Cesium carbonate → tert-Butyl 2-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 1918909Notes

Reaction equation

HRID 1918909 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][C:4]=2[N:3]=1.Br[C:20]1[C:21](=[O:28])[N:22]([CH3:27])[CH:23]=[C:24]([Br:26])[CH:25]=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+]>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].C(Cl)Cl.O1CCOCC1>[Br:26][C:24]1[CH:25]=[C:20]([NH:1][C:2]2[CH:11]=[CH:10][C:9]3[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][C:4]=3[N:3]=2)[C:21](=[O:28])[N:22]([CH3:27])[CH:23]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 58043778tert-Butyl 2-Amino-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Product 1

HCID 58044254tert-Butyl 2-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a round-bottomed flask equipped with a stirring bar, 158b (851 mg, 3.41 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.37 g, 5.12 mmol), Pd2(dba)3 (312.5 mg, 0.341 mmol), XantPhos (316 mg, 0.546 mmol), Cs2CO3 (3.67 g, 11.3 mmol) and dioxane (17 mL) were added. The reaction mixture was heated at 100° C. overnight. DCM (200 mL) was added to the resulting mixture was washed with water (30 mL×3). DCM (200 mL) was added and the resulting mixture was washed with water (30 mL×3), brine (30 mL×1), dried over MgSO4, filtered, and removed solvent in vacuo. DCM/ether (1:2, 5 mL) was added followed by sonication, the precipitation was filtered as 158c, green solids, 865 mg (58%).

Workup

  1. customTo a round-bottomed flask equipped with a stirring bar
  2. washwas washed with water (30 mL×3)
  3. additionDCM (200 mL) was added
  4. washthe resulting mixture was washed with water (30 mL×3), brine (30 mL×1)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customremoved solvent in vacuo
  8. additionDCM/ether (1:2, 5 mL) was added
  9. customfollowed by sonication
  10. customthe precipitation
  11. filtrationwas filtered as 158c, green solids, 865 mg (58%)

Sources & evidence

ORD record
ord-8908064acb4e44eb892f2b273633410c
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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