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

HRID 1501445Notes

Reaction equation

HRID 1501445 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%

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

Sources & evidence

ORD record
ord-c97dd2f89b504bc888984013d057dce3
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

Loading…