N-Iodosuccinimide → Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate

HRID 334366Notes

Reaction equation

HRID 334366 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][C:20]([CH2:28][OH:29])([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:9]=1.C1C(=O)N([I:47])C(=O)C1>CC#N>[CH3:39][Si:2]([CH3:38])([CH3:1])[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][C:16]([I:47])=[C:12]2[N:11]=[C:10]([CH:17]2[CH2:18][CH2:19][C:20]([CH2:28][OH:29])([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:21][CH2:22]2)[CH:9]=1

Participants

4

Reactant 2

HCID 120273N-IodosuccinimideHCID 66584374Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate

Product 1

HCID 66583826Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylateYield 90.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate (733 mg, 1.27 mmol) in CH3CN (10 mL) was added NIS (313 mg, 1.39 mmol). The resulting solution was stirred at rt for 30 min before quenching with Na2S2O3 (sat.). CH3CN was removed under reduced pressure. The residue was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.6 in 50% EtOAc) to afford ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate as a colorless oil (811 mg).

Workup

  1. custombefore quenching with Na2S2O3 (sat.)
  2. customCH3CN was removed under reduced pressure
  3. additionThe residue was diluted with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.6 in 50% EtOAc)

Sources & evidence

ORD record
ord-edf8ca7b735e4bd6bf1b7912a0ad7b8a
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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