Cesium carbonate → tert-Butyl 8-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

HRID 1021756Notes

Reaction equation

HRID 1021756 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH:13]3[CH2:14][CH2:15][CH:9]2[CH2:10][N:11]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]3)=[CH:4][CH:3]=1.Br[C:24]1[C:25](=[O:32])[N:26]([CH3:31])[CH:27]=[C:28]([Br:30])[CH:29]=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].O1CCOCC1>[Br:30][C:28]1[CH:29]=[C:24]([NH:1][C:2]2[N:7]=[CH:6][C:5]([N:8]3[CH:9]4[CH2:15][CH2:14][CH:13]3[CH2:12][N:11]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10]4)=[CH:4][CH:3]=2)[C:25](=[O:32])[N:26]([CH3:31])[CH:27]=1

Participants

7

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 66742564Tert-butyl 8-(6-aminopyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

Product 1

HCID 86684267tert-Butyl 8-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylateYield 43%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A sealed tube equipped with a magnetic stirrer was charged with 152b (1.3 g, 4.3 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.2 g, 4.3 mmol), tris(dibenzylideneacetone)dipalladium(0) (394 mg, 0.43 mmol), XantPhos (497 mg, 0.86 mmol), Cs2CO3 (2.8 g, 8.6 mmol), and 1,4-dioxane (15 mL). After three cycles of vacuum/argon flush, the mixture was stirred at 120° C. for 2 h. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 152c as a yellow solid (900 mg, 43%). MS-ESI: [M+H]+ 490.3.

Workup

  1. customA sealed tube equipped with a magnetic stirrer
  2. customAfter three cycles of vacuum/argon flush
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe resulting residue was purified by silica-gel column chromatography
  5. washeluting with 50:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-b8e55ee925524562b9d099918d44214f
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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