2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 6-[(Ethylcarbamoyl)amino]-N-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-(phenylamino)pyridine-3-carboxamide

HRID 2174252Notes

Reaction equation

[CH2:1]([NH:3][C:4](=[O:22])[NH:5][C:6]1[CH:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]([C:10]([NH2:12])=[O:11])=[CH:8][N:7]=1)[CH3:2].[O-]CCCC.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:64]1[CH:69]=[CH:68][N:67]([CH3:70])[C:66](=[O:71])[CH:65]=1>O1CCOCC1.CO>[CH2:1]([NH:3][C:4]([NH:5][C:6]1[N:7]=[CH:8][C:9]([C:10]([NH:12][C:64]2[CH:69]=[CH:68][N:67]([CH3:70])[C:66](=[O:71])[CH:65]=2)=[O:11])=[C:13]([NH:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:14]=1)=[O:22])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

Compound 61 (20 mg, 0.067 mmol) was suspended in dry dioxane (2 mL) with the sodium butoxide (13 mg, 0.13 mmol), dicyclohexyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane (6 mg, 0.01 mmol), 4-bromo-1-methyl-pyridin-2-one (25 mg, 0.13 mmol) and tris-(dibenzylidineacetone)dipalladium(0) (6 mg, 0.007 mmol). The mixture was placed under N2 and heated in a microwave for 1 h at 120° C. The mixture was left at RT over 2 days. The mixture was transferred to a flask with MeOH and the solvent removed. The residue was suspended in 10% MeOH/DCM and applied to a silica column, eluting with EtOAc/heptane, followed by MeOH/DCM gradient, to afford Compound 134 (6.8 mg). 1H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 9.70 (s, 1H), 9.14 (s, 1H), 8.54 (s, 1H), 7.88 (s, 1H), 7.62 (d, J=7.5 Hz, 1H), 7.47-7.35 (m, 2H), 7.34-7.21 (m, 3H), 7.21-7.11 (m, 1H), 6.87 (d, J=2.3 Hz, 1H), 6.58 (dd, J=7.5, 2.4 Hz, 1H), 3.37 (s, 3H), 3.19-3.09 (m, 2H), 1.06 (t, J=7.2 Hz, 3H), [M+H]+ m/z=407.13.

Workup

customthe solvent removed
washeluting with EtOAc/heptane

Sources & evidence

ORD record: ord-22dedbe417a84c049eb166959093ef25
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09060515B2

Reaction notes

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