Potassium Phosphate, Tribasic → N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide

HRID 62099노트

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HRID 62099 반응식
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH:11]=[O:12])=[N:9][N:8]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:5]2=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:43]1[CH:44]=[C:45]([NH:49][C:50](=[O:53])[CH2:51][CH3:52])[CH:46]=[N:47][CH:48]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.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].O.C(Cl)Cl>[CH:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:43]3[CH:44]=[C:45]([NH:49][C:50](=[O:53])[CH2:51][CH3:52])[CH:46]=[N:47][CH:48]=3)[CH:3]=2)[N:8]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:9]=1)=[O:12]

참가 물질

10

반응물 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 583775865-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehydeHCID 68737458N-(5-bromopyridin-3-yl)propionamide

생성물 1

HCID 58377773N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
90 °C

실험 절차

A solution of 5-bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-carbaldehyde (XI) (0.218 g, 0.70 mmol), bis(pinacolato)diboron (0.213 g, 0.84 mmol), and KOAc (0.206 g, 2.1 mmol) in DMF (10 ml) was purged with argon. PdCl2(dppf)2. DCM was added to the solution and purged again with argon. The solution was heated at 90° C. for 2 h under argon and cooled to the room temperature. N-(5-bromopyridin-3-yl)propionamide (XXXIII) (0.70 mmol), potassium phosphate (0.223 g, 1.05 mmol) and water (1 mL) was added to the solution and purged with argon. Pd(PPh3)4 was added to the solution and again purged with the argon. The solution was heated at 90° C. for 4 h under argon. The solution was filtered through a bed of Celite and the solvent was distilled under vacuum. The residue was treated with water and extracted with DCM. The combined organic phase was dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (100% DCM→5:95 MeOH:DCM) to get N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide (LX) as a off white solid (45% yield). 1H NMR (DMSO-d6) δ ppm 1.13 (t, J=7.55 Hz, 3H), 1.51-1.74 (m, 2H), 1.96-2.18 (m, 2H), 2.41 (q, J=7.55 Hz, 2H), 3.68 (m, 1H), 3.92 (m, 1H), 6.26 (dd, J=10.20, 2.14, 1H), 8.48 (m, 1H), 8.70 (m, 2H), 8.77 (m, 1H), 9.07 (m, 1 Hz), 10.17 (s, 1H), 10.24 (s, 1H); ESIMS found C20H21N5O3 m/z 380 (M+H).

후처리

  1. custompurged again with argon
  2. temperaturecooled to the room temperature
  3. custompurged with argon
  4. additionPd(PPh3)4 was added to the solution
  5. customagain purged with the argon
  6. temperatureThe solution was heated at 90° C. for 4 h under argon
  7. filtrationThe solution was filtered through a bed of Celite
  8. distillationthe solvent was distilled under vacuum
  9. additionThe residue was treated with water
  10. extractionextracted with DCM
  11. dry with materialThe combined organic phase was dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by flash chromatography (100% DCM→5:95 MeOH:DCM)

출처 및 근거

ORD 기록
ord-9822c421cc1643eb96264fd5f8028d67
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446035B2

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