1,2-Dimethoxyethane → (R)-4-(3-Hydroxypyrrolidin-1-yl)-3-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

HRID 73726Notes

Reaction equation

HRID 73726 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].CC1(C)C(C)(C)OB([C:36]2[N:40](COCC[Si](C)(C)C)[N:39]=[CH:38][CH:37]=2)O1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>O.C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCO>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:21]2[CH:20]=[CH:19][C:4]([C:5]([NH:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=3)=[O:6])=[CH:3][C:2]=2[C:36]2[NH:40][N:39]=[CH:38][CH:37]=2)[CH2:23]1

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 447552015-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazoleHCID 86702591(R)-3-bromo-4-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Product 1

HCID 72544441(R)-4-(3-Hydroxypyrrolidin-1-yl)-3-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of (R)-3-bromo-4-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.2, 100 mg, 0.225 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (146 mg, 0.45 mmol), Pd(PPh3)2Cl2 (17.34 mg, 0.025 mmol) and Na2CO3 (119 mg, 1.123 mmol) in a mixture of water (272 μL), DME (953 μL) and EtOH (136 μL) was subjected to MW irradiation at 125° C. for 20 min. The RM was diluted with THF (3 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 94 mg, 0.135 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 40% to 100% EtOAc) to yield the title compound as a yellow oil. UPLC-MS (Condition 1) tR=3.28 min, m/z=563.2 [M+H]+, m/z=561.2 [M−H]−.

Workup

  1. customwas subjected to MW irradiation at 125° C. for 20 min
  2. filtrationfiltered
  3. customthe filtrate was evaporated off under reduced pressure
  4. customto give a residue which
  5. customwas purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 40% to 100% EtOAc)

Sources & evidence

ORD record
ord-669a23ee913d44a8889da1ddfaee4e3f
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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