Ethanol → 2-Cyclohex-1-enyl-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenylamine

HRID 1508056Notes

Reaction equation

HRID 1508056 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][S:9]([N:12]2[CH2:17][C@H:16]([CH3:18])[NH:15][C@H:14]([CH3:19])[CH2:13]2)(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[NH2:20].CCO.C([O-])([O-])=O.[Na+].[Na+].[C:30]1(B(O)O)[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]=1>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:30]1([C:2]2[CH:7]=[C:6]([CH2:8][S:9]([N:12]3[CH2:17][C@H:16]([CH3:18])[NH:15][C@H:14]([CH3:19])[CH2:13]3)(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=2[NH2:20])[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 38629021-Cyclohexenylboronic acidHCID 589945752-Bromo-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenylamine

Product 1

HCID 589943402-Cyclohex-1-enyl-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenylamineYield 86%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 356 mg (0.983 mmol) of 2-bromo-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenylamine (as prepared in the previous step) in toluene (8 mL) and EtOH (4 mL) was treated with 3.93 mL (7.86 mmol) of 2.0 M aqueous Na2CO3 and 186 mg (1.47 mmol) of cyclohex-1-enylboronic acid. The mixture was degassed via sonication, placed under Ar, treated with 170 mg (0.147 mmol) of Pd(PPh3)4, and heated to 80° C. for 4.3 h. The mixture was cooled to RT, diluted with EtOAc (10 mL), and washed with saturated aqueous NaHCO3 (1×10 mL) and brine (1×10 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue with 0-4% MeOH—CH2Cl2 afforded 307 mg (86%) of the title compound as a white solid: 1H-NMR (CDCl3; 400 MHz): δ 7.01 (dd, 1H, J=8.0, 2.0 Hz), 6.99 (d, 1H, J=2.0 Hz), 6.57 (d, 1H, J=8.0 Hz), 5.77-5.72 (m, 1H), 4.07 (s, 2H), 3.85 (br s, 2H), 3.55-3.47 (m, 2H), 2.88-2.77 (m, 2H), 2.26-2.13 (m, 6H), 1.81-1.73 (m, 2H), 1.72-1.64 (m, 2H), 0.99 (d, 6H, J=6.0 Hz).

Workup

  1. customThe mixture was degassed via sonication
  2. temperatureThe mixture was cooled to RT
  3. washwashed with saturated aqueous NaHCO3 (1×10 mL) and brine (1×10 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-78d801ac297241bcaba1ad1dd7682779
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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