Trifluoroacetic acid → 2-(2-methyl-3-((3R)-3-piperidinylamino)-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one

HRID 1055900Notes

Reaction equation

HRID 1055900 reaction equation
[CH3:1][C:2]1[C:3]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24]2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]1[NH:20][C:19]2[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=2[CH:13]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][C:2]1[C:3]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]2)=[N:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89793605tert-butyl (3R)-3-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-quinoxalinyl)amino)-1-piperidinecarboxylate

Product 1

HCID 897936472-(2-methyl-3-((3R)-3-piperidinylamino)-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-oneYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared according to Example 53, using tert-butyl (3R)-3-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-quinoxalinyl)amino)-1-piperidinecarboxylate (Ex. 52) and (2.5:1) DCM:TFA. Purification by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 80%) provided 2-(2-methyl-3-((3R)-3-piperidinylamino)-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one (115 mg, 48%) 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 (DMSO-d6) δ: 7.90-7.95 (m, 1H), 7.62-7.70 (m, 1H), 7.30-7.42 (m, 1H), 7.09 (s, 1H), 5.83 (s, 1H), 4.06 (br. s., 1H), 3.61-3.69 (m, 2H), 3.21-3.31 (m, 1H), 2.89-3.09 (m, 5H), 2.66 (s, 3H), 2.15-2.33 (m, 2H), 2.10 (m, 2H), 1.77-1.89 (m, 2H), 1.55-1.70 (m, 1H). m/z (ESI, +ve) 377.2 (M+H)+.

Workup

  1. customPrepared
  2. customPurification by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 80%)

Sources & evidence

ORD record
ord-43e09b92cd5046c6b1705c33ffaf16b4
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…