Trifluoroacetic acid → 10-(8-Aza-bicyclo[3.2.1]oct-3-yl)-6-methoxy-10H-phenoxazine-3-carboxylic acid diethylamide

HRID 2117040Notes

Reaction equation

HRID 2117040 reaction equation
[C:1](O)(C(F)(F)F)=[O:2].[CH2:8]([N:10]([CH2:36][CH3:37])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:27]3[CH2:33][CH:32]4[N:34](C)[CH:29]([CH2:30][CH2:31]4)[CH2:28]3)[C:18]3[C:23]([O:24][C:25]=2[CH:26]=1)=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:12])[CH3:9].ClC(OC(Cl)C)=O>C(Cl)Cl>[CH2:8]([N:10]([CH2:36][CH3:37])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:27]3[CH2:33][CH:32]4[NH:34][CH:29]([CH2:30][CH2:31]4)[CH2:28]3)[C:18]3[C:23]([O:24][C:25]=2[CH:26]=1)=[C:22]([O:2][CH3:1])[CH:21]=[CH:20][CH:19]=3)=[O:12])[CH3:9]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 5213051-Chloroethyl chloroformateHCID 1169711110-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamide

Product 1

HCID 1158256210-(8-Aza-bicyclo[3.2.1]oct-3-yl)-6-methoxy-10H-phenoxazine-3-carboxylic acid diethylamideYield 44.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the TFA salt of 10-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamide, 4e (110 mg, 0.25 mmol) in methylene chloride (10 mL) was added 1-chloroethyl chloroformate (0.58 mL, 0.75 mmol). The mixture was heated to reflux for 2 h. The mixture was evaporated, dissolved in methanol (5 mL), and heated for 2 h at reflux. Water was added, and the solution was extracted with methylene chloride. The organic phase was separated, evaporated, and purified via reverse phase HPLC to yield 69 mg (44.8%) of title compound 10-(8-aza-bicyclo[3.2.1]oct-3-yl)-6-methoxy-10H-phenoxazine-3-carboxylic acid diethylamide, 5e, as a TFA salt. MS m/z=422 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 h
  3. customThe mixture was evaporated
  4. dissolutiondissolved in methanol (5 mL)
  5. temperatureheated for 2 h
  6. temperatureat reflux
  7. additionWater was added
  8. extractionthe solution was extracted with methylene chloride
  9. customThe organic phase was separated
  10. customevaporated
  11. custompurified via reverse phase HPLC

Sources & evidence

ORD record
ord-264dbf2a7ae2487a83bf4e362b6ce55f
Source dataset
uspto-grants-2008_10
Patent number
US07439239B2

Reaction notes

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