Triethyl phosphite → HCID 137231704, compound

HRID 1604247Notes

Reaction equation

HRID 1604247 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 135502920HCID 135502920, compound

Product 1

HCID 137231704HCID 137231704, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 5-Amino-3-[(Z)-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. The residue was triturated with Et2O (2×50 mL) and then dissolved in MEOH (50 mL). Silica gel (25 g) was added and the mixture was evaporated. The dry powder was placed on a silica gel column (5.5×28 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, 2), (5, 2), (10, 2). 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 (20 mL) to obtain a white solid. The solid was collected and dried in vacuum at 80° C. for 16 h: 0.35 g (0.935 mmol, 34%), mp 186-188° C. Ir (KBr): ν3390, 3310 and 3210 (NH, NH2), 1685 (C=O), and 1660 broad (C=O, C=N, C=C) cm-1. Uv λmax (nm) (ε×10-3): pH 1,302 (10.0), 250 (8.92), 220 (31.2); MEOH, 302 (9.60), 250 (8.79), 220 (29.1); pH 11, 292 (7.94), 248 (8.07), 224 (9.88). 1H nmr (DMSO-d6): δ1.23 (t, 6H, 2 CH3), 2.84 (dd, 2H, PCH2), 3.99 (q, 4H, OCH2), 4.40 (br s, 2H, NCH2), 5.55-5.63 (m,2H, 2 CH), 6.93 (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, 41.55; H, 5.02; N, 14.64; P, 8.00.

Workup

  1. temperatureheated
  2. temperatureat reflux for 6 days
  3. customThe mixture was evaporated
  4. customThe residue was triturated with Et2O (2×50 mL)
  5. dissolutiondissolved in MEOH (50 mL)
  6. additionSilica gel (25 g) was added
  7. customthe mixture was evaporated
  8. washeluted
  9. temperaturewith progressively increasing concentrations of MEOH in CH2Cl2 (%MeOH, vol in L)
  10. additionThe eluate containing the product
  11. customwas evaporated
  12. customthe solid residue was dried in vacuum for 16 h
  13. stirringThe light yellow solid was stirred with 2-PrOH (20 mL)
  14. customto obtain a white solid
  15. customThe solid was collected
  16. customdried in vacuum at 80° C. for 16 h

Sources & evidence

ORD record
ord-4b43a4dcf6b049599a55b9e888661466
Source dataset
uspto-grants-1999_11
Patent number
US05994321

Reaction notes

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