Methanol → HCID 66779989, compound

HRID 1958061Notes

Reaction equation

HRID 1958061 reaction equation
[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([CH2:8][N:9]2[C:14]3[N:15]=[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[S:17][C:13]=3[C:12](=[O:24])[N:11]=[C:10]2SC)[CH:5]=[CH:6][CH:7]=1.B1([O-])OO1.[OH2:32].O.O.O.[Na+].[CH3:37]O>[Cl-].[Na+].O>[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([CH2:8][N:9]2[C:14]3[N:15]=[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[S:17][C:13]=3[C:12](=[O:24])[N:11]=[C:10]2[O:32][CH3:37])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 23693097Sodium;3-oxidodioxaborirane;tetrahydrateHCID 66780292HCID 66780292, compound

Product 1

HCID 66779989HCID 66779989, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 4-[(3-chloro-2-methylphenyl)methyl]-5-(methylthio)-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (500 mg, 1.182 mmol) and sodium perborate tetrahydrate (700 mg, 3.85 mmol) in Methanol (5 mL) was irradiated in a microwave reactor at 110° C. for 15 min. The reaction was repeated three additional times. The four reaction mixtures were poured into brine and extracted with CH2Cl2 (4×). The combined organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified on silica gel (ISCO, 0-7% MeOH in CH2Cl2), but separation failed. The fractions containing product were combined, absorbed onto silica gel and resubmitted for purification on silica gel (ISCO, 0-5% MeOH in CH2Cl2), but again no separation was observed. The residues from the combined fractions were finally purified using Chiralpak IA (101×210 mm, 100% CH3OH, 500 ml/min) to give 4-[(3-chloro-2-methylphenyl)methyl]-5-(methyloxy)-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (820 mg, 1.995 mmol, 42.2% yield) as a white powder. LC/MS (ES+): [M+H]+=407.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.36 (d, J=7.83 Hz, 1H), 7.15 (t, J=7.83 Hz, 1H), 6.72 (d, J=7.58 Hz, 1H), 5.34 (s, 2H), 3.85 (s, 3H), 3.60-3.74 (m, 4H), 3.51 (t, J=4.67 Hz, 4H), 2.41 (s, 3H).

Workup

  1. customwas irradiated in a microwave reactor at 110° C. for 15 min
  2. customThe four reaction mixtures
  3. extractionextracted with CH2Cl2 (4×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified on silica gel (ISCO, 0-7% MeOH in CH2Cl2), but separation
  8. additionThe fractions containing product
  9. customabsorbed onto silica gel
  10. customresubmitted for purification on silica gel (ISCO, 0-5% MeOH in CH2Cl2)
  11. customagain no separation
  12. customThe residues from the combined fractions were finally purified

Sources & evidence

ORD record
ord-782530ad87054865b2e531b11f5f5131
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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