Phenol → Phenyl 1-(7-chloroquinazolin-4-yl)-5-methoxy-2-methylindol-3-ylacetate

HRID 597055Notes

Reaction equation

HRID 597055 reaction equation
[C:1]1(O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([N:19]3[C:27]4[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=4)[C:21]([CH2:30][C:31]([OH:33])=[O:32])=[C:20]3[CH3:34])=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1.C1(N=C=NC2CCCCC2)CCCCC1>COCCOC>[Cl:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([N:19]3[C:27]4[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=4)[C:21]([CH2:30][C:31]([O:33][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[O:32])=[C:20]3[CH3:34])=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 10868DicyclohexylcarbodiimideHCID 101940031-(7-Chloroquinazolin-4-yl)-5-methoxy-2-methylindol-3-ylacetic acid

Product 1

HCID 21449391Phenyl 1-(7-chloroquinazolin-4-yl)-5-methoxy-2-methylindol-3-ylacetate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of phenol (0.27g.) and anhydrous 1-(7-chloroquinazolin-4-yl)-5-methoxy-2-methylindol-3-ylacetic acid (1.0g.) in dry 1,2-dimethoxyethane (20ml.; dried over sodium aluminosilicate powder) was stirred at room temperature and treated with dicyclohexylcarbodiimide (0.75g.). The mixture became opaque, and was stirred overnight at room temperature and then filtered. Evaporation of the filtrate gave a dark yellow syrup, which was purified by chromatography on silica gel (175g.), using an increasing gradient of ether in petroleum ether (b.p. 40°-60° C.) (polarity increased by incremental addition of 10% v/v ether). The major product, phenyl 1-(7-chloroquinazolin-4-yl)-5-methoxy-2-methylindol-3-ylacetate, was obtained as a yellow glass (NMR: OCH3 at 6.20τ; pure by TLC: systems A and D), from the petrol rich fractions. A second product, 1-[1-(7-chloroquinazolin-4-yl)-5-methoxy-2-methylindol-3-ylacetyl]-1,3-dicyclohexylurea, was obtained as a pale yellow solid of m.p. 105°-107° C. NMR: OCH3 at 6.23τ; pure by TLC: system C).

Workup

  1. stirringwas stirred overnight at room temperature
  2. filtrationfiltered
  3. customEvaporation of the filtrate
  4. customgave a dark yellow syrup, which
  5. customwas purified by chromatography on silica gel (175g.)
  6. temperatureincreased by incremental addition of 10% v/v ether)

Sources & evidence

ORD record
ord-9a5a518ee15844219e8a22a3fb2eefe0
Source dataset
uspto-grants-1977_03
Patent number
US04012513

Reaction notes

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