1,1'-Carbonyldiimidazole → 13-Cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 273356ノート

反応式

HRID 273356 の反応式
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:32](O)=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:22][CH:23]=[CH:24][N:25]=4)=[CH:18][C:17]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:35](N1C=CN=C1)([N:37]1[CH:41]=CN=C1)=O.C[NH:48][S:49](NC)(=[O:51])=[O:50].C1CCN2C(=NCCC2)CC1>C1COCC1>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:32]([NH:48][S:49]([N:37]([CH3:41])[CH3:35])(=[O:51])=[O:50])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:22][CH:23]=[CH:24][N:25]=4)=[CH:18][C:17]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89736N,N'-DimethylsulfamideHCID 2473840813-cyclohexyl-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

生成物 1

HCID 2473840713-Cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide収率 131.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

13-Cyclohexyl-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (63 mg, 0.14 mMol) was dissolved in 1.7 mL of THF and carbonyldiimidazole (31 mg, 0.19 mMol) added. The reaction was stirred under a nitrogen atmosphere at room temperature for 1 hr then heated to reflux for 1 hr. The reaction was cooled under nitrogen atmosphere and dimethylsulfamide (91 mg, 0.73 mMol) added followed by DBU (23 uL, 0.15 mMol). The reaction was heated to 50 C under a nitrogen atmosphere for 4 hrs, cooled under nitrogen and stirred at room temperature overnight. The reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The organic phase washed with brine, dried over magnesium sulfate and volatiles removed in vacuuo to yield 103 mg of a crude product as an amorphous yellow film. The crude product was dissolved in methanol and purified by prep HPLC under the following conditions: Shimadzu prep. HPLC using Discovery VP software; % A=10% methanol, 90% water, 0.1% TFA; % B=90% methanol, 10% water, 0.1% TFA; Initial % B=50; Final % B=100; Gradient=15 min; Runtime=25 min; Flow rate=25 ml/min; Column=Waters Sunfire 19 mm×100 mm; Peak collection=12.16 min to 12.96 min. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.23 (1 H, br. s.), 1.36-1.45 (2 H, m), 1.56 (1 H, br. s.), 1.78 (2 H, d, J=10.07 Hz), 2.00 (2 H, br. s.), 2.07 (2 H, br. s.), 2.78-2.91 (1 H, m), 3.09 (6 H, s), 3.94 (3 H, s), 4.43 (1 H, br. s.), 5.91 (1 H, br. s.), 7.03 (1 H, d, J=2.44 Hz), 7.10 (1 H, dd, J=8.55, 2.75 Hz), 7.50 (1 H, d, J=1.53 Hz), 7.55 (1H, d, J=8.55 Hz), 7.65 (1 H, s), 7.69 (1 H, s), 7.89 (1 H, d, J=8.55 Hz), 8.24 (1 H, s), 8.81 (1 H, br. s.). HPLC analysis: Shimadzu Analytical HPLC using Discovery VP software: % A=10% methanol, 90% water, 0.1% trifluoroacetic acid; % B=90% methanol, 10% water, 0.1% trifluoroacetic acid; Initial % B=50; Final % B=100; Gradient=5 min; Runtime=6 min; Flow rate=5 ml/min; Wavelength=220 nm; Column=Phenomenex Luna 3.0 mm×50 mm S10. Retention Time=3.65 min, purity 93%; Flow injection Mass Spectrometry: MS m/z 561(MH+), m/z 559(M-H)−.

後処理

  1. temperaturethen heated
  2. temperatureto reflux for 1 hr
  3. temperatureThe reaction was cooled under nitrogen atmosphere
  4. temperatureThe reaction was heated to 50 C under a nitrogen atmosphere for 4 hrs
  5. temperaturecooled under nitrogen
  6. stirringstirred at room temperature overnight
  7. customThe reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid
  8. washThe organic phase washed with brine
  9. dry with materialdried over magnesium sulfate and volatiles
  10. customremoved in vacuuo

出典と根拠

ORDレコード
ord-98593bc06da94776945bb5f26bc8fc88
出典データセット
uspto-grants-2008_11
特許番号
US07456165B2

反応ノート

読み込み中…