4-Methylmorpholine → N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-ethyl-2-methylamino-nicotinamide

HRID 2244377Notes

Reaction equation

C(O[C:4](=[O:15])[C:5]1[CH:10]=[C:9]([CH2:11][CH3:12])[CH:8]=[N:7][C:6]=1[NH:13][CH3:14])C.[OH-].[K+].[C:18]([C:22]1[CH:39]=[CH:38][C:25]([CH2:26][NH:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=2)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>C1COCC1>[C:18]([C:22]1[CH:39]=[CH:38][C:25]([CH2:26][N:27]([CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=2)[C:4](=[O:15])[C:5]2[CH:10]=[C:9]([CH2:11][CH3:12])[CH:8]=[N:7][C:6]=2[NH:13][CH3:14])=[CH:24][CH:23]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 5-ethyl-2-methylamino-nicotinic acid ethyl ester (40 mg, 0.19 mmol), 2 M aq. potassium hydroxide solution (0.19 mL, 0.38 mmol) and THF was heated at 60° C. for 16 h, then evaporated to dryness. The residue was taken up in DMF (3.2 mL) and treated with (4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amine (71 mg, 0.21 mmol), HBTU (109 mg, 0.29 mmol), and 4-methylmorpholine (58 mg, 0.57 mmol). The homogeneous solution was stirred at RT for 16 h, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2, heptane-ethyl acetate gradient) produced the title compound (77 mg, 80%). Light yellow oil, MS (ISP) 498.4 (M+H)+.

Workup

customevaporated to dryness
custompartitioned between water and ethyl acetate
washThe organic layer was washed with brine
dry with materialdried (MgSO4)
customevaporated

Sources & evidence

ORD record: ord-c8b5fa0b603b4a03af33ace46e8ca29d
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678818B2

Reaction notes

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