2-[5-(3,4-Diamino-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol → HCID 178465305、化合物

HRID 869098ノート

反応式

HRID 869098 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:14]2[CH:15]=[N:16][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[N:18][CH:19]=2)[CH:5]=[C:6]([CH:9]2[CH2:13][CH2:12][CH2:11][O:10]2)[C:7]=1[NH2:8].[CH2:24]([NH:26][C:27]([NH:29][C:30](SC)=NC(=O)NCC)=[O:28])[CH3:25]>O1CCOCC1.OS(O)(=O)=O>[CH2:24]([NH:26][C:27]([NH:29][C:30]1[NH:8][C:7]2[C:6]([CH:9]3[CH2:13][CH2:12][CH2:11][O:10]3)=[CH:5][C:4]([C:14]3[CH:19]=[N:18][C:17]([C:20]([OH:23])([CH3:21])[CH3:22])=[N:16][CH:15]=3)=[CH:3][C:2]=2[N:1]=1)=[O:28])[CH3:25]

参加物

5

反応物 2

HCID 681083372-[5-(3,4-Diamino-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-olHCID 734081491-ethyl-3-(N-(ethylcarbamoyl)-C-methylsulfanyl-carbonimidoyl)urea

生成物 1

HCID 178465305HCID 178465305、化合物収率 82.3%

試薬・触媒・溶媒 2

HCID 1118Sulfuric Acid溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a stirring solution of 2-[5-(3,4-diamino-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol (9) (32.10 g, 102.1 mmol) in 1,4-dioxane (160.5 mL, Sigma-Aldrich 360481) was added pH 3.5 buffer (240.8 mL), prepared by dissolving NaOAc trihydrate (34.5 g) in 1N aqueous H2SO4 (240 mL). Added 1-ethyl-3-(N-(ethylcarbamoyl)-C-methylsulfanyl-carbonimidoyl)urea (10) (28.46 g, 122.5 mmol, CB Research and Development) and stirred at reflux overnight (HPLC showed 99% consumption of starting diamine). The reaction mixture was cooled to room temperature and poured portion-wise (frothing) into a stirring solution of aqueous saturated NaHCO3 (480 mL) and water (120 mL) giving pH 8-9. This was stirred for 30 minutes, the solid was collected by filtration, washed copiously with water to neutral pH, and then more sparingly with EtOH. The solid was dried under reduced pressure giving (11) as an off-white solid (34.48 g, 82% yield; 99.4% HPLC purity). LCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 411.41 (1.73 min). 1H NMR (300 MHz, MeOD) δ 9.02 (s, 2H), 7.62 (s, 1H), 7.37 (s, 1H), 5.31 (s, 1H), 4.23 (dd, J=14.5, 7.3 Hz, 1H), 4.01 (dd, J=15.0, 7.1 Hz, 1H), 3.38-3.28 (m, 2H), 2.58-2.46 (m, 1H), 2.16-2.05 (m, 2H), 2.02-1.88 (m, 1H), 1.63 (s, 6H), 1.22 (t, J=7.2 Hz, 3H) ppm.

後処理

  1. customprepared
  2. temperatureat reflux overnight
  3. custom(HPLC showed 99% consumption of starting diamine)
  4. additionpoured portion-wise (frothing) into a stirring solution of aqueous saturated NaHCO3 (480 mL) and water (120 mL)
  5. customgiving pH 8-9
  6. filtrationthe solid was collected by filtration
  7. washwashed copiously with water to neutral pH
  8. customThe solid was dried under reduced pressure

出典と根拠

ORDレコード
ord-fdc3758b1e7e4c9a80100aa8f8c50978
出典データセット
uspto-grants-2015_03
特許番号
US08969359B2

反応ノート

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