4,6-Dichloro-2-(methylthio)pyrimidine → HCID 86659191, compound

HRID 2367427Notes

Reaction equation

HRID 2367427 reaction equation
[F:1][C:2]([F:13])([F:12])[C@H:3]1[NH:8][CH2:7][C@@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:24][C:25]1[CH:30]=[C:29](Cl)[N:28]=[C:27]([S:32][CH3:33])[N:26]=1>C1COCC1>[Cl:24][C:25]1[N:26]=[C:27]([S:32][CH3:33])[N:28]=[C:29]([N:8]2[C@H:3]([C:2]([F:12])([F:1])[F:13])[CH2:4][CH2:5][C@H:6]([C:9]([OH:11])=[O:10])[CH2:7]2)[CH:30]=1

Participants

5

Reactant 3

HCID 805314,6-Dichloro-2-(methylthio)pyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 66990937HCID 66990937, compound

Product 1

HCID 86659191HCID 86659191, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To cis-6-(trifluoromethyl)-3-piperidinecarboxylic acid (3.393 g, 14.52 mmol) in THF (1.5 mL) were added molecular sieves, and the resulting mixture was stirred for 5 minutes into a 250 mL RB flask. The mixture was cooled in an ice bath, and then LiHMDS (43.6 mL, 43.6 mmol) was added slowly. After the addition was completed, 4,6-dichloro-2-(methylthio)pyrimidine (3.40 g, 17.43 mmol) was added. After 0.5 hours, the reaction was quenched with 30 mL of water and by the dropwise addition of 6N HCl until pH was acidic. The resulting mixture was extracted with EtOAc (3×30 mL). The organics were combined, washed with brine, dried (MgSO4), filtered and concentrated to afford the crude title compound as an oil. LC-MS (ES) m/z=356 [M+H]+.

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. additionAfter the addition
  3. waitAfter 0.5 hours
  4. customthe reaction was quenched with 30 mL of water and by the dropwise addition of 6N HCl until pH
  5. extractionThe resulting mixture was extracted with EtOAc (3×30 mL)
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3288497a8fc94023bcddbed435978404
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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