Hydrochloric Acid → HCID 178497403, compound

HRID 1168188Notes

Reaction equation

HRID 1168188 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 (Prep. 4, 0.23 g), NEt3 (0.15 mL), Pd(PPh3)2Cl2 (0.071 g), methanol (0.85 mL), 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 (1L), 1.5% MeOH/CH2Cl2 (1L), 2% MeOH/CH2Cl2 (3L), 3% MeOH/CH2Cl2 (1L)) affords the desired product as an off-white solid (0.12 g, 64%). Physical characteristics are as follows: m.p. 308-310° C.; 1H NMR (300 MHz, DMSO-d6) δ14.37, 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 (1L), 1.5% MeOH/CH2Cl2 (1L), 2% MeOH/CH2Cl2 (3L), 3% MeOH/CH2Cl2 (1L))

Sources & evidence

ORD record
ord-64b05dbfd5d0403ba0bbff8a1d95747c
Source dataset
uspto-grants-2003_09
Patent number
US06624160B2

Reaction notes

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