Pyridine → N-[4-(3-cyano-1-cyclobutyl-6-ethoxy-indol-2-yl)phenyl]morpholine-4-carboxamide

HRID 252604

Reaction equation

HRID 252604 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:22]3[CH2:25][CH2:24][CH2:23]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH3:21])[CH:11]=3)=[CH:4][CH:3]=1.Cl[C:27](OC1C=CC([N+]([O-])=O)=CC=1)=[O:28].N1C=CC=CC=1.[NH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1>C(Cl)Cl>[C:17]([C:16]1[C:15]2[C:10](=[CH:11][C:12]([O:19][CH2:20][CH3:21])=[CH:13][CH:14]=2)[N:9]([CH:22]2[CH2:23][CH2:24][CH2:25]2)[C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:27]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)=[O:28])=[CH:7][CH:6]=1)#[N:18]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8083MorpholineHCID 821294-Nitrophenyl chloroformateHCID 250520112-(4-Aminophenyl)-1-cyclobutyl-6-ethoxy-indole-3-carbonitrile

Product 1

HCID 49772271N-[4-(3-cyano-1-cyclobutyl-6-ethoxy-indol-2-yl)phenyl]morpholine-4-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(4-aminophenyl)-1-cyclobutyl-6-ethoxy-1H-indole-3-carbonitrile (40 mg, 0.12 mmol), 4-nitrophenyl chloroformate (60 mg, 0.30 mmol), CH2Cl2 (400 μL), and pyridine (25 μL, 0.31 mmol) are stirred at room temperature for 1 hour. Morpholine (60 μL, 0.70 mmol) is added. After stirring at room temperature for an additional 30 minutes, the reaction mixture is diluted in CH2Cl2 and is washed with dilute aqueous NaOH to remove the yellow nitrophenol byproduct. The organic layer is dried and concentrated. Purification by silica gel chromatography (CH2Cl2/EtOAc, 7/3) yields morpholine-4-carboxylic acid [4-(3-cyano-1-cyclobutyl-6-ethoxy-1H-indol-2-yl)-phenyl]-amide (53 mg, 100%) as a white solid.

Workup

  1. washis washed with dilute aqueous NaOH
  2. customto remove the yellow nitrophenol byproduct
  3. customThe organic layer is dried
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (CH2Cl2/EtOAc, 7/3)

Sources & evidence

ORD record
ord-c93187913ef345a497e3afb8e28d734d
Source dataset
uspto-grants-2011_01
Patent number
US07868037B2

Linked notes

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