1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-bromo-N-{4-((7-chloroquinolin-4-yl)amino)cyclohexyl}-5-fluorobenzamide

HRID 2415624Notes

Reaction equation

HRID 2415624 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C@H:13]3[CH2:18][CH2:17][C@@H:16]([NH:19]C4C5C(=CC(Cl)=CC=5)N=CC=4)[CH2:15][CH2:14]3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[Br:31][C:32]1[CH:33]=[C:34]([CH:38]=[C:39]([F:41])[CH:40]=1)[C:35]([OH:37])=O.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>ClCCl>[Br:31][C:32]1[CH:33]=[C:34]([CH:38]=[C:39]([F:41])[CH:40]=1)[C:35]([NH:19][CH:16]1[CH2:15][CH2:14][CH:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=[CH:8][CH:7]=2)[CH2:18][CH2:17]1)=[O:37]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 757711-Hydroxybenzotriazole2×HCID 27733393-Bromo-5-fluorobenzoic acid2×HCID 178477879HCID 178477879, compound

Product 1

HCID 100506923-bromo-N-{4-((7-chloroquinolin-4-yl)amino)cyclohexyl}-5-fluorobenzamideYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 23A cis-N,N′-bis(7-chloroquinolin-4-yl)cyclohexane-1,4-diamine (500 mg, 3.6 mmol), 3-bromo-5-fluorobenzoic acid (600 mg, 5.4 mmol), 1-hydroxybenzotriazole (245 mg, 3.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide(348 mg, 3.6 mmol) in 30 mL dichloromethane was stirred for 3 hours. The reaction was incomplete. 3-bromo-5-fluorobenzoic acid (160 mg, 0.9 mmol), 1-hydroxybenzotriazole (61 mg, 0.9 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (87 mg, 0.9 mmol) was added and the solution was allowed to stir overnight. The solution was then washed with 1N NaOH, dried (Na2SO4), and concentrated. The residue was purified by flash chromatography (10% methanol in dichloromethane) to provide 700 mg of pure compound, an 81% yield. MS (ESI(+)Q1MS m/z 477 (M+2 H)+; 1H NMR (300 MHz, MeOH) δ ppm 8.36-8.42 (m, 3 H), 7.95 (t, 1 H), 7.69-7.79 (m, 3 H), 7.45 (dd, 1 H), 6.83 (d, 1 H), 6.54 (d, 1 H), 3.95 (m, 1 H), 3.68 (m, 1 H), 1.66-1.98 (m, 8 H).

Workup

  1. stirringto stir overnight
  2. washThe solution was then washed with 1N NaOH
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-5943b607e0cc4c4e93bc005d7173c960
Source dataset
uspto-grants-2004_11
Patent number
US06818772B2

Reaction notes

Loading…