Methanol → 7-Amino-1-(n-hexyl)-1,3-azaphospholo[4,5-d]pyrimidine

HRID 1108781Notes

Reaction equation

HRID 1108781 reaction equation
[NH2:1][C:2]1[C:3]2[NH:10][CH:9]=[P:8][C:4]=2[N:5]=[CH:6][N:7]=1.[H-].[Na+].Br[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].CO>CN(C=O)C>[NH2:1][C:2]1[C:3]2[N:10]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:9]=[P:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 81011-BromohexaneHCID 24758Sodium hydrideHCID 178508727HCID 178508727, compound2×

Product 1

HCID 101985937-Amino-1-(n-hexyl)-1,3-azaphospholo[4,5-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-Amino-1H-1,3-azaphospholo[4,5-d]pyrimidine (compound 10, 0.5 g, 3.29 mmol) was suspended in dry DMF to which sodium hydride (160 mg, 4 mmol, 60% dispersion in mineral oil) was added under an argon atmosphere. The mixture was stirred at room temperature for 40 min and 1-bromohexane (0.56 mL, 4 mmol) was added. The reaction was continued for 3 h and the solvent was evaporated. The residue was dissolved in dichloromethane (150 mL) and washed with water (25 mL). Organic layer was separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic layer was dried (Na2SO4) and evaporated. The residue was purified by silica gel column (2×15 cm) chromatography eluting with dichloromethane containing 0-4% methanol. The appropriate fractions containing the desired product were evaporated to yield 0.53 g (68%), mp 220-222° C. Ir (KBr): ν690 (=P-C), 1220 (-P=CH), and 3295 (NH2) cm-1. Uv (pH 1): λmax 254 nm (ε23,700), 282 (11,500), and 314 (5200); (MeOH): λmax 266 (ε31,600); (pH 11): λmax 266 nm (ε33,300), and 330 (2200). 31 p nmr (DMSO-d6): 63.21. 1H nmr (DMSO-d6): δ 0.80(t, 3 H, CH3), 1.23 (br s, 6 H, 3CH2), 1.92 (t, 2 H, CH2), 4.24 (t, 2 H, NCH2), 8.15 and 8.23 (2s, 2 H, NH2), 8.44 (d, 1 H, C5H), and 8.86 (d, 1 H, J=58.5 Hz, C2H). Anal. Calcd. for C11H17N4P: C, 55.92; H, 7.25; N, 23.72. Found: C, 55.49; H, 7.31; N, 23.28.

Workup

  1. additionwas added under an argon atmosphere
  2. waitThe reaction was continued for 3 h
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in dichloromethane (150 mL)
  5. washwashed with water (25 mL)
  6. customOrganic layer was separated
  7. extractionthe aqueous layer was extracted with dichloromethane (2×50 mL)
  8. dry with materialThe combined organic layer was dried (Na2SO4)
  9. customevaporated
  10. customThe residue was purified by silica gel column (2×15 cm) chromatography
  11. washeluting with dichloromethane containing 0-4% methanol
  12. additionThe appropriate fractions containing the desired product
  13. customwere evaporated
  14. customto yield 0.53 g (68%), mp 220-222° C

Sources & evidence

ORD record
ord-3836021922174331bf515d15e2f9bd73
Source dataset
uspto-grants-2000_05
Patent number
US06069132

Reaction notes

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