Sodium Carbonate → (R)-8-cyclopentyl-2-(2-(3,6-dihydro-2H-pyran-4-yl)-1H-imidazol-1-yl)-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

HRID 44848ノート

反応式

HRID 44848 の反応式
Br[C:2]1[N:3]([C:7]2[N:16]=[CH:15][C:14]3[N:13]([CH3:17])[C:12](=[O:18])[C@@H:11]([CH2:19][CH3:20])[N:10]([CH:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[C:9]=3[N:8]=2)[CH:4]=[CH:5][N:6]=1.C([O-])([O-])=O.[Na+].[Na+].[O:32]1[CH2:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH2:34][CH2:33]1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CO.CCOC(C)=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]>[CH:21]1([N:10]2[C:9]3[N:8]=[C:7]([N:3]4[CH:4]=[CH:5][N:6]=[C:2]4[C:35]4[CH2:36][CH2:37][O:32][CH2:33][CH:34]=4)[N:16]=[CH:15][C:14]=3[N:13]([CH3:17])[C:12](=[O:18])[C@H:11]2[CH2:19][CH3:20])[CH2:25][CH2:24][CH2:23][CH2:22]1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 58405307(R)-2-(2-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

生成物 1

HCID 58405609(R)-8-cyclopentyl-2-(2-(3,6-dihydro-2H-pyran-4-yl)-1H-imidazol-1-yl)-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8857Ethyl Acetate溶媒HCID 22592949Dioxane methanol water溶媒

反応条件

温度
110 °C

実験手順

(R)-2-(2-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 65, 130 mg, 1 eq) in dioxane/water/MeOH (2 mL/0.5 mL/0.05 mL) was combined with Pd(dppf)Cl2 (39.6 mg, 0.2 eq), Na2CO3 (100 mg, 3 eq), and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (116 mg, 2 eq). The reaction mixture was stirred at 110° C. overnight. This was diluted with EtOAc and a saturated NaHCO3 solution. The layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by MPLC and further purified by preparative HPLC. LCMS: 409.2 m/z (M+H)+; ret. Time: 2.41 min (Analytical Method A). 1H-NMR (CDCl3, 300 MHz): δ: 7.81 (s, 1H), 7.67 (s, 1H), 7.46 (s, 1H), 6.51 (s, 1H), 4.35-4.30 (m, 4H), 3.90-3.81 (m, 4H), 3.40 (s, 3H), 2.41-2.3 (m, 1H), 2.20-1.54 (m, 9H), 0.89 (t, J=7.5 Hz, 3H).

後処理

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by MPLC
  7. customfurther purified by preparative HPLC

出典と根拠

ORDレコード
ord-194898befb5b4e6daf7fbcba96a62761
出典データセット
uspto-grants-2013_09
特許番号
US08541418B2

反応ノート

読み込み中…