Benzeneethanamine, alpha-methyl-, phosphate (1:1) → 1-(4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone

HRID 473692Notes

Reaction equation

HRID 473692 reaction equation
Cl.Br[C:3]1[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)=[CH:12][CH:11]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.CC1(C)C(C)(C)OB([C:31]2[CH2:36][CH2:35][N:34]([C:37](=[O:39])[CH3:38])[CH2:33][CH:32]=2)O1.C([O-])(=O)C.[K+].CC(N)CC1C=CC=CC=1.OP(O)(O)=O>O.C(#N)C>[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[NH:16][C:13]1[CH:14]=[CH:15][C:10]([O:9][C:4]2[C:3]([C:31]3[CH2:36][CH2:35][N:34]([C:37](=[O:39])[CH3:38])[CH2:33][CH:32]=3)=[CH:8][CH:7]=[CH:6][N:5]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 517044Potassium AcetateHCID 567376781-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl)ethan-1-oneHCID 67425919N-(4-(3-Bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride

Product 1

HCID 593742621-(4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride (0.388 g, 1.14 mmol), 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone (0.30 g, 1.2 mmol), potassium acetate (0.60 g, 10.2 mmol), and Amphos (0.063 g, 0.090 mmol) were taken up in 12 mL of 3:1 mixture of acetonitrile and water. The mixture was purged with nitrogen and heated to 90° C. for 15 h. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organics was washed with 30 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (10 to 100% EtOAc/hexane, then 5% MeOH in EtOAc) afforded 1-(4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone as tan solid. MS (ESI, pos. ion) m/z: 387.0 (M+1). IC50 (uM) 0.002698.

Workup

  1. customThe mixture was purged with nitrogen
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organics was washed with 30 mL of brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-3f5d86f5418c4a48b54ed58a4f56bb5b
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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