Methanol → HCID 3666186, compound

HRID 1465679Notes

Reaction equation

HRID 1465679 reaction equation
Br[C:2]1[C:15]2=[N:16][O:17][C:13]3=[C:14]2[C:5]([C:6](=[O:18])[C:7]2[C:12]3=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:4]([NH:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=2)[CH:3]=1.[CH:29]1([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.CC(OC)(C)C.CO>CS(C)=O>[CH:29]1([N:35]2[CH2:40][CH2:39][N:38]([C:2]3[C:15]4=[N:16][O:17][C:13]5=[C:14]4[C:5]([C:6](=[O:18])[C:7]4[C:12]5=[CH:11][CH:10]=[CH:9][CH:8]=4)=[C:4]([NH:19][C:20]4[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=4)[CH:3]=3)[CH2:37][CH2:36]2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 887MethanolHCID 15413tert-Butyl methyl etherHCID 872981-CyclohexylpiperazineHCID 90410908HCID 90410908, compound

Product 1

HCID 3666186HCID 3666186, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
65 °C

Procedure

About 70 g of 4-((3-bromo-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoic acid was dissolved in 950 mL of DMSO. About 50 mL of TEA and 50 g of 1-cyclohexyl piperazine were added to the reaction. Temperature was raised to 60-70° C. After 2-3 hours, slowly added 500 mL of MTBE and MeOH (10:1) solution and adjusted the temperature to 40-50° C. The solid was centrifuged and washed by 100 mL of MTBE and MeOH solution and followed by 100 mL of MeOH. Solid was dried under reduced pressure at 25-30° C. for 12-24 hours to obtain the 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoic acid at about 98% purity and about 91% yield.

Workup

  1. customto 40-50° C
  2. washwashed by 100 mL of MTBE and MeOH solution
  3. customSolid was dried under reduced pressure at 25-30° C. for 12-24 hours

Sources & evidence

ORD record
ord-90ddf2c800a949ada8b3c97cc1ff27f5
Source dataset
uspto-grants-2015_04
Patent number
US08999992B2

Reaction notes

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