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

HRID 1946410ノート

反応式

HRID 1946410 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8d5663af4f1d4ffbb4147e545e859456
出典データセット
uspto-grants-2013_03
特許番号
US08399436B2

反応ノート

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