Ammonium Hydroxide → 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]heptanenitrile

HRID 1505480Notes

Reaction equation

HRID 1505480 reaction equation
C[Si](C)(C)CC[O:5]C[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][CH2:26][CH2:27][CH3:28])[CH2:22][C:23]#[N:24])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.F[B-](F)(F)F.[Li+].[OH-].[NH4+]>O.C(#N)C>[NH4+:7].[OH-:5].[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]([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:22][C:23]#[N:24])[CH:20]=2)=[N:14][CH:13]=1

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 4298216Lithium tetrafluoroborateHCID 595905383-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]heptanenitrile

Product 2

HCID 14923Ammonium HydroxideYield 0.15%HCID 498192963-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]heptanenitrileYield 147.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Into a 500 mL round bottom flask fitted with stir bar, condenser and nitrogen inlet was charged acetonitrile (58 mL), water (5.0 mL), 3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]heptanenitrile (2nd peak from chiral separation in step 2, 3.50 g, 8.24 mmol), and lithium tetrafluoroborate (7.88 g, 82.4 mmol). The mixture was warmed to reflux overnight. To the reaction mixture was charged 7.2 M of ammonium hydroxide in water (4.3 mL, 31 mmol) in portions over a period of 5 minutes at room temperature adjusting pH to 9-10. The resulting reaction mixture was stirred for 2 hours at room temperature. Solid was removed by filtration and the filtrate was purified on RP-HPLC (XBridge column C18, 30×100 mm 5 μM; with injection volume 5 mL and flow rate 60 mL/min; at a gradient of water and acetonitrile and 0.15% NH4OH) to give desired product (1.79 g, 74%). LCMS calculated for C16H19N6(M+H)+: m/z=295.2. Found: 295.2.

Workup

  1. customInto a 500 mL round bottom flask fitted
  2. temperatureThe mixture was warmed
  3. temperatureto reflux overnight
  4. customThe resulting reaction mixture
  5. stirringwas stirred for 2 hours at room temperature
  6. customSolid was removed by filtration
  7. customthe filtrate was purified on RP-HPLC (XBridge column C18, 30×100 mm 5 μM

Sources & evidence

ORD record
ord-621867605a85426dad8e596b288e7ba3
Source dataset
uspto-grants-2015_12
Patent number
US09216984B2

Reaction notes

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