Tetrabutylammonium Fluoride → HCID 57504419, compound

HRID 1098037Notes

Reaction equation

HRID 1098037 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:43][C:44]1[N:49]=[CH:48][N:47]=[C:46]2[N:50]([C:53]3[C:58]([Cl:59])=[CH:57][CH:56]=[CH:55][N:54]=3)[N:51]=[CH:52][C:45]=12)[C:33]([NH:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][N:37]=1)=[O:34])[CH3:29])(C(C)(C)C)(C)C>C1COCC1>[Cl:59][C:58]1[C:53]([N:50]2[C:46]3=[N:47][CH:48]=[N:49][C:44]([O:43][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]([F:42])=[CH:38][N:37]=4)=[O:34])=[C:45]3[CH:52]=[N:51]2)=[N:54][CH:55]=[CH:56][CH:57]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504539HCID 57504539, compound

Product 1

HCID 57504419HCID 57504419, compoundYield 45.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (604 μl, 0.60 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-fluoropyridin-2-yl)propanamide (Intermediate AN5) (303 mg, 0.50 mmol) in THF (5 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 AS column, eluting isocratically with 30% EtOH in isohexane (modified with Et3N) as eluent to afford the product (112 mg, 45.6%). 1H NMR (400 MHz, CDCl3) δ1.17 (d, 3H), 2.99-3.05 (m, 1H), 3.54-3.61 (m, 1H), 3.62-3.70 (m, 1H), 3.75-3.84 (m, 1H), 4.07-4.13 (m, 1H), 4.25-4.31 (m, 1H), 6.04-6.09 (m, 1H), 7.43-7.50 (m, 2H), 7.99-8.03 (m, 1H), 8.13 (d, 1H), 8.18-8.23 (m, 1H), 8.45 (s, 1H), 8.61-8.63 (m, 1H), 8.64 (s, 1H), 9.17 (s, 1H); m/z (ESI+) (M+H)+=488.42; HPLC tR=1.74 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 AS column
  8. washeluting isocratically with 30% EtOH in isohexane (modified with Et3N) as eluent

Sources & evidence

ORD record
ord-7cdbb08aac0042fea4864564fd1d14df
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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