Hydrazine → HCID 178468612, compound

HRID 1056344Notes

Reaction equation

HRID 1056344 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](=O)[CH2:17][C:18](=O)[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].[NH2:27][NH2:28]>CC(O)=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:28][N:27]=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 89781981Ethyl 4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2,4-dioxobutanoate

Product 1

HCID 178468612HCID 178468612, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
85 °C

Procedure

To a 25-mL round-bottomed flask was added EtOH (4 mL) and sodium ethoxyde (1.01 g of 21% in EtOH, 3.11 mmol). The reaction mixture was cooled to −10° C. and added ethyl oxalate (0.21 mL, 1.55 mmol, Sigma-Aldrich) and 1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606a) (0.4 g, 1.55 mmol) slowly. The reaction mixture was warmed to RT and stirred at RT for 18 h. The reaction mixture was diluted with water (10 mL) and partially concentrated under vacuum. The reaction mixture was diluted with HCl (1 N, 5 mL) and extracted with EtOAc (15 mL). The organic extract was washed with brine (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 10% to 30% EtOAc in hexanes to give ethyl 4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2,4-dioxobutanoate as an orange oil (135 mg, 24% yield). m/z (ESI, +ve) 358.1 (M+H)+. To a 15-mL glass tube was added ethyl 4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2,4-dioxobutanoate (135 mg, 0.38 mmol), hydrazine (12 μL, 0.38 mmol), and AcOH (2 mL). The tube was sealed and heated at 85° C. for 1 h. The reaction mixture was cooled to RT and the solvent was removed under vacuum. The mixture was diluted with EtOAc (10 mL) and NaOH (1 N, 5 mL). The organic extract was washed with water (5 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 ethyl 5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrazole-3-carboxylate (467a) (102 mg, 76% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.82-7.97 (m, 1H), 7.74 (d, J=7.82 Hz, 1H), 7.51-7.60 (m, 1H), 7.40 (t, J=8.90 Hz, 1H), 6.00-6.07 (m, 1H), 4.31 (q, J=7.11 Hz, 2H), 2.56 (s, 3H), 1.53 (s, 9H), 1.33 (t, J=7.14 Hz, 3H). m/z (ESI, +ve) 354.0 (M+H)+.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to RT
  3. customthe solvent was removed under vacuum
  4. additionThe mixture was diluted with EtOAc (10 mL) and NaOH (1 N, 5 mL)
  5. extractionThe organic extract
  6. washwas washed with water (5 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  11. washeluting with a gradient of 30% to 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-feeeca0ce20247f48a9772259b5e0698
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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