1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(3-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-1-methyl-1H-pyrazol-5-yl)-3-isobutylurea

HRID 541431Notes

Reaction equation

HRID 541431 reaction equation
[CH2:1]([NH:5][C:6](=[O:17])[NH:7][C:8]1[N:12]([CH3:13])[N:11]=[C:10]([C:14]([OH:16])=O)[CH:9]=1)[CH:2]([CH3:4])[CH3:3].Cl.[NH:19]1[CH2:24][CH2:23][CH:22]([C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)[CH2:21][CH2:20]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[C:29]([C:28]1[CH:27]=[CH:26][C:25]([CH:22]2[CH2:23][CH2:24][N:19]([C:14]([C:10]3[CH:9]=[C:8]([NH:7][C:6]([NH:5][CH2:1][CH:2]([CH3:3])[CH3:4])=[O:17])[N:12]([CH3:13])[N:11]=3)=[O:16])[CH2:20][CH2:21]2)=[CH:32][CH:31]=1)#[N:30]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 682886485-(3-Isobutylureido)-1-methyl-1H-pyrazole-3-carboxylic acid2×

Product 1

HCID 682883311-(3-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-1-methyl-1H-pyrazol-5-yl)-3-isobutylureaYield 13.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-(3-Isobutylureido)-1-methyl-1H-pyrazole-3-carboxylic acid (compound 351.6, 0.11 g, 0.46 mmol), 4-(piperidin-4-yl)benzonitrile HCl salt (compound 1.5, 0.097 g, 0.4 6 mmol), EDCI (0.090 g, 0.51 mmol), HOBT (0.065 g, 0.51 mmol, with 20% H2O) and DIEA (0.22 ml, 1.38 mmol) in DMF (5 ml) was stirred at room temperature overnight. The reaction mixture was then diluted with 50 ml of ethyl acetate and washed with 2×20 ml of brine. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified using prep.-TLC and developed using neat ethyl acetate to yield 25 mg of the title compound as an off-white solid. m/z (ES+) 409 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ8.46 (s, 1H), 7.76 (d, 2H), 7.49 (d, 2H), 6.48 (t, 1H), 6.37 (s, 1H), 4.84 (d, 1H), 4.63 (d, 1H), 3.65 (s, 3H), 3.14 (m, 1H), 2.92 (t, 3H), 2.79 (m, 2H), 1.85 (m, 1H), 1.67 (m, 1H), 1.57 (m, 2H), 0.87 (d, 6H).

Workup

  1. washwashed with 2×20 ml of brine
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified

Sources & evidence

ORD record
ord-aebb31a162ba44c88eb4ac5fb0fcf557
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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