Tetrabutylammonium Fluoride → HCID 57504441, compound

HRID 1098060Notes

Reaction equation

HRID 1098060 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][CH2:28][CH2:29][C@H:30]([O:42][C:43]1[N:48]=[CH:47][N:46]=[C:45]2[N:49]([C:52]3[C:57]([Cl:58])=[CH:56][CH:55]=[CH:54][N:53]=3)[N:50]=[CH:51][C:44]=12)[C:31]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[CH:36][N:35]=1)=[O:32])(C(C)(C)C)(C)C>C1COCC1>[Cl:58][C:57]1[C:52]([N:49]2[C:45]3=[N:46][CH:47]=[N:48][C:43]([O:42][C@@H:30]([CH2:29][CH2:28][CH2:27][OH:26])[C:31]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[CH:36][N:35]=4)=[O:32])=[C:44]3[CH:51]=[N:50]2)=[N:53][CH:54]=[CH:55][CH:56]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504560HCID 57504560, compound

Product 1

HCID 57504441HCID 57504441, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (1.376 mL, 1.38 mmol) was added to (2S)-5-(tert-butyldimethylsilyloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)pentanamide (Intermediate AW2) (797 mg, 1.38 mmol) in THF (5 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (2 mL), diluted with DCM (25 mL) and poured onto a phase separator. The organic layer was loaded onto a silica column and purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane to afford the product (166 mg, 25.9%, 100% ee). 1H NMR (400 MHz, CDCl3) δ 1.61 (1H, t), 1.81-1.92 (2H, m), 2.22-2.40 (2H, m), 3.76-3.88 (2H, m), 5.95 (1H, t), 7.45-7.50 (1H, m), 7.93-7.98 (1H, m), 7.99-8.04 (1H, m), 8.35-8.41 (1H, m), 8.44 (1H, s), 8.53-8.57 (1H, m), 8.60-8.64 (2H, m), 9.03 (1H, s); m/z (ES−) (M−H)−=463.37; HPLC tR=1.68 min.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl (2 mL)
  2. additiondiluted with DCM (25 mL)
  3. additionpoured onto a phase separator
  4. custompurified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane
  5. customto afford the product (166 mg, 25.9%, 100% ee)

Sources & evidence

ORD record
ord-26f550e53f02475db3fe113dbfabcdb6
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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