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

HRID 2097178Notes

Reaction equation

HRID 2097178 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-2958db5450fd406caf446978c1751e33
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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