Formic Acid → 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acid

HRID 595096Notes

Reaction equation

HRID 595096 reaction equation
[CH2:1]([N:3]([CH2:35][CH3:36])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:30]([C:31]([O:33]C)=[O:32])=[C:22]2[O:23][CH2:24][C:25]3[N:26]([CH:27]=[CH:28][CH:29]=3)[C:21]2=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.C(O)C.C1(C)C=CC=CC=1>[CH2:35]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:30]([C:31]([OH:33])=[O:32])=[C:22]2[O:23][CH2:24][C:25]3[N:26]([CH:27]=[CH:28][CH:29]=3)[C:21]2=[CH:20][CH:19]=1)(=[O:15])=[O:16])[CH3:36]

Participants

8

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86712813methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate2×

Product 1

HCID 714724957-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acidYield 16.7%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (Intermediate 15, 0.074 g) and lithium hydroxide monohydrate (0.060 g) in dioxane (2 mL) and water (0.5 mL) was irradiated in the microwave at 130° C. for 45 minutes. After cooling, the mixture was acidified to pH3 with formic acid, diluted with ethanol and toluene and concentrated in vacuo. The residue was triturated with a solution of methanol in DCM (10%) and the solid was filtered off and washed with DCM. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-6%. The resultant solid was triturated with a mixture of ethyl acetate and ether and the solid obtained was dried in vacuo at 60° C. overnight to give 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acid (0.012 g) as a white solid.

Workup

  1. customwas irradiated in the microwave at 130° C. for 45 minutes
  2. temperatureAfter cooling
  3. concentrationconcentrated in vacuo
  4. customThe residue was triturated with a solution of methanol in DCM (10%)
  5. filtrationthe solid was filtered off
  6. washwashed with DCM
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of methanol and DCM with a gradient of 0-6%
  10. customThe resultant solid was triturated with a mixture of ethyl acetate and ether
  11. customthe solid obtained
  12. customwas dried in vacuo at 60° C. overnight

Sources & evidence

ORD record
ord-6f70ebe0c7e34e2786c7fbe9ab0f40e9
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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