Tetrabutylammonium Fluoride → (S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)-N-(5-methylpyridin-2-yl)propanamide

HRID 1098034Notes

Reaction equation

HRID 1098034 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([N:26]1[C:30]2=[N:31][CH:32]=[N:33][C:34]([O:35][C@@H:36]([CH2:47][O:48][CH2:49][CH2:50][O:51][Si](C(C)(C)C)(C3C=CC=CC=3)C3C=CC=CC=3)[C:37]([NH:39][C:40]3[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][N:41]=3)=[O:38])=[C:29]2[CH:28]=[N:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1>[CH2:19]([N:26]1[C:30]2=[N:31][CH:32]=[N:33][C:34]([O:35][C@@H:36]([CH2:47][O:48][CH2:49][CH2:50][OH:51])[C:37]([NH:39][C:40]3[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][N:41]=3)=[O:38])=[C:29]2[CH:28]=[N:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504536(S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-methylpyridin-2-yl)propanamide

Product 1

HCID 57504411(S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)-N-(5-methylpyridin-2-yl)propanamideYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF) (0.896 mL, 0.90 mmol) was added to a stirred solution of (S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AL1) (342 mg, 0.50 mmol) in tetrahydrofuran (20 mL). The resulting solution was stirred at ambient temperature for 30 minutes. The reaction mixture was quenched with saturated NH4Cl (10 mL), and diluted with water (20 mL) and EtOAc (70 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (70 mL), The combined organics were dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane to afford the product (170 mg, 76%). 1H NMR (400 MHz, CDCl3) 2.28 (3H, s), 2.91 (1H, s), 3.68-3.74 (4H, m), 4.09-4.20 (2H, m), 5.65 (2H, s), 6.05 (1H, t), 7.25-7.36 (5H, m), 7.50-7.53 (1H, m), 8.05-8.07 (2H, m), 8.21 (1H, s), 8.57 (1H, s), 8.88 (1H, s); m/z (ES+) (M+H)+=449; HPLC tR=1.90 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (10 mL)
  2. additiondiluted with water (20 mL) and EtOAc (70 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with EtOAc (70 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto afford crude product
  9. customThe crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-52d7c95302c54022a9e23c3180b11ad4
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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