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

HRID 869098Notes

Reaction equation

HRID 869098 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 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.

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-fdc3758b1e7e4c9a80100aa8f8c50978
Source dataset
uspto-grants-2015_03
Patent number
US08969359B2

Reaction notes

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