Acetonitrile--water (1/1) → HCID 89783511, compound

HRID 1056082Notes

Reaction equation

HRID 1056082 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:31])([F:30])[C:26]([CH3:29])([NH2:28])[CH3:27].C(#N)C.[OH2:35]>CC(N(C)C)=O.C(Cl)Cl>[C:26]([OH:21])([C:25]([F:31])([F:30])[F:24])=[O:35].[CH3:22][C:3]1[C:2]([NH:28][C:26]([CH3:29])([CH3:27])[C:25]([F:31])([F:30])[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

7

Reactant 3

HCID 18373917Acetonitrile--water (1/1)HCID 448907971,1,1-Trifluoro-2-methylpropan-2-amine hydrochlorideHCID 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 89783511HCID 89783511, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (254c, 85 mg, 0.272 mmol), 1,1,1-trifluoro-2-methylpropan-2-amine hydrochloride (178 mg, 1.087 mmol, Oakwood Products, West Columbia, S.C.), Pd(tBu3P)2 (Strem, Newburyport, Mass.; 13.89 mg, 0.027 mmol), and K2PO4 (346 mg, 1.631 mmol) in DMA (2718 μl) was stirred at 120° C. for 5 h; the reaction was then heated to 145° C. for 2.5 d. The mixture was diluted with DCM (100 ml), and washed with saturated aq. NaHCO3 (2×75 ml) before the organic layer was separated, dried over Na2SO4, and concentrated. Purification by silica gel (100% DCM to 5% 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 2-(2-methyl-3-((1,1,1-trifluoro-2-methylpropan-2-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (254, 2% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 404.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 1.81 (s, 6H) 2.63 (s, 3H) 2.97 (t, J=6.94 Hz, 2H) 3.66 (td, J=6.85, 2.54 Hz, 2H) 4.77 (s, 1H) 5.29 (br. s., 1H) 7.10 (d, J=2.15 Hz, 1H) 7.46 (t, J=7.92 Hz, 1H) 7.70 (dd, J=8.12, 1.27 Hz, 1H) 7.95 (dd, J=7.63, 1.37 Hz, 1H) 11.79 (br. s., 1H). 19F NMR (376 MHz, DMSO-d6) δ ppm −78.37 (3F, s).

Workup

  1. temperaturethe reaction was then heated to 145° C. for 2.5 d
  2. washwashed with saturated aq. NaHCO3 (2×75 ml) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by silica gel (100% DCM to 5% 2 M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-2a3b7c62a7c6415dbbaca1d4e9a36942
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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