1-Methylpiperazine → HCID 86711894, compound

HRID 1475199Notes

Reaction equation

HRID 1475199 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=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]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)=[N:15][N:16]=2)=[N:7]1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C[C:39]([O-:42])(C)C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C([O:63]C(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+]>[F:27][C:24]([F:25])([F:26])[C:39]([O-:42])=[O:63].[CH3:31][NH+:32]1[CH2:37][CH2:36][N:35]([C:2]2[CH:30]=[CH:29][CH:28]=[C:4]([CH2:5][N:6]3[C:10]([CH3:11])=[N:9][C:8]([C:12]4[O:13][C:14]([C:17]5[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=5)=[N:15][N:16]=4)=[N:7]3)[CH:3]=2)[CH2:34][CH2:33]1

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 86711892HCID 86711892, compound

Product 1

HCID 86711894HCID 86711894, compoundYield 9.3%

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-(trifluoromethoxy)phenyl)-1,3,4-oxadiazole (84 mg, 0.176 mmol), 1-methylpiperazine (28 μL, 0.26 mmol), NaOtBu (36.4 mg, 0.38 mmol), dicyclohexyl(2′,6′-diisopropoxy-[1,1′-biphenyl]-2-yl)phosphine (8.2 mg, 0.0176 mmol) and chloro-(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (13.6 mg, 0.0176 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 purified by pre-HPLC (Mobile phase: A=H2O, B=MeCN containing 0.1% TFA; Gradient: B=20%-50% in 12 min; Column: Waters C18) to afford 1-methyl-4-(3-((5-methyl-3-(5-(4-(trifluoromethoxy)phenyl)-1,3,4-oxadiazol-2-yl)-1H-1,2,4-triazol-1-yl)methyl)phenyl)piperazin-1-ium trifluoroacetate (1 mg, 1.1%) as a white solid. MS (ES+) C24H24F3N7O2 requires: 499. found: 500 [M+H]+; 1H-NMR (500 MHz, CD3OD) δ ppm 8.26 (d, J=8.9 Hz, 2H), 7.53 (d, J=8.9 Hz, 2H), 7.32 (t, J=7.6 Hz, 1H), 7.02-7.00 (m, 2H), 6.88 (d, J=7.4 Hz, 1H), 5.47 (s, 2H), 3.89-3.79 (m, 2H), 3.60-3.52 (m, 2H), 3.35-3.33 (m, 4H), 2.94 (s, 3H), 2.57 (s, 3H).

Workup

  1. customwas degassed (freeze-pump-thaw, under N2)
  2. customthe solvent was removed under reduced pressure
  3. customThe crude reaction mixture
  4. custompurified by pre-HPLC (Mobile phase
  5. waitGradient: B=20%-50% in 12 min

Sources & evidence

ORD record
ord-c681399c23f44beb88788df6b6c993bd
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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