4-(1-Pyrrolidinyl)piperidine → [5-Methyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1011962Notes

Reaction equation

HRID 1011962 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]([F:17])([F:16])[F:15])[CH:8]=2)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[C:3]=1[C:24]([OH:26])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:60]1([CH:65]2[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]2)[CH2:64][CH2:63][CH2:62][CH2:61]1>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]([F:16])([F:15])[F:17])[CH:8]=2)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[C:3]=1[C:24]([N:68]1[CH2:69][CH2:70][CH:65]([N:60]2[CH2:64][CH2:63][CH2:62][CH2:61]2)[CH2:66][CH2:67]1)=[O:26]

Participants

7

Reactant 4

HCID 787034-(1-Pyrrolidinyl)piperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673151905-Methyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 57555089[5-Methyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

5-Methyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid (76 mg, 0.21 mmol) in 2.5 ml DMF was treated with iPr2NEt (0.11 ml, 0.63 mmol) and HATU (79 mg, 0.21 mmol), then after 20 min a solution of 4-(1-pyrrolidinyl)piperidine (32 mg, 0.21 mmol) in 1.5 ml DMF was added. The reaction mixture was stirred 0.5 h at room temperature, diluted with EtOAc and washed with three portions of saturated solution of NaHCO3 and brine. The aqueous phases were extracted with EtOAc the combined organic layers were dried over magnesium sulfate and evaporated. A column chromatography (amino-phase silica gel, EtOAc:MeOH, 19:1) afforded the title compound as a foam (74 mg, 71%). MS: 500.0 (MH+).

Workup

  1. washwashed with three portions of saturated solution of NaHCO3 and brine
  2. extractionThe aqueous phases were extracted with EtOAc the combined organic layers
  3. dry with materialwere dried over magnesium sulfate
  4. customevaporated

Sources & evidence

ORD record
ord-6227a6ac4ddb48f8925482ce79fb8340
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

Loading…