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

HRID 1098020Notes

Reaction equation

HRID 1098020 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:53][C:54]1[N:59]=[CH:58][N:57]=[C:56]2[N:60]([C:63]3[C:68]([Cl:69])=[CH:67][CH:66]=[CH:65][N:64]=3)[N:61]=[CH:62][C:55]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[Cl:69][C:68]1[C:63]([N:60]2[C:56]3=[N:57][CH:58]=[N:59][C:54]([O:53][C@@H:41]([CH2:40][O:39][CH2:38][CH2:37][OH:36])[C:42]([NH:44][C:45]4[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][N:46]=4)=[O:43])=[C:55]3[CH:62]=[N:61]2)=[N:64][CH:65]=[CH:66][CH:67]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504516(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)propanamide

Product 1

HCID 57504388(2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)-3-(2-hydroxyethoxy)propanamideYield 56.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.139 mL, 0.14 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)propanamide (Intermediate AB1) (100 mg, 0.14 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (1 mL), diluted with DCM (10 ml) and poured onto a phase separator. The organic layer was collected and evaporated. The residue was purified by flash silica chromatography, eluting with 0 to 100% ethyl acetate in isohexane to afford the product (38.0 mg, 56.8%). 1H NMR (300 MHz, CDCl3) δ 2.36 (1H, s), 3.70-3.86 (4H, m), 4.16-4.27 (2H, m), 6.07 (1H, t), 7.45-7.52 (1H, m), 7.93-8.05 (2H, m), 8.32-8.38 (1H, m), 8.46 (1H, s), 8.55-8.58 (1H, m), 8.60-8.65 (2H, m), 9.28 (1H, s). m/z (ES+) (M+H)+=481.31; HPLC tR=1.63 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (1 mL)
  2. additiondiluted with DCM (10 ml)
  3. additionpoured onto a phase separator
  4. customThe organic layer was collected
  5. customevaporated
  6. customThe residue was purified by flash silica chromatography
  7. washeluting with 0 to 100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-9f80bb3d5a314dcd9e5732597dbb8bac
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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