[NH:11]2)=[C:7]([CH3:23])[CH:6]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>C(#N)C.O>[CH:17]1([NH:16][C:14]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[C:7]([CH3:23])[CH:6]=[C:5]([O:4][CH2:3][CH2:2][N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH:13]=3)=[O:15])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 899954026-(2-bromoethoxy)-N-cyclohexyl-4-methyl-1H-indole-2-carboxamide

Product 1

HCID 89995411N-cyclohexyl-4-methyl-6-(2-morpholinoethoxy)-1H-indole-2-carboxamideYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 6-(2-bromoethoxy)-N-cyclohexyl-4-methyl-1H-indole-2-carboxamide (I-9A-c: 0.1 g, 0.26 mmol) in acetonitrile (5 mL) at 0° C. was added Cs2CO3 (172.7 mg, 0.53 mmol) followed by morpholine (46.12 mg, 0.53 mmol) dropwise. The resulting reaction mixture was stirred at room temperature for 16 h, diluted with water (10 mL) and extracted with ethyl acetate (2×20 mL). The combined ethyl acetate layers were washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude compound was purified by preparative HPLC to afford 70 mg (70%) of N-cyclohexyl-4-methyl-6-(2-morpholinoethoxy)-1H-indole-2-carboxamide (9A) as a white solid.

Workup

  1. customThe resulting reaction mixture
  2. extractionextracted with ethyl acetate (2×20 mL)
  3. washThe combined ethyl acetate layers were washed with brine (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude compound was purified by preparative HPLC

Sources & evidence

ORD record
ord-88a5b6c04934474ea7f587dd9ae790d2
Source dataset
uspto-grants-2016_09
Patent number
US09447039B2

Reaction notes

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