1-Methylpiperazine → HCID 86711898, compound

HRID 1475205Notes

Reaction equation

HRID 1475205 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[N:9][C:8]([C:12]2[O:13][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:18]=3)=[N:15][N:16]=2)=[N:7]1.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CC([O-])(C)C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>C1COCC1.CS(C)=O.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[C:23]([C:20]1[CH:21]=[CH:22][C:17]([C:14]2[O:13][C:12]([C:8]3[N:9]=[C:10]([CH3:11])[N:6]([CH2:5][C:4]4[CH:27]=[CH:28][CH:29]=[C:2]([N:34]5[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]5)[CH:3]=4)[N:7]=3)=[N:16][N:15]=2)=[CH:18][CH:19]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 86711897HCID 86711897, compound

Product 1

HCID 86711898HCID 86711898, compoundYield 4.3%

Reagents, catalysts & solvents 3

HCID 771465301375325-68-0CatalystHCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 2-(1-(3-bromobenzyl)-5-methyl-1H-1,2,4-triazol-3-yl)-5-(4-(tert-butyl)phenyl)-1,3,4-oxadiazole (100 mg, 0.22 mmol), 1-methylpiperazine (37 μL, 0.33 mmol), NaOtBu (46.7 mg, 0.48 mmol), dicyclohexyl(2′,6′-diisopropoxy-[1,1′-biphenyl]-2-yl)phosphine (10.3 mg, 0.022 mmol) and chloro-(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)(17.7 mg, 0.022 mmol) in THF (1 mL) was degassed (freeze-pump-thaw, under N2). The reaction mixture was stirred at 65° C. for 2 h, and then the solvent was removed under reduced pressure. The crude reaction mixture was dissolved in DMSO and was purified by pre-HPLC (Mobile phase: A=0.1% CF3CO2H/H2O, B=MeCN; Gradient: B=30%-70% in 12 min; Column: Waters C18) to afford 2-(4-(tert-butyl)phenyl)-5-(5-methyl-1-(3-(4-methylpiperazin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-1,3,4-oxadiazole (4.5 mg, 4.3%) as a white solid. MS (ES+) C27H33N7O requires: 471. found: 472 [M+H]+; 1H-NMR (500 MHz, CDCl3) δ ppm 8.13 (d, J=8.2 Hz, 2H), 7.52 (d, J=8.6 Hz, 2H), 7.25 (d, J=7.9 Hz, 1H), 6.88 (d, J=8.5 Hz, 1H), 6.78 (t, J=2.0 Hz 1H), 6.70 (d, J=7.8 Hz, 1H), 5.38 (s, 2H), 3.27-3.20 (m, 4H), 2.67-2.58 (m, 4H), 2.51 (s, 3H), 2.40-2.37 (m, 3H), (1.36 (s, 9H).

Workup

  1. customwas degassed (freeze-pump-thaw, under N2)
  2. customthe solvent was removed under reduced pressure
  3. customThe crude reaction mixture
  4. customwas purified by pre-HPLC (Mobile phase
  5. waitGradient: B=30%-70% in 12 min

Sources & evidence

ORD record
ord-8bf9f30138ea4ea4a9108f22ae5b11bb
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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