1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57919113, compound

HRID 2381490Notes

Reaction equation

HRID 2381490 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([N:18]([CH3:25])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:13]=[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.[NH2:47][C:48]1[CH:52]=[CH:51][N:50]([CH2:53][C:54]([CH3:57])([OH:56])[CH3:55])[N:49]=1>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([N:18]([CH3:25])[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:13]=[N:12]2)[C:8]([NH:47][C:48]2[CH:52]=[CH:51][N:50]([CH2:53][C:54]([OH:56])([CH3:55])[CH3:57])[N:49]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol2×HCID 66875666HCID 66875666, compound

Product 1

HCID 57919113HCID 57919113, compoundYield 45.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-[4-(methyl-phenyl-amino)-6-oxo-6H-pyridazin-1-yl]-propionic acid (assume 0.18 mmol) in methylene chloride (1.8 mL, 0.1M) at 25° C. was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (34 μL, 0.19 mmol) followed by 1-hydroxybenzotriazole (26.3 mg, 0.19 mmol). The resulting solution was stirred at 25° C. for 3.5 h. After this time, the reaction was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1, 36.8 mg, 0.23 mmol). The resulting solution was stirred at 25° C. for 2 d. After this time, the reaction was diluted with methylene chloride (25 mL) and was washed consecutively with a saturated ammonium chloride solution (1×25 mL), a saturated sodium bicarbonate solution (1×25 mL), water (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL). The organics were then dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (AnaLogix 8 g, 50-100% ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(methyl-phenyl-amino)-6-oxo-6H-pyridazin-1-yl]-propionamide (39.4 mg, 44% over two steps) as a yellow solid; ES+-HRMS m/e calcd for C26H34N6O3 [M+H+] 479.2765, found 479.2764. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.04 (s, 3H) 1.05 (s, 3H) 1.06-1.11 (m, 1H) 1.16-1.33 (m, 1H) 1.37-1.74 (m, 7H) 1.84-1.99 (m, 1H) 2.17-2.30 (m, 1H) 3.33 (s, 3H) 3.88 (s, 2H) 4.66 (s, 1H) 5.39 (dd, J=10.5, 4.8 Hz, 1H) 6.40 (d, J=2.1 Hz, 1H) 6.71 (d, J=4.9 Hz, 1H) 6.96-7.03 (m, 2H) 7.03-7.11 (m, 1H) 7.22-7.31 (m, 2H) 7.51 (d, J=2.1 Hz, 1H) 7.82 (d, J=4.9 Hz, 1H) 10.55 (s, 1H).

Workup

  1. stirringThe resulting solution was stirred at 25° C. for 2 d
  2. washwas washed consecutively with a saturated ammonium chloride solution (1×25 mL)
  3. dry with materialThe organics were then dried over magnesium sulfate
  4. filtrationfiltered
  5. washrinsed
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c7c36ffc0f2547de8bbc688f8a1756eb
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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