1H-Indole-5-Carboxylic Acid → 1h-Indole-5-carboxamide,n-(cyclopentylmethyl)-

HRID 1904478Notes

Reaction equation

HRID 1904478 reaction equation
[CH:1]1([CH2:6][NH2:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:8]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2)(O)=[O:9].Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:1]1([CH2:6][NH:7][C:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[CH:14]3)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 742801H-Indole-5-Carboxylic AcidHCID 80153CyclopentanemethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 100373961h-Indole-5-carboxamide,n-(cyclopentylmethyl)-Yield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of cyclopentylmethylamine (2.66 g), 5-carboxyindole (4.76 g), 4-(dimethylamino)pyridine (3.60 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.67 g) in methylene chloride (60 ml) was stirred for 12 hours under an atmosphere of nitrogen. The amber solution was diluted with methylene chloride (150 ml); washed successively wth 10% (w/v) aqueous sodium carbonate, 10% (v/v) hydrochloric acid, water, and brine; dried (MgSO4); and evaporated. The residual amber oil was purified by flash chromatography on silica gel (700 ml), eluting with 1:3 v/v ethyl acetate:chloroform, to yield 5-(N-cyclopentylmethylcarbamoyl)indole (CC) (5.17 g, 80%) as a white crystalline solid; mp 110°-112° C.; NMR (80 MHz, CDCl3): 1.0-2.4(broad m, 9H, cyclopentyl), 3.4(dd, 2H, CH2N), 6.2(broad, 1H, NH), 6.6(m, 1H, H3 -indole), 7.3(t, 1H, H2 -indole), 7.4(d, 1H, H7 -indole), 8.5(broad, 1H, CONH).

Workup

  1. washwashed successively wth 10% (w/v) aqueous sodium carbonate, 10% (v/v) hydrochloric acid, water, and brine
  2. dry with materialdried (MgSO4)
  3. customand evaporated
  4. customThe residual amber oil was purified by flash chromatography on silica gel (700 ml)
  5. washeluting with 1:3 v/v ethyl acetate

Sources & evidence

ORD record
ord-b1faaf6381f9479781e4804593ea954f
Source dataset
uspto-grants-1989_06
Patent number
US04837235

Reaction notes

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