Cesium carbonate → 2-(2-(2-(5-Chloro-2-(pyridazin-4-ylamino)pyrimidin-4-yl)ethyl)phenyl)propanamide

HRID 592423Notes

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[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])[C:5]([Cl:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][N:26]=[N:25][CH:24]=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:21][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])=[N:7][C:2]([NH:22][C:23]2[CH:28]=[CH:27][N:26]=[N:25][CH:24]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)propanamide (A30) 2-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)propanamide (A30 (0.080 g, 0.25 mmol), 4-aminopyridazine (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, 0-15% MeOH in DCM) to give the title compound 42 as a light yellow solid (0.020 g, 21%). LCMS-C: rt 4.23 min; m/z 383 [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, 0-15% MeOH in DCM)

Sources & evidence

ORD record: ord-08746a9aa87e48438907ea895daca77f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

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