Ammonium Hydroxide → 4-[1-(1-methyl-2-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}ethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 1772781Notes

Reaction equation

HRID 1772781 reaction equation
[CH3:1][CH:2]([N:19]1[CH:23]=[C:22]([C:24]2[C:25]3[CH:32]=[CH:31][N:30](COCC[Si](C)(C)C)[C:26]=3[N:27]=[CH:28][N:29]=2)[CH:21]=[N:20]1)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([S:10]([C:13]2[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=2)(=[O:12])=[O:11])[CH2:6][CH2:5]1.F[B-](F)(F)F.[Li+].[OH-].[NH4+]>C(#N)C.O>[CH3:1][CH:2]([N:19]1[CH:23]=[C:22]([C:24]2[C:25]3[CH:32]=[CH:31][NH:30][C:26]=3[N:27]=[CH:28][N:29]=2)[CH:21]=[N:20]1)[CH2:3][N:4]1[CH2:5][CH2:6][N:7]([S:10]([C:13]2[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=2)(=[O:12])=[O:11])[CH2:8][CH2:9]1

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 4298216Lithium tetrafluoroborateHCID 670549524-[1-(1-methyl-2-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}ethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 581809464-[1-(1-methyl-2-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}ethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidineYield 84.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-[1-(1-methyl-2-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}ethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.243 g, 0.415 mmol) in acetonitrile (10 mL) and water (1 mL; ˜8% water/acetonitrile) was added lithium tetrafluoroborate (1.02 g, 10.7 mmol). The solution was refluxed at 100° C. overnight. The mixture was cooled down and 7.2 M of ammonium hydroxide in water (0.346 mL, 2.49 mmol) was added in portions over a period of 5 min at RT, adjusting pH to 9-10 with stirring for 2 h. The solids were removed by filtration and the filtrate was purified on RP-HPLC (XBridge C-18 Column, eluting with a gradient of acetonitrile/water containing 0.15% NH4OH, at flow rate 60 mL/min) to give the desired product (0.159 g, 84.1%). LCMS calculated for C20H26N9O2S(M+H)+: m/z=456.2; Found: 456.4.

Workup

  1. temperatureThe mixture was cooled down
  2. customThe solids were removed by filtration
  3. customthe filtrate was purified on RP-HPLC (XBridge C-18 Column
  4. washeluting with a gradient of acetonitrile/water containing 0.15% NH4OH, at flow rate 60 mL/min)

Sources & evidence

ORD record
ord-06fd2536727a4669b2233235175f69f9
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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