Dicyclohexylcarbodiimide → N-(3-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-3-oxopropyl)-2,2-difluoro-1-methylcyclopropanecarboxamide

HRID 929293Notes

Reaction equation

HRID 929293 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]([N:6]([C:9]1[C:10]([Cl:20])=[N:11][N:12]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH:13]=1)[CH2:7][CH3:8])=[O:5].[F:21][C:22]1([F:29])[CH2:24][C:23]1([CH3:28])[C:25](O)=[O:26].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:20][C:10]1[C:9]([N:6]([CH2:7][CH3:8])[C:4](=[O:5])[CH2:3][CH2:2][NH:1][C:25]([C:23]2([CH3:28])[CH2:24][C:22]2([F:29])[F:21])=[O:26])=[CH:13][N:12]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[N:11]=1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 146952292,2-Difluoro-1-methylcyclopropane-1-carboxylic acidHCID 1180239933-amino-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylpropanamide

Product 1

HCID 118023931N-(3-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-3-oxopropyl)-2,2-difluoro-1-methylcyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-amino-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylpropanamide (0.074 mg, 0.25 mmol), DMAP (0.047 mg, 0.38 mmol), 2,2-difluoro-1-methylcyclopropanecarboxylic acid (0.052 mg, 0.38 mmol) in dry CH2Cl2 (1.69 mL) was cooled to a temperature of about 0° C. under N2. DCC (0.13 g, 0.61 mmol) was added, and the reaction was slowly warmed up to room temperature under N2, then stirred at room temperature overnight. The reaction mixture was filtered using additional CH2Cl2 (0.5 mL) to remove solids and concentrated under reduced pressure. The product was purified by silica gel chromatography eluting with 0%-10% MeOH/CH2Cl2 to afford the title compound F113 as a yellow viscous oil (0.029 g, 26% over 2 steps from compound C2).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customto remove solids
  3. concentrationconcentrated under reduced pressure
  4. customThe product was purified by silica gel chromatography
  5. washeluting with 0%-10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-0d6663eea46844c9a5812442902c93ab
Source dataset
uspto-grants-2016_03
Patent number
US09295260B2

Reaction notes

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