2-Aminothiazole → HCID 54767967, compound

HRID 1925911Notes

Reaction equation

HRID 1925911 reaction equation
[CH3:1][O:2][C:3]1[C:24]2[O:23][C:10]3[C:11](=[O:22])[N:12]([C@@H:14]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15](O)=[O:16])[CH2:13][C:9]=3[CH2:8][C:7]=2[C:6]([O:25][CH3:26])=[CH:5][CH:4]=1.[NH2:27][C:28]1[S:29][CH:30]=[CH:31][N:32]=1.ON1[C:38]2C=CC=[CH:42][C:37]=2N=N1>C(Cl)Cl.O>[CH:19]1([CH2:18][C@H:14]([N:12]2[CH2:13][C:9]3[CH2:8][C:7]4[C:6]([O:25][CH3:26])=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:24]=4[O:23][C:10]=3[C:11]2=[O:22])[C:15]([NH:27][C:28]2[S:29][CH:30]=[CH:31][N:32]=2)=[O:16])[CH2:20][CH2:42][CH2:37][CH2:38][CH2:21]1

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 757711-HydroxybenzotriazoleHCID 67520997HCID 67520997, compound

Product 1

HCID 54767967HCID 54767967, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (Example 13, step 2c) (100 mg, 0.21 mmol), commercially available 2-aminothiazole (30 mg, 0.30 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (52 mg, 0.27 mmol), and N-hydroxybenzotriazole (HOBt) (37 mg, 0.27 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)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-N-thiazol-2-yl-propionamide (68 mg, 56.6%), as a white solid. 1H NMR (DMSO-d6) δ: 12.55 (br. s., 1H), 7.50 (d, J=2.9 Hz, 1H), 7.25 (br. s., 1H), 6.92 (d, J=8.8 Hz, 1H), 6.67 (d, J=8.8 Hz, 1H), 5.06 (d, J=5.4 Hz, 1H), 4.35 (d, J=18.6 Hz, 1H), 4.04 (d, J=18.6 Hz, 1H), 3.76 (s, 6H), 3.56 (br. s., 2H), 1.45-1.91 (m, 7H), 0.76-1.30 (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 gradient elution

Sources & evidence

ORD record
ord-f1dc89e414b74fc3a8de3c63ce2a63a1
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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