Triethylamine → N-(6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl)-1-methyl-1H-imidazole-5-carboxamide

HRID 28709Notes

Reaction equation

HRID 28709 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][N:4]=[CH:3]1.[Cl:10][C:11]1[CH:12]=[C:13]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]1[CH:18]([NH2:24])[CH2:17][CH2:16][CH2:15][C:14]2=1.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[Cl:10][C:11]1[CH:12]=[C:13]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]1[CH:18]([NH:24][C:7]([C:6]3[N:2]([CH3:1])[CH:3]=[N:4][CH:5]=3)=[O:9])[CH2:17][CH2:16][CH2:15][C:14]2=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27735071-methyl-1H-imidazole-5-carboxylic acidHCID 177434976-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-amine

Product 1

HCID 11427450N-(6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl)-1-methyl-1H-imidazole-5-carboxamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-methyl-1H-imidazole-5-carboxylic acid (45 mg, 0.36 mmol) in dichloromethane (3.6 mL) was added 6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-amine (95 mg, 0.43 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (83 mg, 0.43 mmol), and 1-hydroxybenzotriazole (54 mg, 0.40 mmol). After 5 minutes, triethylamine (100 μL, 0.72 mmol) was added and the reaction was stirred at room temperature for 15 hours. The reaction mixture was diluted with dichloromethane, washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide, brine, dried with magnesium sulfate, filtered, and concentrated. The residue was purified by preparative chromatography (10-90% acetonitrile-water (0.1% trifluoroacetic acid)) and then diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, and dried with magnesium sulfate to give 43 mg (36% yield) of a white solid. 1H-NMR (CDCl3): δ 9.21 (s, 1H), 7.43 (m, 1H), 7.32 (s, 1H), 7.30 (s, 1H), 7.20 (d, 1H), 7.07 (dd, 1H), 6.60 (d, 1H), 5.25 (m, 1H), 3.81 (s, 3H), 2.67 (m, 2H), 2.21 (m, 1H), 1.90 (m, 3H); MS m/z 327 (M−1).

Workup

  1. washwashed with water, 1 N hydrochloric acid, 1 N sodium hydroxide, brine
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by preparative chromatography (10-90% acetonitrile-water (0.1% trifluoroacetic acid))
  6. additiondiluted with ethyl acetate
  7. washwashed with saturated aqueous sodium bicarbonate
  8. dry with materialdried with magnesium sulfate

Sources & evidence

ORD record
ord-24367cc40bbc4785afdfd6a5d5ba5c11
Source dataset
uspto-grants-2008_09
Patent number
US07419997B2

Reaction notes

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