2,4-Dichloro-5-(trifluoromethyl)pyrimidine → HCID 89815972, compound

HRID 1482996Notes

Reaction equation

HRID 1482996 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[CH:13]([C@H:16]1[NH:21][CH2:20][CH2:19][N:18]2[C:22]3[CH:28]=[C:27]([S:29]([CH3:32])(=[O:31])=[O:30])[C:26]([C:33]([O:35][CH3:36])=[O:34])=[CH:25][C:23]=3[N:24]=[C:17]12)([CH3:15])[CH3:14]>ClCCCl.CC(O)(C)C.[Cl-].[Cl-].[Zn+2]>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([N:21]2[CH2:20][CH2:19][N:18]3[C:22]4[CH:28]=[C:27]([S:29]([CH3:32])(=[O:30])=[O:31])[C:26]([C:33]([O:35][CH3:36])=[O:34])=[CH:25][C:23]=4[N:24]=[C:17]3[C@H:16]2[CH:13]([CH3:15])[CH3:14])[N:7]=1

Participants

6

Reactant 2

HCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 89815671(R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Product 1

HCID 89815972HCID 89815972, compoundYield 42.6%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolvent2×HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (20.0 mg, 0.092 mmol) in DCE (1 mL) and t-BuOH (1 mL) was added ZnCl2 (1M in diethyl ether, 0.2 mL, 0.2 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h. Then a solution of (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (31 mg, 0.09 mmol) in DCE (1 mL) and t-BuOH (1 mL) was added to the reaction mixture via syringe over 1 min at 0° C. After addition, the resulting mixture was stirred at rt overnight. The reaction mixture was concentrated under vacuum. Water (5 mL) and EtOAc (5 mL) were added to the mixture. The aqueous phase was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC to afford (R)-methyl 2-(4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (20 mg, 42.6% yield) as a white solid.

Workup

  1. additionAfter addition
  2. stirringthe resulting mixture was stirred at rt overnight
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. additionWater (5 mL) and EtOAc (5 mL) were added to the mixture
  5. extractionThe aqueous phase was extracted with EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-85028cc51dc34338bd98b6acfa620227
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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