Methylamine → HCID 178482991, compound

HRID 2409787Notes

Reaction equation

HRID 2409787 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15]([C:17]1[N:18]=[C:19]([NH:22][C:23]([C:25]2[C:26]3[N:27]=[CH:28][CH:29]=[N:30][C:31]=3[C:32]([C:35]3[C:40]([F:41])=[C:39]([O:42][CH3:43])[CH:38]=[C:37]([O:44][CH3:45])[C:36]=3[F:46])=[CH:33][CH:34]=2)=[O:24])[NH:20][CH:21]=1)=O.[CH3:47][NH2:48]>C(Cl)Cl.CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH3:47][NH:48][CH2:15][C:17]1[N:18]=[C:19]([NH:22][C:23]([C:25]2[C:26]3[N:27]=[CH:28][CH:29]=[N:30][C:31]=3[C:32]([C:35]3[C:36]([F:46])=[C:37]([O:44][CH3:45])[CH:38]=[C:39]([O:42][CH3:43])[C:40]=3[F:41])=[CH:33][CH:34]=2)=[O:24])[NH:20][CH:21]=1

Participants

7

Reactant 3

HCID 6329Methylamine2×HCID 5049666Sodium triacetoxyborohydride3×HCID 178493498HCID 178493498, compound

Product 1

HCID 178482991HCID 178482991, compoundYield 39.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Sodium triacetoxyborohydride (72.4 mg, 0.341 mmol, 1.5 equiv) was added to a suspension of 8-(2,6-difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-formyl-1H-imidazol-2-yl)-amide (100 mg, 0.228 mmol) (Example 185) and methylamine (40% wt in H2O, 40 μL, 0.455 mmol, 2 equiv) in DCM (4 mL) at rt, under an argon atmosphere. The reaction mixture was stirred for 4 h at rt. After further addition of sodium triacetoxyborohydride (72.4 mg, 0.341 mmol, 1.5 equiv), the reaction mixture was stirred for additional 16 h at rt. Then, methylamine (50 μL) and sodium triacetoxyborohydride (150 mg) were added. The reaction mixture was stirred for 4 h at rt, diluted with EtOAc/saturated aqueous solution of NaHCO3 and extracted with DCM. The organic phase was dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 91.5:7.5:1) to afford 41 mg of the title compound as a yellow solid: ES-MS: 455 [M+H]+; tR=3.00 min (System 1); TLC: Rf=0.10 (DCM/MeOH/NH3aq, 91.5:7.5:1).

Workup

  1. stirringthe reaction mixture was stirred for additional 16 h at rt
  2. stirringThe reaction mixture was stirred for 4 h at rt
  3. extractionextracted with DCM
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 91.5:7.5:1)

Sources & evidence

ORD record
ord-6d383a91425547b2b897703928e23fe1
Source dataset
uspto-grants-2014_08
Patent number
US08815901B2

Reaction notes

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