Hydrochloric Acid → 2,6-diamino-N-(5-phenoxy-thiophene-2-ylmethyl)-nicotinamide

HRID 2080185Notes

Reaction equation

HRID 2080185 reaction equation
C(O[C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[N:7][C:6]=1[NH2:12])C.[OH-].[Na+].Cl.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[O:51]([C:58]1[S:62][C:61]([CH2:63][NH2:64])=[CH:60][CH:59]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>C(O)C.[Cl-].[Na+].O>[NH2:12][C:6]1[N:7]=[C:8]([NH2:11])[CH:9]=[CH:10][C:5]=1[C:4]([NH:64][CH2:63][C:61]1[S:62][C:58]([O:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)=[CH:59][CH:60]=1)=[O:13]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 23130515C-(5-Phenoxy thiophen-2-yl)methylamineHCID 58784252Ethyl 2,6-diaminonicotinate

Product 1

HCID 231303952,6-diamino-N-(5-phenoxy-thiophene-2-ylmethyl)-nicotinamideYield 25%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 2,6-diamino-nicotinic acid ethyl ester described in Preparation Example A-14 (18 mg, 0.1 mmol) in ethanol (10 mL) was added 1N sodium hydroxide aqueous solution (5 mL), and the solution was stirred for 1 hour 10 minutes under reflux. After cooling the reaction solution, the solution was neutralized with 1N hydrochloric acid and concentrated. The resulting crude product was suspended in N,N-dimethylformamide (3 mL), triethylamine (0.02 mL, 0.15 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (65 mg, 0.15 mmol) and C-(5-phenoxy-thiophen-2-yl)-methylamine described in Preparation Example 26 (30 mg, 0.15 mmol) were added thereto, followed by stirring at room temperature for 19 hours 40 minutes. After the reaction was completed, reaction solution was poured into brine, and the solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate then concentrated, the obtained residue was purified by NH silica gel column chromatography (ethyl acetate), and the title compound (8.7 mg, 0.025mol, 25%) was obtained.

Workup

  1. temperatureunder reflux
  2. temperatureAfter cooling the reaction solution
  3. concentrationconcentrated
  4. additionwere added
  5. stirringby stirring at room temperature for 19 hours 40 minutes
  6. customreaction solution
  7. extractionthe solution was extracted with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. concentrationthen concentrated
  10. customthe obtained residue was purified by NH silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-27bae6c7c33f40f0a2ee4b49e2c73db0
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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