1-Acetylpiperazine → HCID 86690642, compound

HRID 1505607Notes

Reaction equation

HRID 1505607 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:20][C:21]([F:24])([F:23])[F:22])[S:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:12])=[O:11])=[C:4]([F:25])[CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.CC(C)([O-])C.[Na+].[N:65]1([C:71](=[O:73])[CH3:72])[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:71]([N:65]1[CH2:70][CH2:69][N:68]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:20][C:21]([F:24])([F:23])[F:22])[S:10]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:12])=[O:11])=[C:4]([F:25])[CH:3]=2)[CH2:67][CH2:66]1)(=[O:73])[CH3:72]

Participants

7

Reactant 4

HCID 837951-AcetylpiperazineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 86690639HCID 86690639, compound

Product 1

HCID 86690642HCID 86690642, compoundYield 40.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a vial, N-[(4-bromo-2-fluoro-phenyl)methyl]-1-phenyl-N-(2,2,2-trifluoroethyl)methanesulfonamide (Example 2, step 2) (100 mg; 0.22 mmol), palladium(II) acetate (3 mg, 0.011 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl (11 mg, 0.022 mmol) and sodium tert-butoxide (34 mg, 0.34 mmol) were weighed out and the vial was purged with nitrogen. 1,4-Dioxane (1 mL) and 1-piperazin-1-ylethanone (45 mg, 0.34 mmol) were then added and the reaction was stirred at 100° C. for 16 hours. The reaction was then filtered through diatomaceous earth, concentrated and purified by preparative reverse phase HPLC to yield 43 mg of N-(4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl)-1-phenyl-N-(2,2,2-trifluoroethyl)methanesulfonamide. 1H NMR (400 MHz, DMSO) δ 7.44-7.34 (m, 5H), 7.27 (t, J=8.8 Hz, 1H), 6.83-6.71 (m, 2H), 4.53 (s, 2H), 4.34 (s, 2H), 3.86 (q, J=9.4 Hz, 2H), 3.63-3.52 (m, 4H), 3.24-3.20 (m, 2H), 3.18-3.11 (m, 2H), 2.03 (s, 3H); LCMS (m/z) ES+ 488.1 [M+1]+.

Workup

  1. customthe vial was purged with nitrogen
  2. filtrationThe reaction was then filtered through diatomaceous earth
  3. concentrationconcentrated
  4. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-d5b705b1ddcb4947b896521a2f19cd02
Source dataset
uspto-grants-2015_12
Patent number
US09216988B2

Reaction notes

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