Ethyl Acetate → N-{2-(5-Chloro-8-hydroxyquinolin-7-yl)-1-[3-(5-methyl-2-thienyl)phenyl]ethyl}-2-phenoxyacetamide

HRID 551131Notes

Reaction equation

HRID 551131 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH2:20][CH:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]3[S:30][C:31]([CH3:34])=[CH:32][CH:33]=3)[CH:24]=2)[NH2:22])=[CH:11][C:12]([Cl:19])=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:35]([CH2:42][C:43](Cl)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(OCC)(=O)C.[Si](I)(C)(C)C>ClCCCl>[CH2:1]([O:8][C:9]1[C:10]([CH2:20][CH:21]([NH:22][C:43](=[O:44])[CH2:42][O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]3[S:30][C:31]([CH3:34])=[CH:32][CH:33]=3)[CH:24]=2)=[CH:11][C:12]([Cl:19])=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:19][C:12]1[CH:11]=[C:10]([CH2:20][CH:21]([NH:22][C:43](=[O:44])[CH2:42][O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]3[S:30][C:31]([CH3:34])=[CH:32][CH:33]=3)[CH:24]=2)[C:9]([OH:8])=[C:18]2[C:13]=1[CH:14]=[CH:15][CH:16]=[N:17]2

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 69703Phenoxyacetyl chlorideHCID 85247Trimethylsilyl iodideHCID 671714492-[8-(Benzyloxy)-5-chloroquinolin-7-yl]-1-[3-(5-methyl-2-thienyl)phenyl]ethanamine

Product 2

HCID 59829667N-{2-(5-Chloro-8-hydroxyquinolin-7-yl)-1-[3-(5-methyl-2-thienyl)phenyl]ethyl}-2-phenoxyacetamideYield 84.7%HCID 67172341N-{2-(8-Benzyloxy-5-chloro-quinolin-7-yl)-1-[3-(5-methyl-thiophen-2-yl)-phenyl]-ethyl}-2-phenoxy-acetamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

N-{2-(8-Benzyloxy-5-chloro-quinolin-7-yl)-1-[3-(5-methyl-thiophen-2-yl)-phenyl]-ethyl}-2-phenoxy-acetamide was prepared from 2-[8-(benzyloxy)-5-chloroquinolin-7-yl]-1-[3-(5-methyl-2-thienyl)phenyl]ethanamine (0.404 mmol) and phenoxyacetyl chloride (0.445 mmol, 1.1 eq.) according to the general procedure described above (Alternate General Procedure for N-Acylations). Ethyl acetate was used in place of dichloromethane in the workup procedure. Crude product obtained was a white foam that was subjected to the conditions described above for TMSI-mediated O-benzyl deprotection. After stirring 16 h at 70° C., 1,2-dichloroethane (5.6 mL) was added and the reaction was stirred 3 h at 70° C. after which time the reaction was quenched and worked up as described above. Crude product obtained was a brown oil that was purified by column chromatography using 10% acetone/dichloromethane followed by concentration and washing the solid with diethyl ether (3×5 mL) to give the title compound as a tan solid (0.171 mmol, 42% for 2 steps). MS (ESI) m/z 529.4.

Workup

  1. customCrude product obtained
  2. stirringthe reaction was stirred 3 h at 70° C. after which time the reaction
  3. customwas quenched
  4. customCrude product obtained
  5. customwas purified by column chromatography
  6. concentrationfollowed by concentration
  7. washwashing the solid with diethyl ether (3×5 mL)

Sources & evidence

ORD record
ord-9b50c4129e184e1bba08ee53664df763
Source dataset
uspto-grants-2011_05
Patent number
US07947712B2

Reaction notes

Loading…