1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178523522, compound

HRID 1093886Notes

Reaction equation

HRID 1093886 reaction equation
CC[N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[C:31]1([C:37]2[NH:41][N:40]=[C:39]([C:42]([NH:44][CH2:45][C:46]([OH:48])=O)=[O:43])[CH:38]=2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl.[F:50][C:51]1[CH:52]=[C:53]([CH:59]=[C:60]([C:62]([F:65])([F:64])[F:63])[CH:61]=1)[O:54][CH:55]1CNC1>CN(C=O)C>[F:50][C:51]1[CH:52]=[C:53]([CH:59]=[C:60]([C:62]([F:63])([F:64])[F:65])[CH:61]=1)[O:54][CH:55]1[CH2:6][CH2:4][N:3]([C:46](=[O:48])[CH2:45][NH:44][C:42]([C:39]2[CH:38]=[C:37]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[NH:41][N:40]=2)=[O:43])[CH2:7][CH2:9]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 665922143-(3-Fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochlorideHCID 178525878HCID 178525878, compound

Product 1

HCID 178523522HCID 178523522, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (97 mg, 0.75 mmol) followed by HOBt (35 mg, 0.26 mmol) and EDCI (50 mg, 0.26 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (62 mg, 0.25 mmol) in DMF (2 mL). After 2 minutes of stirring, 3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 15) (75 mg, 0.25 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (using silica gel 60-120 and 40% EtOAc in hexane as eluent) afforded 54 mg (45% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 491, 94%. 1H NMR (300 MHz, DMSO-d6): δ 13.8 (s, 1H), 8.5 (b, 1H), 7.8 (d, 2H), 7.4 (m, 2H), 7.3 (m, 2H), 7.2 (m, 2H), 7.1 (m, 1H), 4.8 (m, 1H), 4.2 (m, 2H), 3.8 (m, 1H), 3.6 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. customThe reaction mixture was partitioned between cold water and ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (using silica gel 60-120 and 40% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-785d632d7a1e4b4cb0ca7cb4318dcde4
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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