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 540056노트

반응식

HRID 540056 반응식
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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9832798Tris(dibenzylideneacetone) dipalladium촉매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-c47b5fd4896c4a95ae73e64d5fae2657
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871756B2

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