Methanol → (R)-N-[9-(2,3-Dihydro-2-furanyl)-9H-Purin-6-yl]-2,2-dimethylpropanamide

HRID 1558

Reaction equation

HRID 1558 reaction equation
[O:1]1[CH:5]=[CH:4][CH2:3][C@@H:2]1[N:6]1[CH:14]=[N:13][C:12]2[C:7]1=[N:8][CH:9]=[N:10][C:11]=2[NH2:15].[CH3:16][C:17]([CH3:22])([CH3:21])[C:18](Cl)=[O:19].C(Cl)Cl.CO.CO>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[O:1]1[CH:5]=[CH:4][CH2:3][C@@H:2]1[N:6]1[CH:14]=[N:13][C:12]2[C:7]1=[N:8][CH:9]=[N:10][C:11]=2[NH:15][C:18](=[O:19])[C:17]([CH3:22])([CH3:21])[CH3:16]

Participants

7

Reactant 4

HCID 887MethanolHCID 62493Pivaloyl chlorideHCID 14861975(R)-9-(2,3-Dihydro-2-furanyl)-9H-purin-6-amineHCID 21226129Dichloromethane methanol

Product 1

HCID 14888168(R)-N-[9-(2,3-Dihydro-2-furanyl)-9H-Purin-6-yl]-2,2-dimethylpropanamideYield 94%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of the product of Step C (196 g, 0.97 mole), 4-dimethylaminopyridine (5.9 g, 0.048 mole) in dry pyridine (970 mL) at 26° C. was added dropwise over 1 hr trimethylacetylchloride (145 mL, 142.1 g, 1.18 mole, 1.2 equiv.). A slight 3° C. exotherm was noted. The reaction mixture was then heated to 55° C. for 4 hr becoming a pale yellow-orange solution. Analysis by TLC (methylene chloride:methanol (90:10), Rf (product) 0.75) showed the reaction was complete. The reaction solution was cooled to 25° C. and methanol (40 mL) was slowly added. The reaction solution was then stirred for 30 min, then concentrated in vacuo to a thick orange syrup. The residue was dissolved in methylene chloride (1.5 liters) and washed with 0.5N sodium bisulfate (3×500 mL), 1N sodium bisulfate (2×500 mL), then brine (1×500 mL). All aqueous washes were combined and extracted with methylene chloride (1×500 mL). All methylene chloride extracts were combined and dried over anhydrous sodium sulfate, then filtered and concentrated in vacuo to a light orange oil. The oil was suspended in toluene (200 mL) and concentrated in vacuo. The product solidified to a pale yellow solid weighing 262 g for a yield of 94%.

Workup

  1. customA slight 3° C. exotherm
  2. temperatureThe reaction solution was cooled to 25° C.
  3. concentrationconcentrated in vacuo to a thick orange syrup
  4. dissolutionThe residue was dissolved in methylene chloride (1.5 liters)
  5. washwashed with 0.5N sodium bisulfate (3×500 mL), 1N sodium bisulfate (2×500 mL)
  6. extractionextracted with methylene chloride (1×500 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a light orange oil
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a66c33e4b2254f71b2ba86198e200a69
Source dataset
uspto-grants-1998_03
Patent number
US05726174

Linked notes

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