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

HRID 1098054Notes

Reaction equation

HRID 1098054 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[CH:68]=[CH:67][CH:66]=[C:65]([C:69]#[N:70])[C:64]=3[CH3:71])[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>[C:69]([C:65]1[C:64]([CH3:71])=[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)[CH:68]=[CH:67][CH:66]=1)#[N:70]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504555(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)propanamide

Product 1

HCID 57504435(2S)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)-3-(2-hydroxyethoxy)propanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.346 mL, 0.35 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)propanamide (Intermediate AT1) (250 mg, 0.35 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 90 minutes. The reaction mixture was quenched with saturated NH4Cl, diluted with DCM and poured onto a phase separator. The organic layer was evaporated to a gum. The crude product was purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane to afford the product (69.0 mg, 41.2%, 92% ee). 1H NMR (400 MHz, CDCl3) δ 2.37-2.44 (4H, m), 3.73-3.86 (4H, m), 4.15-4.26 (2H, m), 6.07 (1H, t), 7.49 (1H, t), 7.63-7.68 (1H, m), 7.77-7.82 (1H, m), 7.94-8.00 (1H, m), 8.34-8.38 (1H, m), 8.43 (1H, s), 8.55-8.60 (2H, m), 9.34 (1H, s); m/z (ES−) (M−H)−=483.52; HPLC tR=1.95 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl
  2. additiondiluted with DCM
  3. additionpoured onto a phase separator
  4. customThe organic layer was evaporated to a gum
  5. customThe crude product was purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane
  6. customto afford the product (69.0 mg, 41.2%, 92% ee)

Sources & evidence

ORD record
ord-f5268c50b8f448bda657280160ca8f70
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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