Hydrochloric Acid → HCID 11664244, compound

HRID 20782Notes

Reaction equation

HRID 20782 reaction equation
C1C=C2N=NN([O:10][C:11]([C:13](ON3N=NC4C3=CC=CC=4)=O)=O)C2=CC=1.[F:25][C:26]1[C:27]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:28]([CH:36]=[C:37]([CH2:40][NH:41][CH2:42][CH2:43][OH:44])[C:38]=1[F:39])[C:29]([NH:31][O:32][CH2:33][CH2:34][OH:35])=[O:30].[OH2:54].Cl>CN(C)C1C=CN=CC=1.CN(C)C=O.C(Cl)Cl.CO>[O:44]=[C:43]1[O:10][CH2:11][CH2:13][N:41]([CH2:40][C:37]2[C:38]([F:39])=[C:26]([F:25])[C:27]([NH:45][C:46]3[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=3[F:53])=[C:28]([CH:36]=2)[C:29]([NH:31][O:32][CH2:33][CH2:34][OH:35])=[O:30])[C:42]1=[O:54]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 32926301,1'-[(1,2-Dioxoethane-1,2-diyl)bis(oxy)]bis(1H-benzotriazole)HCID 593480303,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethylamino)-methyl]-benzamide

Product 1

HCID 11664244HCID 11664244, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

4-Dimethylaminopyridine (12.1 mg) and dibenzotriazol-1-yl oxalate (9.2 mg, 27.4 μmol) were added to a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethylamino)-methyl]-benzamide (15.9 mg, 30.2 μmol) obtained in Step B (or Step B′) of Example 72 in anhydrous N,N-dimethylformamide (1.5 ml) at room temperature. The mixture was stirred at room temperature for 2 hours. Water (6 ml) and 1 N hydrochloric acid (0.5 ml) were added, and the reaction mixture was extracted with ethyl acetate (2×10 ml). The combined organic layers were washed with saturated brine (8 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with a preparative silica gel plate (No. 5744, Merck, CH2Cl2/MeOH (10:1) as a developing solvent) to give 5-(2,3-dioxo-morpholin-4-ylmethyl)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (Compound H-7, 1.0 mg, 6% yield).

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate (2×10 ml)
  2. washThe combined organic layers were washed with saturated brine (8 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified with a preparative silica gel plate (No

Sources & evidence

ORD record
ord-167e4ec2917248a6bdcfe9082e33dba2
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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