Triethylamine → 7-Chloro-4-[[4-[[[1-(phenylmethyl)-4piperidinyl]amino]carbonyl]phenyl]amino]-3-quinolinecarboxylic acid ethyl ester

HRID 1755942Notes

Reaction equation

Cl.[CH2:2]([O:4][C:5]([C:7]1[CH:8]=[N:9][C:10]2[C:15]([C:16]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([C:24](O)=[O:25])=[CH:20][CH:19]=1)=[CH:14][CH:13]=[C:12]([Cl:27])[CH:11]=2)=[O:6])[CH3:3].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:58][CH:59]1[CH2:64][CH2:63][N:62]([CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[CH2:61][CH2:60]1>CN(C=O)C.C(Cl)Cl>[CH2:2]([O:4][C:5]([C:7]1[CH:8]=[N:9][C:10]2[C:15]([C:16]=1[NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([NH:58][CH:59]3[CH2:64][CH2:63][N:62]([CH2:65][C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)[CH2:61][CH2:60]3)=[O:25])=[CH:22][CH:23]=1)=[CH:14][CH:13]=[C:12]([Cl:27])[CH:11]=2)=[O:6])[CH3:3]

Participants

Conditions

Temperature: 85 °C

Procedure

4-[(4-Carboxyphenyl)amino]-7-chloro-3-quinolinecarboxylic acid ethyl ester hydrochloride (40.0 g, 98.2 mmol), 1-hydroxybenzotriazole hydrate (16.2 g, 120 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (24.5 g, 128 mmol) were stirred in 560 ml of DMF and treated with triethylamine (39.8 g, 54.8 ml, 393 mmol) followed by 4-amino-1-benzylpiperidine (20.6 g, 22.0 ml, 108 mmol). The reaction mixture was heated at 85° C. for 3.5 h, poured into 1.3 L of CH2Cl2 and washed with 3×500 ml of water. The organic phase was dried over Na2SO4 and concentrated in vacuo for 3 days. This afforded 51.7 g (95.2 mmol, 97% yield) of 7 -chloro-4-[[4 -[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]phenyl]amino]-3-quinolinecarboxylic acid ethyl ester as a yellow solid.

Workup

washwashed with 3×500 ml of water
dry with materialThe organic phase was dried over Na2SO4
concentrationconcentrated in vacuo for 3 days

Sources & evidence

ORD record: ord-104c0e4a15804cf981bb1199eb28093c
Source dataset: uspto-grants-1995_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05438064

Reaction notes

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