4-(2-Aminoethyl)-1lambda~6~,4-thiazinane-1,1-dione → 2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-[2-(1,1-dioxidothiomorpholin-4-yl)ethyl]-6-methylquinolin-4-amine

HRID 540056ノート

反応式

HRID 540056 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.CC(C)([O-])C.[Na+].[O:32]=[S:33]1(=[O:42])[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][NH2:41])[CH2:35][CH2:34]1>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[O:24]=[S:16]1(=[O:25])[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH2:19][N:13]([C:4]2[CH:3]=[C:2]([NH:41][CH2:40][CH2:39][N:36]3[CH2:37][CH2:38][S:33](=[O:42])(=[O:32])[CH2:34][CH2:35]3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=2)[CH2:14][CH2:15]1

参加物

7

反応物 3

HCID 27606184-(2-Aminoethyl)-1lambda~6~,4-thiazinane-1,1-dioneHCID 23676156Sodium t-butoxideHCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

生成物 1

HCID 712620942-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-[2-(1,1-dioxidothiomorpholin-4-yl)ethyl]-6-methylquinolin-4-amine

試薬・触媒・溶媒 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9832798Tris(dibenzylideneacetone) dipalladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To a solution 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) in 1,4-dioxane (4 mL) was added tris(dibenzylideneacetone) dipalladium (0) (40 mg, 0.04 mmol), 1,1′-bis(diphenyphosphino)ferrocene (25 mg, 0.04 mmol), sodium tert-butoxide (77 mg, 0.80 mmol) and 2-(1,1-dioxidothio-morpholin-4-yl)ethanamine (107 mg, 0.60 mmol). The resulting mixture was evacuated and refilled with nitrogen, sealed and heated at 120° C. overnight. After being cooled to room temperature, the mixture was filtered and washed with ethyl acetate, the organic layers were combined and concentrated in vacuo, the residue was purified by flash chromatography (eluenting with 2% methanol in dichloromethane) to afford 67 mg of the title compound as a light solid (yield was 40%). MS obsd. (ESI+) [(M+H)+] 515, 1H NMR (400 MHz, CDCl3) 8.05 (d, J=7.6 Hz, 1 H), 7.66 (d, J=7.2 Hz, 1 H), 7.53-7.48 (m, 2 H), 7.37-7.28 (m, 2 H), 7.21 (s, 1 H), 5.88 (s, 1 H), 5.26 (m, 1 H), 5.12 (s, 1 H), 4.6 (brs, 1 H), 3.56 (m, 1 H), 3.33 (m, 2 H), 3.14 (m, 8 H), 2.99 (t, J=4.8 Hz, 2 H), 2.46 (s, 3 H), 2.0 (d, J=4.5 Hz, 2 H).

後処理

  1. customThe resulting mixture was evacuated
  2. additionrefilled with nitrogen
  3. customsealed
  4. temperatureAfter being cooled to room temperature
  5. filtrationthe mixture was filtered
  6. washwashed with ethyl acetate
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by flash chromatography (eluenting with 2% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-c47b5fd4896c4a95ae73e64d5fae2657
出典データセット
uspto-grants-2014_10
特許番号
US08871756B2

反応ノート

読み込み中…