Sodium Cyanide → 3-[5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]pentanedinitrile

HRID 44943노트

반응식

HRID 44943 반응식
O[CH2:2][CH:3]([C:7]1[S:8][C:9]([C:12]2[C:13]3[CH:20]=[CH:19][N:18](COCC[Si](C)(C)C)[C:14]=3[N:15]=[CH:16][N:17]=2)=[CH:10][N:11]=1)[CH2:4][C:5]#[N:6].CS(Cl)(=O)=O.[C-:34]#[N:35].[Na+]>C(Cl)Cl.O>[N:15]1[C:14]2[NH:18][CH:19]=[CH:20][C:13]=2[C:12]([C:9]2[S:8][C:7]([CH:3]([CH2:2][C:34]#[N:35])[CH2:4][C:5]#[N:6])=[N:11][CH:10]=2)=[N:17][CH:16]=1

참가 물질

6

반응물 3

HCID 8929Sodium CyanideHCID 31297Methanesulfonyl chlorideHCID 574780724-hydroxy-3-[5-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]butanenitrile

생성물 1

HCID 177549033-[5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]pentanedinitrile수율 7%

시약·촉매·용매 2

HCID 962Water용매2회HCID 6344Dichloromethane용매

실험 절차

A solution of the above prepared 4-hydroxy-3-[5-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]butanenitrile in DCM (12 mL) at 0° C. was treated sequentially with TEA (130 μL, 0.94 mmol) and methanesulfonyl chloride (73 μL, 0.94 mmol). After 1 hour reaction time, the mixture was diluted with water and extracted with ethyl acetate three times. The extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was then dissolved in DMSO (5 mL) and sodium cyanide (110 mg, 2.3 mmol) was added. After 30 minutes, the mixture was diluted with water, extracted with ether, washed with water, brine and dried over sodium sulfate. Concentration and purification by flash column chromatography (ethyl acetate/hexanes) afforded the desired product (14 mg, 7%). MS(ES): 425 (M+1).

후처리

  1. customAfter 1 hour reaction time
  2. extractionextracted with ethyl acetate three times
  3. washThe extracts were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was then dissolved in DMSO (5 mL)
  8. extractionextracted with ether
  9. washwashed with water, brine
  10. dry with materialdried over sodium sulfate
  11. concentrationConcentration and purification by flash column chromatography (ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-7f0e09f2fbc44768a327fdd819a81142
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541425B2

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