Ammonium Hydroxide → 2-(2-(4-((6-Amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol

HRID 1972646Notes

Reaction equation

HRID 1972646 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:22]=[CH:21][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=3)[CH:13]([C:30]#[C:31][CH3:32])[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[NH4+:34]>CCO>[NH2:34][C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:22]=[CH:21][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=3)[CH:13]([C:30]#[C:31][CH3:32])[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14923Ammonium HydroxideHCID 86670426HCID 86670426, compound

Product 1

HCID 569329932-(2-(4-((6-Amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanolYield 79.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

To a 330-mL pressure vessel was added 2-(2-(4-((6-chloro-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (6.50 g, 13.3 mmol), EtOH (80 mL), and ammonium hydroxide (30%, 80.0 mL, 616 mmol, J. T. Baker, Philipsburg, N.J.). The tube was sealed and heated at 120° C. for 10 h and then the solvent was removed in vacuo. The residue was partitioned between water (100 mL) and DCM (200 mL). The aqueous layer was extracted with DCM (2×100 mL) and the combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography (330 g of silica, 1 to 5% 2 M NH3 in MeOH in DCM) to afford 2-(2-(4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (5.0 g) as a mixture of four isomers.

Workup

  1. customThe tube was sealed
  2. customthe solvent was removed in vacuo
  3. customThe residue was partitioned between water (100 mL) and DCM (200 mL)
  4. extractionThe aqueous layer was extracted with DCM (2×100 mL)
  5. dry with materialthe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (330 g of silica, 1 to 5% 2 M NH3 in MeOH in DCM)

Sources & evidence

ORD record
ord-2066f7965b4f476eb6eb310f9879acb2
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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