4-Methylmorpholine → 5-amino-N-(3-{(1S)-1-[(6-chloropyrazin-2-yl)amino]ethyl}phenyl)nicotinamide

HRID 572205

Reaction equation

HRID 572205 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[NH2:11][C:12]1[CH:13]=[C:14]([C@@H:18]([NH:20][C:21]2[CH:26]=[N:25][CH:24]=[C:23]([Cl:27])[N:22]=2)[CH3:19])[CH:15]=[CH:16][CH:17]=1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>CN(C)C=O.C(OCC)(=O)C>[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C@@H:18]([NH:20][C:21]2[CH:26]=[N:25][CH:24]=[C:23]([Cl:27])[N:22]=2)[CH3:19])[CH:13]=1)=[O:9]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 3543165-Aminonicotinic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 25218447(S)-N-(1-(3-aminophenyl)ethyl)-6-chloropyrazin-2-amine

Product 1

HCID 593317385-amino-N-(3-{(1S)-1-[(6-chloropyrazin-2-yl)amino]ethyl}phenyl)nicotinamideYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-aminonicotinic acid (35 mg, 0.25 mmol), N-[(1S)-1-(3-aminophenyl)ethyl]-6-chloropyrazin-2-amine (125 mg, 0.5 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (95 mg, 0.5 mmol) in N,N-dimethylformamide (2 mL) was added 1-hydroy-7-azabenzotriazole (1 mL, 0.5-0.7M in N,N-dimethylformamide, 0.5 mmol) then N-methylmorpholine (0.055 mL, 0.5 mmol) and the mixture was stirred at room temperature for 16 hours. After this time the mixture was diluted with ethyl acetate (40 mL), washed successively with saturated aqueous sodium hydrogen carbonate (2×30 mL) and brine (30 mL), dried (Na2SO4) and concentrated under reduced pressure to give a yellow oil which was purified by flash chromatography (silica, ethyl acetate/methanol) to give 5-amino-N-(3-{(1S)-1-[(6-chloropyrazin-2-yl)amino]ethyl}phenyl)nicotinamide (35 mg, 38%) as a pale yellow solid.

Workup

  1. washwashed successively with saturated aqueous sodium hydrogen carbonate (2×30 mL) and brine (30 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customto give a yellow oil which
  5. customwas purified by flash chromatography (silica, ethyl acetate/methanol)

Sources & evidence

ORD record
ord-bb941c54a4cd44a8bf80f79806521a7f
Source dataset
uspto-grants-2015_05
Patent number
US09029386B2

Linked notes

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