2-Aminothiazole → (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamide

HRID 1925901Notes

Reaction equation

HRID 1925901 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[CH2:5][C:6]3[CH2:10][N:9]([C@@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)[C:8](=[O:19])[C:7]=3[O:20][C:21]=2[CH:22]=[CH:23][CH:24]=1.[NH2:25][C:26]1[S:27][CH:28]=[CH:29][N:30]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[S:27]1[CH:28]=[CH:29][N:30]=[C:26]1[NH:25][C:12](=[O:14])[C@@H:11]([N:9]1[CH2:10][C:6]2[CH2:5][C:4]3[C:3]([O:2][CH3:1])=[CH:24][CH:23]=[CH:22][C:21]=3[O:20][C:7]=2[C:8]1=[O:19])[CH2:15][CH:16]([CH3:17])[CH3:18]

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 757711-HydroxybenzotriazoleHCID 67520964(S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid

Product 1

HCID 54767808(S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamideYield 27.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (100 mg, 0.30 mmol), commercially available 2-amino-thiazole (37 mg, 0.36 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (66 mg, 0.33 mmol), and N-hydroxybenzotriazole (HOBt) (44 mg, 0.33 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 gradient elution, afforded (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamide (34 mg, 27.2%), as an off white solid. 1H NMR (DMSO-d6) δ: 12.58 (br. s., 1H), 7.50 (d, J=3.4 Hz, 1H), 7.12-7.34 (m, 2H), 6.76 (d, J=7.8 Hz, 1H), 6.68 (d, J=8.3 Hz, 1H), 5.04 (d, J=5.9 Hz, 1H), 4.36 (d, J=19.1 Hz, 1H), 4.05 (d, J=18.6 Hz, 1H), 3.82 (s, 3H), 3.55 (br. s., 2H), 1.83 (d, J=9.3 Hz, 1H), 1.68 (br. s., 1H), 1.45 (br. s., 1H), 0.93 (t, J=7.3 Hz, 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 gradient elution

Sources & evidence

ORD record
ord-86c26fa2965242e3ac11a5febe0ced56
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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