Isopropanol → 2-[(1-Methylethyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 527806Notes

Reaction equation

HRID 527806 reaction equation
[CH3:1][C:2](C)([O-:4])[CH3:3].[Na+].CC(O)C.F[C:12]1[N:20]=[C:19]2[C:15]([N:16]=[CH:17][N:18]2[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)=[C:14]([NH2:27])[N:13]=1>C(OCC)(=O)C>[CH3:1][CH:2]([O:4][C:12]1[N:20]=[C:19]2[C:15]([N:16]=[CH:17][N:18]2[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)=[C:14]([NH2:27])[N:13]=1)[CH3:3]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 23676156Sodium t-butoxideHCID 592525662-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 592526442-[(1-Methylethyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amineYield 98.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Sodium t-butoxide (1.30 g, 13.53 mmol) was added to 2-propanol (16.95 ml, 220 mmol) portionwise with stirring over 5 mins. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added and the reaction mixture heated and stirred at 50° C. for 4 hours and then allowed to cool to room temperature. The reaction mixture was then diluted with ethyl acetate (75 ml), washed with water (3×25 ml) and the combined aqueous layers extracted again with ethyl acetate (2×25 ml). The combined organic layers were dried by passage through a hydrophobic frit, filtered and evaporated to give an off-white solid (2.30 g). This material was dissolved in dichloromethane and purified using an aminopropyl SPE cartridge (70 g) eluted with a 0-100% ethyl acetate in cyclohexane gradient. The appropriate fractions were combined and evaporated to give a white solid (1.6 g) which was further purified by column chromatography using a reverse phase (C18) Flashmaster II system loading in 1:1 MeOH/DMSO and eluting with 0-50% acetonitrile (+0.1% TFA) in water (+0.1% TFA) gradient over 40 mins. collecting fractions in vials containing ca. 2 mL of saturated aqueous sodium bicarbonate solution. The appropriate fractions were combined, and extracted with dichloromethane (3×100 mL). The combined organic extracts were dried by passage through a hydrophobic frit and evaporated to give the title compound as a white solid (888 mg).

Workup

  1. temperaturethe reaction mixture heated
  2. stirringstirred at 50° C. for 4 hours
  3. washwashed with water (3×25 ml)
  4. extractionthe combined aqueous layers extracted again with ethyl acetate (2×25 ml)
  5. customThe combined organic layers were dried by passage through a hydrophobic frit
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-017807ce6575453d89d14051bc14144b
Source dataset
uspto-grants-2016_05
Patent number
US09346806B2

Reaction notes

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