Pyrrolidine → HCID 66780214, compound

HRID 1958059Notes

Reaction equation

HRID 1958059 reaction equation
Br[CH2:2][C:3]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=2[CH3:17])[C:7]2[N:18]=[C:19]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[S:20][C:6]=2[C:5](=[O:27])[N:4]=1.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>O1CCCC1.ClCCl>[Cl:16][C:12]1[C:11]([CH3:17])=[C:10]([CH2:9][N:8]2[C:7]3[N:18]=[C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[S:20][C:6]=3[C:5](=[O:27])[N:4]=[C:3]2[CH2:2][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 2

HCID 31268PyrrolidineHCID 66779869HCID 66779869, compound

Product 1

HCID 66780214HCID 66780214, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 20 mL I-CHEM reaction vial was added a solution of 5-(bromomethyl)-4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (188 mg, 0.400 mmol) in tetrahydrofuran (THF) (4002 μL). The solution was then treated with pyrrolidine (331 μL, 4.00 mmol) and the resulting reaction mixture was allowed to stir at room temperature and was found to have completely converted to the desired material by LCMS in less than 5 minutes. Reaction mixture was placed under a nitrogen stream and warmed to 50° C. to concentrate the reaction to a residue. The residue was then re-dissolved in dichloromethane (DCM) (750 μL) and injected onto a 10 g SNAP silica cartridge for purification [eluting with a gradient: 0-95% THF (1% methanol (MeOH)) into DCM, over 30 column volumes]. Fractions containing the desired material were pooled and concentrated to afford a residue which was subsequently triturated with ethyl acetate and hexanes to afford pure 4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)-5-(1-pyrrolidinylmethyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (38 mg, 0.082 mmol, 20.44% yield). LCMS Theoretical m/z MH+=460.99 Found: 461.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.47 (br. s., 4H) 2.37 (br. s., 4H) 2.41 (s, 3H) 3.46-3.52 (m, 4H) 3.52 (s, 2H) 3.62-3.74 (m, 4H) 5.66 (s, 2H) 6.45 (d, J=7.83 Hz, 1H) 7.11 (t, J=8.21 Hz, 1H) 7.33 (d, J=7.33 Hz, 1H).

Workup

  1. customreaction
  2. customthe resulting reaction mixture
  3. customReaction mixture
  4. temperaturewarmed to 50° C.
  5. concentrationto concentrate
  6. customthe reaction to a residue
  7. custominjected onto a 10 g SNAP silica cartridge for purification [
  8. washeluting with a gradient
  9. additionFractions containing the desired material
  10. concentrationconcentrated
  11. customto afford a residue which
  12. customwas subsequently triturated with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-69fb3319f9db421c9b9a78185a74d3af
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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