Potassium Phosphate, Tribasic → Ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoate

HRID 515235노트

반응식

HRID 515235 반응식
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:19])[S:9](=[O:18])(=[O:17])[N:10]([CH2:11][CH:12]3[CH2:14][C:13]3([F:16])[F:15])[C:5]2=[CH:4][CH:3]=1.[CH2:20]([O:22][C:23]([C:25]1[C:26]([F:34])=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)=[O:24])[CH3:21].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:15][C:13]1([F:16])[CH2:14][CH:12]1[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([C:27]3[C:26]([F:34])=[C:25]([CH:30]=[CH:29][CH:28]=3)[C:23]([O:22][CH2:20][CH3:21])=[O:24])=[CH:3][CH:4]=2)[N:8]([CH3:19])[S:9]1(=[O:18])=[O:17]

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 447176532-Fluoro-3-(ethoxycarbonyl)benzeneboronic acidHCID 866879055-Chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

생성물 1

HCID 68245322Ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoate

시약·촉매·용매 4

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

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온도
75 °C

실험 절차

5-chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (29-1) (2.2 g, 7.1 mmol, 1.0 eq), [3-(ethoxycarbonyl)-2-fluorophenyl]boronic acid (3.0 g, 14 mmol, 2.0 eq), tripotassium phosphate (3.0 g, 14.2 mmol, 2.0 eq), S-Phos (0.29 g, 0.71 mmol, 0.1 eq), and palladium(II) acetate (0.080 mg, 0.36 mmol, 0.05 eq) were combined in THF (15 mL) and water (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 (100 mL), washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (120 g SiO2, 0-60% EtOAc in hexanes) to afford ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoate (37-1) as a yellow solid. LRMS m/z (M+H) 442.2 found, 442.1 required.

후처리

  1. temperatureto cool to room temperature
  2. washwashed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography (120 g SiO2, 0-60% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-547f57e1d9984bdf98ac510bfc52ae11
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108937B2

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