Triethyl phosphite → HCID 137231705, compound

HRID 1604248Notes

Reaction equation

HRID 1604248 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:17])[C:5]2[S:10][C:9](=[O:11])[N:8]([CH2:12]/[CH:13]=[CH:14]/[CH2:15]Cl)[C:6]=2[N:7]=1.[P:18]([O:25]CC)([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21]>CC#N>[NH2:1][C:2]1[NH:3][C:4](=[O:17])[C:5]2[S:10][C:9](=[O:11])[N:8]([CH2:12]/[CH:13]=[CH:14]/[CH2:15][P:18]([O:22][CH2:23][CH3:24])([O:19][CH2:20][CH3:21])=[O:25])[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 31215Triethyl phosphite2×HCID 135508872HCID 135508872, compound

Product 1

HCID 137231705HCID 137231705, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 5-Amino-3-[(E)-4-chloro-2-buten-1-yl]thiazolo[4,5-d]pyrimidine-2,7(3H, 6H)-dione (0.75 g, 2.75 mmol), anhydrous CH3CN (75 mL) and triethyl phosphite (10 mL) was stirred and heated at reflux for 6 days while adding additional quantities of triethyl phosphite (2×5 mL) at 2 day intervals. The mixture was evaporated and the residue was dissolved in CH2Cl2 (50 mL). The solution was applied to a silica gel column (5.5×20 cm) and the column was flash eluted with progressively increasing concentrations of MeOH in CH2Cl2 (%MeOH, vol in L): (0, 1), (1, 1), (2, 1), (3, 3), (5, 2), (10, 1). The eluate containing the product was evaporated and the solid residue was dried in vacuum for 16 h. The light yellow solid was stirred with 2-PrOH (10 mL) to obtain a white solid. The solid was collected and dried in vacuum at 85° C. for 3 days; 0.38 g (1.02 mmol, 37%), mp 191-192° C. Ir (KBr): ν3420, 3300 and 3190 (NH, NH2), 1690 (C=O), and 1666 broad (C=O, C=N, C=C) cm1. Uv, λmax (nm) (ε×10-3): pH 1, 302 (9.6), 250 (8.71), 220 (29.5); MeOH, 302 (9.00), 250 (8.55), 220 (29.0); pH 11, 292 (7.61), 248 (7.77), 224 (10.1). 1H nmr (DMSO-d6): δ1.17 (t, 6H, 2 CH3), 2.63 (dd, 2H, PCH2), 3.93 (q, 4H, OCH2), 4.34 (br s, 2H, NCH2), 5.43-5.49 (m, 1H, CH), 5.67-5.73 (m, 1H, CH), 6.95 (br s, 2H, NH2), and 11.14 (br s, 1H, NH). Anal. Calc'd for C13H19N4O5PS (374.35): C, 41.71; H, 5.11; N, 14.97; P, 8.27. Found: C, 41.68; H, 4.93; N, 15.01; P, 8.11.

Workup

  1. temperatureheated
  2. temperatureat reflux for 6 days
  3. customThe mixture was evaporated
  4. dissolutionthe residue was dissolved in CH2Cl2 (50 mL)
  5. washeluted
  6. temperaturewith progressively increasing concentrations of MeOH in CH2Cl2 (%MeOH, vol in L)
  7. additionThe eluate containing the product
  8. customwas evaporated
  9. customthe solid residue was dried in vacuum for 16 h
  10. stirringThe light yellow solid was stirred with 2-PrOH (10 mL)
  11. customto obtain a white solid
  12. customThe solid was collected
  13. customdried in vacuum at 85° C. for 3 days

Sources & evidence

ORD record
ord-57e7a306c22a4b96b677f19d0bca9a4e
Source dataset
uspto-grants-1999_11
Patent number
US05994321

Reaction notes

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