Binap, (A+-)- → N-methyl-6-(4-(methylsulfonyl)piperazin-1-yl)-4-o-tolylpyridin-3-amine

HRID 877980Notes

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.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[CH3:69][S:70]([N:73]1[CH2:78][CH2:77][NH:76][CH2:75][CH2:74]1)(=[O:72])=[O:71]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:9][NH:8][C:5]1[CH:6]=[N:7][C:2]([N:76]2[CH2:77][CH2:78][N:73]([S:70]([CH3:69])(=[O:72])=[O:71])[CH2:74][CH2:75]2)=[CH:3][C:4]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH3:16]

Participants

Conditions

Temperature: 150 °C

Procedure

6-Chloro-N-methyl-4-o-tolylpyridin-3-amine (58 mg, 0.25 mmol, prepared as described in WO2005/002577), sodium tert-butoxide (72 mg, 0.75 mmol), palladium acetate (5.6 mg, 0.025 mmol, CAS RN 3375-31-3) and BINAP (47 mg, 0.075 mmol, CAS RN 76189-55-4) were dissolved in toluene (3 mL) and stirred under an argon atmosphere for 10 minutes. 1-(Methylsulfonyl)piperazine (82 mg, 0.5 mmol, CAS RN 55276-43-2) was added and the reaction mixture was sealed and heated to 150° C. under microwave irradiation for 30 min. The reaction mixture was loaded directly onto a silica gel column (elute with EtOAc) to yield the desired compound (39 mg, 43%) as a brown oil which was used in the next step without further purification.

Workup

customthe reaction mixture was sealed
washThe reaction mixture was loaded directly onto a silica gel column (elute with EtOAc)

Sources & evidence

ORD record: ord-3f1dd48021d74431b96f30c91f8d4f9a
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987307B2

Reaction notes

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