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

HRID 44943Notes

Reaction equation

HRID 44943 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-7f0e09f2fbc44768a327fdd819a81142
Source dataset
uspto-grants-2013_09
Patent number
US08541425B2

Reaction notes

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