Cesium carbonate → N-(4,5-Dihydro-1H-imidazol-2-yl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

HRID 540069ノート

反応式

HRID 540069 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[NH:26]1[CH2:30][CH2:29][N:28]=[C:27]1[NH2:31].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[NH:28]1[CH2:29][CH2:30][N:26]=[C:27]1[NH:31][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 1347844,5-Dihydro-1H-imidazol-2-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

生成物 1

HCID 71255577N-(4,5-Dihydro-1H-imidazol-2-yl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (150 mg, 0.40 mmol, prepared in analogy to the one in Example 2-1), hydrogen iodide salt of 4,5-dihydro-1H-imidazol-2-amine (110 mg, 0.515 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (25 mg, 0.043 mmol), tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol), cesium carbonate (525 mg, 1.6 mmol) and 1,4-dioxane (3 mL) was heated with stirring in a 5 mL of microwave process vial for 2 hours at 120° C. under microwave irradiation. The resulting mixture was filtered and washed with ethyl acetate. The filtrate was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford the product as a solid. MS obsd. (ESI+) [(M+H)+] 422, 1H NMR (400 MHz, CD3OD) δ ppm 7.68-7.59 (m, 2 H), 7.56 (s, 1 H), 7.50-7.41 (m, 2 H), 7.08 (s, 1 H), 5.23 (brs, 2 H), 4.62 (s, 3 H), 3.76 (s, 3 H), 3.61 (t, J=4.93 Hz, 2 H), 2.68 (s, 4 H), 2.45 (s, 2 H).

後処理

  1. temperaturewas heated
  2. filtrationThe resulting mixture was filtered
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-c6a6780dcf0e4dcea58ce628436d19fa
出典データセット
uspto-grants-2014_10
特許番号
US08871756B2

反応ノート

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