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

HRID 447247Notes

Reaction equation

HRID 447247 reaction equation
[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]

Participants

5

Reactant 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

Product 1

HCID 178465305HCID 178465305, compoundYield 82.3%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirring solution of 245-(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.

Workup

  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

Sources & evidence

ORD record
ord-4c518bb09f084a0a969b4850efc080d7
Source dataset
uspto-grants-2013_07
Patent number
US08481551B2

Reaction notes

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