HCID 57504489, compound → HCID 57504350, compound

HRID 1097997Notes

Reaction equation

HRID 1097997 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:34]([F:37])([F:36])[F:35])[C:5]([N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([O:17][C@@H:18]([CH2:29][O:30][CH:31]([CH3:33])[CH3:32])[C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=4)=[O:20])=[C:11]3[CH:10]=[N:9]2)=[N:6][CH:7]=1>[Pd].CO>[CH:31]([O:30][CH2:29][C@H:18]([O:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([C:5]3[C:4]([C:34]([F:37])([F:36])[F:35])=[CH:3][CH:2]=[CH:7][N:6]=3)[N:9]=[CH:10][C:11]=12)[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=1)=[O:20])([CH3:33])[CH3:32]

Participants

4

Reactant 1

HCID 57504489HCID 57504489, compound

Product 1

HCID 57504350HCID 57504350, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

(2S)-2-(1-(5-Chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxy-N-(5-methylpyridin-2-yl)propanamide (Intermediate K6) (1 g, 0.73 mmol), and 10% Palladium on Carbon (100 mg, 0.09 mmol) in MeOH (25 mL) were stirred under an atmosphere of hydrogen for 16 hours. The reaction mixture was filtered through celite. 10% Palladium on Carbon (100 mg, 0.09 mmol) added and stirred under an atmosphere of hydrogen for a further 16 hours. The reaction mixture was filtered through celite and evaporated. The residue was purified by flash silica chromatography, elution gradient 1 to 5% MeOH in DCM to afford (2S)-3-isopropoxy-N-(5-methylpyridin-2-yl)-2-(1-(3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (0.173 g, 47%). 1H NMR (400 MHz, DMSO) δ 1.08-1.14 (6H, m), 2.24 (3H, s), 3.73-3.79 (1H, m), 3.96-4.05 (2H, m), 5.90 (1H, s), 7.57-7.60 (1H, m), 7.86-7.90 (1H, m), 7.94-7.98 (1H, m), 8.17 (1H, s), 8.55 (1H, s), 8.58-8.61 (1H, m), 8.65 (1H, s), 8.97-9.00 (1H, m), 10.82 (1H, s). m/z (ESI+) (M+H)+=502; HPLC tR=2.30 min.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. filtrationThe reaction mixture was filtered through celite
  3. customevaporated
  4. customThe residue was purified by flash silica chromatography, elution gradient 1 to 5% MeOH in DCM

Sources & evidence

ORD record
ord-1409ec3896304ae5a5fa3c174f95d145
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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