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

HRID 515237노트

반응식

HRID 515237 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.[CH3:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=1B1OC(C)(C)C(C)(C)O1.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:22]3[CH:23]=[C:24]([CH:29]=[CH:30][C:21]=3[CH3:20])[C:25]([O:27][CH3:28])=[O:26])=[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 532171365-Methoxycarbonyl-2-methylphenylboronic acid pinacol esterHCID 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 67411535Methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzoate

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) (6.6 g, 21.3 mmol, 1.0 eq), methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (8.8 g, 32.0 mmol, 1.5 eq), tripotassium phosphate (9.0 g, 42.6 mmol, 2.0 eq), S-Phos (875 mg, 2.1 mmol, 0.1 eq), and palladium(II) acetate (239 mg, 1.1 mmol, 0.05 eq) were combined in THF (90 mL) and water (15 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 (300 mL), washed with water (100 mL) and brine (100 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (330 g SiO2, 0-60% EtOAc in hexanes) to afford methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzoate (38-1) as a yellow solid. HRMS m/z (M+H) 424.1135 found, 424.1137 required.

후처리

  1. temperatureto cool to room temperature
  2. washwashed with water (100 mL) and brine (100 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography (330 g SiO2, 0-60% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-ff03e975577b4fa08c8d71e1aa2b634e
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108937B2

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