Cesium fluoride → methyl 4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 513192노트

반응식

HRID 513192 반응식
Cl[C:2]1[C:7]2[CH:8]=[C:9]([C:18]([O:20][CH3:21])=[O:19])[N:10](C(OC(C)(C)C)=O)[C:6]=2[CH:5]=[CH:4][N:3]=1.[F:22][C:23]1[CH:28]=[C:27]([Sn](CCCC)(CCCC)CCCC)[CH:26]=[CH:25][N:24]=1.[F-].[Cs+]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O1CCOCC1>[F:22][C:23]1[CH:28]=[C:27]([C:2]2[C:7]3[CH:8]=[C:9]([C:18]([O:20][CH3:21])=[O:19])[NH:10][C:6]=3[CH:5]=[CH:4][N:3]=2)[CH:26]=[CH:25][N:24]=1

참가 물질

6

반응물 3

HCID 25953Cesium fluorideHCID 164270992-Fluoro-4-(tributylstannyl)pyridineHCID 717430591-Tert-butyl 2-methyl 4-chloro-1H-pyrrolo[3,2-C]pyridine-1,2-dicarboxylate

생성물 1

HCID 71212871methyl 4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate수율 77%

시약·촉매·용매 2

HCID 178418851HCID 178418851, 화합물촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

1-Tert-butyl 2-methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-1,2-dicarboxylate (100 mg, 0.322 mmole), 2-fluoro-4-(tributylstannyl)pyridine (162 mg, 0.418 mmole), CsF (108 mg, 0.708 mmole), and bis(tri-t-butylphosphine)palladium(0) (16 mg, 0.031 mmole) were combined in a screw cap vial. To this was added 1,4-dioxane (1 mL). N2 was bubbled through the mixture for 10 seconds. The vial was capped then heated to 100° C. After 6 hr was cooled to RT, diluted with EtOAc, filtered through a pad of Celite washing with EtOAc, and concentrated. The residue was taken up in 2 mL CH2Cl2. To this was added 2 mL TFA. After 2 hr the mixture was concentrated. The residue was taken up in saturated NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (Biotage-SNAP-10 g SiO2, 70% EtOAc/hexanes) gave the title compound (67 mg, 77%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 9.23 (bs, 1 H); 8.56 (d, J=5.8 Hz, 1 H); 8.40 (d, J=5.2 Hz, 1 H); 7.82-7.79 (m, 1 H); 7.56 (s, 1 H); 7.50 (dd, J=2.0, 1.1 Hz, 1 H); 7.43 (dd, J=5.8, 1.1 Hz, 1 H); 4.00 (s, 3 H).

후처리

  1. customcap vial
  2. customN2 was bubbled through the mixture for 10 seconds
  3. customThe vial was capped
  4. temperatureAfter 6 hr was cooled to RT
  5. additiondiluted with EtOAc
  6. filtrationfiltered through a pad of Celite
  7. washwashing with EtOAc
  8. concentrationconcentrated
  9. additionTo this was added 2 mL TFA
  10. concentrationAfter 2 hr the mixture was concentrated
  11. extractionextracted with CH2Cl2 (3×)
  12. dry with materialThe combined organic layers were dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated

출처 및 근거

ORD 기록
ord-8cbfd12dd1c3428180e4299ead8cb923
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102673B2

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