Diisopropylethylamine → 5-(3,3-Difluoropyrrolidine-1-carbonyl)-4'-methyl-N-((2-methylpyrimidin-5-yl)methyl)biphenyl-3-carboxamide

HRID 1845186Notes

Reaction equation

HRID 1845186 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14](=[O:24])[NH:15][CH2:16][C:17]3[CH:18]=[N:19][C:20]([CH3:23])=[N:21][CH:22]=3)[CH:11]=[C:10]([C:25]([OH:27])=O)[CH:9]=2)=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.Cl.[F:52][C:53]1([F:58])[CH2:57][CH2:56][NH:55][CH2:54]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:52][C:53]1([F:58])[CH2:57][CH2:56][N:55]([C:25]([C:10]2[CH:11]=[C:12]([C:14]([NH:15][CH2:16][C:17]3[CH:22]=[N:21][C:20]([CH3:23])=[N:19][CH:18]=3)=[O:24])[CH:13]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=3)[CH:9]=2)=[O:27])[CH2:54]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 581879464'-Methyl-5-((2-methylpyrimidin-5-yl)methylcarbamoyl)-biphenyl-3-carboxylic acid

Product 1

HCID 442230385-(3,3-Difluoropyrrolidine-1-carbonyl)-4'-methyl-N-((2-methylpyrimidin-5-yl)methyl)biphenyl-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4′-methyl-5-((2-methylpyrimidin-5-yl)methylcarbamoyl)-biphenyl-3-carboxylic acid (11 mg, 0.030 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (12 mg, 0.061 mmol), 1-hydroxybenzotriazole hydrate (5 mg, 0.030 mmol), CH2Cl2 (2 mL) were added 3,3-difluoropyrrolidine hydrochloride (9 mg, 0.061 mmol) and N,N-diisopropylethylamine (21 μL, 0.12 mmol). The mixture was stirred at room temperature overnight, and then concentrated in vacuo. The residue was purified by preparative HPLC (100×21.2 mm C18 column, 30-70% MeCN/water[10 mM Et2NH]) to afford a white foam.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative HPLC (100×21.2 mm C18 column, 30-70% MeCN/water[10 mM Et2NH])
  3. customto afford a white foam

Sources & evidence

ORD record
ord-65a08c2c2eaf4b77b7d1a7ea81569bfb
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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