Methanol → HCID 59753959, compound

HRID 750804Notes

Reaction equation

HRID 750804 reaction equation
[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[C:10]1[C:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[C:14](SC)[N:13]=[C:12]([S:25][CH3:26])[N:11]=1.[CH3:27][OH:28]>>[CH3:26][S:25][C:12]1[N:13]=[C:14]([O:28][CH3:27])[C:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[C:10]([C:4]2[CH:5]=[CH:6][C:7]([Cl:9])=[CH:8][C:3]=2[Cl:2])[N:11]=1

Participants

4

Reactant 3

HCID 887Methanol2×HCID 5360545SodiumHCID 59753880HCID 59753880, compound

Product 1

HCID 59753959HCID 59753959, compound

Procedure

To a round bottom flask fitted with a magnetic stir bar and small reflux condenser was added 0.25 mL methanol, sodium metal (23 mg, 1.0 mmol). The flask was flushed with nitrogen. When the sodium dissolved, 2,4-bis(methylthio)-5-[4-chlorophenyl]-6-[2,4-dichlorophenyl]-pyrimidine (Reference Example 4, 215 mg, 0.5 mmol) in 500 μL methanol was added by syringe. The methanol was removed under high vacuum and 2 mL scrupulously dried DMF (15X sieve and 3A sieve, respectively) added to the mixture. The mixture was stirred for 5 h, quenched in aqueous NH4Cl and immediately extracted with ether. Starting material and product were observed by LC. The organic layer was dried over MgSO4 and filtered. The solvent removed under reduced pressure. Flash column chromatography on silica gel (eluted with 98/2 hexanes/ethyl acetate) gave pure product and mixed starting material/product fraction. The title compound eluted by LC at Rt=4.62 min, m/e=313 (M++1). 1H-NMR 500 MHz (CDCl3): δ 2.64 (s, 3H), 4.05 (s, 3M), 7.08 (d, J=8 Hz, 2H), 7.13 (d, J=8 Hz, 1H), 7.19-7.24 (m, 3H), 7.34 (d, J=2 Hz, 1H).

Workup

  1. customTo a round bottom flask fitted with a magnetic stir bar and small reflux condenser
  2. customThe flask was flushed with nitrogen
  3. dissolutionWhen the sodium dissolved
  4. customThe methanol was removed under high vacuum and 2 mL scrupulously dried DMF (15X sieve and 3A sieve
  5. additionrespectively) added to the mixture
  6. customquenched in aqueous NH4Cl
  7. extractionimmediately extracted with ether
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. customThe solvent removed under reduced pressure
  11. customFlash column chromatography on silica gel (eluted with 98/2 hexanes/ethyl acetate) gave pure product
  12. additionmixed
  13. washThe title compound eluted by LC at Rt=4.62 min, m/e=313 (M++1)

Sources & evidence

ORD record
ord-f9b723308812436f9b8f4204301a886e
Source dataset
uspto-grants-2008_07
Patent number
US07405221B2

Reaction notes

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