1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-cyclopentyl-N-(1-methyl-1H-pyrazol-3-yl)-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionamide

HRID 2381508Notes

Reaction equation

HRID 2381508 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[CH:14][C:13]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:46][N:47]1[CH:51]=[CH:50][C:49]([NH2:52])=[N:48]1>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[CH:14][C:13]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:12]2)[C:8]([NH:52][C:49]2[CH:50]=[CH:51][N:47]([CH3:46])[N:48]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1372541-Methyl-3-aminopyrazoleHCID 668752903-cyclopentyl-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionic acid

Product 1

HCID 579192373-cyclopentyl-N-(1-methyl-1H-pyrazol-3-yl)-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionamideYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionic acid (0.30 g, 0.91 mmol) in methylene chloride (9.0 mL, 0.10M) at 25° C. was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (164 μL, 0.92 mmol) and 1-hydroxybenzotriazole (0.13 g, 0.96 mmol). The solution was stirred at 25° C. for 1.8 h. After this time, the reaction was treated with a solution of 1-methyl-1H-pyrazol-3-ylamine in methylene chloride at 25° C. The reaction was stirred at 25° C. for 5 d. After this time, the reaction was diluted with methylene chloride (100 mL) and was washed with a 1N aqueous hydrochloric acid solution (2×100 mL), a saturated aqueous sodium bicarbonate solution (2×100 mL), water (1×100 mL), and a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, rinsed with methylene chloride and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 50-100% ethyl acetate/hexanes gradient) afforded 3-cyclopentyl-N-(1-methyl-1H-pyrazol-3-yl)-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionamide (76.7 mg, 21%) as a white solid; ES+-HRMS m/e calcd for C22H25N5O3 [M+H+] 408.2030 found 408.2030. 1H-NMR (400 MHz, DMSO-d6) δ ppm 0.87-0.98 (m, 1H), 1.17-1.31 (m, 1H), 1.35-1.63 (m, 7H), 1.69 (ddd, J=13.1, 9.3, 3.6 Hz, 1H), 1.88-2.00 (m, 1H), 3.73 (s, 3H), 5.29 (dd, J=11.1, 3.6 Hz, 1H), 6.33 (d, J=2.0 Hz, 1H), 7.09 (d, J=9.8 Hz, 1H), 7.17-7.26 (m, 3H), 7.34-7.43 (m, 2H), 7.46 (d, J=9.8 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 10.66 (s, 1H).

Workup

  1. stirringThe reaction was stirred at 25° C. for 5 d
  2. washwas washed with a 1N aqueous hydrochloric acid solution (2×100 mL)
  3. dry with materiala saturated aqueous sodium bicarbonate solution (2×100 mL), water (1×100 mL), and a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate
  4. filtrationfiltered
  5. washrinsed with methylene chloride
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-91cff1f2c84d4a2b96703ed24ebfb702
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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