Water → 4-(5-{4-[2-(4-Methoxy-phenyl)-ethyl]-piperazin-1-yl}-[1,2,4]thiadiazol-3-yl)-benzonitrile

HRID 570575Notes

Reaction equation

HRID 570575 reaction equation
Cl[C:2]1[N:6]=[C:5]([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH2:9][CH2:8]2)[S:4][N:3]=1.[C:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)#[N:24].C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(C)=O>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][CH2:13][N:10]2[CH2:11][CH2:12][N:7]([C:5]3[S:4][N:3]=[C:2]([C:28]4[CH:29]=[CH:30][C:25]([C:23]#[N:24])=[CH:26][CH:27]=4)[N:6]=3)[CH2:8][CH2:9]2)=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 711872633-Chloro-5-(4-(4-methoxyphenethyl)piperazin-1-yl)-1,2,4-thiadiazole

Product 1

HCID 711862924-(5-{4-[2-(4-Methoxy-phenyl)-ethyl]-piperazin-1-yl}-[1,2,4]thiadiazol-3-yl)-benzonitrile

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A 5 ml micro wave vial was charged with 3-chloro-5-(4-(4-methoxyphenethyl)piperazin-1-yl)-1,2,4-thiadiazole (50 mg, 148 μmol) in 3 mL DME. 4-Cyanophenylboronic acid (26.0 mg, 177 μmol), Na2CO3 (18.8 mg, 177 μmol), tetrakis(triphenylphosphine) palladium (0) (3.41 mg, 2.95 μmol) and water (1.5 mL) was added. The vial was capped and the mixture was heated in oil bath at 110° C. over night. 2 mL EtOAc were added and the aqueous part was separated. The organic layer was dried over Na2SO4, filtered off and concentrated in vacuo. The crude product was dissolved in MeCN (3 mL)/DIPEA (100 μL) and purified by preparative HPLC on reversed phase eluting with a gradient formed from MeCN, water and NEt3 to yield, after evaporation of the product containing fractions, 13.6 mg (23%) of the title compound as white solid. MS (m/e): 406.3 (MH+).

Workup

  1. customThe vial was capped
  2. customthe aqueous part was separated
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude product was dissolved in MeCN (3 mL)/DIPEA (100 μL)
  7. custompurified by preparative HPLC on reversed phase
  8. washeluting with a gradient
  9. customformed from MeCN, water and NEt3
  10. customto yield
  11. customafter evaporation of the product
  12. additioncontaining fractions, 13.6 mg (23%) of the title compound as white solid

Sources & evidence

ORD record
ord-afadf81c9ca348a28614ed5d8b059866
Source dataset
uspto-grants-2015_05
Patent number
US09023852B2

Reaction notes

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