1-Hydroxybenzotriazole → HCID 54765574, compound

HRID 1925922Notes

Reaction equation

HRID 1925922 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.[CH3:24][O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][C:30]([NH2:33])=[N:29][CH:28]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[CH3:24][O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:14](=[O:15])[C@@H:13]([N:11]2[CH2:12][C:8]3[CH2:7][C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[C:23]=4[O:22][C:9]=3[C:10]2=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[N:29][CH:28]=1

Participants

6

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 737487Methyl 6-aminonicotinateHCID 67521758HCID 67521758, compound

Product 1

HCID 54765574HCID 54765574, compoundYield 33.1%

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 (100 mg, 0.27 mmol), commercially available 6-aminonicotinic acid methylester (109 mg, 0.71 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (125 mg, 0.66 mmol), and N-hydroxybenzotriazole (HOBt) (88 mg, 0.66 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 gradient elution, afforded 6-[(S)-2-(5-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoyl-amino]-nicotinic acid methyl ester (42 mg, 15%), as a white solid. 1H NMR (DMSO-d6) δ: 11.35 (s, 1H), 8.88 (s, 1H), 8.29 (d, J=8.8 Hz, 1H), 8.15 (d, J=8.8 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.23 (d, J=7.3 Hz, 1H), 7.08-7.16 (m, 1H), 5.10 (d, J=7.3 Hz, 1H), 4.42 (d, J=19.1 Hz, 1H), 4.07 (d, J=18.6 Hz, 1H), 3.86 (s, 3H), 3.83 (br. s., 2H), 1.76-2.02 (m, 1H), 1.69 (t, J=9.3 Hz, 1H), 1.48 (br. s., 1H), 0.87-0.99 (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-73c08e4ac7794f5394feaa10b5f4e5df
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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