Potassium Phosphate, Tribasic → HCID 89784660, compound

HRID 1056084Notes

Reaction equation

HRID 1056084 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 18373917Acetonitrile--water (1/1)HCID 44593757(2R)-1,1,1-Trifluoropropan-2-amine--hydrogen chloride (1/1)HCID 897835202-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 89784660HCID 89784660, compoundYield 10%

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; 47 mg, 0.150 mmol), (R)-1,1,1-trifluoropropan-2-amine hydrochloride (44.9 mg, 0.301 mmol, SynQuest Laboratories, Alachua, Fla.), Pd(tBu3P)2 (Strem, Newburyport, Mass.; 7.68 mg, 0.015 mmol), and K3PO4 (128 mg, 0.601 mmol), heating at 100° C. for 18 h. Purification by silica gel (100% DCM to 4% 2 M NH3 in MeOH/DCM) then by rpHPLC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% ACN/water with 0.1% TFA) provided (R)-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 (10% yield). MS (ESI, pos. ion) m/z: 390.2 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 1.61 (br. s., 3H) 2.66 (s, 3H) 2.96 (t, J=6.85 Hz, 2H) 3.66 (td, J=6.90, 2.45 Hz, 2H) 4.81 (s, 1H) 4.91 (dq, J=14.04, 6.93 Hz, 1H) 5.29 (br. s., 1H) 7.12 (d, J=2.15 Hz, 1H) 7.48 (t, J=7.82 Hz, 1H) 7.73 (d, J=7.04 Hz, 1H) 7.95 (dd, J=7.63, 1.17 Hz 1H) 11.59 (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-fab5cba29cc74d589f2414b8e0d39b25
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…