1,2-Dichloroethane → N-methyl-1H-indole-2-carboxamide

HRID 1362430Notes

Reaction equation

HRID 1362430 reaction equation
C(Cl)CCl.[NH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:6]1[C:14]([OH:16])=O.CN.C(O)C.C1C=CC2N(O)N=[N:28][C:26]=2C=1.CCN(C(C)C)C(C)C>C1COCC1>[CH3:26][NH:28][C:14]([C:6]1[NH:5][C:13]2[C:8]([CH:7]=1)=[CH:9][CH:10]=[CH:11][CH:12]=2)=[O:16]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 702EthanolHCID 6329MethylamineHCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine

Product 1

HCID 12461785N-methyl-1H-indole-2-carboxamideYield 153.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

EDC (7.7 g, 40.3 mmol) was added to a solution of indole-2-carboxylic acid (5 g, 13.1 mmol), methylamine, 33% in ethanol (5.6 mL, 15.5 mmol), HOBT (4.1 g, 13.1 mmol) and DIPEA (2.1 mL, 12.4 mmol) in THF, anhydrous (45 mL) and stirred overnight. The crude mixture was evaporated in vacuo and chromatographed over silica eluting with methanol/dichloromethane (0-2%) to afford the title compound (3.51 g, 66%). 1H NMR (300 MHz, DMSO-d6) δ 11.53 (s, 1H), 8.43 (s, 1H), 7.57 (d, J=7.9 Hz, 1H), 7.39 (d, J=8.2 Hz, 1H), 7.15 (t, J=8.2 Hz, 1H), 7.03 (s, 1H), 6.98 (t, J=7.9 Hz, 1H), 2.79 (d, J=4.7 Hz, 3H)

Workup

  1. customThe crude mixture was evaporated in vacuo
  2. customchromatographed over silica eluting with methanol/dichloromethane (0-2%)

Sources & evidence

ORD record
ord-ec51eab26da8492aa2c1e886d434cd7b
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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