2-Bromobenzonitrile → 7-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,1'-isoindol]-3'-amine

HRID 1409505노트

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HRID 1409505 반응식
C([Li])CCC.Br[C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[C:9]#[N:10].[Br:15][C:16]1[CH:17]=[C:18]2[C:29](=[CH:30][CH:31]=1)[O:28][C:21]1[C:22]([F:27])=[N:23][C:24]([Cl:26])=[CH:25][C:20]=1[C:19]2=[N:32]S(C(C)(C)C)=O>C1COCC1>[Br:15][C:16]1[CH:17]=[C:18]2[C:19]3([C:11]4[C:8](=[CH:7][CH:14]=[CH:13][CH:12]=4)[C:9]([NH2:10])=[N:32]3)[C:20]3[CH:25]=[C:24]([Cl:26])[N:23]=[C:22]([F:27])[C:21]=3[O:28][C:29]2=[CH:30][CH:31]=1

참가 물질

5

반응물 3

HCID 162722-BromobenzonitrileHCID 86658361N-(7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-ylidene)-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

생성물 1

HCID 866892407-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,1'-isoindol]-3'-amine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

A solution of n-butyllithium (1.6 M in hexane, 0.75 mL, 1.2 mmol, Aldrich) was added dropwise to a solution of 2-bromobenzonitrile (219 mg, 1.2 mmol, Oakwood Products) in THF (30 mL) at −78° C. under nitrogen atmosphere. The reaction mixture was allowed to stir for 5 min at −78° C. Subsequently, a solution of N-(7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-ylidene)-2-methylpropane-2-sulfinamide (400 mg, 0.93 mmol, step 1) in THF (30 mL) was added. After 5 min, the reaction mixture was quenched with aqueous, saturated solution of NH4Cl and EtOAc was added. The organic phase was separated and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (55-100% EtOAc/hexanes) to afford the title compound as a yellow solid. MS m/z=431.9 [M+H]+. Calculated for C19H10BrClFN3O: 430.7.

후처리

  1. waitAfter 5 min
  2. customthe reaction mixture was quenched with aqueous, saturated solution of NH4Cl and EtOAc
  3. additionwas added
  4. customThe organic phase was separated
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by flash chromatography on silica gel (55-100% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-4e5bfd54534643e4acde9c0ea850b394
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921363B2

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