Cesium carbonate → 6-(3-Hydroxyazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile

HRID 75310Notes

Reaction equation

HRID 75310 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:12]([CH3:13])[CH:11]=[CH:10][C:5]2=[N:6][C:7]=1[C:8]#[N:9].[NH:14]1[CH2:17][CH:16]([OH:18])[CH2:15]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.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:18][CH:16]1[CH2:17][N:14]([C:2]2[CH:3]=[C:4]3[N:12]([CH3:13])[CH:11]=[CH:10][C:5]3=[N:6][C:7]=2[C:8]#[N:9])[CH2:15]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 15142903-HydroxyazetidineHCID 867079636-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile

Product 1

HCID 867080096-(3-Hydroxyazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridine-5-carbonitrileYield 67.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile (4.27 g, 18.1 mmol), azetidin-3-ol (2.36 g, 18.1 mmol), Xantphos (1.05 g, 1.81 mmol), Pd(OAc)2 (0.406 g, 1.81 mmol) and cesium carbonate (11.8 g, 36.2 mmol) in dioxane (100 mL) were combined in a flask to give an orange suspension. The flask was purged with N2, sealed, and heated to 90° C. for 3 hours. The crude material was diluted with EtOAc (25 mL) and filtered through a pad of Celite. The filtrate was washed with saturated aqueous NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was loaded onto a silica gel cartridge (ISCO®, 120 g) and eluted using an EtOAc/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow solid (2.8 g, 67%). ESI-MS m/z [M+H]+ calc'd for C12H12N4O, 229; found 229.

Workup

  1. customto give an orange suspension
  2. customThe flask was purged with N2
  3. customsealed
  4. additionThe crude material was diluted with EtOAc (25 mL)
  5. filtrationfiltered through a pad of Celite
  6. washThe filtrate was washed with saturated aqueous NH4Cl (3×)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluted
  11. customThe product was collected
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-24e3425239c04fd8aef104dd6d32f3cf
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

Loading…