Triethylamine → N-(3,4-Difluorobenzyl)-2-isopropyl-6-methoxy-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

HRID 40154Notes

Reaction equation

HRID 40154 reaction equation
[CH:1]([C:4]1[N:5]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[C:6]2[C:11]([C:12]=1[C:13]([OH:15])=O)=[CH:10][CH:9]=[C:8]([O:16][CH3:17])[CH:7]=2)([CH3:3])[CH3:2].C(Cl)(C(Cl)=O)=O.[F:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:35][NH2:36].CCN(CC)CC>C(Cl)Cl.CCOC(C)=O.CN(C=O)C>[F:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:35][NH:36][C:13]([C:12]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[CH:9][CH:10]=2)[N:5]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[C:4]=1[CH:1]([CH3:2])[CH3:3])=[O:15]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1235723,4-DifluorobenzylamineHCID 597624242-isopropyl-6-methoxy-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxylic acid2×

Product 1

HCID 59762372N-(3,4-Difluorobenzyl)-2-isopropyl-6-methoxy-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-isopropyl-6-methoxy-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxylic acid (Compound 139, 415 mg, 1.28 mmol) in CH2Cl2 (20 ml) at 0° C. was added (COCl)2 (2 M in CH2Cl2, 1.6 ml, 3.20 mmol) and a catalytic amount of DMF. The mixture was stirred at room temperature for 1 h, and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (20 ml), cooled to 0° C., and 3,4-difluorobenzylamine (0.23 ml, 1.92 mmol) was added, followed by Et3N (0.53 ml, 3.84 mmol). The reaction was stirred at room temperature for 4 h, diluted with EtOAc, washed with H2O, brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound as a yellow solid.

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (20 ml)
  3. temperaturecooled to 0° C.
  4. stirringThe reaction was stirred at room temperature for 4 h
  5. washwashed with H2O, brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

Sources & evidence

ORD record
ord-72d8100e71874c62a97578767e519a77
Source dataset
uspto-grants-2013_09
Patent number
US08524917B2

Reaction notes

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