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 928170ノート

反応式

HRID 928170 の反応式
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]

参加物

9

反応物 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

生成物 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)-carboxylate収率 205.5%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-71ebbbf7f0974db696dfcbc783da0c2d
出典データセット
uspto-grants-2016_03
特許番号
US09290496B2

反応ノート

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