Methylamine → N2,N5-dimethyl-4-o-tolylpyridine-2,5-diamine

HRID 877976Notes

Reaction equation

HRID 877976 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([NH:8][CH3:9])=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])[CH:3]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].[CH3:69][NH2:70]>C1(C)C=CC=CC=1.CCCCCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[CH3:69][NH:70][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])[C:5]([NH:8][CH3:9])=[CH:6][N:7]=1

Participants

9

Reactant 4

HCID 6329MethylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 577104436-chloro-N-methyl-4-(2-methylphenyl)pyridin-3-amine

Product 1

HCID 70663324N2,N5-dimethyl-4-o-tolylpyridine-2,5-diamine

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6-chloro-N-methyl-4-o-tolylpyridin-3-amine (74 mg, 0.318 mmol, prepared as described in WO2005/002577), palladium(II) acetate (7 mg, 0.031 mmol, CAS RN 3375-31-3) and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (60 mg, 0.96 mmol, CAS RN 76189-55-4) in toluene (2.5 mL) was added sodium tert-butoxide (92 mg, 0.96 mmol). After stirring for 5 min, methylamine (2.0 M solution in THF, 400 μL, 0.80 mmol, CAS RN 74-89-5) was added and the reaction mixture was heated by microwave irradiation to 150° C. for 30 min. The reaction mixture was applied directly to a silica gel column. Flash chromatography (33-50% EtOAc in n-hexane) gave the product, as a light brown oil which was used in the next step without further purification.

Workup

  1. customas a light brown oil which was used in the next step without further purification

Sources & evidence

ORD record
ord-3f3ae2b6053d482081ff773843f5e508
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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