Ammonium formate → (S)-N-methyl-N-(piperidin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 919557Notes

Reaction equation

HRID 919557 reaction equation
C([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([N:14]([CH3:32])[C:15]2[N:20]=[CH:19][N:18]=[C:17]3[N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[N:22]=[CH:23][C:16]=23)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>[Pd]>[CH3:32][N:14]([C@H:10]1[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]1)[C:15]1[N:20]=[CH:19][N:18]=[C:17]2[N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:30])[CH3:31])[N:22]=[CH:23][C:16]=12

Participants

4

Reactant 2

HCID 2723923Ammonium formateHCID 86706438(S)-N-(1-benzylpiperidin-3-yl)-N-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 86706439(S)-N-methyl-N-(piperidin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 80%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

To a solution of (S)—N-(1-benzylpiperidin-3-yl)-N-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (540 mg, 1.19 mmol) in McOH under nitrogen, 10% Pd/C (540 mg) was added. To this suspension, ammonium formate (752 mg, 11.9 mmol) was added and the reaction mixture was refluxed under nitrogen for 4 h. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to rt and filtered over celite. The filtrate was concentrated in vacuo to give a residue that was purified by column chromatography (silica gel, gradient EtOAc in hexanes) to afford the titled intermediate (325 mg, 80%). 1H NMR (400 MHz, CD3OD): δ 8.34 (s, 1H), 8.29 (s, 1H), 5.70 (s, 2H), 3.63 (t, J=8.4 Hz, 2H), 3.39 (s, 3H), 3.22 (m, 2H), 3.03 (m, 1H), 2.11 (m, 1H), 2.00 (m, 1H), 1.32 (m, 4H), 0.87 (t, J=8.4 Hz, 2H), 0.00 (9H). LC-MS: m/z [M+1]=363.

Workup

  1. temperaturethe reaction mixture was refluxed under nitrogen for 4 h
  2. customAfter completion of the reaction
  3. filtrationfiltered over celite
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto give a residue that
  6. customwas purified by column chromatography (silica gel, gradient EtOAc in hexanes)

Sources & evidence

ORD record
ord-db8fa1286e1b421791c98e7dc743b2bf
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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