Tetrabutylammonium Fluoride → HCID 57504437, compound

HRID 1098056Notes

Reaction equation

HRID 1098056 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[CH:67]=[CH:66][CH:65]=[C:64]([C:68]#[N:69])[C:63]=3[CH3:70])[N:60]=[CH:61][C:54]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[Cl:51][C:48]1[CH:49]=[CH:50][C:45]([NH:44][C:42](=[O:43])[C@@H:41]([O:52][C:53]2[N:58]=[CH:57][N:56]=[C:55]3[N:59]([C:62]4[CH:67]=[CH:66][CH:65]=[C:64]([C:68]#[N:69])[C:63]=4[CH3:70])[N:60]=[CH:61][C:54]=23)[CH2:40][O:39][CH2:38][CH2:37][OH:36])=[N:46][CH:47]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504557(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

Product 1

HCID 57504437HCID 57504437, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (1.174 mL, 1.17 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AT7) (860 mg, 1.17 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 2 hours. 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 evaporated to a gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane to afford the product (284 mg, 49.0%, 91% ee). 1H NMR (300 MHz, CDCl3) δ 2.40 (3H, s), 2.55-2.65 (1H, m), 3.70-3.86 (4H, m), 4.14-4.27 (2H, m), 6.08 (1H, t), 7.49 (1H, t), 7.63-7.73 (2H, m), 7.76-7.82 (1H, m), 8.15-8.25 (2H, m), 8.44 (1H, s), 8.59 (1H, s), 9.03 (1H, s); m/z (ES+) (M+H)+=494.45; HPLC tR=2.13 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 evaporated to a gum
  5. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane
  6. customto afford the product (284 mg, 49.0%, 91% ee)

Sources & evidence

ORD record
ord-ee1c185eecb34f1892250f00937554ed
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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