Carbamate → HCID 86667383, compound

HRID 334171Notes

Reaction equation

HRID 334171 reaction equation
[C:1]([O:5][C:6](=[O:32])[NH:7][CH:8]([C:10]1[N:11]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[C:12]2[C:17]([N:18]=1)=[C:16]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:15]=[C:14]([Cl:25])[N:13]=2)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].IC.[C:37](=O)([O-])N.Cl.C(=O)(O)[O-].[Na+]>C1COCC1.O>[C:1]([O:5][C:6](=[O:32])[N:7]([CH:8]([C:10]1[N:11]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[C:12]2[C:17]([N:18]=1)=[C:16]([N:19]1[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1)[N:15]=[C:14]([Cl:25])[N:13]=2)[CH3:9])[CH3:37])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 6

HCID 276Carbamate2×HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 86667382HCID 86667382, compound

Product 1

HCID 86667383HCID 86667383, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of {1-[2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethyl}-carbamic acid tert-butyl ester (218 mg, 0.47 mmol) in anhydrous THF (15 mL) was cooled to 0° C. Sodium hydride (60% suspension in oil, 22 mg, 0.56 mmol) was added and the mixture was stirred at 0° C. for 30 min. Iodomethane (10 vol. % solution in THF, 0.35 mL, 0.56 mmol) was added and the mixture was stirred for 16 h at RT. The reaction mixture was combined with another mixture, prepared in a similar manner from 210 mg of the carbamate starting-material, and diluted with water. After adjustment to pH7 by addition of 1M aqueous HCl and aqueous sodium bicarbonate, the mixture was extracted three times with ethyl acetate. The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo, to give a 2:1 mixture of the title compound and carbamate starting-material (0.46 g). This mixture was dissolved in anhydrous THF (20 mL) and treated with sodium hydride (19 mg) and iodomethane (10 vol. % solution in THF, 0.29 mL) as before. After addition of more iodomethane (neat, 0.050 mL) and stirring for another 8 h, the reaction mixture was diluted with water, neutralized and extracted as before. The organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2) gradient 0-20% ethyl acetate in cyclohexane) to give {1-[2-Chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethyl}-methyl-carbamic acid tert-butyl ester (316 mg, 72%). LCMS RT=4.48 min, [M+H]+=481/483

Workup

  1. stirringthe mixture was stirred for 16 h at RT
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give

Sources & evidence

ORD record
ord-05c2dfe1626548b0a81caadc985e384d
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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