Pyridine → HCID 66893065, compound

HRID 1162046Notes

Reaction equation

HRID 1162046 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14](Cl)(=[O:16])=[O:15].C(OC([N:25]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[C:40]3[O:39][CH:38]=[CH:37][C:36]=3[CH:35]=[C:34]([NH2:41])[CH:33]=2)[CH2:27][CH2:26]1)=O)(C)(C)C>C(Cl)Cl.C1COCC1>[ClH:7].[ClH:7].[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14]([NH:41][C:34]1[CH:33]=[C:32]([CH2:31][N:28]2[CH2:27][CH2:26][NH:25][CH2:30][CH2:29]2)[C:40]2[O:39][CH:38]=[CH:37][C:36]=2[CH:35]=1)(=[O:16])=[O:15]

Participants

5

Reactant 3

HCID 1049PyridineHCID 761872-Chlorobenzenesulfonyl chlorideHCID 668930201,1-Dimethylethyl 4-[(5-amino-7-benzofuranyl)methyl]-1-piperazinecarboxylate

Product 1

HCID 66893065HCID 66893065, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Dry pyridine (20 μL, 0.24 mmol) and 2-chlorobenzenesulfonyl chloride (25 μL, 0.18 mmol) were added to a solution of 4-(5-amino-benzofuran-7-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (40 mg, 0.12 mmol; obtained in Step 2) in a mixture of dry DCM:THF (2:1; 3 mL). The resulting mixture was stirred for 3 h and volatiles were then evaporated. The product was purified using flashtube (15% MeOH in DCM). The residue was dissolved in TFA:water (9:1; 2 mL) and the mixture was stirred at room temperature for 30 min to accomplish removal of the N-t-BOC group. The reaction mixture was made basic by addition of saturated aqueous Na2CO3 (pH 8-9) and extracted with DCM (×2). The organic layers were combined, dried (Na2SO4) and concentrated. The crude product was purified with preparative HPLC (System A; 10-40% MeCN). Pure fractions were combined and concentrated. The obtained TFA salt was dissolved in MeOH and 1 M HCl in ether was added, followed by concentration to give the title compound (10 mg, 18%) as a light yellow solid. HPLC 100%, RT=1.38 min (System A; 10-97% MeCN over 3 min), 100%, RT=1.23 min (System B; 10-97% MeCN over 3 min). 1H NMR (400 MHz, methanol-d4) δ ppm 2.86-2.92 (m, 4H) 3.25-3.28 (m, 4H) 4.04-4.08 (m, 2H) 6.73 (d, J=2.26 Hz, 1H) 7.15 (d, J=2.01 Hz, 1H) 7.26-7.31 (m, 1H) 7.32 (d, J=2.26 Hz, 1H) 7.42-7.47 (m, 1H) 7.47-7.52 (m, 1H) 7.70 (d, J=2.26 Hz, 1H) 7.90 (dd, J=8.03, 1.51 Hz, 1H). MS (ESI+) for C19H20ClN3O3S m/z 406 (M+H).

Workup

  1. customvolatiles were then evaporated
  2. customThe product was purified
  3. dissolutionThe residue was dissolved in TFA:water (9:1; 2 mL)
  4. stirringthe mixture was stirred at room temperature for 30 min
  5. customremoval of the N-t-BOC group
  6. additionThe reaction mixture was made basic by addition of saturated aqueous Na2CO3 (pH 8-9)
  7. extractionextracted with DCM (×2)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude product was purified with preparative HPLC (System A
  11. concentrationconcentrated
  12. dissolutionThe obtained TFA salt was dissolved in MeOH
  13. addition1 M HCl in ether was added
  14. concentrationfollowed by concentration

Sources & evidence

ORD record
ord-5dc75e22968445f6b0d9284f7a0cca43
Source dataset
uspto-grants-2010_10
Patent number
US07820675B2

Reaction notes

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