Methanol → 2-Amino-9-(4-butyryloxy-3-hydroxymethylbut-1-yl)purine

HRID 5870

Reaction equation

HRID 5870 reaction equation
OCC(C(OC(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)OC)CC[N:6]1[C:14]([NH:15]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[N:13][C:12]2C1=NC(OC)=[N:10][CH:11]=2.[C:60]([O:65][C:66](=O)[CH2:67][CH2:68][CH3:69])(=[O:64])[CH2:61][CH2:62][CH3:63].[CH3:71][OH:72].C[N:74]([CH3:77])[CH:75]=O>CN(C)C1C=CN=CC=1>[NH2:15][C:14]1[N:6]=[C:77]2[C:11]([N:10]=[CH:75][N:74]2[CH2:69][CH2:68][CH:67]([CH2:71][OH:72])[CH2:66][O:65][C:60](=[O:64])[CH2:61][CH2:62][CH3:63])=[CH:12][N:13]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 7798Butyric anhydrideHCID 678620909-(3-Hydroxymethyl-4-monomethoxytrityloxybut-1-yl)-2-monomethoxytritylaminopurine

Product 1

HCID 138831932-Amino-9-(4-butyryloxy-3-hydroxymethylbut-1-yl)purine

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a solution of 9-(3-hydroxymethyl-4-monomethoxytrityloxybut-1-yl)-2-monomethoxytritylaminopurine (0.70 g, 0.9 mmol) and 4-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (5 ml) was added butyric anhydride (0.29 ml, 1.8 mmol) and the solution was stirred for 15 minutes. Methanol (1 ml) was added and the solvent was removed. The residue was taken up in 80% acetic acid (9 ml) and the solution was stirred at 70° for 30 minutes. Water (2 ml) was added and the solution was extracted with hexane (2×10 ml). The aqueous layer was retained and the solvent was removed. The residue was partitioned between saturated aqueous sodium bicarbonate and chloroform and the organic layer was dried (magnesium sulphate) and the solvent removed. The residue was purified by column chromatography on silica gel eluting with chloroform-methanol (16:1 to afford 2-amino-9-(4-butyryloxy-3-hydroxymethylbut-1-yl)purine which was obtained as a white crystalline solid after trituration with methanol (188 mg, 68%), m.p. 125°-127°; λmax (MeOH) 222 (27,600), 243 (4,830), and 308 (6,950)nm; νmax (KBr) 3190, 1730, 1640, 1620, and 1580 cm-1 ; δH [(CD3)2SO]0.85 (3H, t, J 7.4 Hz, CH3), 1.50 (2H, sextet, J 7.3 Hz, CH2CH2CH3), 1.68 (1H, m, 3'-H), 1.82 (2H, m, 2'-H), 2.23 (2H, t, J 7.4 Hz, CH2CH2CH3), 3.42 (2H, t, J 5.2 Hz, D2O exchange gives d, CH2OH), 3.95-4.1 (2H, ABX, JAB 11.0 Hz, JAX =JBX 5.8 Hz, CH2OOC), 4.12 (2H, t, J 7.3 Hz, 1'-H), 4.62 (1H, t, J 4.9 Hz, D2O exchangeable, OH), 6.44 (2H, s, D2O exchangeable, 2-NH2), 8.06 (1H, s, 8-H), and 8.56 (1H, s, 6-H); (Found: C, 54.41; H, 6.91; N, 22.70%. C14H21N5O3 requires C, 54.71; H, 6.89; N, 22.79%).

Workup

  1. customthe solvent was removed
  2. stirringthe solution was stirred at 70° for 30 minutes
  3. additionWater (2 ml) was added
  4. extractionthe solution was extracted with hexane (2×10 ml)
  5. customthe solvent was removed
  6. customThe residue was partitioned between saturated aqueous sodium bicarbonate and chloroform
  7. dry with materialthe organic layer was dried (magnesium sulphate)
  8. customthe solvent removed
  9. customThe residue was purified by column chromatography on silica gel eluting with chloroform-methanol (16:1

Sources & evidence

ORD record
ord-4d1fd178952846efa63a1421db1f7aea
Source dataset
uspto-grants-1993_09
Patent number
US05246937

Linked notes

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