Tetrabutylammonium Fluoride → 2-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246320Notes

Reaction equation

HRID 246320 reaction equation
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([C:25](C)(C)[O:26][SiH2]C(C)(C)C)[CH:23]=4)[N:18]([CH3:34])[N:17]=3)[N:14]=2)[N:9]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:8]=1)=[O:6])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][OH:26])[CH:23]=4)[N:18]([CH3:34])[N:17]=3)[N:14]=2)[N:9]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:41])([CH3:40])[CH3:42])[CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 1317312222-[5-(2-tert-butylsilyloxypropan-2-yl)-1-methylindazol-3-yl]-N-propan-2-yl-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712804422-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask, 2-[5-(tert-butyl-dimethyl-silanyloxymethyl)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (425 mg, 0.66 mmol) was dissolved in THF (6 ml). The light yellow solution was cooled to 0° C. and tetrabutylammonium fluoride (1.0 M in THF, 0.24 ml, 0.240 mmol) was added dropwise. The reaction mixture was allowed to warm slowly to room temperature over 2 h then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then concentrated. The residue was triturated with diethyl ether to afford 2-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a yellow powder which was used without further purification.

Workup

  1. temperatureto warm slowly to room temperature over 2 h
  2. customthen quenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with water and brine
  5. concentrationthen concentrated
  6. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-cb2ec57301da4dce816533f1861d2ac9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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