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

HRID 1852886Notes

Reaction equation

HRID 1852886 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-a300dfd634e849449aec623132b7dc32
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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