1,4-Dioxane → HCID 178428701, compound

HRID 81247Notes

Reaction equation

HRID 81247 reaction equation
Br[C:2]1[C:3]2[N:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][C@@H:22]4[CH2:26][CH2:27][CH2:28][C@@H:21]34)[N:17]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]3)[C:4]=2[C:5]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([Cl:16])[CH:15]=2)=[N:6][C:7]=1[C:8]#[N:9].[CH3:37]B1OB(C)OB(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:16][C:14]1[CH:15]=[C:10]([C:5]2[C:4]3[N:17]([CH2:29][C@H:30]4[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]4)[C:18]([N:20]4[CH2:25][CH2:24][O:23][C@@H:22]5[CH2:26][CH2:27][CH2:28][C@@H:21]45)=[N:19][C:3]=3[C:2]([CH3:37])=[C:7]([C:8]#[N:9])[N:6]=2)[CH:11]=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 574072TrimethylboroxineHCID 178461228HCID 178461228, compound

Product 1

HCID 178428701HCID 178428701, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 7-bromo-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (40 mg, 0.07 mmol), trimethylboroxine (10 μL, 0.07 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (5 mg, 0.007 mmol), K3PO4 (37.2 mg, 0.175 mmol), dioxane (0.8 mL), and water (0.2 mL). The mixture was sparged with N2, the vial was sealed, and the reaction was heated at 100° C. for 90 minutes. The reaction was then cooled to room temperature, diluted with EtOAc (40 mL), and washed with water (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes to afford 4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-7-methyl-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C28H33ClN6O [M+H]+=505. found=505.

Workup

  1. customThe mixture was sparged with N2
  2. customthe vial was sealed
  3. temperatureThe reaction was then cooled to room temperature
  4. additiondiluted with EtOAc (40 mL)
  5. washwashed with water (10 mL) and brine (10 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-7ddac62605464255a8448ff2c1612a64
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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