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

HRID 1897805ノート

反応式

HRID 1897805 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b653f3d1327c4ef2ae2634805fe25967
出典データセット
uspto-grants-2013_08
特許番号
US08519142B2

反応ノート

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