1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44466353, compound

HRID 2381424Notes

Reaction equation

HRID 2381424 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[C:28]4[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=4[CH:22]=[CH:21][CH:20]=3)[CH:13]=[N:12]2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:50][C:51]1[CH:55]=[CH:54][N:53]([CH2:56][C:57]([CH3:60])([OH:59])[CH3:58])[N:52]=1>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[C:28]4[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=4[CH:22]=[CH:21][CH:20]=3)[CH:13]=[N:12]2)[C:8]([NH:50][C:51]2[CH:55]=[CH:54][N:53]([CH2:56][C:57]([OH:59])([CH3:58])[CH3:60])[N:52]=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 57919149HCID 57919149, compound2×HCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol2×

Product 1

HCID 44466353HCID 44466353, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-[6-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-6H-pyridazin-1-yl]-propionic acid (Intermediate 39, 1.0 g, 2.61 mmol) in methylene chloride (26 mL, 0.10 M) at 25° C. was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (470 μL, 2.65 mmol) and 1-hydroxybenzotriazole (370 mg, 2.73 mmol). The solution was stirred at 25° C. for 2.5 h. After this time, the reaction was treated with a slurry of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1, 490 mg, 3.15 mmol) in methylene chloride at 25° C. The reaction was stirred at 25° C. overnight. After this time, the reaction was diluted with methylene chloride (250 mL) and was washed with a 1N aqueous hydrochloric acid solution (2×250 mL), a saturated aqueous sodium bicarbonate solution (1×250 mL), water (1×250 mL), and a saturated aqueous sodium chloride solution (1×250 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 115 g, 35-75% ethyl acetate/hexanes gradient) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[6-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-6H-pyridazin-1-yl]-propionamide (730 mg, 54%) as a white solid; ES+-HRMS m/e calcd for C29H37N5O4 [M+H+] 520.2919, found 520.2920. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.05 (s, 3H), 1.06 (s, 3H), 1.09 (m, 1H), 1.27-1.78 (m, 12H), 1.91 (m, 1H), 2.27 (m, 1H), 2.50 (m, 2H), 2.78 (m, 2H), 3.89 (s, 2H), 4.67 (s, 1H), 5.45 (dd, J=4.3, J=10.9 Hz, 1H), 5.57 (d, J=2.8 Hz, 1H), 6.40 (d, J=2.2 Hz, 1H), 7.01 (d, J=7.7 Hz, 1H), 7.09 (d, J=7.7 Hz, 1H), 7.23 (t, J=7.7 Hz, 1H), 7.53 (d, J=2.2 Hz, 1H), 8.13 (d, J=2.8 Hz, 1H), 10.80 (s, 1H).

Workup

  1. stirringThe reaction was stirred at 25° C. overnight
  2. washwas washed with a 1N aqueous hydrochloric acid solution (2×250 mL)
  3. dry with materiala saturated aqueous sodium bicarbonate solution (1×250 mL), water (1×250 mL), and a saturated aqueous sodium chloride solution (1×250 mL), dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8c22baecfc234fc9ae0cc8863c4a2210
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

Loading…