3-Aminopyridine → 1-(2-(2-(5-Chloro-2-(pyridin-3-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592378Notes

Reaction equation

HRID 592378 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[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=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>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:22][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)=[N:7][C:2]([NH:29][C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=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 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 732964291-(2-(2-(5-Chloro-2-(pyridin-3-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 25%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (A14) (100 mg, 297 μmol), Cs2CO3 (291 mg, 892 μmol) and 3-aminopyridine (56.0 mg, 595 μmol) in 1,4-dioxane (2.0 mL) was sonicated for 10 minutes. To this Xantphos (6.88 mg, 11.9 μmol) and Pd(OAc)2 (1.33 mg, 5.95 μmol) were added and the resulting mixture heated under microwave irradiation for 20 minutes at 120° C. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-50% MeOH in EtOAc) to yield a tan solid. This was sonicated for 10 min in water (50 mL) and filtered to give the title compound 6 as a green solid (29 mg, 25%); 1H NMR (400 MHz, CDCl3) δ 8.80-8.74 (d, J=2.5 Hz, 1H), 8.33 (s, 1H), 8.32-8.28 (dd, J=4.7, 1.3 Hz, 1H), 8.18-8.12 (m, 1H), 7.47-7.42 (d, J=7.2 Hz, 1H), 7.38-7.34 (m, 3H), 7.34-7.25 (m, 2H), 5.56 (s, 1H), 5.37 (s, 1H), 3.34-3.14 (m, 4H), 1.78 (s, 2H), 1.16 (s, 2H). LCMS-A: rt 4.502 min; m/z 394 [M+H]+.

Workup

  1. customwas sonicated for 10 minutes
  2. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-50% MeOH in EtOAc)
  3. customto yield a tan solid
  4. filtrationfiltered

Sources & evidence

ORD record
ord-4aeb4f3a1782440694e1adbef1ed604c
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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