M-Phenylenediamine → N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzene-1,3-diamine

HRID 540101노트

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HRID 540101 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.[C:26]1([NH2:33])[CH:31]=[CH:30][CH:29]=[C:28]([NH2:32])[CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[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:32][C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([NH2:33])[CH:27]=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 4

HCID 7935M-PhenylenediamineHCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

생성물 1

HCID 86691382N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzene-1,3-diamine

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

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), benzene-1,3-diamine (86 mg, 0.80 mmol), palladium acetate (18 mg, 0.04 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (50 mg, 0.04 mmol), potassium phosphate (169.6 mg, 0.8 mmol) and 1,4-dioxane (3 mL) in a 2-5 mL of process vial was heated at 140° C. under microwave irradiation for 1.5 hours. After being cooled to room temperature, the 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 pure product as a solid. MS obsd. (ESI+) [(M+H)+] 445, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.31 (s, 1 H), 7.88 (dd, J=6.06, 1.52 Hz, 2 H), 7.63 (td, J=7.52, 1.14 Hz, 1 H), 7.54-7.46 (m, 1 H), 7.42-7.33 (m, 2 H), 7.33-7.27 (m, 1 H), 7.16 (t, J=7.83 Hz, 1 H), 6.52 (t, J=1.89 Hz, 1 H), 6.49-6.34 (m, 3 H), 5.23 (s, 2 H), 4.86 (s, 2 H), 3.60 (brs, 2 H), 2.38 (s, 3 H).

후처리

  1. temperatureAfter being cooled to room temperature
  2. filtrationthe 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

출처 및 근거

ORD 기록
ord-f20aa9189a604cb7a9bcab6117e174cc
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871756B2

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