Sodium Carbonate → 1-[4'-Fluoro-2'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-5-methyl-1h-pyrazole-3-carboxamide

HRID 733131노트

반응식

HRID 733131 반응식
C([C:3]1[C:4]([C:16]([NH2:18])=[O:17])=[N:5][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11](Br)[CH:10]=2)[C:7]=1[CH3:8])C.C([O-])(=O)C.[K+].Br[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[C:32]([F:35])([F:34])[F:33].C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([N:6]3[C:7]([CH3:8])=[CH:3][C:4]([C:16]([NH2:18])=[O:17])=[N:5]3)[CH:10]=2)=[C:26]([C:32]([F:33])([F:34])[F:35])[CH:27]=1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 5209832-Bromo-5-fluorobenzotrifluorideHCID 69062233ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide

생성물 1

HCID 114171631-[4'-Fluoro-2'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-5-methyl-1h-pyrazole-3-carboxamide수율 41%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 679Dimethyl Sulfoxide용매

실험 절차

To a solution of ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide (from step 2 of EXAMPLE 1) (0.069 g, 0.24 mmol) in DMSO (1.14 mL), bis(pinacoloato)diboron (0.075 g, 0.3 mmol) was added followed by potassium acetate (0.072 g, 0.74 mmol) and PdCl2(dppf)2 (0.005 g, 3 mol %). The solution was heated in a Smith Creator™ microwave reactor (commercially available from Personal Chemistry, Inc.) at 140° C. for 1200 seconds. The reaction mixture was cooled to room temperature, and 2-bromo-5-fluorobenzotrifluoride (0.12 g, 0.5 mmol), PdCl2(dppf)2 (0.005 g, 3 mol %) and 2M sodium carbonate (0.61 mL, 1.2 mmol) were added to the reaction mixture. The reaction was then subjected to microwave radiation at 140° C. for 2800 seconds. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The organic layer was washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate, filtered and concentrated. Purification of the crude product by reverse phase HPLC (acetonitrile/water system) (gradient: 45% to 100% acetonitrile over 10 minutes) yielded 0.036 mg of the product (41% yield, retention time 5.1 minutes).

후처리

  1. temperatureThe solution was heated in a Smith Creator™ microwave reactor (commercially available from Personal Chemistry, Inc
  2. customat 140° C.
  3. customfor 2800 seconds
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was partitioned between EtOAc and water
  6. washThe organic layer was washed with saturated sodium bicarbonate and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the crude product by reverse phase HPLC (acetonitrile/water system) (gradient: 45% to 100% acetonitrile over 10 minutes)

출처 및 근거

ORD 기록
ord-337a3bc5ca0a46a6a8bace89eaf0c5be
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07589116B2

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