Cesium carbonate → HCID 178461220, compound

HRID 1852888Notes

Reaction equation

HRID 1852888 reaction equation
Cl[C:2]1[C:7]2[N:8]([CH2:23][C@H:24]3[CH2:29][CH2:28][C@H:27]([CH3:30])[CH2:26][CH2:25]3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][C@H:12]3[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:10][C:6]=2[CH:5]=[C:4]([Cl:31])[N:3]=1.[CH:32]1([CH2:36][OH:37])[CH2:35][CH2:34][CH2:33]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CS(C)=O.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]>[Cl:31][C:4]1[N:3]=[C:2]([O:37][CH2:36][CH:32]2[CH2:35][CH2:34][CH2:33]2)[C:7]2[N:8]([CH2:23][C@H:24]3[CH2:25][CH2:26][C@H:27]([CH3:30])[CH2:28][CH2:29]3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][C@H:12]3[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:10][C:6]=2[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 78130CyclobutylcarbinolHCID 634876Binap, (A+-)-HCID 178461219HCID 178461219, compound

Product 1

HCID 178461220HCID 178461220, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4,6-dichloro-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (Example 2.1, Step 2; 400 mg, 0.87 mmol) in DMSO (5 mL) was added cyclobutylmethanol (337 mg, 3.92 mmol), Cs2CO3 (848 mg, 2.61 mmol) and BINAP (108 mg, 0.17 mmol). The reaction mixture was deoxygenated by purging with nitrogen for 10 minutes and then Pd2 dba3 (159 mg, 0.17 mmol) was added. The reaction was again deoxygenated for 5 minutes by purging with nitrogen. The reaction flask was sealed, and the mixture was heated at 100° C. for 16 h. The reaction mixture was then cooled, diluted with water (30 ml) and EtOAc (60 mL), and the organic layer was separated. The organic layer was washed with water (2×10 mL), followed by saturated brine (2×30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column (30% EtOAc/petroleum ether) to yield 6-chloro-4-(cyclobutylmethoxy)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine. MS ES/APCI calc'd. for C29H37ClN4O2 [M+H]+ 509. found 509.

Workup

  1. customThe reaction mixture was deoxygenated
  2. customby purging with nitrogen for 10 minutes
  3. customThe reaction was again deoxygenated for 5 minutes
  4. customby purging with nitrogen
  5. customThe reaction flask was sealed
  6. temperatureThe reaction mixture was then cooled
  7. additiondiluted with water (30 ml) and EtOAc (60 mL)
  8. customthe organic layer was separated
  9. washThe organic layer was washed with water (2×10 mL)
  10. dry with materialThe organic layer was dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified on a silica gel column (30% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-0a6c1d3559a44854b368e23d49dab3a6
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

Loading…