Ammonium formate → (R)-N-methyl-N-(piperidin-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 919564Notes

Reaction equation

HRID 919564 reaction equation
C([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([CH3:34])[C:15]2[C:16]3[CH:23]=[CH:22][N:21]([S:24]([C:27]4[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:17]=3[N:18]=[CH:19][N:20]=2)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[Pd]>[CH3:34][N:14]([C@@H:10]1[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]1)[C:15]1[C:16]2[CH:23]=[CH:22][N:21]([S:24]([C:27]3[CH:28]=[CH:29][C:30]([CH3:31])=[CH:32][CH:33]=3)(=[O:26])=[O:25])[C:17]=2[N:18]=[CH:19][N:20]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 86706441(R)-N-(1-benzylpiperidin-3-yl)-N-methyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 86706443(R)-N-methyl-N-(piperidin-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 68.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (R)—N-(1-benzylpiperidin-3-yl)-N-methyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (750 mg, 1.5 mmol) in MeOH under nitrogen, 10% Pd/C (750 mg) was added. To this suspension, ammonium formate (995 mg, 15 mmol) was added and the reaction mixture was refluxed under nitrogen for 2 h. After completion of the reaction (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 (395 mg, 65%). 1H NMR (400 MHz, DMSO-d6): δ 8.27 (s, 1H), 7.97 (d, J=7.6 Hz, 2H), 7.65 (d, J=2.8 Hz, 1H), 7.43 (d, J=8.0 Hz, 2H), 7.01 (d, J=3.2 Hz, 1H), 5.03 (bs, 1H), 3.10-2.95 (m, 3H), 2.82-2.76 (m, 2H), 2.50 (s, 3H), 2.36 (s, 3H), 1.89-1.75 (m, 4H). LC-MS: m/z [M+1]=386.

Workup

  1. temperaturethe reaction mixture was refluxed under nitrogen for 2 h
  2. customAfter completion of the reaction (TLC)
  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-c74f88addbb54fc88b597d4b9136df3d
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

Loading…