Pyridine → HCID 10455065, compound

HRID 549284Notes

Reaction equation

HRID 549284 reaction equation
[Cl:1][C:2]1[C:7]2[CH:8]=[C:9]([S:11](Cl)(=[O:13])=[O:12])[S:10][C:6]=2[CH:5]=[CH:4][N:3]=1.N1C=CC=CC=1.[CH3:21][C:22]1[CH:23]=[CH:24][C:25]([NH2:28])=[CH:26][CH:27]=1.C(OC([N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CCOC(C)=O>[ClH:1].[C:22]1([CH3:21])[CH:27]=[CH:26][C:25]([NH:28][S:11]([C:9]2[S:10][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([N:36]4[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]4)[C:7]=3[CH:8]=2)(=[O:13])=[O:12])=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 7813p-ToluidineHCID 11430Potassium CarbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 19350980HCID 19350980, compound

Product 1

HCID 10455065HCID 10455065, compoundYield 13.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-chloro-thieno[3,2-c]pyridine-2-sulfonyl chloride (0.640 g, 2.39 mmol) in DCM (20 mL) was added pyridine (1.9 mL, 23.9 mmol) followed by p-tolylamine (0.307 g, 2.86 mmol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was concentrated and re-dissolved in DMSO (10 mL), piperazine-1-carboxylic acid tert-butyl ester (1.34 g, 7.17 mmol) and K2CO3 (0.989 g, 7.17 mmol) were added. The mixture was stirred at 100° C. for 16 hours and then concentrated. The crude reaction mixture was dissolved in EtOAc (100 mL) and washed with brine (2×50 mL). The organic phase was dried (Na2SO4) and concentrated. The crude intermediate was purified by column chromatography on silica using EtOAc/n-pentane (1:1) as eluent. The intermediate was dissolved in EtOAc/MeOH and diethyl ether saturated with HCl (g) was added. The mixture was stirred at room temperature for 16 hours. The precipitate was collected by filtration and washed with diethyl ether/n-pentane to give 0.475 g of the crude product. Purification by preparative reversed phase HPLC gave 0.133 g of the pure product: 1H NMR (DMSO-d6, 25° C., 270.17 MHz) δ 10.61 (br s, 1H), 9.23 (br s, 2H), 8.13 (d, J=5.80 Hz, 1H), 7.91 (s, 1H); 7.67 (d, J=5.80 Hz, 1H), 7.09-7.07 (m, 4H), 3.68-3.59 (m, 4H), 3.33-3.22 (m, 4H), 2.20 (s, 3H); m/z (posESI) 399 (M+H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionre-dissolved in DMSO (10 mL)
  3. stirringThe mixture was stirred at 100° C. for 16 hours
  4. concentrationconcentrated
  5. customThe crude reaction mixture
  6. washwashed with brine (2×50 mL)
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude intermediate was purified by column chromatography on silica
  10. dissolutionThe intermediate was dissolved in EtOAc/MeOH
  11. additiondiethyl ether saturated with HCl (g) was added
  12. stirringThe mixture was stirred at room temperature for 16 hours
  13. filtrationThe precipitate was collected by filtration
  14. washwashed with diethyl ether/n-pentane
  15. customto give 0.475 g of the crude product
  16. customPurification by preparative reversed phase HPLC

Sources & evidence

ORD record
ord-fca0156a243a40de8336e2ea8c40c0e7
Source dataset
uspto-grants-2011_05
Patent number
US07943639B2

Reaction notes

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