Potassium Phosphate, Tribasic → N-(1-{[4-cyclopropyl-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-3-fluoro-4-pyridinecarboxamide

HRID 1946410노트

반응식

HRID 1946410 반응식
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]([NH:10][C:11]1[CH:15]=[CH:14][N:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20](I)=[CH:19][C:18]=2[C:24]([F:27])([F:26])[F:25])[N:12]=1)=[O:9].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P([CH:49]2[CH2:54][CH2:53]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:53]1([C:20]2[CH:21]=[CH:22][C:17]([CH2:16][N:13]3[CH:14]=[CH:15][C:11]([NH:10][C:8]([C:7]4[CH:6]=[CH:5][N:4]=[CH:3][C:2]=4[F:1])=[O:9])=[N:12]3)=[C:18]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[CH2:54][CH2:49]1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 595480203-Fluoro-N-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-4-pyridinecarboxamide

생성물 1

HCID 59547933N-(1-{[4-cyclopropyl-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-3-fluoro-4-pyridinecarboxamide

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
100 °C

실험 절차

To a solution of 3-fluoro-N-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-4-pyridinecarboxamide (for a preparation see Example 88)(40 mg, 0.082 mmol) in toluene (2 ml) was added potassium phosphate tribasic (52 mg, 0.245 mmol, Aldrich), tricyclohexyl phosphine (7 mg, 0.025 mmol, Aldrich), cyclopropyl boronic acid (21 mg, 0.244 mmol, Fluorochem), water (0.1 ml) and then palladium (II) acetate (6 mg, 0.027 mmol. ABCR). The resulting slight suspension was heated to 100° C. and stirred under nitrogen overnight. The reaction mixture was partitioned between DCM (10 ml) and water (10 ml). The phases were separated using a hydrophobic frit and the aqueous phase washed with DCM (10 ml). The organic phases were combined and the solvent removed in vacuo. The residue was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP on Sunfire C18 column (Method B) using Acetonitrile-Water with a Formic acid modifier. The solvent was evaporated in vacuo to give the title compound as a white solid (16 mg); LCMS: (System 4) MH+=405, tRET=2.98 min.

후처리

  1. customThe reaction mixture was partitioned between DCM (10 ml) and water (10 ml)
  2. customThe phases were separated
  3. washthe aqueous phase washed with DCM (10 ml)
  4. customthe solvent removed in vacuo
  5. dissolutionThe residue was dissolved in 1:1 MeOH
  6. customDMSO (1 ml) and purified by MDAP on Sunfire C18 column (Method B)
  7. customThe solvent was evaporated in vacuo

출처 및 근거

ORD 기록
ord-8d5663af4f1d4ffbb4147e545e859456
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399436B2

반응 노트

불러오는 중…