Methanol → 2-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylic acid

HRID 1896572Notes

Reaction equation

HRID 1896572 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([N:13]1[CH2:18][CH2:17][O:16][C:15]2[CH:19]=[CH:20][C:21]([C:23]3[S:24][C:25]([N:33]([CH3:43])[CH2:34][CH2:35][O:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[C:26]([C:28]([O:30]CC)=[O:29])[N:27]=3)=[CH:22][C:14]1=2)=[O:12].[OH-].[K+].CO>O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([N:13]1[CH2:18][CH2:17][O:16][C:15]2[CH:19]=[CH:20][C:21]([C:23]3[S:24][C:25]([N:33]([CH3:43])[CH2:34][CH2:35][O:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[C:26]([C:28]([OH:30])=[O:29])[N:27]=3)=[CH:22][C:14]1=2)=[O:12]

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 59418665ethyl 2-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylate

Product 1

HCID 468407892-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylic acidYield 8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

The title compound 2-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylic acid (20) was prepared by the following procedure: To ethyl 2-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylate (20C) (0.210 g, 0.34 mmol) and KOH (0.1 g, 1.8 mmol) was added MeOH (2 mL) and water (5 mL). The reaction mixture was allowed to heat to 55° C. and stirred 24 hours. The reaction was monitored by LCMS. To the reaction mixture was added (0.1 g, 1.8 mmol). The reaction mixture was allowed to heat to 55° C. and stirred for 24 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure. To the crude residue was added EtOAc and water. The layers were separated and extracted with EtOAc and the combined organic extracts were washed sequentially with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by reverse phase HPLC to provide 0.015 g (8%) of the desired product 2-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylic acid (20): LC/MS (APCI): m/z 588.1 (M+H).

Workup

  1. customThe title compound 2-(4-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-(methyl(2-phenoxyethyl)amino)thiazole-4-carboxylic acid (20) was prepared by the following procedure
  2. additionTo the reaction mixture was added (0.1 g, 1.8 mmol)
  3. temperatureto heat to 55° C.
  4. stirringstirred for 24 hours
  5. temperatureThe reaction mixture was cooled to rt
  6. concentrationconcentrated under reduced pressure
  7. additionTo the crude residue was added EtOAc and water
  8. customThe layers were separated
  9. extractionextracted with EtOAc
  10. washthe combined organic extracts were washed sequentially with water, brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe crude residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-62bb903e2cf540a6a54147cf734def8e
Source dataset
uspto-grants-2013_08
Patent number
US08518970B2

Reaction notes

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