3-Aminopyridine → 2-(2-(2-(5-Methyl-2-(pyridin-3-ylamino)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1779067Notes

Reaction equation

HRID 1779067 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([NH2:19])=[O:18])[C:5]([CH3:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:20][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([NH2:19])=[O:18])=[N:7][C:2]([NH:21][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867126242-(2-(2-Chloro-5-methylpyrimidin-4-ylethyl)phenyl)acetamide

Product 1

HCID 730554482-(2-(2-(5-Methyl-2-(pyridin-3-ylamino)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 10.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamide (K6) (0.050 g, 0.17 mmol), 3-aminopyridine (0.019 g, 0.21 mmol), Pd(OAc)2 (0.8 mg, 0.003 mmol), Cs2CO3 (0.169 g, 0.518 mmol) and Xantphos (4 mg, 0.007 mmol) in 1,4-dioxane (1 mL) was heated under microwave irradiation at 150° C. for 10 minutes. Water (30 mL) was added and the resulting suspension was sonicated for 1 minute. The precipitate was collected by filtration then adsorbed onto silica gel and purified by silica gel column chromatography (CombiFlash Rf, 12 g SiO2 cartridge, 0-10% MeOH in DCM) to give the title compound 24 as a light pink solid (6 mg, 10%); 1H NMR (300 MHz, d4-MeOH) δ 8.87 (s, 1H), 8.26 (d, J=7.4 Hz, 1H), 8.16 (s, 1H), 8.10 (s, 1H), 7.34 (dd, J=8.1, 4.6 Hz, 1H), 7.23-7.27 (m, 1H), 7.16-7.20 (m, 3H), 3.65 (s, 2H), 3.12-3.17 (m, 2H), 2.97-3.02 (m, 2H), 2.12 (s, 3H). LCMS-B: rt 4.649 min; m/z 348 [M+H]+.

Workup

  1. customthe resulting suspension was sonicated for 1 minute
  2. filtrationThe precipitate was collected by filtration
  3. custompurified by silica gel column chromatography (CombiFlash Rf, 12 g SiO2 cartridge, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-4cb444be143c449bbe2ad0d23244aba5
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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