Potassium Phosphate, Tribasic → (S)-2-(2-methyl-3-((1,1,1-trifluoropropan-2-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056083Notes

Reaction equation

HRID 1056083 reaction equation
Cl[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.Cl.[F:24][C:25]([F:30])([F:29])[C@@H:26]([NH2:28])[CH3:27].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(#N)C.[OH2:42]>>[C:26]([OH:21])([C:25]([F:30])([F:29])[F:24])=[O:42].[CH3:22][C:3]1[C:2]([NH:28][C@@H:26]([CH3:27])[C:25]([F:30])([F:29])[F:24])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=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:4]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 130939192-Propanamine, 1,1,1-trifluoro-, hydrochloride (1:1), (2S)-HCID 18373917Acetonitrile--water (1/1)HCID 89783520HCID 89783520, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 89793696(S)-2-(2-methyl-3-((1,1,1-trifluoropropan-2-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 16%

Conditions

Temperature
100 °C

Procedure

Prepared similarly to that described in Example 254 using 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 254c; 34 mg, 0.109 mmol), (S)-1,1,1-trifluoropropan-2-amine hydrochloride (32.5 mg, 0.217 mmol, SynQuest Laboratories, Alachua, Fla.), Pd(tBu3P)2 (Strem, Newburyport, Mass.; 5.56 mg, 10.87 μmol), and K3PO4 (92 mg, 0.435 mmol), heating at 100° C. for 2 h. Purification by silica gel (100% DCM to 4% 2 M NH3 in MeOH/DCM) then by rpHPLC (Phenomenex Gemini C18, 10 pan, 150×30 mm; 10-100% ACN/water with 0.1% TFA) provided (S)-2-(2-methyl-3-((1,1,1-trifluoropropan-2-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (16% yield). MS (ESI, pos. ion) m/z: 390.2 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 1.61 (d, J=6.85 Hz, 3H) 2.66 (s, 3H) 2.96 (t, J=6.85 Hz, 2H) 3.66 (td, J=6.85, 2.54 Hz, 2H) 4.85 (s, 1H) 4.86-4.96 (m, 1H) 5.35 (br. s., 1H) 7.12 (d, J=2.35 Hz, 1H) 7.47 (t, J=7.82 Hz, 1H) 7.73 (dd, J=8.12, 1.27 Hz, 1H) 7.94 (dd, J=7.63, 1.17 Hz, 1H) 11.60 (br. s., 1H). 19F NMR (376 MHz, DMSO-d6) δ ppm −76.30 (3F, s).

Workup

  1. customPrepared similarly to that
  2. customPurification by silica gel (100% DCM to 4% 2 M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-d9a0f2a8132c46a4bc2eaf95655c02ca
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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