2-Aminopyridine → (S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-pyridin-2-ylpropionamide

HRID 1925881Notes

Reaction equation

HRID 1925881 reaction equation
[Cl:1][C:2]1[C:3]2[CH2:4][C:5]3[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]4)[C:11]([OH:13])=O)[C:7](=[O:21])[C:6]=3[O:22][C:23]=2[CH:24]=[CH:25][CH:26]=1.[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[Cl:1][C:2]1[C:3]2[CH2:4][C:5]3[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]4)[C:11]([NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[O:13])[C:7](=[O:21])[C:6]=3[O:22][C:23]=2[CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 104392-AminopyridineHCID 757711-HydroxybenzotriazoleHCID 67520747(S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid

Product 1

HCID 54767631(S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-pyridin-2-ylpropionamideYield 20.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid (200 mg, 2.1 mmol), commercially available 2-aminopyridine (60 mg, 0.63 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (112 mg, 0.59 mmol), and N-hydroxybenzotriazole (HOBt) (79 mg, 0.59 mmol) in methylene chloride (10 mL) was stirred for 16 hours at 25° C. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradiant elution, to afford (S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-pyridin-2-ylpropionamide (50 mg, 20.8%), as a white solid. 1H NMR (DMSO-d6) δ: 10.87 (s, 1H), 8.28-8.41 (m, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.70-7.86 (m, 1H), 7.20-7.40 (m, 2H), 7.03-7.16 (m, 2H), 5.09 (br. s., 1H), 5.00-5.01 (m, 1H), 4.36-4.37 (m, 1H), 4.43 (d, J=18.6 Hz, 1H), 4.07 (d, J=18.6 Hz, 3H), 3.99-4.15 (m, 1H), 3.75 (s, 2H), 1.49-1.90 (m, 6H), 1.05-1.29 (m, 4H), 0.88-1.02 (m, 2H).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. washhexane-ethyl acetate gradiant elution

Sources & evidence

ORD record
ord-1652241d281142aea4f9fa14a311fa34
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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