Tetrabutylammonium Fluoride → HCID 46175432, compound

HRID 1098036Notes

Reaction equation

HRID 1098036 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]([Cl:42])=[CH:38][N:37]=1)=[O:34])[CH3:29])(C(C)(C)C)(C)C>C1COCC1>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([NH:35][C:33](=[O:34])[C@@H:32]([O:43][C:44]2[N:49]=[CH:48][N:47]=[C:46]3[N:50]([C:53]4[C:58]([Cl:59])=[CH:57][CH:56]=[CH:55][N:54]=4)[N:51]=[CH:52][C:45]=23)[CH2:31][O:30][C@H:28]([CH3:29])[CH2:27][OH:26])=[N:37][CH:38]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504538HCID 57504538, compound

Product 1

HCID 46175432HCID 46175432, compoundYield 68.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.892 mL, 0.89 mmol) was added to (2S)-3-((R)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AN4) (460 mg, 0.74 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 EtOAc (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 flash silica chromatography, eluting with 0 to 90% EtOAc in isohexane to afford the product (256 mg, 68.3%). 1H NMR (400 MHz, DMSO) δ1.07 (d, 3H), 3.26-3.37 (m, 1H), 3.38-3.47 (m, 1H), 3.61-3.71 (m, 1H), 4.07-4.18 (m, 2H), 4.57 (t, 1H), 5.87-5.93 (m, 1H), 7.74-7.79 (m, 1H), 7.88-7.93 (m, 1H), 8.00-8.06 (m, 1H), 8.32-8.37 (m, 1H), 8.41 (d, 1H), 8.57 (s, 1H), 8.66 (s, 1H), 8.67-8.70 (m, 1H), 11.15 (s, 1H) m/z (ESI+) (M+H)+=504.37; HPLC tR=1.96 min

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (10 mL)
  2. extractionextracted with EtOAc (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 flash silica chromatography
  8. washeluting with 0 to 90% EtOAc in isohexane

Sources & evidence

ORD record
ord-b8cbc9025e8e4a2f81a7e96a4e4abd1b
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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