Cesium fluoride → (2S)-ethyl 2-(2-(azetidin-1-yl)-7-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

HRID 879263노트

반응식

HRID 879263 반응식
[N:1]1([C:5]2[S:6][C:7]3[C:13](OS(C(F)(F)F)(=O)=O)=[C:12]([C@H:22]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:11]([CH3:33])=[CH:10][C:8]=3[N:9]=2)[CH2:4][CH2:3][CH2:2]1.Cl.[O:35]1[C:46]2[C:47]3[C:42]([C:43](B(O)O)=[CH:44][CH:45]=2)=[N:41][CH:40]=[CH:39][C:38]=3[CH2:37][CH2:36]1.[F-].[Cs+].C([O-])(O)=O.[Na+]>CC(OC)(C)C.COC1C=CC=C(OC)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].COCCOC>[N:1]1([C:5]2[S:6][C:7]3[C:13]([C:43]4[C:42]5[C:47]6=[C:38]([CH2:37][CH2:36][O:35][C:46]6=[CH:45][CH:44]=4)[CH:39]=[CH:40][N:41]=5)=[C:12]([C@H:22]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:11]([CH3:33])=[CH:10][C:8]=3[N:9]=2)[CH2:2][CH2:3][CH2:4]1

참가 물질

7

반응물 4

HCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 66631384(2,3-Dihydropyrano[4,3,2-de]quinolin-7-yl)boronic acid hydrochlorideHCID 86699784(S)-ethyl 2-(2-(azetidin-1-yl)-5-methyl-7-(trifluoromethylsulfonyloxy)benzo[d]thiazol-6-yl)-2-tert-butoxyacetate

생성물 1

HCID 71003367(2S)-ethyl 2-(2-(azetidin-1-yl)-7-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate수율 52.7%

시약·촉매·용매 2

HCID 71311105SPhos Palladacycle촉매2회HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
110 °C

실험 절차

To a solution of 33 (38 mg, 0.075 mmol) in freshly distilled DME (1 mL) was added 2,3-dihydropyrano[4,3,2-de]quinolin-7-ylboronic acid hydrochloride (24 mg, 0.097 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct, [SPhos Palladacycle] (5 mg, 0.0075 mmol), and cesium fluoride (46 mg, 0.3 mmol). The reaction mixture was heated in the microwave at 110° C. for 45 min. A saturated solution of NaHCO3 (3 mL) was added, and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layer were dried, filtered, and concentrated in vacuo. The crude material was purified by column chromatography (EtOAc/hexanes) to give 21 mg of 34. LCMS-ESI+: calc'd for C30H33N3O4S: 532.2 (M+H+); Found: 532.0 (M+H+).

후처리

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc
  3. customThe combined organic layer were dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by column chromatography (EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-27253c9b8893499482a678da4061947c
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987250B2

반응 노트

불러오는 중…