Triethylamine → Methyl 3-(3,4-Difluorobenzylcarbamoyl)-6-methoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylate

HRID 40100

Reaction equation

HRID 40100 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:23]([OH:25])=O)=[C:8]([C:19]([O:21][CH3:22])=[O:20])[N:9]2[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:5][CH:4]=1.C(Cl)(C(Cl)=O)=O.[F:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][C:40]=1[F:41])[CH2:36][NH2:37].CCN(CC)CC>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[F:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][C:40]=1[F:41])[CH2:36][NH:37][C:23]([C:7]1[C:6]2[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:8]=1[C:19]([O:21][CH3:22])=[O:20])=[O:25]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1235723,4-DifluorobenzylamineHCID 597623576-Methoxy-2-(methoxycarbonyl)-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxylic Acid2×

Product 1

HCID 59762310Methyl 3-(3,4-Difluorobenzylcarbamoyl)-6-methoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-methoxy-2-(methoxycarbonyl)-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxylic acid (Compound 92, 1.59 g, 4.7 mmol) in anhydrous CH2Cl2 (50 ml) was added DMF (3 drops, catalytic amount) and (COCl)2 (2M in CH2Cl2, 5.9 ml, 11.8 mmol). The resulting mixture was stirred at room temperature for 1 h, and was concentrated in vacuo. To a solution of the crude product in CH2Cl2 (50 ml) was added 3,4-difluorobenzylamine (0.84 ml, 7.05 mmol), followed by Et3N (2.0 ml, 14.1 mmol). The reaction was stirred at room temperature for 1 h, diluted with EtOAc, washed with H2O and 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 white solid.

Workup

  1. concentrationwas concentrated in vacuo
  2. stirringThe reaction was stirred at room temperature for 1 h
  3. washwashed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

Sources & evidence

ORD record
ord-21500f5beb23491a83ce2c5100e1d2b2
Source dataset
uspto-grants-2013_09
Patent number
US08524917B2

Linked notes

Loading…