Potassium Phosphate, Tribasic → HCID 67410738、化合物

HRID 515228ノート

反応式

HRID 515228 の反応式
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].Cl[C:29]1[N:34]=[C:33]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:32]=[CH:31][C:30]=1[CH3:40].P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1COCC1.O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:29]3[N:34]=[C:33]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:32]=[CH:31][C:30]=3[CH3:40])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:25])=[O:26]

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 9837074Ethyl 6-chloro-5-methylpicolinateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67413064HCID 67413064、化合物

生成物 1

HCID 67410738HCID 67410738、化合物

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
75 °C

実験手順

1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (12-1) (100 mg, 0.25 mmol, 1 eq), ethyl 6-chloro-5-methylpyridine-2-carboxylate (26-4) (75 mg, 0.38 mmol, 1.5 eq), tripotassium phosphate (106 mg, 0.50 mmol, 2.0 eq), S-Phos (10 mg, 0.025 mmol, 0.1 eq), and palladium(II) acetate (2.8 mg, 0.012 mmol, 0.05 eq) were combined in THF (1 mL) and water (0.2 mL). The resulting mixture was heated at 75° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (10 mL), washed with water (1 mL) and brine (1 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (12 g SiO2, 0-80% EtOAc in hexanes) to afford ethyl 6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridine-2-carboxylate (26-5). HRMS m/z (M+H) 438.1291 found, 438.1294 required.

後処理

  1. temperatureto cool to room temperature
  2. washwashed with water (1 mL) and brine (1 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography (12 g SiO2, 0-80% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-b1cbd84b772342b88a999ab02934d2be
出典データセット
uspto-grants-2015_08
特許番号
US09108937B2

反応ノート

読み込み中…