Diisopropylethylamine → Methyl 4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)amino]carbonyl}benzoate

HRID 1874773Notes

Reaction equation

HRID 1874773 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:19])=[C:7]([O:9][C:10]2[CH:11]=[C:12]([CH:15]=[C:16]([Cl:18])[CH:17]=2)[C:13]#[N:14])[CH:8]=1.Cl[C:21]([C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1)=[O:22].CCN(C(C)C)C(C)C>>[Cl:19][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:21]([C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)=[O:22])=[CH:8][C:7]=1[O:9][C:10]1[CH:11]=[C:12]([C:13]#[N:14])[CH:15]=[C:16]([Cl:18])[CH:17]=1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 81850Methyl 4-(chlorocarbonyl)benzoateHCID 594514053-{[5-(Aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 59451388Methyl 4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)amino]carbonyl}benzoateYield 45.2%

Procedure

Methyl 4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)amino]carbonyl}benzoate was prepared in a similar manner as described herein from 3-{[5-(aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile (0.05 g, 0.17 mmol), methyl 4-(chlorocarbonyl)benzoate (0.05 g, 0.25 mmol) and DIPEA (0.05 mL, 0.25 mmol). The crude material was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA). The desired fractions were lyophilized, neutralized and extracted with EtOAc. The organic extracts were combined, dried over Na2SO4, filtered and evaporated to afford the title compound (0.035 g, 45%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 9.22 (s, 1H), 7.98-8.06 (m, 2H), 7.92-7.98 (m, 2H), 7.80 (s, 1H), 7.60 (d, 1H), 7.45 (s, 1H), 7.38 (t, 1H), 7.25 (s, 1H), 7.23 (d, 1H), 4.47 (d, 2H), 3.86 (s, 3H). MS: m/z 455.0 (M+1).

Workup

  1. customMethyl 4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)amino]carbonyl}benzoate was prepared in a similar manner
  2. customThe crude material was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA)
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-b46761c8d8dc41d69946e413b080ea9c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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