Tetrabutylammonium Fluoride → HCID 46175517, compound

HRID 1098063Notes

Reaction equation

HRID 1098063 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]#[N:27])[C:21]=1[N:28]1[C:32]2=[N:33][CH:34]=[N:35][C:36]([O:37][C@@H:38]([CH2:49][O:50][C@H:51]([CH3:64])[CH2:52][O:53][Si](C(C)C)(C(C)C)C(C)C)[C:39]([NH:41][C:42]3[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][N:43]=3)=[O:40])=[C:31]2[CH:30]=[N:29]1>O1CCCC1>[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]#[N:27])[C:21]=1[N:28]1[C:32]2[N:33]=[CH:34][N:35]=[C:36]([O:37][C@@H:38]([CH2:49][O:50][C@H:51]([CH3:64])[CH2:52][OH:53])[C:39]([NH:41][C:42]3[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][N:43]=3)=[O:40])[C:31]=2[CH:30]=[N:29]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504562HCID 57504562, compound

Product 1

HCID 46175517HCID 46175517, compoundYield 59.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF) (0.891 mL, 0.89 mmol) was added in one portion to a stirred solution of (2S)-2-(1-(2-chloro-6-cyanophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-chloropyridin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (Intermediate AY1) (610 mg, 0.89 mmol) 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 (70 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (70 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 50 to 80% EtOAc in isohexane to afford the product (281 mg, 59.7%). 1H NMR (400 MHz, DMSO) δ 1.07 (3H, d), 3.33 (1H, q), 3.40-3.46 (1H, m), 3.61-3.69 (1H, m), 4.09-4.16 (2H, m), 4.57 (1H, t), 5.90 (1H, s), 7.87-7.91 (2H, m), 8.01-8.05 (1H, m), 8.16-8.19 (2H, m), 8.40-8.41 (1H, m), 8.61 (1H, s), 8.78 (1H, t), 11.17 (1H, d); m/z (ES−) (M−H)−=526; HPLC tR=2.94 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (10 mL)
  2. additiondiluted with water (20 mL) and EtOAc (70 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with EtOAc (70 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 50 to 80% EtOAc in isohexane

Sources & evidence

ORD record
ord-de1dece6019540f09704e3f32406b908
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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