4-Chlorobenzylamine → 3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide

HRID 646673Notes

Reaction equation

HRID 646673 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15]([OH:17])=O)=[N:6][C:7]=1[C:8]([NH:10][CH3:11])=[O:9].ON1C2C=CC=CC=2N=N1.[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][NH2:37])=[CH:34][CH:33]=1.Cl.C(N=C=NCCCN(C)C)C>C(OCC)(=O)C.O1CCCC1>[NH2:1][C:2]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[N:6][C:5]([C:12]2[CH:20]=[CH:19][CH:18]=[C:14]([C:15]([NH:37][CH2:36][C:35]3[CH:38]=[CH:39][C:32]([Cl:31])=[CH:33][CH:34]=3)=[O:17])[CH:13]=2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 660364-ChlorobenzylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 587105713-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid

Product 1

HCID 686519573-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamideYield 55.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with 3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (48.9 mg, 0.18 mmol), 1-hydroxybenzotriazole (HOBT, 39.7 mg, 0.294 mmol), 2.00 mL of tetrahydrofuran, 4-chlorobenzylamine (28.2 mg, 0.2 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (66.2 mg, 0.353 mmol). The reaction was stirred at room temperature for 2 h. The reaction was diluted with ethyl acetate, washed sequentially saturated aqueous NaCl, saturated aqueous sodium carbonate, 1.0 M aqueous hydrochloric acid, and saturated aqueous sodium bicarbonate The organic layer was dried over sodium sulfate, filtered, and concentrated on a rotary evaporator under reduced pressure. The crude product was purified by chromatography on silica gel using EtOAc as the eluent. After concentration, the product was triturated in 5% ethyl acetate in hexanes. The solid product was filtered, and after drying afforded 3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide (39.8 mg, 50% yield). 1H NMR (400 MHz; DMSO-d6): 9.15 (m, 1H); 8.87 (s, 1H); 8.80 (m, 1H); 8.50 (s, 1H); 8.35 (d, 1H); 7.85 (d, 1H); 7.53 (d, 1H); 7.37 (m, 2H); 4.51 (d, 2H); 2.83 (s, 3H): MS (EI) for C20H18N5O2Cl: 396 (MH+).

Workup

  1. washwashed sequentially saturated aqueous NaCl, saturated aqueous sodium carbonate, 1.0 M aqueous hydrochloric acid, and saturated aqueous sodium bicarbonate The organic layer
  2. dry with materialwas dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated on a rotary evaporator under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel
  6. concentrationAfter concentration
  7. customthe product was triturated in 5% ethyl acetate in hexanes
  8. filtrationThe solid product was filtered
  9. customafter drying

Sources & evidence

ORD record
ord-b18923437e404321a45668e6d9a35754
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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