Oxalyl chloride → HCID 71657267, compound

HRID 1049830Notes

Reaction equation

HRID 1049830 reaction equation
[CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:30](=[O:31])[CH2:29][C:28](=[O:32])[NH:27][C:26]3[C:33]4[C:38]([CH:39]=[CH:40][C:25]2=3)=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:20][CH:19]=1.C(=O)([O-])O.[Na+]>ClCCl.C(N(CC)CC)C.O1CCCC1.CN(C=O)C>[CH3:1][C:2]1[C:3]([C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[C:30](=[O:31])[CH2:29][C:28](=[O:32])[NH:27][C:26]4[C:33]5[C:38]([CH:39]=[CH:40][C:25]3=4)=[CH:37][CH:36]=[CH:35][CH:34]=5)=[CH:20][CH:19]=2)=[O:6])=[CH:7][CH:8]=[CH:9][N:10]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 6433732-Methylnicotinic acidHCID 1176991675-(4-Aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione

Product 1

HCID 71657267HCID 71657267, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

2-Methylnicotinic acid (55 mg, 0.4 mmol) was suspended in dry dichloromethane (4 mL), the suspension was added with DMF (0.08 mL) and oxalyl dichloride (0.05 mL, 0.6 mmol), and the mixture was stirred at room temperature for 21 hours. The solvent was evaporated under reduced pressure, and the residue was concentrated twice from dry dichloromethane (1 mL) under reduced pressure. The resultant was added with 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (63 mg, 0.2 mmol) obtained in Example 1, (3), dry tetrahydrofuran (4 mL), and triethylamine (0.11 mL), and the mixture was stirred at room temperature for 24 hours. This reaction mixture was added with saturated aqueous sodium hydrogencarbonate, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol/chloroform=1/20) to give 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (68 mg, yield 80%) as white crystals.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. concentrationthe residue was concentrated twice from dry dichloromethane (1 mL) under reduced pressure
  3. stirringthe mixture was stirred at room temperature for 24 hours
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (methanol/chloroform=1/20)

Sources & evidence

ORD record
ord-eb4ae34d68b144abb341e15f82ed8a66
Source dataset
uspto-grants-2016_07
Patent number
US09382236B2

Reaction notes

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