Lithium Hydroxide → HCID 178432145, compound

HRID 1056345Notes

Reaction equation

HRID 1056345 reaction equation
[C:1]([NH:5][C:6]1[C:7]([CH3:26])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:20][N:19]=[C:18]([C:21]([O:23]CC)=[O:22])[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].O1CCOCC1>O>[C:1]([NH:5][C:6]1[C:7]([CH3:26])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:20][N:19]=[C:18]([C:21]([OH:23])=[O:22])[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 312751,4-DioxaneHCID 178468612HCID 178468612, compound

Product 1

HCID 178432145HCID 178432145, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a 10-mL reaction vial was added ethyl 5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrazole-3-carboxylate (467a) (94 mg, 0.27 mmol), LiOH hydrated (56 mg, 1.33 mmol), dioxane (4 mL), and water (1 mL). The reaction mixture was heated at 50° C. for 1 h and at 100° C. for 2 h and then cooled to RT. The solvent was removed under vacuum and HCl (1N, 3 mL) was added, the yellow precipitate obtained was filtered off, washed with water, and dried. 5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrazole-3-carboxylic acid (467b) was obtained as a yellow solid and used without further purification. To a 50-mL round-bottomed flask was added 5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrazole-3-carboxylic acid (467b) (77 mg, 0.24 mmol), DCM (3 mL), DMF (1 mL), DIPEA (82 μL, 0.47 mmol), ammonia (0.95 mL, 0.47 mmol, 0.5 M in dioxane), and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (123 mg, 0.24 mmol) (Sigma-Aldrich). The reaction mixture was stirred at RT for 30 min, concentrated to half of its volume, and diluted with EtOAc (20 mL). The organic extract was washed with sat NaHCO3 (10 mL), dried over Na2SO4, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 30% to 40% EtOAc in hexanes to give 5-(3-(tert-butylamino)-2-methyl-quinoxalin-5-yl)-1H-pyrazole-3-carboxamide (467) (65 mg, 85% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.38 (br. s, 1H), 7.85 (dd, J=1.08, 7.34 Hz, 1H), 7.76 (d, J=7.63 Hz, 1H), 7.53 (br. s., 1H), 7.41 (t, J=7.73 Hz, 1H), 7.30 (s, 1H), 7.18 (br. s, 1H), 6.06 (br. s., 1H), 2.58 (s, 3H), 1.52 (s, 9H). m/z (ESI, +ve) 325.1 (M+H)+.

Workup

  1. customTo a 10-mL reaction
  2. temperaturecooled to RT
  3. customThe solvent was removed under vacuum and HCl (1N, 3 mL)
  4. additionwas added
  5. customthe yellow precipitate obtained
  6. filtrationwas filtered off
  7. washwashed with water
  8. customdried

Sources & evidence

ORD record
ord-ccd614469e324e1a8a24801f975235ab
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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