Hydrochloric Acid → 2-Methoxy-5-methyl-n-{7-[(3-methylpiperazin-1-yl)methyl]-1-benzofuran-5-yl}benzenesulfonamide, dihydrochloride

HRID 1162058ノート

反応式

HRID 1162058 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:11][N:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH:14]([CH3:25])[CH2:13]2)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.N1C=CC=CC=1.CO[C:34]1[C:39]([CH3:40])=[CH:38][C:37]([S:41]([Cl:44])(=[O:43])=[O:42])=[CH:36][CH:35]=1.[ClH:45].C[CH2:47][O:48]CC>C(Cl)Cl.C1COCC1.CO>[ClH:44].[ClH:45].[CH3:47][O:48][C:36]1[CH:35]=[CH:34][C:39]([CH3:40])=[CH:38][C:37]=1[S:41]([NH:1][C:2]1[CH:3]=[C:4]([CH2:11][N:12]2[CH2:17][CH2:16][NH:15][CH:14]([CH3:25])[CH2:13]2)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1)(=[O:42])=[O:43]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 3283Diethyl EtherHCID 159153174-Methoxy-3-methylbenzene-1-sulfonyl chlorideHCID 66894181Tert-butyl 4-[(5-amino-1-benzofuran-7-yl)methyl]-2-methylpiperazine-1-carboxylate

生成物 1

HCID 1317283902-Methoxy-5-methyl-n-{7-[(3-methylpiperazin-1-yl)methyl]-1-benzofuran-5-yl}benzenesulfonamide, dihydrochloride収率 29%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 21919333Tetrahydrofurane dichloromethane溶媒

実験手順

tert-Butyl 4-[(5-amino-1-benzofuran-7-yl)methyl]-2-methylpiperazine-1-carboxylate (41 mg crude starting material, 0.11 mmol; obtained in Step 3) was dissolved in dry DCM:THF (2:1; 3 mL). Pyridine (18 μL, 0.22 mmol) and 6-methoxy-m-toluenesulfonyl chloride (36 mg, 0.17 mmol) were added. The resultant mixture was stirred at room temperature for 2 h and the solvent was evaporated under reduced pressure followed by purification by flashtube (11% 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 (16 mg, 29%) as an off-white solid. HPLC 99%, RT=1.48 min (System A; 10-97% MeCN over 3 min), 100%, RT=1.30 min (System B; 10-97% MeCN over 3 min). 1H NMR (400 MHz, methanol-d4) δ ppm 1.38-1.45 (m, J=6.53 Hz, 3H) 2.20 (s, 3H) 3.34-3.42 (m, J=13.30 Hz, 1H) 3.46-3.78 (m, 5H) 3.79-3.91 (m, 1H) 3.98 (s, 3H) 4.71 (s, 2H) 6.87 (d, J=2.26 Hz, 1H) 7.04 (d, J=8.53 Hz, 1H) 7.29-7.34 (m, J=8.78, 2.01 Hz, 1H) 7.37 (d, J=2.26 Hz, 1H) 7.51-7.53 (m, J=2.01 Hz, 1H) 7.54 (d, J=2.26 Hz, 1H) 7.85 (d, J=2.01 Hz, 1H). MS (ESI+) for C22H27N3O4S m/z 430 (M+H)+.

後処理

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

出典と根拠

ORDレコード
ord-59baf85284ee4d589b81d8ef0558876b
出典データセット
uspto-grants-2010_10
特許番号
US07820675B2

反応ノート

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