Water → HCID 49779329, compound

HRID 1910990Notes

Reaction equation

HRID 1910990 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][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][C:23]#[N:24])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.C(#N)C.O.F[B-](F)(F)F.[Li+].[OH-].[NH4+]>>[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][CH2:28][CH3:29])[CH2:22][C:23]#[N:24])[CH:20]=2)=[N:14][CH:13]=1

Participants

6

Reactant 5

HCID 962Water2×HCID 6342AcetonitrileHCID 14923Ammonium HydroxideHCID 4298216Lithium tetrafluoroborateHCID 59590537HCID 59590537, compound

Product 1

HCID 49779329HCID 49779329, compoundYield 64%

Conditions

Temperature
100 °C

Procedure

To a solution of 3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]octanenitrile (13 g, 0.030 mol) (peak 2 from chiral separation in Step 2) in acetonitrile (200.0 mL, 3.829 mol) and water (16.0 mL, 0.888 mol, ˜8% acetonitrile/water) was added lithium tetrafluoroborate (28.4 g, 0.297 mol). The reaction was refluxed at 100° C. overnight. The mixture was cooled down and 7.2 M of ammonium hydroxide in water (17 mL, 0.12 mol) was added in portions over a period of 5 minutes at room temperature, adjusting pH to 9-10 with stirring for 2 h. The solid was removed by filtration and the filtrate was diluted with acetonitrile, water and MeOH for purification by preparative LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile/water containing 0.15% NH4OH) to give the desired product (5.9 g, 64%). MS calculated for C17H21N6(M+H)+: m/z=309.183. Found: 309.3. 1H NMR (300 MHz, DMSO-D6) δ 12.10 (1H, s), 8.78 (1H, s), 8.66 (1H, s), 8.36 (1H, s), 7.458 (1H), m), 6.97 (1H, m), 4.71 (1H, m), 3.18 (1H, m), 3.16 (1H, br s), 1.93 (1H, m), 1.81 (1H, m) 1.19 (5H, m), 0.97 (1H, m), 0.78 (3H, t, J=6.3 Hz) ppm.

Workup

  1. temperatureThe mixture was cooled down
  2. customThe solid was removed by filtration
  3. additionthe filtrate was diluted with acetonitrile, water and MeOH for purification by preparative LCMS (XBridge C18 Column
  4. washeluting with a gradient of acetonitrile/water containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-2709b967f2804ed3885190844e473324
Source dataset
uspto-grants-2013_12
Patent number
US08604043B2

Reaction notes

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