Ethyl Acetate → tert-butyl 3-(9-isopropyl-6((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 928170노트

반응식

HRID 928170 반응식
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][C:15]2[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH2:34][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:32][CH2:31][CH:30]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.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]>[NH3:3].[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([C:31]1[CH2:32][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:34][CH2:29][CH:30]=1)=[N:3][C:4]=2[NH:14][C:15]1[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=1)([CH3:13])[CH3:12]

참가 물질

9

반응물 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 49835909Tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 1180736892-chloro-9-isopropyl-N-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine

생성물 2

HCID 222AmmoniaHCID 118073695tert-butyl 3-(9-isopropyl-6((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate수율 205.5%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

A mixture of 2-chloro-9-isopropyl-N-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine (600 mg, 2 mmol), as prepared in step 1 of Example 2, tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (700 mg, 2.3 mmol, 1.1 mol eq), tripotassium phosphate (1.11 g, 5.1 mmol, 2.5 mol eq), PdCl2(dppf) (75 mg, 0.1 mmol, 0.05 mol eq) in dioxane (10 mL) and water (5 mL) was degassed, stirred and heated at 80° C. (using microwave at normal absorption level) for 30 min. The reaction was then diluted with ethyl acetate (120 mL), washed with brine (20 mL), dried over Na2SO4 and evaporated to give a residue that was purified via flash chromatography with gradients from 50% ethyl acetate-50% heptane to 100% ethyl acetate and then to 10% ammonia (7 N in methanol)-90% ethyl acetate to give the title product as a red solid (901 mg, 100% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.89 (s, 1 H) 8.29 (s, 1 H) 8.00 (br. s., 1 H) 7.79 (br. s., 1 H) 7.22 (br. s., 1 H) 4.77 (dt, J=13.39, 6.76 Hz, 1 H) 4.45 (br. s., 2 H) 3.84 (s, 3 H) 3.50 (t, J=5.38 Hz, 2 H) 2.36 (d, J=3.18 Hz, 2 H) 1.57 (d, J=6.72 Hz, 6 H) 1.44 (s, 9 H). m/z (APCI+) for C22H30N8O2 439.3 (M+H)+.

후처리

  1. customwas degassed
  2. additionThe reaction was then diluted with ethyl acetate (120 mL)
  3. washwashed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customto give a residue that
  7. customwas purified via flash chromatography with gradients from 50% ethyl acetate-50% heptane to 100% ethyl acetate

출처 및 근거

ORD 기록
ord-71ebbbf7f0974db696dfcbc783da0c2d
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290496B2

반응 노트

불러오는 중…