Tetrabutylammonium Fluoride → HCID 57504434, compound

HRID 1098053Notes

Reaction equation

HRID 1098053 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH:27]1[CH2:30][N:29]([CH2:31][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)[C:33]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][N:37]=2)=[O:34])[CH2:28]1)(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][N:29]4[CH2:30][CH:27]([OH:26])[CH2:28]4)[C:33]([NH:35][C:36]4[CH:41]=[CH:40][C:39]([CH3:42])=[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 57504554HCID 57504554, compound

Product 1

HCID 57504434HCID 57504434, compoundYield 24.12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.328 mL, 0.33 mmol) was added to (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AD9) (195 mg, 0.33 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 6 hours. The reaction mixture was quenched with saturated NH4Cl, diluted with DCM and poured onto a phase separator. The organic layer was evaporated to a gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc to afford the product (38.0 mg, 24.12%). 1H NMR (400 MHz, CDCl3) δ 1.23-1.29 (1H, m), 2.29 (3H, s), 3.16-3.32 (4H, m), 3.76-3.87 (2H, m), 4.46-4.53 (1H, m), 5.91 (1H, t), 7.44-7.49 (1H, m), 7.50-7.55 (1H, m), 7.97-8.03 (1H, m), 8.07-8.15 (2H, m), 8.42 (1H, s), 8.59-8.65 (2H, m), 9.58 (1H, s) m/z (ES+) (M+H)+=481.51; HPLC tR=1.14 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl
  2. additiondiluted with DCM
  3. additionpoured onto a phase separator
  4. customThe organic layer was evaporated to a gum
  5. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-7804ac4d36014ba59680ac574c29730a
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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