3-Aminopyridine → 2-(2-(5-Chloro-2-(pyridin-3-ylamino)pyrimidin-4-ylethyl)phenyl)propanamide

HRID 592420Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH:23]([CH3:27])[C:24]([NH2:26])=[O:25])=[N:4][C:5]([NH:8][C:9]2[CH:10]=N[N:12]([CH3:14])[CH:13]=2)=[N:6][CH:7]=1.N[C:29]1C=NC=CC=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.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[C:3]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH:23]([CH3:27])[C:24]([NH2:26])=[O:25])=[N:4][C:5]([NH:8][C:9]2[CH:13]=[N:12][CH:14]=[CH:29][CH:10]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(2-(2-(5-chloro-2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-ylethyl)phenyl)propanamide A30 (0.080 g, 0.25 mmol), 3-aminopyridine (0.046 g, 0.49 mmol), Xantphos (0.0057 g, 0.010 mmol) and Cs2CO3 (0.24 g, 0.74 mmol) in 1,4-dioxane (3 mL) was bubbled with nitrogen for 10 minutes. Palladium (II) acetate (0.0011 g, 0.0049 mmol) was added and the mixture was heated at 120° C. under microwave irradiation for 28 minutes. The volatiles were removed in vacuo and the residue was purified by silica gel column chromatography (Combiflash Rf, 0-10% MeOH in DCM) to give the title compound 39 as a pink solid (0.029 g, 31%). LCMS-C: rt 4.30 min; m/z 382 [M+H]+.

Workup

customwas bubbled with nitrogen for 10 minutes
customThe volatiles were removed in vacuo
customthe residue was purified by silica gel column chromatography (Combiflash Rf, 0-10% MeOH in DCM)

Sources & evidence

ORD record: ord-9be0dae21c004756a55ea18718714018
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

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