4-Fluorobenzylamine → 7-Bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide

HRID 2093724Notes

Reaction equation

C(O[C:4]([C:6]1[C:7]([CH:18]2[CH2:20][CH2:19]2)=[N:8][C:9]2[C:14]([C:15]=1[CH3:16])=[CH:13][CH:12]=[C:11]([Br:17])[CH:10]=2)=[O:5])C.C[Al](C)C.[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1.CCOC(C)=O.C1CCCCC1>C1(C)C=CC=CC=1>[Br:17][C:11]1[CH:10]=[C:9]2[C:14]([C:15]([CH3:16])=[C:6]([C:4]([NH:31][CH2:30][C:29]3[CH:32]=[CH:33][C:26]([F:25])=[CH:27][CH:28]=3)=[O:5])[C:7]([CH:18]3[CH2:19][CH2:20]3)=[N:8]2)=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a stirred solution of 1.0 g (2.99 mmol) 7-bromo-2-cyclopropyl-4-methylquinoline-3-carboxylic acid ethyl ester in toluene (10 ml) were added 10.5 ml (2M solution in toluene, 20.9 mmol) Me3Al at RT followed by the addition of 3.74 g (29.9 mmol) 4-fluorobenzylamine. The reaction mixture was heated at 120° C. for 16 h. Then the reaction was quenched with water (15 ml) and extracted with EtOAc (3×30 ml). The combined organic layers were washed with 2N aq. HCl and brine, dried over MgSO4 and concentrated in vacuum. After CC (EtOAc/cyclohexane 1:2) of the residue, 900 mg (2.2 mmol, 73%) 7-Bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide (example 28) were obtained. MS: m/z 413.1 [M+H]+.

Workup

customThen the reaction was quenched with water (15 ml)
extractionextracted with EtOAc (3×30 ml)
washThe combined organic layers were washed with 2N aq. HCl and brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuum

Sources & evidence

ORD record: ord-993d7fc1c5b04994a7772756a0b843fd
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445512B2

Reaction notes

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