2-Aminothiazole → (S)-2-(8-Chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-thiazol-2-yl-propionamide

HRID 1925882Notes

Reaction equation

HRID 1925882 reaction equation
[Cl:1][C:2]1[C:3]2[CH2:4][C:5]3[CH2:9][N:8]([C@@H:10]([CH2:20][CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)[C:11]([NH:13][C:14]4C=C[CH:17]=[CH:16][N:15]=4)=[O:12])[C:7](=[O:27])[C:6]=3[O:28][C:29]=2[CH:30]=[CH:31][CH:32]=1.NC1[S:35]C=CN=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]([CH2:20][CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)[C:11]([NH:13][C:14]4[S:35][CH:17]=[CH:16][N:15]=4)=[O:12])[C:7](=[O:27])[C:6]=3[O:28][C:29]=2[CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 757711-HydroxybenzotriazoleHCID 54767631(S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-pyridin-2-ylpropionamide

Product 1

HCID 54767632(S)-2-(8-Chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-thiazol-2-yl-propionamideYield 46.3%

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) (from Example 1, Step 3), commercially available 2-aminothiazole (110 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 silical gel flash chromatography using hexane-ethyl acetate gradiant elution, afforded (S)-2-(8-Chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-thiazol-2-yl-propionamide (113 mg, 46.3%) as a white solid. 1H NMR (DMSO-d6) δ: 12.56 (br. s., 1H), 7.50 (d, J=3.4 Hz, 3H), 7.20-7.36 (m, 10H), 7.05-7.15 (m, 3H), 5.06 (d, J=5.9 Hz, 3H), 4.40 (d, J=18.6 Hz, 3H), 4.09 (d, J=18.6 Hz, 3H), 3.76 (s, 6H), 1.52-1.91 (m, 24H), 1.04-1.32 (m, 17H), 0.90-1.03 (m, 7H), 0.79-0.88 (m, 3H).

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-cc9f4b5129274c3ab3252a5b3d80d56e
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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