Triethyl phosphite → HCID 86662603, compound

HRID 1958066Notes

Reaction equation

HRID 1958066 reaction equation
Br[CH:2]([C:4]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[CH3:18])[C:8]2[N:19]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[S:21][C:7]=2[C:6](=[O:28])[N:5]=1)[CH3:3].[P:29]([O:36]CC)([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32]>>[Cl:17][C:13]1[C:12]([CH3:18])=[C:11]([CH2:10][N:9]2[C:8]3[N:19]=[C:20]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[S:21][C:7]=3[C:6](=[O:28])[N:5]=[C:4]2[CH:2]([P:29](=[O:36])([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32])[CH3:3])[CH:16]=[CH:15][CH:14]=1

Participants

3

Reactant 2

HCID 31215Triethyl phosphiteHCID 66780709HCID 66780709, compound

Product 1

HCID 86662603HCID 86662603, compoundYield 25.5%

Procedure

Added 5-(1-bromoethyl)-4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (179 mg, 0.370 mmol) and triethyl phosphite (4 mL, 22.87 mmol) to a 20 mL screw capped vial and stirred overnight (14 hours) at room temperature. The next morning, starting material was still present, so the contents were transferred to a 25 mL round bottom flask and the contents were heated to 155° C. for 2 hours, whereupon LC/MS showed that the bromo starting material was consumed and a molecular ion corresponding to the desired product was present along with an impurity (believed to be the des-bromo compound by LC/MS). The yellow solution was distilled to remove the unreacted triethyl phosphite, then the residue was purified by column chromatography on silica gel eluted with 0-10% of a (2N solution of NH3 in methanol)/chloroform. The fractions containing product by TLC were combined, then concentrated to provide diethyl {1-[4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)-7-oxo-4,7-dihydro[1,3]thiazolo[4,5-d]pyrimidin-5-yl]ethyl}phosphonate (51 mg, 0.094 mmol, 25.5% yield) as a light tan solid. LC/MS m/z MH+=541 (theoretical), found=541.1, 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.23-1.36 (m, 6H) 1.47 (dd, J=17.31, 6.95 Hz, 3H) 2.46 (s, 3H) 3.02-3.18 (m, 1H) 3.49-3.60 (m, 4H) 3.71-3.82 (m, 4H) 4.00-4.27 (m, 4H) 5.67 (d, J=−17.68 Hz, 1H) 5.90 (d, J=17.68 Hz, 1H) 6.41 (d, J=7.58 Hz, 1H) 7.05 (t, J=7.83 Hz, 1H) 7.32 (d, J=7.58 Hz, 1H)

Workup

  1. customcapped vial
  2. customwere transferred to a 25 mL round bottom flask
  3. temperaturethe contents were heated to 155° C. for 2 hours, whereupon LC/MS
  4. customwas consumed
  5. distillationThe yellow solution was distilled
  6. customto remove the unreacted triethyl phosphite
  7. customthe residue was purified by column chromatography on silica gel
  8. washeluted with 0-10% of a (2N solution of NH3 in methanol)/chloroform
  9. additionThe fractions containing product by TLC
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0cd04492f9e044ff9a0f085f35145c71
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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