Tetrabutylammonium Fluoride → (2S)-N-(5-chloropyridin-2-yl)-2-(1-(5-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)propanamide

HRID 1098033Notes

Reaction equation

HRID 1098033 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]([F: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]([F: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 57504535(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(5-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

Product 1

HCID 57504410(2S)-N-(5-chloropyridin-2-yl)-2-(1-(5-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)propanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (0.538 mL, 0.54 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(5-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AK5) (390 mg, 0.54 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 phase was evaporated to give the crude product. This was 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 (136 mg, 51.9%, 75% ee). 1H NMR (400 MHz, DMSO) δ 1.88 (3H, s), 3.35 (2H, m), 3.43 (2H, m), 3.84 (1H, dd), 3.92 (1H, dd), 4.47 (1H, t), 5.74 (1H, m), 7.19 (2H, m), 7.36-7.29 (1H, m), 7.71 (1H, dd), 7.83 (1H, d), 8.23 (1H, d), 8.37 (1H, s), 8.43 (1H, s), 11.05 (1H, s). m/z (ES+) (M+H)+=487; HPLC tR=2.28 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. customThe organic phase was evaporated

Sources & evidence

ORD record
ord-7cbd2bb54c4f485eaa95a8e58ec04f1c
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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