Dichloromethane → 2-Chloro-4-[5-(1,1-dioxo-isothiazolidin-2-ylmethyl)-pyridin-3-yl]-benzonitrile

HRID 391321노트

반응식

HRID 391321 반응식
[Cl:1][C:2]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[C:20]1[CH:21]=[N:22][CH:23]=[C:24]([CH2:26][N:27]2[CH2:31][CH2:30][CH2:29][S:28]2(=[O:33])=[O:32])[CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:9]=[C:8]([C:20]2[CH:21]=[N:22][CH:23]=[C:24]([CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][S:28]3(=[O:32])=[O:33])[CH:25]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 579261132-Chloro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 595783953-Bromo-5-(1,1-dioxo-isothiazolidin-2-ylmethyl)-pyridine

생성물 1

HCID 498209032-Chloro-4-[5-(1,1-dioxo-isothiazolidin-2-ylmethyl)-pyridin-3-yl]-benzonitrile

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

To 2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (217 mg, 0.824 mmol) in DMF (4 mL) were added 3-bromo-5-(1,1-dioxo-isothiazolidin-2-ylmethyl)-pyridine (200 mg, 0.687 mmol) and 2M aqueous sodium carbonate (0.687 mL, 1.374 mmol). The reaction mixture was flushed and evacuated with N2 thrice followed by the addition of PdCl2(dppf).CH2Cl2 adduct (28.0 mg, 0.034 mmol). The reaction mixture was stirred at 100° C. for 1 hour. The reaction was cooled to room temperature, diluted with ethyl acetate and washed with water thrice. The organic layer was separated, dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in DMF (5 mL) and purified using Xbridge C18 eluting with a 10 to 100% ACN-water to afford 2-chloro-4-[5-(1,1-dioxo-isothiazolidin-2-ylmethyl)-pyridin-3-yl]-benzonitrile as a white solid. HRMS: (ESI) m/z 348.0575 [(M+H)+ Calcd for C16H14ClN3O2S 348.0573]. 1H NMR (400 MHz, MeOD) δ ppm 2.33-2.47 (m, 2H), 3.24-3.33 (m, 4H), 4.37 (s, 2H), 7.87 (dd, J=8.2, 1.6 Hz, 1H), 7.97 (d, J=8.1 Hz, 1H), 8.06 (d, J=1.5 Hz, 1H), 8.22 (t, J=2.1 Hz, 1H), 8.68 (d, J=2.0 Hz, 1H), 8.87 (d, J=2.3 Hz, 1H).

후처리

  1. customThe reaction mixture was flushed
  2. customevacuated with N2 thrice
  3. additionfollowed by the addition of PdCl2(dppf)
  4. temperatureThe reaction was cooled to room temperature
  5. washwashed with water thrice
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude was dissolved in DMF (5 mL)
  10. custompurified
  11. washC18 eluting with a 10 to 100% ACN-water

출처 및 근거

ORD 기록
ord-49440cdaa2a548339841f20f43862440
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383827B2

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