Cesium carbonate → (s)-Tert-butyl 2-((7-(4-(benzyloxy)-2-oxopyridin-1(2h)-yl)-5-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-2(5h)-yl)methyl)pyrrolidine-1-carboxylate

HRID 930767Notes

Reaction equation

HRID 930767 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13]Br)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][N:26]([C:29]2[CH:37]=[C:36]3[C:32](C4CCNCC=4[N:35]3[CH3:38])=[CH:31][CH:30]=2)[C:25](=[O:43])[CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O.CCOC(C)=O>[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][N:26]([C:29]2[CH:30]=[CH:31][C:32]3[C:24]4[CH2:25][N:26]([CH2:13][C@@H:9]5[CH2:10][CH2:11][CH2:12][N:8]5[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:27][CH2:28][C:23]=4[N:35]([CH3:38])[C:36]=3[CH:37]=2)[C:25](=[O:43])[CH:24]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 10264762tert-butyl (2S)-2-(bromomethyl)pyrrolidine-1-carboxylateHCID 50908737HCID 50908737, compound

Product 1

HCID 57950323(s)-Tert-butyl 2-((7-(4-(benzyloxy)-2-oxopyridin-1(2h)-yl)-5-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-2(5h)-yl)methyl)pyrrolidine-1-carboxylateYield 7.9%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (S)-tert-butyl-2-(bromomethyl)pyrrolidine-1-carboxylate (0.45 g, 1.7 mmol) in DMSO (1.5 mL) was added to a solution of 4-(benzyloxy)-1-(9-methyl-2,3,4,9,-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridine-2(1H)-one (0.33 g, 0.85 mmol), and Cs2CO3 (1.10 g, 3.4 mmol) in DMSO (2.8 mL), and the resulting solution was heated at 60° C. for 18 h. The reaction mixture was diluted with H2O and extracted with CH2Cl2 (3×25 mL). The combined organic extracts were washed with brine (2×25 mL), dried over Na2SO4 and concentrated to dryness under reduced pressure. Purification by flash column chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 hold 5 column volumes, increased to 0:100:0 over 20 column volumes) provided a clear film. The film was diluted with EtOAc and washed with brine (4×10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to provide the title compound (19 mg, 3%) as a clear film: ESI MS m/z 569 [M+H]+.

Workup

  1. extractionextracted with CH2Cl2 (3×25 mL)
  2. washThe combined organic extracts were washed with brine (2×25 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness under reduced pressure
  5. customPurification
  6. temperatureby flash column chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 hold 5 column volumes, increased to 0:100:0 over 20 column volumes)
  7. customprovided a clear film
  8. washwashed with brine (4×10 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-08eb505384fe4849872b539831e28da6
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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