Hydrochloric Acid → 2-Methoxy-5-methyl-n-{7-[(2-methylpiperazin-1-yl)methyl]-1-benzofuran-5-yl}benzenesulfonamide, dihydrochloride

HRID 1162054Notes

Reaction equation

HRID 1162054 reaction equation
N1C=CC=CC=1.CO[C:9]1[C:14]([CH3:15])=[CH:13][C:12]([S:16]([Cl:19])(=[O:18])=[O:17])=[CH:11][CH:10]=1.[NH2:20][C:21]1[CH:22]=[C:23]([CH2:30][N:31]2[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH:32]2[CH3:44])[C:24]2[O:28][CH:27]=[CH:26][C:25]=2[CH:29]=1.[ClH:45].C[CH2:47][O:48]CC>C(Cl)Cl.C1COCC1.CO>[ClH:19].[ClH:45].[CH3:47][O:48][C:11]1[CH:10]=[CH:9][C:14]([CH3:15])=[CH:13][C:12]=1[S:16]([NH:20][C:21]1[CH:22]=[C:23]([CH2:30][N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH:32]2[CH3:44])[C:24]2[O:28][CH:27]=[CH:26][C:25]=2[CH:29]=1)(=[O:17])=[O:18]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 3283Diethyl EtherHCID 159153174-Methoxy-3-methylbenzene-1-sulfonyl chlorideHCID 66892829Tert-butyl 4-[(5-amino-1-benzofuran-7-yl)methyl]-3-methylpiperazine-1-carboxylate

Product 1

HCID 1317283892-Methoxy-5-methyl-n-{7-[(2-methylpiperazin-1-yl)methyl]-1-benzofuran-5-yl}benzenesulfonamide, dihydrochlorideYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Pyridine (17 μL, 0.20 mmol) and 6-methoxy-m-toluenesulfonyl chloride (34 mg, 0.15 mmol) were added to a solution of tert-butyl 4-[(5-amino-1-benzofuran-7-yl)methyl]-3-methylpiperazine-1-carboxylate (45 mg crude material, 0.10 mmol; obtained in Step 2) in dry DCM:THF (2:1; 3 mL). The reaction mixture was stirred at room temperature for 2 h and the solvent was evaporated under reduced pressure followed by purification by flashtube (15% MeOH in DCM). The residue was dissolved in TFA:water (9:1; 4.5 mL) and the mixture was stirred at room temperature for 1 h to accomplish removal of the N-t-BOC group. The reaction mixture was diluted with DCM (10 mL) and saturated aqueous Na2CO3 was added to reach pH 8-9 (˜15 mL). The phases were separated using “phase separator” filters and the organic phase was concentrated. The crude product was purified by preparative HPLC (System B; 10-40% MeCN). Pure fractions were combined and concentrated to give the product as the free base, which was dissolved in MeOH and 1 M HCl in ether (200 μL, 0.2 mmol) was added. The solvent was evaporated to give the title compound (19 mg, 38%) as an off-white solid. HPLC 99%, RT=1.46 min (System A; 10-97% MeCN over 3 min), 100%, RT=1.29 min (System B; 10-97% MeCN over 3 min). 1H NMR (400 MHz, methanol-d4) δ ppm 1.72 (d, J=6.53 Hz, 3H) 2.20 (s, 3H) 3.39-3.62 (m, 5H) 3.67-3.74 (m, 1H) 3.87-3.96 (m, 1H) 3.98 (s, 3H) 4.60 (d, J=13.55 Hz, 1H) 4.93 (d, J=13.80 Hz, 1H) 6.87 (d, J=2.26 Hz, 1H) 7.04 (d, J=8.53 Hz, 1H) 7.28-7.37 (m, 2H) 7.52 (d, J=2.26 Hz, 1H) 7.54 (d, J=2.01 Hz, 1H) 7.85 (d, J=2.01 Hz, 1H). MS (ESI+) for C22H27N3O4S m/z 430 (M+H)+.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customfollowed by purification by flashtube (15% MeOH in DCM)
  3. dissolutionThe residue was dissolved in TFA:water (9:1; 4.5 mL)
  4. stirringthe mixture was stirred at room temperature for 1 h
  5. customremoval of the N-t-BOC group
  6. additionThe reaction mixture was diluted with DCM (10 mL) and saturated aqueous Na2CO3
  7. additionwas added
  8. customThe phases were separated
  9. concentration” filters and the organic phase was concentrated
  10. customThe crude product was purified by preparative HPLC (System B; 10-40% MeCN)
  11. concentrationconcentrated
  12. customto give the product as the free base, which
  13. customThe solvent was evaporated

Sources & evidence

ORD record
ord-5892e27890354f35accf232c8da976e2
Source dataset
uspto-grants-2010_10
Patent number
US07820675B2

Reaction notes

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