Morpholine → HCID 56941121, compound

HRID 341418Notes

Reaction equation

HRID 341418 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.Cl.CN(C)CCCN=C=NCC.C1C=NC2N(O)N=NC=2C=1.[NH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>CN(C=O)C.C(OCC)(=O)C>[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]([N:51]4[CH2:56][CH2:55][O:54][CH2:53][CH2:52]4)=[O:27])=[CH:23][CH:22]=3)[O:18][N:17]=2)[N:3]=1

Participants

7

Reactant 4

HCID 8083Morpholine2×HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 66802876HCID 66802876, compound2×

Product 1

HCID 56941121HCID 56941121, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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 (prepared in an analogous manner to Intermediate 62, 24 mg, 61 μmol) in anhydrous DMF (0.5 mL) was added (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (17 mg, 73 μmol), HOAt (4.1 mg, 31 μmol) and morpholine (10 μL, 92 μmol). The reaction mixture was stirred for 2 h, further morpholine (10 μL, 92 μmol) and (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (9 mg, 39 μmol) were added. The mixture was stirred for a further 2 h then diluted with ethyl acetate (5 mL) and extracted with aqueous citric acid (1M, 5 mL), 1 M NaOH (5 mL), saturated brine (5 mL) and dried over sodium sulphate. Removal of the solvent gave a gum with was purified on silica eluting with ethyl acetate-10% heptanes to give the title compound (20 mg, 71%).

Workup

  1. stirringThe mixture was stirred for a further 2 h
  2. extractionextracted with aqueous citric acid (1M, 5 mL), 1 M NaOH (5 mL), saturated brine (5 mL)
  3. dry with materialdried over sodium sulphate
  4. customRemoval of the solvent
  5. customgave a gum
  6. customwith was purified on silica eluting with ethyl acetate-10% heptanes

Sources & evidence

ORD record
ord-460a3cee6b724825865ac10416866bf8
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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