3-Methylpyrrolidin-2-one → HCID 178428189, compound

HRID 2047573Notes

Reaction equation

HRID 2047573 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@H:11]([N:13]4[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:63][CH:64]1[CH2:68][CH2:67][NH:66][C:65]1=[O:69].[Al]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:13]1([C@H:11]2[CH2:12][C@H:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([N:66]5[CH2:67][CH2:68][CH:64]([CH3:63])[C:65]5=[O:69])[CH:20]=[CH:19][C:5]=4[N:6]=3)[CH2:10]2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 1028483-Methylpyrrolidin-2-oneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 5359268AluminumHCID 178419317HCID 178419317, compound

Product 1

HCID 178428189HCID 178428189, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

To a microwave vial equipped with magnetic stir bar, 6-bromo-2-[trans-3-(piperidin-1-yl)cyclobutyl]-1,3-benzothiazole (3, 50 mg, 0.14 mmol) was added, Pd2(dba)3 (4.0 mg, 0.004 mmol), Xantphos (6.9 mg, 0.012 mmol) and CsCO3 (68 mg, 0.2 mmol), followed by 3-methylpyrrolidin-2-one (50 mg, 0.5 mmol). The reaction vial was then sealed with an aluminum cap, and placed under inert atmosphere by purging with N2. Dioxane (2 mL) was then introduced via a syringe. The reaction mixture was then subjected to sonication briefly to ensure mixing of the contents, and then heated in a commercial microwave oven at 150° C. for 60 min. The reaction mixture was cooled down to 23° C., and filtered to remove solids. The solvent was removed under vacuum, and from this, the residual mixture was purified by chromatography (SiO2, ethyl acetate (0-80%)/hexanes) to give the title compound as a pure product (28 mg, 55%). 1H NMR (300 MHz, CDCl3): δ=8.33 ppm (d, J=2.1 Hz, 1H), 7.94 (d, J=9.2 Hz, 1H), 7.61 (dd, J=9.2, 2.1 Hz, 1H), 3.85 (m, 3H), 2.72 (m, 1H), 2.59 (m, 4H), 2.43 (m, 2H), 2.40 (m, 2H), 1.82 (m, 1H), 1.40-1.75 (m, 8H), 1.33 (d, J=7.1 Hz, 3H). MS (ESI, M+H+): 370.1.

Workup

  1. customTo a microwave vial equipped with magnetic stir bar
  2. customcap
  3. customby purging with N2
  4. additionDioxane (2 mL) was then introduced via a syringe
  5. customThe reaction mixture was then subjected to sonication briefly
  6. additionto ensure mixing of the contents
  7. temperatureThe reaction mixture was cooled down to 23° C.
  8. filtrationfiltered
  9. customto remove solids
  10. customThe solvent was removed under vacuum
  11. customfrom this, the residual mixture was purified by chromatography (SiO2, ethyl acetate (0-80%)/hexanes)

Sources & evidence

ORD record
ord-5e4c8f291c424dc197f1e1a4a73ed0cd
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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