Hydrochloric Acid → HCID 178497403, compound

HRID 989666Notes

Reaction equation

HRID 989666 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16](I)=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:31][OH:32].Cl.CN([CH:37]=[O:38])C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([C:31]([O:38][CH3:37])=[O:32])=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 178522950HCID 178522950, compound

Product 1

HCID 178497403HCID 178497403, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
70 °C

Procedure

A flame-dried flask is charged with N-(4-chlorobenzyl)-4-hydroxy-6-iodo-3-cinnolinecarboxamide (0.23 g, 0.52 mmol), NEt3 (0.15 mL, 1.08 mmol), Pd(PPh3)2Cl2 (0.071 g, 0.10 mmol), methanol (0.85 mL, 20.98 mmol), and anhydrous DMF (5 mL). The reaction is placed under a CO balloon atmosphere and heated at 70° C. for 5 h at which point TLC shows disappearance of starting material. The reaction is cooled to room temperature and poured into 40 mL 1N HCl. The resulting solid is filtered and dried. The crude solid is dissolved in CH2Cl2/MeOH and adsorbed onto silica. Purification by chromatography (eluent 1% MeOH/CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), 2% MeOH/CH2Cl2 (3L), 3% MeOH/CH2Cl2 (1 L)) affords the desired product as an off-white solid (0.12 g, 0.33 mmol, 64%). Physical characteristics are as follows: m.p. 308-310° C.; 1H NMR (300 MHz, DMSO-d6) δ 14.37, 9.80, 8.72, 8.34, 7.83, 7.41, 4.55, 3.92; IR (drift) 1725, 1661, 1625, 1600, 1581, 1535, 1486, 1296, 1276, 1245, 1237, 1129, 823, 806, 761 cm−1; MS (EI) m/z 371 (M+), 142, 141, 140, 139, 125, 89, 88, 74, 73, 51; HRMS (FAB) calcd for C18H14ClN3O4+H1 372.0751, found 372.0757.

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. filtrationThe resulting solid is filtered
  3. customdried
  4. dissolutionThe crude solid is dissolved in CH2Cl2/MeOH
  5. customPurification by chromatography (eluent 1% MeOH/CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), 2% MeOH/CH2Cl2 (3L), 3% MeOH/CH2Cl2 (1 L))

Sources & evidence

ORD record
ord-2936b988a63345a6b3ea1c98497f1df1
Source dataset
uspto-grants-2002_10
Patent number
US06458788B1

Reaction notes

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