Piperidine → cis-N-{[2-chloro-4-(1-piperidinyl)phenyl]methyl}-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide

HRID 1510957Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].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.Br[C:54]1[CH:59]=[CH:58][C:57]([CH2:60][NH:61][C:62]([CH:64]2[CH2:69][CH2:68][CH2:67][CH:66]([NH:70][C:71]3[N:76]=[C:75]([CH3:77])[N:74]=[C:73]([NH:78][CH3:79])[N:72]=3)[CH2:65]2)=[O:63])=[C:56]([Cl:80])[CH:55]=1.[NH:81]1[CH2:86][CH2:85][CH2:84][CH2:83][CH2:82]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:80][C:56]1[CH:55]=[C:54]([N:81]2[CH2:86][CH2:85][CH2:84][CH2:83][CH2:82]2)[CH:59]=[CH:58][C:57]=1[CH2:60][NH:61][C:62]([C@H:64]1[CH2:69][CH2:68][CH2:67][C@@H:66]([NH:70][C:71]2[N:76]=[C:75]([CH3:77])[N:74]=[C:73]([NH:78][CH3:79])[N:72]=2)[CH2:65]1)=[O:63]

Participants

Conditions

Temperature: 100 °C

Procedure

In a microwave reaction vessel was added cesium carbonate (0.049 g, 0.150 mmol) under nitrogen. Next, Pd2(dba)3 (4.89 mg, 5.34 μmol), BINAP (4.99 mg, 8.02 μmol), N-[(4-bromo-2-chlorophenyl)methyl]-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide (0.050 g, 0.107 mmol) and piperidine (10.58 μl, 0.107 mmol) were then added to the reaction vial. Toluene (4.00 ml) was added and the reaction was heated to 100° C. for 16 hours. LCMS showed the formation of the desired product and the consumption of the starting materials. The reaction was cooled, the solvent was removed under vacuum, and the residue was purified by preparative HPLC to provide cis-N-{[2-chloro-4-(1-piperidinyl)phenyl]methyl}-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide (19 mg, 0.032 mmol, 30%). MS (ES+): m/e 472, 474 [M+H]+.

Workup

customIn a microwave reaction vessel

Sources & evidence

ORD record: ord-fb0823ee512d4b278a2d7bcf3adb218c
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08212032B2

Reaction notes

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