1,2-Dichloroethane → 2-(3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carbonyl)-N-phenylhydrazinecarboxamide

HRID 634189Notes

Reaction equation

HRID 634189 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([OH:21])=O)[CH:17]=4)[NH:12][CH:11]=3)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[C:22]1([NH:28][C:29](=[O:32])[NH:30][NH2:31])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([NH:31][NH:30][C:29]([NH:28][C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)=[O:32])=[O:21])[CH:17]=4)[NH:12][CH:11]=3)[CH:7]=[N:6][CH:5]=2)[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 111,2-Dichloroethane2×HCID 108374-Phenylsemicarbazide2×HCID 757711-Hydroxybenzotriazole2×HCID 81531DiisopropylethylamineHCID 683288133-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carboxylic acid

Product 1

HCID 867251092-(3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carbonyl)-N-phenylhydrazinecarboxamideYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carboxylic acid (204.5 mg, 0.732 mmol), 4-phenylsemicarbazide (111 mg, 0.732 mmol), EDC (140 mg, 0.732 mmol), and HOBT (112 mg, 0.732 mmol) in DMF (3.5 mL) was stirred at 25° C. for 3 h. DIPEA (0.255 mL, 1.464 mmol) was added and the resulting mixture was stirred at 25° C. for 2 h. Additional 4-phenylsemicarbazide (111 mg, 0.732 mmol), HOBT (112 mg, 0.732 mmol), and EDC (140 mg, 0.732 mmol) were sequentially added, and the resulting mixture was stirred at 25° C. for 17 h. The mixture was diluted with H2O (40 mL), and the precipitated solid was collected by vacuum filtration, sequentially washed with H2O (2×30 mL) and Et2O (2×15 mL), and dried in vacuo to provide 2-(3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carbonyl)-N-phenylhydrazinecarboxamide (262 mg, 0.635 mmol, 87%) as a tan solid: MS (ESI, pos. ion) m/z: 413.2 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.90-11.97 (1H, m), 10.19-10.25 (1H, m), 8.97-9.00 (1H, m), 8.94-8.97 (1H, m), 8.84 (1H, s), 8.36 (1H, s), 8.32 (1H, d, J=2.7 Hz), 8.15 (1H, s), 7.79 (1H, d, J=8.4 Hz), 7.51-7.55 (1H, m), 7.50 (2H, d, J=8.0 Hz), 7.27 (2H, t, J=7.7 Hz), 6.96 (1H, t, J=7.3 Hz), 2.18-2.27 (1H, m), 1.16-1.22 (2H, m), 1.04-1.13 (2H, m).

Workup

  1. stirringthe resulting mixture was stirred at 25° C. for 2 h
  2. stirringthe resulting mixture was stirred at 25° C. for 17 h
  3. filtrationthe precipitated solid was collected by vacuum filtration
  4. washsequentially washed with H2O (2×30 mL) and Et2O (2×15 mL)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-437eac118366421a93f08b9da5637edf
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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