Sodium Carbonate → (R)-4-((R)-1-(7-(1,2,3,4-tetrahydroisoquinolin-7-yl)quinolin-5-yloxy)ethyl)pyrrolidin-2-one

HRID 1402719Notes

Reaction equation

HRID 1402719 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([O:12][C@@H:13]([C@H:15]2[CH2:19][NH:18][C:17](=[O:20])[CH2:16]2)[CH3:14])[CH:3]=1.C(OC([N:28]1[CH2:37][CH2:36][C:35]2[C:30](=[CH:31][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:34]=2)[CH2:29]1)=O)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH2:29]1[C:30]2[C:35](=[CH:34][CH:33]=[C:32]([C:2]3[CH:11]=[C:10]4[C:5]([CH:6]=[CH:7][CH:8]=[N:9]4)=[C:4]([O:12][C@@H:13]([C@H:15]4[CH2:19][NH:18][C:17](=[O:20])[CH2:16]4)[CH3:14])[CH:3]=3)[CH:31]=2)[CH2:36][CH2:37][NH:28]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 53302321tert-Butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 71238288(R)-4-((R)-1-(7-bromoquinolin-5-yloxy)ethyl)pyrrolidin-2-one

Product 1

HCID 71238155(R)-4-((R)-1-(7-(1,2,3,4-tetrahydroisoquinolin-7-yl)quinolin-5-yloxy)ethyl)pyrrolidin-2-oneYield 43.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

150 mg Example 27, 241 mg 7-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester, 15 mg bis(triphenylphosphine)palladium(II) chloride, 671 μL 2N aqueous sodium carbonate and 2 mL DMF were heated for 2 hours at 90° C. The mixture was partitioned between DCM and NaHCO3 (sat aq) and the organic layer was separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue was dissolved in 10 ml 25% TFA in DCM and stirred at 25° C. overnight then concentrated in vacuo. Purification by flash chromatography using 0-25% MeOH/DCM gave 75 mg (43%) of Example 101 (R)-4-{(R)-1-[7-(1,2,3,4-Tetrahydroisoquinolin-7-yl)-quinolin-5-yloxy]-ethyl}-pyrrolidin-2-one as yellow solid.

Workup

  1. customwere heated for 2 hours at 90° C
  2. customThe mixture was partitioned between DCM and NaHCO3 (sat aq)
  3. customthe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in 10 ml 25% TFA in DCM
  8. concentrationthen concentrated in vacuo
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-0dfa3ea561244403ba4fdc3ad8803357
Source dataset
uspto-grants-2014_12
Patent number
US08912173B2

Reaction notes

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