Methylamine → HCID 56941119, compound

HRID 341416Notes

Reaction equation

HRID 341416 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([C:16]2[N:20]=[C:19]([C:21]3[S:25][C:24]([C:26](O)=[O:27])=[CH:23][CH:22]=3)[O:18][N:17]=2)[N:3]=1.C1N=C[N:31](C(N2C=NC=C2)=O)[CH:30]=1.CN>CN(C=O)C.C(Cl)Cl>[CH3:30][NH:31][C:26]([C:24]1[S:25][C:21]([C:19]2[O:18][N:17]=[C:16]([C:4]3[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([N:8]([CH3:15])[C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[N:5]=3)[N:20]=2)=[CH:22][CH:23]=1)=[O:27]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 682631,1'-Carbonyldiimidazole2×HCID 66802876HCID 66802876, compound2×

Product 1

HCID 56941119HCID 56941119, compoundYield 8.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 5-{3-[4-Amino-6-(methyl-phenyl-amino)-[1,3,5]triazin-2-yl]-[1,2,4]oxadiazol-5-yl}-thiophene-2-carboxylic acid (Intermediate 62, 316 mg, 0.80 mmol) in anhydrous DMF (4 mL) was added CDI (190 mg, 1.17 mmol). The mixture was stirred for 2 h and then heated at 50 C for 3 h. After this time more CDI (190 mg, 1.17 mmol) was added and the mixture heated at 65 C for 18 h. After cooling to room temperature, methylamine (2 M in THF, 3.5 mL, 7 mmol) was added and the mixture stirred at room temperature for 1 hr The reaction mixture was then diluted with DCM (20 mL), extracted with aqueous sodium hydroxide solution (1M, 20 mL), saturated brine (20 mL) and dried over sodium sulfate. Evaporation of the solvent gave an orange gum which was purified by preparative HPLC (Method A) and then by chromatography on silica eluting with 4% MeOH-DCM to give the title compound (27 mg, 8%).

Workup

  1. temperatureheated at 50 C for 3 h
  2. temperaturethe mixture heated at 65 C for 18 h
  3. stirringthe mixture stirred at room temperature for 1 hr The reaction mixture
  4. extractionextracted with aqueous sodium hydroxide solution (1M, 20 mL), saturated brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. customEvaporation of the solvent
  7. customgave an orange gum which
  8. customwas purified by preparative HPLC (Method A)

Sources & evidence

ORD record
ord-cb3e91f0cb3c434590ccf56f216f9713
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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