Acetonitrile → 3-[4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile

HRID 1843518Notes

Reaction equation

HRID 1843518 reaction equation
C[Si](C)(C)CCOC[N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([CH:21]([CH2:25][C:26]#[N:27])[CH2:22][C:23]#[N:24])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.C(#N)C.F[B-](F)(F)F.[Li+].[OH-].[NH4+]>O>[N:12]1[C:11]2[NH:7][CH:8]=[CH:9][C:10]=2[C:15]([C:16]2[CH:17]=[N:18][N:19]([CH:21]([CH2:22][C:23]#[N:24])[CH2:25][C:26]#[N:27])[CH:20]=2)=[N:14][CH:13]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 14923Ammonium HydroxideHCID 4298216Lithium tetrafluoroborateHCID 574778773-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile

Product 1

HCID 574777833-[4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrileYield 91.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile (10.0 g, 0.0245 mol) was dissolved in ACN (200 mL, 3.83 mol) and water (20 g, 1.1 mol) at rt. To this lithium tetrafluoroborate (23.0 g, 0.245 mol) was added giving a cloudy solution. The reaction was heated to reflux and monitored by HPLC. After heating for 24 h the reaction was allowed to cool to rt and then cooled in an ice bath. To this, ammonium hydroxide (23 mL, 0.59 mol) was added slowly. The reaction was allowed to warm to rt. After stirring for 18 hs the reaction was diluted with water and concentrated in vacuo to remove the ACN, giving a precipitate. The solids were collected, washed with water and dried to give the title compound as an off-white solid (6.2 gm, 91%), LC/MS (M+H)+: 278, 1H NMR (DMSO-d6) δ 8.9 (s, 1H), 8.72 (s, 1H), 8.43 (s, 1H), 7.59 (d, 1H), 6.92 (d, 1H), 5.21 (m, 1H), 3.25 (m, 4H).

Workup

  1. customat rt
  2. customgiving a cloudy solution
  3. temperatureThe reaction was heated
  4. temperatureto reflux
  5. temperatureAfter heating for 24 h the reaction
  6. temperaturecooled in an ice bath
  7. temperatureto warm to rt
  8. concentrationconcentrated in vacuo
  9. customto remove the ACN
  10. customgiving a precipitate
  11. customThe solids were collected
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-2f907b54db4b404fb4eda0a40dc189b0
Source dataset
uspto-grants-2015_02
Patent number
US08946245B2

Reaction notes

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