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 82079ノート

反応式

HRID 82079 の反応式
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]

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1c54b8639c3e46d9a691df941ae82c4d
出典データセット
uspto-grants-2014_09
特許番号
US08846714B2

反応ノート

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