tert-Butyl methyl ether → HCID 86690648, compound

HRID 1505615Notes

Reaction equation

HRID 1505615 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:20][CH:21]([CH3:23])[CH3:22])[S:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:12])=[O:11])=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.COC(C)(C)C.CC(C)([O-])C.[Na+].[CH:69]1([C:72]([N:74]2[CH2:79][CH2:78][NH:77][CH2:76][CH2:75]2)=[O:73])[CH2:71][CH2:70]1>O1CCOCC1>[CH:69]1([C:72]([N:74]2[CH2:79][CH2:78][N:77]([C:2]3[CH:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:20][CH:21]([CH3:23])[CH3:22])[S:10]([CH2:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)(=[O:12])=[O:11])=[CH:4][CH:3]=3)[CH2:76][CH2:75]2)=[O:73])[CH2:70][CH2:71]1

Participants

7

Reactant 5

HCID 15413tert-Butyl methyl etherHCID 20642351-(Cyclopropylcarbonyl)piperazineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 86690647HCID 86690647, compound

Product 1

HCID 86690648HCID 86690648, compoundYield 44.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

In a vial, N-[(4-bromophenyl)methyl]-N-isobutyl-1-phenyl-methanesulfonamide (53 mg, 0.13 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl (3.2 mg, 0.0067 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl)[2-(2 aminoethylphenyl)]palladium(II), methyl-t-butylether adduct (6 mg, 0.0067 mmol) and sodium tert-butoxide (20 mg, 0.20 mmol) were combined and the vial was purged with nitrogen. 1,4-Dioxane (1 mL) and cyclopropyl(piperazin-1-yl)methanone (31 mg, 0.20 mmol) were then added and the reaction was stirred at ambient temperature for 16 hours. The reaction was then partitioned between water and dichloromethane and the dichloromethane layer was isolated with a phase separator cartridge, concentrated and purified by preparative reverse phase HPLC to yield 27 mg of N-[4-(4-cyclopropanecarbonyl-piperazin-1-yl)-benzyl]-N-isobutyl-C-phenyl-methanesulfonamide. 1H NMR (400 MHz, DMSO) δ 7.38-7.34 (m, 5H), 7.21 (d, J=8.5 Hz, 2H), 6.94 (d, J=6.8 Hz, 2H), 4.40 (s, 2H), 4.16 (s, 2H), 3.82-3.78 (m, 2H), 3.62-3.58 (m, 2H), 3.20-3.05 (m, 4H), 2.80 (d, J=7.5, 2H), 2.12-1.92 (m, 1H), 1.60-1.45 (m, 1H), 0.83-0.69 (m, 4H), 0.67 (d, J=7.1 Hz, 6H); LCMS (m/z) ES+ 470.2 [M+1]+.

Workup

  1. customthe vial was purged with nitrogen
  2. customThe reaction was then partitioned between water and dichloromethane
  3. customthe dichloromethane layer was isolated with a phase separator cartridge
  4. concentrationconcentrated
  5. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-ba16a589f1a246d28610c9daa52921c3
Source dataset
uspto-grants-2015_12
Patent number
US09216988B2

Reaction notes

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