Diisopropylethylamine → HCID 58577838, compound

HRID 473960Notes

Reaction equation

HRID 473960 reaction equation
C(N(C(C)C)C(C)C)C.[Br:10][C:11]1[CH:12]=[N:13][C:14](Cl)=[N:15][CH:16]=1.[NH:18]1[CH2:22][CH2:21][CH:20]([CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]1>FC(F)(F)C1C=CC=CC=1.C(Cl)Cl>[Br:10][C:11]1[CH:12]=[N:13][C:14]([N:18]2[CH2:22][CH2:21][CH:20]([CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]2)=[N:15][CH:16]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 53350396tert-Butyl (pyrrolidin-3-yl)acetate

Product 1

HCID 58577838HCID 58577838, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7368(Trifluoromethyl)benzeneSolvent

Conditions

Temperature
120 °C

Procedure

N-Ethyl-N,N-diisopropylamine (1.80 mL, 10.34 mmol) was added dropwise at room temperature to a solution of 5-bromo-2-chloropyrimidine B-5 (1.00 g, 5.17 mmol) and tert-butyl 2-(pyrrolidin-3-yl)acetate (1.00 g, 5.40 mmol) in anhydrous α,α,α-trifluorotoluene (10.2 mL) under an argon atmosphere, in a 20 mL microwave reactor vial. The reaction mixture was sealed and heated at 120° C. for 30 mins under microwave irradiation, then successively cooled to room temperature, diluted with methylene chloride (100 mL), quenched with a 1 N aqueous solution of hydrogen chloride (30 mL) and decanted. The aqueous layer was extracted with methylene chloride (2×150 mL); the combined extracts were sequentially washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient) to give tert-butyl 2-(1-(5-bromopyrimidin-2-yl)pyrrolidin-3-yl)acetate B-6 (1.22 g, Yield=69%). MS (ESI), [M+1]+ 342, 344.

Workup

  1. customThe reaction mixture was sealed
  2. temperaturesuccessively cooled to room temperature
  3. customquenched with a 1 N aqueous solution of hydrogen chloride (30 mL)
  4. customdecanted
  5. extractionThe aqueous layer was extracted with methylene chloride (2×150 mL)
  6. washthe combined extracts were sequentially washed with brine (100 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe crude residue was purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient)

Sources & evidence

ORD record
ord-e9ed01d55a9d4e0ca3861d21cef61e4f
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

Loading…