2-Aminopyridine → HCID 54765575, compound

HRID 1925923Notes

Reaction equation

HRID 1925923 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]([OH:16])=O)[CH2:12][C:8]=3[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[N:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[NH:24][C:14](=[O:16])[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]([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 104392-AminopyridineHCID 757711-HydroxybenzotriazoleHCID 67521758HCID 67521758, compound

Product 1

HCID 54765575HCID 54765575, compoundYield 49.5%

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) (Example 22, Step 1c), commercially available 2-aminopyridine (33 mg, 0.36 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (63 mg, 0.32 mmol), and N-hydroxybenzotriazole (HOBt) (44 mg, 0.32 mmol) in methylene chloride (1 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 pyridin-2-ylamide (55 mg, 45%), as a white solid. 1H NMR (DMSO-d6) δ: 10.88 (s, 1H), 8.34 (d, J=3.4 Hz, 1H), 8.01 (d, J=7.8 Hz, 1H), 7.77 (t, J=7.8 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.13 (d, J=7.8 Hz, 2H), 5.08 (d, J=6.8 Hz, 1H), 4.43 (d, J=18.6 Hz, 1H), 4.06 (d, J=19.1 Hz, 1H), 3.82 (br. s., 2H), 1.78-1.94 (m, 1H), 1.61-1.74 (m, 1H), 1.47 (br. s., 1H), 0.94 (t, J=4.9 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-ce760f596e964030a10837417faf6952
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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