2-Methoxy-6-(tributylstannyl)pyridine → HCID 178489657, compound

HRID 81281Notes

Reaction equation

HRID 81281 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=2)[C:5]2[N:15]([CH2:30][C@H:31]3[CH2:36][CH2:35][C@H:34]([CH3:37])[CH2:33][CH2:32]3)[C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][C@H:19]3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:17][C:4]=2[CH:3]=1.[CH3:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([Sn](CCCC)(CCCC)CCCC)[N:41]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:14][C:12]1[CH:13]=[C:8]([C:6]2[C:5]3[N:15]([CH2:30][C@H:31]4[CH2:36][CH2:35][C@H:34]([CH3:37])[CH2:33][CH2:32]4)[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][C@H:19]4[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[N:17][C:4]=3[CH:3]=[C:2]([C:42]3[CH:43]=[CH:44][CH:45]=[C:40]([O:39][CH3:38])[N:41]=3)[N:7]=2)[CH:9]=[N:10][CH:11]=1

Participants

5

Reactant 2

HCID 105248912-Methoxy-6-(tributylstannyl)pyridineHCID 178461217HCID 178461217, compound

Product 1

HCID 178489657HCID 178489657, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (Example 2.1, Step 3; 130 mg, 0.242 mmol), 2-methoxy-6-(tri-n-butylstannyl)pyridine (122 mg, 0.308 mmol), and Pd(PPh3)4 (28.0 mg, 0.0242 mmol) in DMF (2.9 mL) was degassed and heated at 100° C. for 16 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with water (10 mL). The reaction mixture was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with saturated aqueous KF solution (10 mL), water (2×10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column (0 to 50% EtOAc/hexanes) afforded 4-(5-chloropyridin-3-yl)-6-(6-methoxypyridin-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine. MS ES calc'd. for C35H37ClN6O2 [M+H]+ 609. found 609.

Workup

  1. customwas degassed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with water (10 mL)
  4. extractionThe reaction mixture was extracted with ethyl acetate (3×10 mL)
  5. washThe combined organic layers were washed with saturated aqueous KF solution (10 mL), water (2×10 mL) and brine (10 mL)
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue on a silica gel column (0 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bc4b6a3613f644d2857b977947755de5
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

Loading…