N-Iodosuccinimide → Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

HRID 2047127Notes

Reaction equation

HRID 2047127 reaction equation
[CH3:1][Si:2]([CH3:39])([CH3:38])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:8]1[N:13]2[N:14]=[CH:15][CH:16]=[C:12]2[N:11]=[C:10]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:9]=1.[I:40]N1C(=O)CCC1=O>CN(C=O)C.CCOC(C)=O>[CH3:37][Si:34]([CH3:36])([CH3:35])[CH2:33][CH2:32][O:31][CH2:30][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:1])([CH3:38])[CH3:39])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([I:40])=[C:12]2[N:11]=[C:10]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:9]=1

Participants

5

Reactant 2

HCID 120273N-IodosuccinimideHCID 66738492tert-Butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

Product 1

HCID 66584511Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylateYield 78.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (5 g, 8.65 mmol) in DMF (15 mL) was added N-iodosuccinimide (1.86 g, 8.27 mmol) and the resulting mixture was allowed to stir at room temperature for 1 hour. The mixture diluted with EtOAc (100 mL), washed with water (20 mL). The aqueous layer was extracted with EtOAc (20 mL) once, and combined organic layer was washed with water (20 mL) three times, brine once and dried (MgSO4). After concentration, the residue was purified by column chromatography on silica gel. Elution with EtOAc/Hex (0-30%) gave tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (4.55 g, 75%). (Note: DMF could be replaced by acetonitrile.)

Workup

  1. washwashed with water (20 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (20 mL) once
  3. washwas washed with water (20 mL) three times, brine once
  4. dry with materialdried (MgSO4)
  5. concentrationAfter concentration
  6. customthe residue was purified by column chromatography on silica gel
  7. washElution with EtOAc/Hex (0-30%)

Sources & evidence

ORD record
ord-d1dfb37a82d64178a3d96bfdc5e286c6
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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