1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridin-4-ylsulfanylmethyl)pyrimidine

HRID 2353707Notes

Reaction equation

HRID 2353707 reaction equation
[SH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Cl:8][C:9]1[N:14]=[C:13]([CH2:15]I)[CH:12]=[C:11]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]2[CH3:23])[N:10]=1.C1CCN2C(=NCCC2)CC1>C(#N)C>[Cl:8][C:9]1[N:10]=[C:11]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]2[CH3:23])[CH:12]=[C:13]([CH2:15][S:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)[N:14]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59380103(S)-4-(2-Chloro-6-(iodomethyl)pyrimidin-4-YL)-3-methylmorpholineHCID 178418431pyridine-4-thiol

Product 1

HCID 593801062-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridin-4-ylsulfanylmethyl)pyrimidineYield 64.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Mercaptopyridine (0.752 g, 6.77 mmol) was added to 2-chloro-4-(iodomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine (1.596 g, 4.51 mmol) in acetonitrile (100 mL) at RT under air. DBU (0.3 mL, 2.01 mmol) was then added and the resulting solution was stirred at RT for 2 minutes. The solvent was removed and DCM was added. The reaction mixture was washed sequentially with water, the organic layer dried (MgSO4), filtered and evaporated. The crude product was chromatographed on silica, eluting with 0-2% methanol in DCM. Impure fractions were further chromatographed on silica, eluting with 0-4.5% methanol in DCM and combined with the initial pure fractions to give the desired material as a yellow gum (0.980 g).

Workup

  1. customThe solvent was removed
  2. additionDCM was added
  3. washThe reaction mixture was washed sequentially with water
  4. dry with materialthe organic layer dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was chromatographed on silica
  8. washeluting with 0-2% methanol in DCM
  9. customImpure fractions were further chromatographed on silica
  10. washeluting with 0-4.5% methanol in DCM

Sources & evidence

ORD record
ord-59bf4c156f0f46aab3998ce9937417b8
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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