Diisopropylethylamine → HCID 178493498, compound

HRID 43222Notes

Reaction equation

HRID 43222 reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[C:22]2[N:21]=[CH:20][CH:19]=[N:18][C:17]=2[C:16]([C:23](O)=[O:24])=[CH:15][CH:14]=1.C(OC([N:33]1[CH:37]=[C:36]([CH:38](OCC)[O:39]CC)[N:35]=[C:34]1[NH2:45])=O)(C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[CH:38]([C:36]1[N:35]=[C:34]([NH:45][C:23]([C:16]2[C:17]3[N:18]=[CH:19][CH:20]=[N:21][C:22]=3[C:13]([C:3]3[C:4]([F:12])=[C:5]([O:10][CH3:11])[CH:6]=[C:7]([O:8][CH3:9])[C:2]=3[F:1])=[CH:14][CH:15]=2)=[O:24])[NH:33][CH:37]=1)=[O:39]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 592928212-Amino-4-diethoxymethyl-imidazole-1-carboxylic acid tert-butyl esterHCID 592928348-(2,6-Difluoro-3,5-dimethoxy-phenyl)quinoxaline-5-carboxylic acid

Product 1

HCID 178493498HCID 178493498, compoundYield 68.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

A mixture of 8-(2,6-difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (200 mg, 0.578 mmol) (Step 185.1), 2-amino-4-diethoxymethyl-imidazole-1-carboxylic acid tert-butyl ester (198 mg, 0.693 mmol, 1.2 equiv) (Step 179.8), TBTU (223 mg, 0.693 mmol, 1.2 equiv), DIEA (74.7 mg, 0.578 mmol) in DMF (4 mL) was stirred for 18 h at rt. The reaction mixture was diluted in EtOAc/H2O and extracted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The resulting yellow foam (405 mg) was dissolved in acetone (5 mL) and H2O (3 mL) and treated with PPTS (30 mg). The reaction mixture was heated to 50° C., stirred for 2 h, allowed to cool to rt and diluted with EtOAc/H2O. The resulting yellow precipitate was collected by vacuum filtration and dried to provide 174 mg of the title compound: ES-MS: 440 [M+H]+; tR=3.89 min (System 1).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with H2O and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resulting yellow foam (405 mg) was dissolved in acetone (5 mL)
  7. additionH2O (3 mL) and treated with PPTS (30 mg)
  8. temperatureThe reaction mixture was heated to 50° C.
  9. stirringstirred for 2 h
  10. temperatureto cool to rt
  11. additiondiluted with EtOAc/H2O
  12. filtrationThe resulting yellow precipitate was collected by vacuum filtration
  13. customdried

Sources & evidence

ORD record
ord-c451f92c1a10417599046efe7e39cebd
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Reaction notes

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