Tetrabutylammonium Fluoride → HCID 57504428, compound

HRID 1098046Notes

Reaction equation

HRID 1098046 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N:26]1[C:30]2=[N:31][CH:32]=[N:33][C:34]([O:35][C@@H:36]([CH2:46][O:47][C@H:48]([CH3:61])[CH2:49][O:50][Si](C(C)C)(C(C)C)C(C)C)[C:37]([NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)=[O:38])=[C:29]2[CH:28]=[N:27]1>O1CCCC1>[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N:26]1[C:30]2=[N:31][CH:32]=[N:33][C:34]([O:35][C@@H:36]([CH2:46][O:47][C@H:48]([CH3:61])[CH2:49][OH:50])[C:37]([NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)=[O:38])=[C:29]2[CH:28]=[N:27]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504547HCID 57504547, compound

Product 1

HCID 57504428HCID 57504428, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF) (0.526 mL, 0.53 mmol) was added in one portion to a stirred solution of (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(pyridin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (0.329 g, 0.53 mmol) (Intermediate AQ3) in tetrahydrofuran (15 mL). The resulting solution was stirred at ambient temperature for 30 minutes. The reaction mixture was quenched with saturated NH4Cl (10 mL), and diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (50 mL), The combined organics were dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane to afford the product (0.247 g, 100%). 1H NMR: (400 MHz, CDCl3) δ 1.16-1.19 (3H, m), 3.45-3.85 (4H, m), 4.1-4.31 (2H, m), 6.06-6.09 (1H, m), 7.05-7.09 (1H, m), 7.46-7.63 (4H, m), 7.73-7.75 (1H, m), 8.17 (1H, d), 8.26-8.28 (1H, m), 8.43 (1H, d), 8.60 (1H, s), 9.23 (1H, s); m/z (ES+) (M+H)+=469.24; HPLC tR=1.91 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (10 mL)
  2. additiondiluted with water (20 mL) and EtOAc (50 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with EtOAc (50 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto afford crude product
  9. customThe crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-66e9078862ad49a390ba990138ad4b4f
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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