Tetrabutylammonium Fluoride → (2S)-2-[1-(2,6-dichlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-N-(5-fluoro-2-pyridyl)-3-(2-hydroxyethoxy)propanamide

HRID 1098065Notes

Reaction equation

HRID 1098065 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:52][C:53]1[N:58]=[CH:57][N:56]=[C:55]2[N:59]([C:62]3[C:67]([Cl:68])=[CH:66][CH:65]=[CH:64][C:63]=3[Cl:69])[N:60]=[CH:61][C:54]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([F:51])=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[Cl:68][C:67]1[CH:66]=[CH:65][CH:64]=[C:63]([Cl:69])[C:62]=1[N:59]1[C:55]2[N:56]=[CH:57][N:58]=[C:53]([O:52][C@@H:41]([CH2:40][O:39][CH2:38][CH2:37][OH:36])[C:42]([NH:44][C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][N:46]=3)=[O:43])[C:54]=2[CH:61]=[N:60]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504563(S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide

Product 1

HCID 46175518(2S)-2-[1-(2,6-dichlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-N-(5-fluoro-2-pyridyl)-3-(2-hydroxyethoxy)propanamideYield 72.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.838 mL, 0.84 mmol) was added dropwise to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide (Intermediate BA1) (0.625 g, 0.84 mmol) in THF (10.34 mL) at ambient temperature under nitrogen. The resulting solution was stirred at ambient temperature for 1 hour. 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 25 to 100% EtOAc in isohexane to afford the product (0.307 g, 72.1%). 1H NMR (400 MHz, CDCl3) δ 2.60 (1H, t), 3.71-3.81 (4H, m), 4.16-4.25 (2H, m), 6.10 (1H, t), 7.43-7.49 (2H, m), 7.53-7.55 (2H, m), 8.14 (1H, d), 8.22-8.25 (1H, m), 8.48 (1H, s), 8.60 (1H, s), 9.00 (1H, s); m/z (ES−) (M+H)+=507.31; HPLC tR=2.67 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 25 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-278a009d83bb4a199827aa4c5300ac0c
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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