Cesium carbonate → 2-Methyl-4-pyrrolidin-1-yl-quinoline-7-carboxylic acid (4-cyano-phenyl)-amide

HRID 1374754Notes

Reaction equation

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

Participants

Conditions

Temperature: 50 °C

Procedure

A suspension of 2-methyl-4-pyrrolidin-1-yl-quinoline-7-carboxylic acid amide (50 mg, 0.20 mmol), 4-iodobenzonitrile (45 mg, 0.20 mmol), xantphos (6.8 mg, 12 μmol), cesium carbonate (89 mg, 0.27 mmol), and palladium(II) acetate (1.8 mg, 8 μmol) in 1,4-dioxane (0.5 mL) was stirred under argon at 50° C. for 22 h, then the reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and dichloromethane. The organic layer was separated, washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2, dichloromethane/methanol 19:1) afforded the title compound (18 mg, 26%). Light yellow solid, ISP-MS: m/e=357.3 ([M+H]+).

Workup

customthe reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and dichloromethane
customThe organic layer was separated
washwashed with brine
dry with materialdried (MgSO4)
customevaporated

Sources & evidence

ORD record: ord-98a1bcbf14fd45e0bf11c3eb7f7c0861
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07166589B2

Reaction notes

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