Tetrabutylammonium Fluoride → HCID 57504440, compound

HRID 1098059Notes

Reaction equation

HRID 1098059 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][CH2:28][CH2:29][C@H:30]([O:41][C:42]1[N:47]=[CH:46][N:45]=[C:44]2[N:48]([C:51]3[C:56]([Cl:57])=[CH:55][CH:54]=[CH:53][N:52]=3)[N:49]=[CH:50][C:43]=12)[C:31]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][N:35]=1)=[O:32])(C(C)(C)C)(C)C>C1COCC1>[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([NH:33][C:31](=[O:32])[C@@H:30]([O:41][C:42]2[N:47]=[CH:46][N:45]=[C:44]3[N:48]([C:51]4[C:56]([Cl:57])=[CH:55][CH:54]=[CH:53][N:52]=4)[N:49]=[CH:50][C:43]=23)[CH2:29][CH2:28][CH2:27][OH:26])=[N:35][CH:36]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504559HCID 57504559, compound

Product 1

HCID 57504440HCID 57504440, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (1.177 mL, 1.18 mmol) was added to (2S)-5-(tert-butyldimethylsilyloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pentanamide (Intermediate AW1) (693 mg, 1.18 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 (171 mg, 30.6%, 95% ee). 1H NMR (400 MHz, CDCl3) δ 1.59 (1H, t), 1.81-1.91 (2H, m), 2.21-2.39 (2H, m), 3.73-3.86 (2H, m), 5.95 (1H, t), 7.44-7.50 (1H, m), 7.64-7.72 (1H, m), 7.98-8.04 (1H, m), 8.20-8.27 (2H, m), 8.44 (1H, s), 8.59-8.65 (2H, m), 8.72 (1H, s); m/z (ES+) (M+H)+=474.36; HPLC tR=1.89 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 (171 mg, 30.6%, 95% ee)

Sources & evidence

ORD record
ord-c5e6aa291116431581080198057d263f
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

Loading…