1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67971131, compound

HRID 889543Notes

Reaction equation

HRID 889543 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]1([C:6](O)=[O:7])[CH2:5][CH2:4]1.Cl.Cl.[NH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([Cl:29])=[C:19]([CH:28]=1)[C:20]([NH:22][C:23]1[NH:24][CH:25]=[CH:26][N:27]=1)=[O:21].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C1COCC1>[Cl:29][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][NH:13][C:6]([C:3]2([C:2]([F:10])([F:9])[F:1])[CH2:5][CH2:4]2)=[O:7])=[CH:28][C:19]=1[C:20]([NH:22][C:23]1[NH:27][CH:26]=[CH:25][N:24]=1)=[O:21]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27783061-(Trifluoromethyl)cyclopropane-1-carboxylic acidHCID 67970680HCID 67970680, compound

Product 1

HCID 67971131HCID 67971131, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-(trifluoromethyl)cyclopropanecarboxylic acid (54 mg, 0.34 mmol, 1.1 equiv) and 5-(aminomethyl)-2-chloro-N-(1H-imidazol-2-yl)benzamide dihydrochloride (100 mg, 0.31 mmol, 1.0 equiv) in THF (1.55 mL), add DIEA (0.189 mL, 1.08 mmol, 3.5 equiv), HOBt (59.2 mg, 0.386 mmol, 1.08 equiv), EDCI (74 mg, 0.386 mmol, 1.08 equiv), and stir the reaction mixture at room temperature for three days. Concentrate under reduced pressure, and subject the crude mixture to chromatography on a C18 reversed-phase stationary phase eluting with a 5-60% (0.1% TFA in acetonitrile) in (0.1% TFA in water) gradient to give the title compound as a white solid (39 mg, 33%). 1H NMR (DMSO-d6, 400 MHz): δ 11.80 (br s, 2H), 8.41 (t, 1H, J=5.8 Hz), 7.46 (d, 1H, J=8.3 Hz), 7.40 (d, 1H, J=2.1 Hz), 7.30 (dd, 1H, J=8.3, 2.1 Hz), 6.75 (br s, 2H), 4.28 (d, 2H, J=6.0 Hz), 1.33-1.20 (m, 4H). MS (m/z) (35Cl/37Cl) 387/389 (M+1).

Workup

  1. concentrationConcentrate under reduced pressure
  2. washeluting with a 5-60% (0.1% TFA in acetonitrile) in (0.1% TFA in water) gradient

Sources & evidence

ORD record
ord-6506af8f884d450392be63bd88b59418
Source dataset
uspto-grants-2012_08
Patent number
US08252831B2

Reaction notes

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