Dimethylformamide → 3-{4-[(2S)-1-cyclopropanecarbonyl-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinolin-6-yl]-1H-pyrazol-1-yl}-1lambda6-thiane-1,1-dione

HRID 1051675노트

반응식

HRID 1051675 반응식
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:12]([C:16]4[CH:17]=[N:18][NH:19][CH:20]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:28])=[O:5])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.Br[CH:41]1[CH2:46][CH2:45][S:44](=[O:48])(=[O:47])[CH2:43][CH2:42]1>C(OCC)(=O)C>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:12]([C:16]4[CH:20]=[N:19][N:18]([CH:42]5[CH2:41][CH2:46][CH2:45][S:44](=[O:48])(=[O:47])[CH2:43]5)[CH:17]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:28])=[O:5])[CH2:2][CH2:3]1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 615632594-bromotetrahydro-2H-thiopyran-1,1-dioxideHCID 118075498(S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

생성물 1

HCID 1183060293-{4-[(2S)-1-cyclopropanecarbonyl-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinolin-6-yl]-1H-pyrazol-1-yl}-1lambda6-thiane-1,1-dione

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A 100-mL, round-bottom flask was charged with (S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.200 g, 0.56 mmol), cesium carbonate (0.114 g, 0.35 mmol), N,N-dimethylformamide (5 mL), and 4-bromo-1λ6-thiane-1,1-dione (0.114 g, 0.53 mmol). The resulting mixture stirred at 100° C. for 4 h and was then cooled to room temperature. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (3×10 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (gradient elution with 25-50% ethyl acetate/petroleum). The product was further purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 5 um, 19×100 mm; mobile phase, Water and acetonitrile (55% to 75% acetonitrile in 7 min, flow rate: 20 mL/min); Detector, UV 220&254 nm. This afforded 3-{4-[(2S)-1-cyclopropanecarbonyl-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinolin-6-yl]-1H-pyrazol-1-yl}-1λ6-thiane-1,1-dione (0.122 g, 43%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 0.76-0.82 (m, 1H), 0.92-1.02 (m, 2H), 1.13-1.22 (m, 4H), 1.42-1.50 (m, 1H), 1.95-2.08 (m, 3H), 2.08-2.13 (m, 1H), 2.14-2.37 (m, 3H), 2.68-2.77 (m, 1H), 3.11-3.19 (m, 2H), 3.37 (s, 1H), 3.53-3.60 (m, 1H), 4.66-4.72 (m, 1H), 4.74-4.81 (m, 1H), 6.79 (d, J=8.00 Hz, 2H), 6.98 (t, J=7.60 Hz, 1H), 7.23 (t, J=7.60 Hz, 2H), 7.62 (d, J=8.40 Hz, 1H), 7.83 (s, 1H), 8.05 (s, 1H). MS (ESI, pos. ion) m/z 506 [M+H]+.

후처리

  1. temperaturewas then cooled to room temperature
  2. washwashed with water (3×10 mL)
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified via column chromatography on silica gel (gradient elution with 25-50% ethyl acetate/petroleum)
  7. customThe product was further purified by preparative-HPLC with the following conditions (Waters I)
  8. custommobile phase, Water and acetonitrile (55% to 75% acetonitrile in 7 min, flow rate: 20 mL/min)

출처 및 근거

ORD 기록
ord-85ae844a119745cb99f4b6703cd0d3d9
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388161B2

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