Potassium Phosphate, Tribasic → Ethyl (2R)-4-{5-fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoate

HRID 468645

반응식

HRID 468645 반응식
[F:1][C:2]1[C:3](I)=[CH:4][C:5](=[O:21])[N:6]([CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][C:34]([N:37]3[N:41]=[CH:40][CH:39]=[N:38]3)=[CH:33][CH:32]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC1CCCO1.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[C:3]([C:31]2[CH:36]=[CH:35][C:34]([N:37]3[N:41]=[CH:40][CH:39]=[N:38]3)=[CH:33][CH:32]=2)=[CH:4][C:5](=[O:21])[N:6]([CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=1

참가 물질

8

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 67249679Ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateHCID 672515672-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2H-1,2,3-triazole

생성물 1

HCID 86670651Ethyl (2R)-4-{5-fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoate수율 67.4%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 73012-Methyltetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

Pd(dppf)Cl2 (484 mg, 0.59 mmol) was added to a mixture of ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate, T2, (2.20 g, 4.94 mmol), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole (2.01 g, 7.41 mmol), and potassium phosphate (3.95 g, 14.8 mmol) in 2-methyltetrahydrofuran (200 mL) and deionized water (40 mL). The reaction was heated to 60° C. and was vigorously stirred at this temperature overnight. The reaction was diluted with EtOAc (100 mL) and water (100 mL) and was filtered through a celite pad (˜1 inch). The filter pad was washed with EtOAc (100 mL) and the filtrates were combined. The aqueous layer was separated and was extracted with EtOAc (2×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated. The crude material was purified via flash chromatography using a Varian SF25-40 g column and an eluent of EtOAc in hexanes (30-100%) to afford the title compound as a yellow solid (1.54 g, 67.4%). MS (LCMS) m/z 463.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (t, 3H) 1.62 (s, 3H) 2.18-2.32 (m, 1H) 2.52-2.66 (m, 1H) 3.16 (s, 3H) 3.92-4.07 (m, 2H) 4.08-4.24 (m, 2H) 6.59 (d, J=7.81 Hz, 1H) 7.72-7.84 (m, 2H) 8.10 (d, J=6.63 Hz, 1H) 8.12-8.17 (m, 2H) 8.18 (s, 2H).

후처리

  1. filtrationwas filtered through a celite pad (˜1 inch)
  2. washThe filter pad was washed with EtOAc (100 mL)
  3. customThe aqueous layer was separated
  4. extractionwas extracted with EtOAc (2×100 mL)
  5. washThe combined organics were washed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified via flash chromatography

출처 및 근거

ORD 기록
ord-dca7c565ae7848afb167b2c0c84db1e2
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08624034B2

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