Dichloromethane → N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)propanamide

HRID 1842924Notes

Reaction equation

HRID 1842924 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]([CH3:18])[C:15]([OH:17])=O)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][CH2:11][O:12][CH3:13].CCN([CH:25]([CH3:27])[CH3:26])C(C)C.CCN=C=[N:32][CH2:33][CH2:34][CH2:35][N:36]([CH3:38])C.Cl.C1C=CC2N(O)N=[N:46][C:44]=2C=1.[Cl:50][C:51]1[CH:52]=C(N2C(CN)=CC(C(F)(F)F)=N2)[CH:54]=[CH:55][CH:56]=1.[CH2:68](Cl)Cl>>[C:25]([C:33]1[CH:34]=[C:35]([CH2:44][NH:46][C:15](=[O:17])[CH:14]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][O:9][CH2:10][CH2:11][O:12][CH3:13])=[C:2]([F:1])[CH:3]=2)[CH3:18])[N:36]([C:38]2[CH:54]=[CH:55][CH:56]=[C:51]([Cl:50])[CH:52]=2)[N:32]=1)([CH3:26])([CH3:27])[CH3:68]

Participants

7

Reactant 6

HCID 6344DichloromethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596372702-(3-Fluoro-4-((2-methoxyethoxy)methyl)phenyl)propanoic acidHCID 66644230(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine

Product 1

HCID 66644251N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)propanamideYield 70%

Procedure

To a stirred DCM (5.0 mL) solution of 2-(3-fluoro-4-((2-methoxyethoxy)methyl)-phenyl)propanoic acid (82.0 mg, 0.321 mmol, 1.0 eq), DIPEA (0.168 mL, 0.961 mmol, 3.0 eq), EDC.HCl (74.0 mg, 0.387 mmol, 1.2 eq) and HOBt (59.0 mg, 0.387 mmol, 1.2 eq) were sequentially added at RT and the mixture stirred for 15 min. (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine (100 mg, 0.321 mmol, 1 eq) was then added and the mixture stirred for 16 h. On completion of the reaction the mixture was washed with H2O (20 mL), brine (10 mL), the layers were separated, dried (Na2SO4) and the solvent evaporated. The crude product was purified by CC using EtOAc/CHCl3 (1:9) to get N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)propanamide (115 mg; 70%, white solid; TLC system: EtOAc/CHCl3 (1:9), Rf: 0.5).

Workup

  1. additionwas then added
  2. customOn completion of the reaction the mixture
  3. washwas washed with H2O (20 mL), brine (10 mL)
  4. customthe layers were separated
  5. dry with materialdried (Na2SO4)
  6. customthe solvent evaporated
  7. customThe crude product was purified by CC

Sources & evidence

ORD record
ord-9a60736103d64cc69234ec0de7a2c0be
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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