Tetrabutylammonium Fluoride → HCID 57504409, compound

HRID 1098032Notes

Reaction equation

HRID 1098032 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:52][C:53]1[N:58]=[CH:57][N:56]=[C:55]2[N:59]([C:62]3[CH:67]=[C:66]([CH3:68])[CH:65]=[CH:64][C:63]=3[CH3:69])[N:60]=[CH:61][C:54]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[Cl:51][C:48]1[CH:49]=[CH:50][C:45]([NH:44][C:42](=[O:43])[C@@H:41]([O:52][C:53]2[N:58]=[CH:57][N:56]=[C:55]3[N:59]([C:62]4[CH:67]=[C:66]([CH3:68])[CH:65]=[CH:64][C:63]=4[CH3:69])[N:60]=[CH:61][C:54]=23)[CH2:40][O:39][CH2:38][CH2:37][OH:36])=[N:46][CH:47]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504534HCID 57504534, compound

Product 1

HCID 57504409HCID 57504409, compoundYield 42.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.455 mL, 0.45 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(2,5-dimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AJ1) (328 mg, 0.45 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. This was further purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents to afford the product (93 mg, 42.4%). 1H NMR (400 MHz, DMSO) δ 2.00 (3H, s), 2.33 (3H, s), 3.53 (2H, m), 3.57-3.68 (2H, m), 4.03 (1H, m), 4.11 (1H, m), 4.66 (1H, t), 5.92 (1H, m), 7.23 (1H, s), 7.28 (1H, d), 7.34 (1H, d), 7.90 (1H, dd), 8.02 (1H, d), 8.41 (1H, d), 8.52 (1H, s), 8.57 (1H, s), 11.23 (1H, s). m/z (ES+) (M+H)+=481; HPLC tR=2.35 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. customThis was further purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)

Sources & evidence

ORD record
ord-e57b25d680f5420d9399ddf36c21c635
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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