Acetic Acid → 6-chloro-N-[(1S)-1-(3-{[1-(3-methylphenyl)ethyl]amino}phenyl)ethyl]pyrazin-2-amine

HRID 572210

Reaction equation

HRID 572210 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH3:9])[CH:5]=N[CH:7]=1.[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.[C:28](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.Cl>ClCCCl>[Cl:27][C:23]1[N:22]=[C:21]([NH:20][C@H:18]([C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([NH:11][CH:5]([C:4]3[CH:8]=[CH:9][CH:7]=[C:2]([CH3:1])[CH:3]=3)[CH3:28])[CH:13]=2)[CH3:19])[CH:26]=[N:25][CH:24]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5775691-(5-Methylpyridin-3-yl)ethan-1-oneHCID 5049666Sodium triacetoxyborohydrideHCID 25218447(S)-N-(1-(3-aminophenyl)ethyl)-6-chloropyrazin-2-amine

Product 1

HCID 875330326-chloro-N-[(1S)-1-(3-{[1-(3-methylphenyl)ethyl]amino}phenyl)ethyl]pyrazin-2-amineYield 14.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(5-methylpyridin-3-yl)ethanone (135 mg, 1 mmol) and N-[(1S)-1-(3-aminophenyl)ethyl]-6-chloropyrazin-2-amine (248 mg, 1 mmol) in 1,2-dichloroethane (5 mL) was added sodium triacetoxyborohydride (300 mg, 1.4 mmol), in one portion, and glacial acetic acid (0.18 mL, 3 mmol). The mixture was heated in the microwave reactor at 80° C. for 1 hour. After this time the mixture was stirred with dilute aqueous hydrochloric acid (2M, 7 mL) for 15 minutes and the two phases were separated. The aqueous phase was basified to pH 9 with solid potassium hydroxide and was extracted with dichloromethane (2×20 mL). The extracts were washed with brine (20 mL), dried (MgSO4) and concentrated under reduced pressure to give an orange oil which was purified by flash chromatography (silica, ethyl acetate/methanol) to give 6-chloro-N-[(1S)-1-(3-{[1-(3-methylphenyl)ethyl]amino}phenyl)ethyl]pyrazin-2-amine (52 mg, 14%) as a pale yellow oil.

Workup

  1. customthe two phases were separated
  2. extractionwas extracted with dichloromethane (2×20 mL)
  3. washThe extracts were washed with brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give an orange oil which
  7. customwas purified by flash chromatography (silica, ethyl acetate/methanol)

Sources & evidence

ORD record
ord-0be33a69c4534afe957e0d5d4eb4bbc3
Source dataset
uspto-grants-2015_05
Patent number
US09029386B2

Linked notes

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