Nitrogen → tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 473707Notes

Reaction equation

HRID 473707 reaction equation
N#N.Cl[C:4]1[C:5]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[CH:13][CH:12]=2)=[N:6][CH:7]=[CH:8][N:9]=1.C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB([C:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH:38]=2)O1>O.O1CCOCC1>[N:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[NH:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][C:5]2[C:4]([C:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH:38]=3)=[N:9][CH:8]=[CH:7][N:6]=2)=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 517044Potassium AcetateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 53485989N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amine

Product 1

HCID 59374036tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a N2 purged solution of N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amine (4.891 g, 16.37 mmol), potassium acetate (6.54 g, 66.6 mmol), dioxane:water (160 mL, 10:1), and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (6.03 g, 19.50 mmol) was added A-Phos (1.5 g, 2.118 mmol). The vial was capped and placed in a preheated oil bath (120° C.) and stirred for 1.5 hours. The solution was allowed to cool to room temperature and poured into water. The aqueous solution was extracted with EtOAc (3×70 mL). The combined organic layers were concentrated in vacuo and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (120 g), eluting with 0% to 50% EtOAc in hexane, to provide tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate as a yellow foam. MS (ESI, pos. ion) m/z: 446.1 (M+1). IC50 (uM) 0.01298.

Workup

  1. customThe vial was capped
  2. customplaced in a preheated oil bath
  3. temperatureto cool to room temperature
  4. extractionThe aqueous solution was extracted with EtOAc (3×70 mL)
  5. concentrationThe combined organic layers were concentrated in vacuo
  6. customchromatographed through a Redi-Sep® pre-packed silica gel column (120 g)
  7. washeluting with 0% to 50% EtOAc in hexane

Sources & evidence

ORD record
ord-a2397622cde64208bde32647c8fbade3
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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