4-Methylmorpholine → 1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1522520노트

반응식

HRID 1522520 반응식
[CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:11]=[C:12]([C:13](OCC)=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3].[OH-].[Na+].[Al].[NH2:27][CH2:28][C:29]1[C:30](=[O:39])[NH:31][C:32]([CH3:38])=[CH:33][C:34]=1[CH2:35][CH2:36][CH3:37].Cl.CN(C)CCCN=C=NCC.O.N1C2C(=NC=CC=2)N(O)N=1.CN1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CO.O.CS(C)=O>[CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:11]=[C:12]([C:13]([NH:27][CH2:28][C:29]3[C:30](=[O:39])[NH:31][C:32]([CH3:38])=[CH:33][C:34]=3[CH2:35][CH2:36][CH3:37])=[O:14])[C:7]=2[CH:6]=[N:5]1)([CH3:1])[CH3:3]

참가 물질

13

반응물 8

HCID 79724-MethylmorpholineHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5359268AluminumHCID 219174661-Hydroxy-7-azabenzotriazol hydrateHCID 46538388Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylateHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetate

생성물 1

HCID 894448521-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

시약·촉매·용매 4

HCID 679Dimethyl Sulfoxide용매HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (270 mg, 0.873 mmol) was suspended in THF (1913 μl) and Methanol (6378 μl). To the mixture was added 3N NaOH (436 μl, 1.309 mmol) and the contents heated on an aluminum block at 55° C. overnight. The solvent was removed in vacuo. The remaining orange residue was dissolved with water (10 mL) and cooled with stirring in an ice bath. The contents were acidified by dropwise addition 1N HCl until precipitation ceased. The white solid was collected via vacuum filtration and the filter cake was dried open to the air, under vacuum overnight. The white solid was added to a 20 mL vial followed by 3-(aminomethyl)-6-methyl-4-propyl-2(1H)-pyridinone (208 mg, 0.960 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (251 mg, 1.309 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol hydrate (202 mg, 1.309 mmol) and DMSO (4 ml). To the same was added a magnetic stir bar and 4-methylmorpholine (618 mg, 6.11 mmol). The reaction was stirred at room temperature overnight. The reaction contents were slowly poured onto an aqueous solution of sat Na2CO3 (6 mL) and water (20 mL) and stirred in an ice bath. The resulting suspension was stirred 20 minutes. The solid was collected by vacuum filtration and dried under high vacuum overnight. The title compound was obtained as an off-white solid (388 mg, 99%). 1H NMR (400 MHz, DMSO-δ6) δ 9.00 (t, J=3.92 Hz, 1H), 8.38 (s, 1H), 8.23-8.29 (m, 2H), 8.16 (s, 1H), 7.46-7.62 (m, 3H), 5.93 (s, 1H), 5.34 (quin, J=6.63 Hz, 1H), 4.45 (d, J=4.55 Hz, 2H), 2.55 (s, 2H), 2.14 (s, 3H), 1.56 (d, J=6.57 Hz, 6H), 1.45-1.54 (m, 2H), 0.88 (t, J=7.20 Hz, 3H). LCMS(ES) [M+H]+ 444.3.

후처리

  1. customThe solvent was removed in vacuo
  2. dissolutionThe remaining orange residue was dissolved with water (10 mL)
  3. temperaturecooled
  4. additionThe contents were acidified by dropwise addition 1N HCl until precipitation
  5. filtrationThe white solid was collected via vacuum filtration
  6. customthe filter cake was dried open to the air, under vacuum overnight
  7. additionThe white solid was added to a 20 mL
  8. additionTo the same was added a magnetic stir bar
  9. stirringThe reaction was stirred at room temperature overnight
  10. customThe reaction contents
  11. stirringstirred in an ice bath
  12. stirringThe resulting suspension was stirred 20 minutes
  13. filtrationThe solid was collected by vacuum filtration
  14. customdried under high vacuum overnight

출처 및 근거

ORD 기록
ord-5c9b46903e77485fa948253117b6fbc5
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073924B2

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