2-Aminothiazole → HCID 54765734, compound

HRID 1925924Notes

Reaction equation

HRID 1925924 reaction equation
[Cl:1][C:2]1[C:23]2[O:22][C:9]3[C:10](=[O:21])[N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14](O)=[O:15])[CH2:12][C:8]=3[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:24][C:25]1[S:26][CH:27]=[CH:28][N:29]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[S:26]1[CH:27]=[CH:28][N:29]=[C:25]1[NH:24][C:14](=[O:15])[C@@H:13]([N:11]1[CH2:12][C:8]2[CH2:7][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[C:23]=3[O:22][C:9]=2[C:10]1=[O:21])[CH2:17][CH:18]([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 757711-HydroxybenzotriazoleHCID 67521758HCID 67521758, compound

Product 1

HCID 54765734HCID 54765734, compoundYield 99.1%

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)-4-methyl-pentanoic acid (130 mg, 0.35 mmol) (Example 22, Step 1c), commercially available 2-aminothiazole (47 mg, 0.36 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (82 mg, 0.43 mmol), and N-hydroxybenzotriazole (HOBt) (57 mg, 0.43 mmol) in methylene chloride (15 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-(5-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamide (145 mg, 58.2%), as a white solid. 1H NMR (DMSO-d6) δ: 12.57 (s, 1H), 7.50 (d, J=3.4 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.20-7.29 (m, 2H), 7.08-7.16 (m, 1H), 5.05 (dd, J=10.8, 4.4 Hz, 1H), 4.39 (d, J=19.1 Hz, 1H), 4.09 (d, J=19.1 Hz, 1H), 3.75-3.91 (m, 2H), 1.80-1.93 (m, 1H), 1.62-1.75 (m, 1H), 1.46 (br. s., 1H), 0.94 (t, J=6.6 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-1f22d000a2e94814b39e0a55a61326f5
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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