1-Isopropylpiperazine → HCID 68876458, compound

HRID 1454229Notes

Reaction equation

HRID 1454229 reaction equation
[C:1]([O:5][C:6](=[O:26])[N:7]([CH2:9][C:10]1[CH:15]=[C:14](Br)[CH:13]=[CH:12][C:11]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH:27]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)([CH3:29])[CH3:28].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(O[Na])(C)(C)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6](=[O:26])[N:7]([CH2:9][C:10]1[CH:15]=[C:14]([N:33]2[CH2:34][CH2:35][N:30]([CH:27]([CH3:29])[CH3:28])[CH2:31][CH2:32]2)[CH:13]=[CH:12][C:11]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 780131-IsopropylpiperazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 44118842HCID 44118842, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 68876458HCID 68876458, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of [5-bromo-2-(4-methylsulfanyl-phenoxy)-benzyl]-methyl-carbamic acid tert-butyl ester (300 mg, 0.684 mmol) {prepared in an analogous fashion to Example 1, Steps A-C}, isopropyl piperazine (132 mg, 1.02 mmol), XPHOS (39 mg, 0.082 mmol), Pd2(dba)3 (62.6 mg, 0.0684 mmol), and t-BuONa (98.0 mg, 1.02 mmol) in toluene was heated in a sealed tube overnight at 120° C. After cooling to rt, the mixture was filtered through diatomaceous earth and the filtrate was concentrated. Purification by FCC gave the desired product (180 mg, 54%). MS (ESI): mass calcd. for C27H39N3O3S, 485.27; m/z found, 486.4 [M+H]+. 1H NMR (CDCl3): 7.22 (d, J=8.5, 2H), 6.86-6.83 (m, 1H), 6.83-6.80 (m, 4H), 4.42-4.35 (m, 2H), 3.19-3.16 (m, 4H), 2.87-2.83 (m, 2H), 2.80-2.75 (m, 1H), 2.75-2.71 (m, 1H), 2.71-2.67 (m, 4H), 2.44 (s, 3H), 1.48-1.40 (m, 9H), 1.10 (d, J=6.5, 6H).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationthe mixture was filtered through diatomaceous earth
  3. concentrationthe filtrate was concentrated
  4. customPurification by FCC

Sources & evidence

ORD record
ord-08ce3a80338649d09a134fab0ac8aa4a
Source dataset
uspto-grants-2009_01
Patent number
US07479493B2

Reaction notes

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