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

HRID 506117Notes

Reaction equation

HRID 506117 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-e2becac2bad74c2f9b39e7de91b0b2dc
Source dataset
uspto-grants-2010_08
Patent number
US07781478B2

Reaction notes

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