Potassium Phosphate, Tribasic → HCID 67410738, 화합물

HRID 515228노트

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HRID 515228 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

HCID 67410738HCID 67410738, 화합물

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
75 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b1cbd84b772342b88a999ab02934d2be
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108937B2

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