2-Chloropyrimidine → Rislenemdaz

HRID 734384Notes

Reaction equation

HRID 734384 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[O:10])[CH2:5][C@H:4]1[F:20].Cl[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C([O-])(O)=O.[Na+]>C(O)CCC.C(N(C(C)C)CC)(C)C.CCOC(C)=O>[F:20][C@H:4]1[C@@H:3]([CH2:2][NH:1][C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=2)=[O:10])[CH2:5]1

Participants

6

Reactant 3

HCID 744042-ChloropyrimidineHCID 516892Sodium BicarbonateHCID 57845344HCID 57845344, compound

Product 1

HCID 11394238RislenemdazYield 145.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 131727637HCID 131727637, compoundSolvent

Conditions

Temperature
140 °C

Procedure

Two sealed tubes were each charged with a mixture of crude (±)-cis-4-methylbenzyl 4-(aminomethyl)-3-fluoropiperidine-1-carboxylate (Step 6, 3.7 g, 13.2 mmol) and 2-chloropyrimidine (1.51 g, 13.2 mmol) in n-butanol/diisopropyl-ethylamine (1:1, 13 mL). The tubes were sealed and the mixtures heated to 140° C. and stirred for 2 h. After cooling to RT, the reaction mixtures were combined and diluted with EtOAc and sat NaHCO3. The layers were separated and the organic was washed with H2O and brine, dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (gradient elution: 1:1 hexanes:EtOAc to EtOAc) gave racemic cis-4-methylbenzyl 3-fluoro-4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate (6.9 g, 65% yield, 3 steps) as a white solid.

Workup

  1. customThe tubes were sealed
  2. temperatureAfter cooling to RT
  3. customthe reaction mixtures
  4. customThe layers were separated
  5. washthe organic was washed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification
  10. washby silica gel chromatography (gradient elution: 1:1 hexanes:EtOAc to EtOAc)

Sources & evidence

ORD record
ord-97a9903c758c4c098700575bda6ceaf4
Source dataset
uspto-grants-2009_09
Patent number
US07592360B2

Reaction notes

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