2-Aminothiazole → HCID 54765573, compound

HRID 1925919Notes

Reaction equation

HRID 1925919 reaction equation
[Cl:1][C:2]1[C:26]2[O:25][C:9]3[C:10](=[O:24])[N:11]([C@@H:13]([CH2:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)[C:14](O)=[O:15])[CH2:12][C:8]=3[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:27][C:28]1[S:29][CH:30]=[CH:31][N:32]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[Cl:1][C:2]1[C:26]2[O:25][C:9]3[C:10](=[O:24])[N:11]([C@@H:13]([CH2:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)[C:14]([NH:27][C:28]4[S:29][CH:30]=[CH:31][N:32]=4)=[O:15])[CH2:12][C:8]=3[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 757711-HydroxybenzotriazoleHCID 67521062HCID 67521062, compound

Product 1

HCID 54765573HCID 54765573, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-(5-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid (100 mg, 0.27 mmol) (Example 20, Step 2c), commercially available 2-aminothiazole (32 mg, 0.32 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (40 mg, 0.29 mmol), and N-hydroxybenzotriazole (HOBt) (56 mg, 0.29 mmol) in methylene chloride (5 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, afforded (S)-2-(5-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-N-thiazol-2-yl-propionamide (104 mg, 85.2%), as a white solid. 1H NMR (DMSO-d6) δ: 12.55 (s, 1H), 7.50 (d, J=2.9 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.20-7.28 (m, 2H), 7.07-7.17 (m, 1H), 5.07 (dd, J=10.5, 4.2 Hz, 1H), 4.39 (d, J=19.1 Hz, 1H), 4.08 (d, J=18.6 Hz, 1H), 3.84 (br. s., 2H), 1.52-1.90 (m, 7H), 0.76-1.29 (m, 6H).

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-65765f044bc5440e97059a1a9657f0a3
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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