4-Methylmorpholine → 4'-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide

HRID 418397Notes

Reaction equation

HRID 418397 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:16][C:15]3=[O:23])[CH:11]=[C:10]([C:24](O)=[O:25])[CH:9]=2)=[CH:4][CH:3]=1.[CH3:27][C:28]1[N:29]=[CH:30][C:31]([CH2:34][NH2:35])=[N:32][CH:33]=1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH3:27][C:28]1[N:29]=[CH:30][C:31]([CH2:34][NH:35][C:24]([C:10]2[CH:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=3)[CH:13]=[C:12]([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:16][C:15]3=[O:23])[CH:11]=2)=[O:25])=[N:32][CH:33]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 27564962-(Aminomethyl)-5-methylpyrazineHCID 596277614'-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid

Product 1

HCID 498479604'-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amideYield 5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 4′-methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid from step 3 was added to DMF (3 mL), together with C-(5-methyl-pyrazin-2-yl)-methylamine (0.1 mL), HOAt (15 mg, catalytic amount), NMM (0.4 mL) and EDCI (200 mg). The reaction mixture was stirred overnight at room temperature, then partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer chromatography (7% MeOH in dichloromethane) to give 20 mg (5% overall) of 4′-methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide, MS (M+H)=449.

Workup

  1. custompartitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. concentrationconcentrated under reduced pressure
  4. customthe resulting residue was purified by preparative thin layer chromatography (7% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-a0301f117f804596b0200b072b47f3cf
Source dataset
uspto-grants-2012_01
Patent number
US08093275B2

Reaction notes

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