Tetrabutylammonium Fluoride → (2S)-3-(2-hydroxyethoxy)-N-(pyridin-2-yl)-2-(1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

HRID 1098045Notes

Reaction equation

HRID 1098045 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:51][C:52]1[N:57]=[CH:56][N:55]=[C:54]2[N:58]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[C:67]([F:70])([F:69])[F:68])[N:59]=[CH:60][C:53]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>O1CCCC1>[OH:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:51][C:52]1[N:57]=[CH:56][N:55]=[C:54]2[N:58]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[C:67]([F:70])([F:68])[F:69])[N:59]=[CH:60][C:53]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=1)=[O:43]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504546(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(pyridin-2-yl)-2-(1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

Product 1

HCID 57504427(2S)-3-(2-hydroxyethoxy)-N-(pyridin-2-yl)-2-(1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF) (1.275 mL, 1.28 mmol) was added in one portion to a stirred solution of (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(pyridin-2-yl)-2-(1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (0.927 g, 1.28 mmol) (Intermediate AQ1) in tetrahydrofuran (15 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 (50 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (50 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 (0.226 g, 36.3%). 1H NMR: (400 MHz, CDCl3) δ 2.90 (1H, s), 3.75-3.80 (4H, m), 4.16-4.25 (2H, m), 6.09 (1H, t), 7.06-7.10 (1H, m), 7.53-7.92 (5H, m), 8.18-8.20 (1H, m), 8.28-8.30 (1H, m), 8.41 (1H, s), 8.57 (1H, s), 9.01 (1H, s); m/z (ES+) (M+H)+=489.31; HPLC tR=1.74 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (10 mL)
  2. additiondiluted with water (20 mL) and EtOAc (50 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with EtOAc (50 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-432ad1a5d4fe48c997fe63d388894ea0
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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