Cesium carbonate → 6-methoxy-5-((1-methylpiperidin-4-yl)amino)-2-(4-((trifluoromethyl)thio)benzyl)-2,3-dihydro-1H-inden-1-one

HRID 62265

반응식

HRID 62265 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C:7](=[O:13])[CH:6]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1)[CH2:5]2.[CH3:26][N:27]1[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:12][O:11][C:10]1[CH:9]=[C:8]2[C:4]([CH2:5][CH:6]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[C:7]2=[O:13])=[CH:3][C:2]=1[NH:33][CH:30]1[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27375314-Amino-1-methylpiperidineHCID 1179400865-bromo-6-methoxy-2-(4-((trifluoromethyl)thio)benzyl)-2,3-dihydro-1H-inden-1-one

생성물 1

HCID 1179401896-methoxy-5-((1-methylpiperidin-4-yl)amino)-2-(4-((trifluoromethyl)thio)benzyl)-2,3-dihydro-1H-inden-1-one

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

반응 조건

온도
110 °C

실험 절차

To a solution of 143 (75 mg, 0.174 mol) and 1-methylpiperidin-4-amine 134 (23.8 mg, 0.0208 mol) in toluene 15 mL was added cesium carbonate (113.3 mg, 0.348 mol). The reaction was degassed and purged with nitrogen for 10 min. Pd2(dba)3 (7.96 mg, 0.0087 mol) and BINAP (10.8 mg, 0.0174 mol) was added and again degassed and purged with nitrogen for another 10 min. The reaction was heated to 110° C. overnight under sealed conditions. The reaction was diluted with chloroform and filtered through celite bed. The organic layer was concentrated to get the crude compound 144 and was purified through flash chromatography by using 100-200 mesh silica gel eluting the compound at 7.5% methanol in chloroform as brown coloured solid 6-methoxy-5-((1-methylpiperidin-4-yl)amino)-2-(4-((trifluoromethyl)thio)benzyl)-2, 3-dihydro-1H-inden-1-one 144. 1HNMR (400 MHz, CDCl3) δ ppm 7.55 (bs, 2H), 7.28 (bs, 2H), 7.08 (s, 1H), 6.42 (s, 1H), 4.99 (s, 1H), 3.89 (s, 3H), 3.37 (m, 4H), 2.84 (m, 6H), 2.66 (m, 3H), 2.09 (m, 4H); MS (ESI) m/z 465.0 (M+H).

후처리

  1. customThe reaction was degassed
  2. custompurged with nitrogen for 10 min
  3. customagain degassed
  4. custompurged with nitrogen for another 10 min
  5. additionThe reaction was diluted with chloroform
  6. filtrationfiltered through celite bed
  7. concentrationThe organic layer was concentrated

출처 및 근거

ORD 기록
ord-ca441a85ebbb44bd96faed89664648e9
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446047B2

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