L-Methionine → 2,4-Dichloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[D]pyrimidine

HRID 474272Notes

Reaction equation

HRID 474272 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([Cl:18])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[CH3:19][Si]([N-][Si](C)(C)C)(C)C.[K+].N[C@H](C(O)=O)CCSC.CCOC(C)=O>COCCOC>[Cl:1][C:2]1[N:3]=[C:4]([Cl:18])[C:5]2[CH2:10][CH2:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)([CH3:19])[C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 6137L-MethionineHCID 8857Ethyl AcetateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 580758222,4-Dichloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[D]pyrimidineYield 81%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine, (Preparation S, 3.56 g, 12.57 mmol) in DME (Volume: 84 mL) at −78° C. was added KHMDS (0.91 M in THF, 15.20 ml, 13.83 mmol) dropwise. After 10 min, Met (2.36 mL, 37.7 mmol) was added. The reaction was kept at −78° C. for 10 min, then allowed to come to rt. An aliquot taken while the reaction was still cool was quenched with water and extracted with EtOAc. TLC (10% EtOAc/Hex) and LC/MS showed the clean conversion to a new product. The bulk of the material was then quenched and extracted as above. The combined organic extracts were dried over MgSO4, filtered, and the solvent removed in vacuo. SG chromatography (0 to 40% EtOAc/Hex) gave 2,4-dichloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (3.01 g, 10.13 mmol, 81% yield). LC-MS (*M*+H)+=293.1 (*product reacts with methanol during analysis*). 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.29 (2H, m), 6.96-7.04 (2H, m), 2.88-3.02 (2H, m), 2.62 (1H, ddd, J=13.28, 7.93, 5.04 Hz), 2.26-2.35 (1H, m), 1.68 (3H, s).

Workup

  1. waitThe reaction was kept at −78° C. for 10 min
  2. customto come to rt
  3. temperaturewas still cool
  4. customwas quenched with water
  5. extractionextracted with EtOAc
  6. customThe bulk of the material was then quenched
  7. extractionextracted as above
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. filtrationfiltered
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-692da40ce9f24642936027125fd73a68
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

Loading…