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 1468703노트

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HRID 1468703 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

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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.

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-98fdbc255f3a42f1aa67970aa221677e
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006229B2

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