Sodium Carbonate → tert-butyl 4-(3-(4-aminophenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 473703Notes

Reaction equation

HRID 473703 reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.CC1(C)C(C)(C)OB([C:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH:25]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC.O>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:13][C:12]1[CH:14]=[CH:15][C:9]([O:8][C:3]2[C:2]([C:24]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH:25]=3)=[N:7][CH:6]=[CH:5][N:4]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 18180031Water 1,2-dimethoxyethaneHCID 201339744-(3-Chloropyrazin-2-yloxy)benzenamine

Product 1

HCID 59374116tert-butyl 4-(3-(4-aminophenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Into a sealed 150-mL flask were placed 4-(3-chloropyrazin-2-yloxy)aniline (2 g, 9 mmol) (see Step 1, Example 215), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (4.19 g, 13.5 mmol), trans-dichlorobis-(triphenylphosphine)palladium (II) (0.5 g, 0.72 mmol), sodium carbonate (4.78 g, 45.1 mmol) and 30 mL of 4:1 DME-water. After the mixture was degassed for 5 min, the reaction was stirred at 80° C. for 18 h. The cooled reaction was diluted with CH2Cl2 and washed with aqueous saturated NaHCO3 solution; the aqueous layer was back-extracted with CH2Cl2 (2×). The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (20% to 60% EtOAc/Hexanes) afforded tert-butyl 4-(3-(4-aminophenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate) as a cream solid. MS (ESI, pos. ion) m/z: 369.0 (M+1).

Workup

  1. customInto a sealed 150-mL flask were placed
  2. customAfter the mixture was degassed for 5 min
  3. customThe cooled reaction
  4. washwashed with aqueous saturated NaHCO3 solution
  5. extractionthe aqueous layer was back-extracted with CH2Cl2 (2×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-622429a4b3ba4b12ae9e5f076aad2b1b
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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