Diisopropylethylamine → HCID 10162188, compound

HRID 1835658Notes

Reaction equation

HRID 1835658 reaction equation
FC1C(O[C:9](=[O:27])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[C:12]([F:17])[C:11]=2[NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[Cl:26])=C(F)C(F)=C(F)C=1F.[NH2:32][O:33][CH2:34][CH2:35][OH:36].C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:26][C:20]1[CH:21]=[C:22]([I:25])[CH:23]=[CH:24][C:19]=1[NH:18][C:11]1[C:12]([F:17])=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[C:9]([NH:32][O:33][CH2:34][CH2:35][OH:36])=[O:27]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3014186Ethanol, 2-(aminooxy)-HCID 23516247HCID 23516247, compound2×

Product 1

HCID 10162188HCID 10162188, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the product of Example 6, Step B, 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid pentafluorophenyl ester (10.0 g, 17.4 mmol), in anhydrous dimethylformamide (36 mL) was added 2-(aminooxy)-ethanol [prepared by the literature procedure: Dhanak, D.; Reese, C. B. J. Chem. Soc., Perkin Trans. 1 1987, 2829] (1.6 g, 20.8 mmol) and N,N-diisopropylethylamine (6.0 mL, 34.8 mmol). The resultant solution was stirred at ambient temperature for 16 h. The reaction mixture was concentrated to 20% volume then diluted with ethyl acetate (360 mL). The resultant solution was washed with water (6×60 mL) and brine (2×60 mL). The organics were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford a white solid that was purified on silica gel. Elution with ethyl acetate-methanol (9:1) afforded 2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (7.31 g, 90%) as a white solid. Recrystallization from methanol afforded analytically pure material: m.p. 173-175° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.93 (br s, 1 H), 8.85 (br s, 1 H), 7.76 (d, J=1.7 Hz, 1 H), 7.48 (dd, J=8.6, 1.7 Hz, 1 H), 7.44 (dd, J=8.5, 6.2 Hz, 1 H), 7.25 (dt, J=8.5, 9.3 Hz, 1 H), 6.58 (dd, J=8.5, 6.4 Hz, 1 H), 4.70 (br s, 1 H), 3.86 (br s, 2 H), 3.56 (br d, J=3.9 Hz, 2 H); MS (APCI+)=469.0; MS (APCI−)=467.0; Anal. Calcd/found for C15H12ClF21N2O3: C, 38.45/38.60; H, 2.58/2.53; N, 5.98/5.91; F, 8.11/8.08; I, 27.08/27.43.

Workup

  1. customprepared by the literature procedure
  2. concentrationThe reaction mixture was concentrated to 20% volume
  3. additionthen diluted with ethyl acetate (360 mL)
  4. washThe resultant solution was washed with water (6×60 mL) and brine (2×60 mL)
  5. dry with materialThe organics were dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto afford a white solid
  8. customthat was purified on silica gel
  9. washElution with ethyl acetate-methanol (9:1)

Sources & evidence

ORD record
ord-340b7cf8cc984ea5a3c17a420b911150
Source dataset
uspto-grants-2004_08
Patent number
US06770778B2

Reaction notes

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