tert-butyl (3S)-3-aminopiperidine-1-carboxylate → tert-butyl (3S)-3-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-quinoxalinyl)amino)-1-piperidinecarboxylate

HRID 1055882Notes

Reaction equation

HRID 1055882 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.F[C:16]1[C:17]([CH3:36])=[N:18][C:19]2[C:24]([N:25]=1)=[C:23]([C:26]1[NH:34][C:33]3[CH2:32][CH2:31][NH:30][C:29](=[O:35])[C:28]=3[CH:27]=1)[CH:22]=[CH:21][CH:20]=2>CS(C)=O>[CH3:36][C:17]1[C:16]([NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)=[N:25][C:24]2[C:19]([N:18]=1)=[CH:20][CH:21]=[CH:22][C:23]=2[C:26]1[NH:34][C:33]2[CH2:32][CH2:31][NH:30][C:29](=[O:35])[C:28]=2[CH:27]=1

Participants

4

Reactant 2

HCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylateHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89793610tert-butyl (3S)-3-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-quinoxalinyl)amino)-1-piperidinecarboxylateYield 4.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

Prepared according to Example 131, (S)-3-amino-1-Boc-piperidine (180 μL, 0.759 mmol, CNH Technologies, Inc., Woburn, Mass.), 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 75 mg, 0.253 mmol), and DMSO (2.5 mL) stirring at 100° C. for 2. Purification by sequential column chromatography (silica gel: 0.5 to 10% MeOH/DCM) and reverse phase chromatography (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 95%) provided tert-butyl (3S)-3-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-quinoxalinyl)amino)-1-piperidinecarboxylate (5.2 mg, 4.3%) as the free base after washing with saturated aq. NaHCO3, extracting with 10% MeOH/DCM, drying over Na2SO4, and concentrating under reduced pressure. 1H NMR (CDCl3) δ: 7.92-7.97 (m, 1H), 7.65-7.71 (m, 1H), 7.37-7.45 (m, 1H), 7.13 (s, 2H), 5.42 (br. s., 1H), 4.12 (s, 1H), 3.62-3.70 (m, 3H), 2.91-2.99 (m, 2H), 2.57 (s, 3H), 1.94-2.07 (m, 1H), 1.89-1.90 (m, 1H), 1.80-1.91 (m, 1H), 1.68 (s, 9H), 1.33-1.55 (m, 5H). m/z (ESI, +ve) 477.2 (M+H)+.

Workup

  1. customPrepared
  2. customPurification by sequential column chromatography (silica gel: 0.5 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-41fae2100b73415f8633e8afd24cb0dd
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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