Triethylamine → N-(1-Cyclopropyl-3,3-dimethyl-2-oxoindolin-6-yl)-2-methylisonicotinamide

HRID 1507562Notes

Reaction equation

HRID 1507562 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.ClC(N(C)C)=C(C)C.[NH2:19][C:20]1[CH:28]=[C:27]2[C:23]([C:24]([CH3:34])([CH3:33])[C:25](=[O:32])[N:26]2[CH:29]2[CH2:31][CH2:30]2)=[CH:22][CH:21]=1.C(N(CC)CC)C>ClCCl.O.C(=O)([O-])[O-].[Na+].[Na+]>[CH:29]1([N:26]2[C:27]3[C:23](=[CH:22][CH:21]=[C:20]([NH:19][C:5](=[O:7])[C:4]4[CH:8]=[CH:9][N:10]=[C:2]([CH3:1])[CH:3]=4)[CH:28]=3)[C:24]([CH3:33])([CH3:34])[C:25]2=[O:32])[CH2:31][CH2:30]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 27628212-Methylpyridine-4-carboxylic acidHCID 1184151856-Amino-1-cyclopropyl-3,3-dimethyl-1,3-dihydro-indol-2-one

Product 1

HCID 73425624N-(1-Cyclopropyl-3,3-dimethyl-2-oxoindolin-6-yl)-2-methylisonicotinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 10340Sodium CarbonateSolvent

Procedure

To a solution of 2-methylisonicotinic acid (95.1 mg, 694 μmol) in dry dichloromethane (3.64 ml) under an argon atmosphere at 0° C. was added a solution of 1-chloro-N,N,2-trimethylpropenylamine (104 mg, 763 μmol) in dry dichloromethane (1 ml). After 2 hours 6-amino-1-cyclopropyl-3,3-dimethyl-1,3-dihydro-indol-2-one (example 14c, 150 mg, 694 μmol) and triethyl amine (140 mg, 193 μl, 1.39 mmol) were added at 0° C. The reaction mixture was warmed to room temperature, kept at this temperature for 16 hours, then diluted with dichloromethane, water and 1 M aqueous sodium carbonate solution. The aqueous phase was extracted with dichloromethane. The combined organic layers were washed with 1 M aqueous sodium carbonate solution, dried over sodium sulfate, the solvent was evaporated and the residue was purified by silica gel chromatography using dichloromethane/methanol as eluent. The title compound was obtained as light yellow oil (207 mg).

Workup

  1. extractionThe aqueous phase was extracted with dichloromethane
  2. washThe combined organic layers were washed with 1 M aqueous sodium carbonate solution
  3. dry with materialdried over sodium sulfate
  4. customthe solvent was evaporated
  5. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-66ef3689711349a68c1bb211520cdff5
Source dataset
uspto-grants-2015_12
Patent number
US09221816B2

Reaction notes

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