Tetrabutylammonium Fluoride → HCID 57504418, compound

HRID 1098035Notes

Reaction equation

HRID 1098035 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][C@H:28]([O:30][CH2:31][C@H:32]([O:44][C:45]1[N:50]=[CH:49][N:48]=[C:47]2[N:51]([C:54]3[C:59]([Cl:60])=[CH:58][CH:57]=[CH:56][N:55]=3)[N:52]=[CH:53][C:46]=12)[C:33]([NH:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[CH:38][N:37]=1)=[O:34])[CH3:29])(C(C)(C)C)(C)C>C1COCC1>[Cl:60][C:59]1[C:54]([N:51]2[C:47]3=[N:48][CH:49]=[N:50][C:45]([O:44][C@@H:32]([CH2:31][O:30][C@H:28]([CH3:29])[CH2:27][OH:26])[C:33]([NH:35][C:36]4[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[CH:38][N:37]=4)=[O:34])=[C:46]3[CH:53]=[N:52]2)=[N:55][CH:56]=[CH:57][CH:58]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504537HCID 57504537, compound

Product 1

HCID 57504418HCID 57504418, compoundYield 29.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.973 mL, 0.97 mmol) was added to (2S)-3-((R)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)propanamide (Intermediate AN3) (395 mg, 0.65 mmol) in THF (10 mL) under nitrogen. The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (10 mL), extracted with Et2O (3×15 mL), the combined organic layers were back washed with water (10 mL), dried (MgSO4), and evaporated to afford crude product. The crude product was purified by preparative chiral-HPLC on a Merck 50 mm 20 μm Chiralpak column, eluting isocratically with 30% EtOH in isohexane (modified with Et3N) as eluent to afford the product (95 mg, 29.6%). 1H NMR (400 MHz, CDCl3) δ1.17 (d, 3H), 2.71-2.78 (m, 1H), 3.56-3.72 (m, 2H), 3.78-3.87 (m, 1H), 4.09-4.16 (m, 1H), 4.26-4.32 (m, 1H), 6.01-6.05 (m, 1H), 7.46-7.50 (m, 1H), 7.94-7.98 (m, 1H), 7.99-8.04 (m, 1H), 8.32-8.36 (m, 1H), 8.45 (s, 1H), 8.54-8.56 (m, 1H), 8.60-8.63 (m, 1H), 8.64 (s, 1H), 9.51 (s, 1H); m/z (ESI+) (M+H)+=495.42; HPLC tR=1.75 min

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (10 mL)
  2. extractionextracted with Et2O (3×15 mL)
  3. washthe combined organic layers were back washed with water (10 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto afford crude product
  7. customThe crude product was purified by preparative chiral-HPLC on a Merck 50 mm 20 μm Chiralpak column
  8. washeluting isocratically with 30% EtOH in isohexane (modified with Et3N) as eluent

Sources & evidence

ORD record
ord-e49779b1722340309be39715f3297d1b
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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