1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178523520, compound

HRID 1093855Notes

Reaction equation

HRID 1093855 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[NH:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[F:50][C:51]1[CH:62]=[CH:61][C:60]([F:63])=[CH:59][C:52]=1[O:53][CH:54]1[CH2:58][CH2:57][NH:56][CH2:55]1>CN(C=O)C.O>[F:50][C:51]1[CH:62]=[CH:61][C:60]([F:63])=[CH:59][C:52]=1[O:53][CH:54]1[CH2:58][CH2:57][N:56]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:18]2[CH:17]=[C:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:20][N:19]=2)=[O:22])[CH2:55]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 450755433-(2,5-Difluorophenoxy)pyrrolidine hydrochlorideHCID 178525878HCID 178525878, compound

Product 1

HCID 178523520HCID 178523520, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (166 mg, 1.28 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (70 mg, 0.28 mmol) in DMF (5 mL) followed by HOBt (42 mg, 0.31 mmol) and EDCI (136 mg, 0.71 mmol). After 2 minutes of stirring, 3-(2,5-difluoro-phenoxy)-pyrrolidine hydrochloride (prepared by the method used for the synthesis of Intermediate 72) (74 mg, 0.3 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was added and the precipitate was collected. The solid was purified by recrystallisation from a mixture of 20% ethyl acetate in hexane (15 mL), water (0.5 mL) and MeOH (0.03 mL) to afford 92 mg (76% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(2,5-difluoro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 427.15. 1H NMR (300 MHz, DMSO-d6): δ 13.8 (s, 1H), 8.1 (s, 1H), 7.84 (d, 2H), 7.54-7.12 (m, 6H), 7.14 (s, 1H), 6.88 (t, 1H), 5.3 (d, 1H), 4.1 (d, 2H), 3.9-3.5 (m, 4H), 2.3 (s, 1H), 2.1 (s, 1H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. customthe precipitate was collected
  4. customThe solid was purified by recrystallisation from a mixture of 20% ethyl acetate in hexane (15 mL), water (0.5 mL) and MeOH (0.03 mL)

Sources & evidence

ORD record
ord-ab8f9298abfc4c19a295daa0e6d20ff7
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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