Ammonia → 5-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxamide

HRID 1056291Notes

Reaction equation

HRID 1056291 reaction equation
[F:1][C:2]1[C:3]([C:18]2[NH:22][C:21]([CH3:23])=[C:20]([C:24]([OH:26])=O)[CH:19]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([NH:13][C:14]1([CH3:17])[CH2:16][CH2:15]1)=[N:5]2.CC[N:29](C(C)C)C(C)C.N>CN(C=O)C.C(Cl)Cl>[F:1][C:2]1[C:3]([C:18]2[NH:22][C:21]([CH3:23])=[C:20]([C:24]([NH2:29])=[O:26])[CH:19]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([NH:13][C:14]1([CH3:17])[CH2:15][CH2:16]1)=[N:5]2

Participants

6

Reactant 3

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 897838105-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylic acid

Product 1

HCID 897833735-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(6-fluoro-2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylic acid (417c) (0.119 g, 0.336 mmol), 0-(˜7-azabenzotriazol-1-yl)-n,′n,′n,′n′-tetramethyluronium-hexafluorophosphate (GenScript Corporation, 0.160 g, 0.420 mmol), DIPEA (0.146 mL, 0.839 mmol), in DMF (1.679 mL) was stirred at RT for 5 min before addition of ammonia (2.0 M solution in MeOH, Sigma Aldrich, 0.336 mL, 0.672 mmol). The resulting mixture was stirred at RT overnight. Reaction mixture was diluted with DCM and washed with water and brine to remove DMF. Purification by Biotage (0-100% EtOAc/hexanes then 30-100% EtOAc:EtOH(3:1)/hexanes) produced desired product. The residue was diluted with DCM and re-washed two times with alternating water and brine washes to remove DMF and provide 5-(6-fluoro-2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxamide (0.031 g, 0.88 mmol, 26% yield). 1H NMR (300 MHz, MeOH) δ ppm 0.84-0.94 (m, 4H) 1.56 (s, 3H) 2.38 (s, 3H) 2.55 (s, 3H) 7.01-7.17 (m, 2H) 7.25-7.35 (m, 1H) 7.37-7.47 (m, 1H) 12.84-13.00 (m, 1H). m/z (ESI, +ve) 354.0 (M+H).

Workup

  1. customReaction mixture
  2. washwashed with water and brine
  3. customto remove DMF
  4. customPurification by Biotage (0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-c07b9ebc494a48ac992deefc2a20c719
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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