1,1'-Carbonyldiimidazole → HCID 10287424, compound

HRID 1835656Notes

Reaction equation

HRID 1835656 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][CH2:21][O:22][CH3:23])=[CH:15][C:14]=2[F:24])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[N-]1C=CN=C1.[NH2:42][O:43][CH2:44][CH2:45][OH:46]>C1COCC1>[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][CH2:21][O:22][CH3:23])=[CH:15][C:14]=2[F:24])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([NH:42][O:43][CH2:44][CH2:45][OH:46])=[O:7]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 3014186Ethanol, 2-(aminooxy)-HCID 3386966ImidazolateHCID 12135109HCID 12135109, compound

Product 1

HCID 10287424HCID 10287424, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The title compound was prepared from reaction of the product of Example 5, Step B, 3,4-difluoro-2-[[2-fluoro-4-(3-methoxy-1-propynyl)phenyl]-amino]benzoic acid. This product (200 mg, 0.60 mmol) was dissolved in dry THF (5 mL) and CDI (193 mg, 1.19 mmol) added. After 0.5 hours at room temperature, TLC showed complete conversion to the desired imidazolide. A solution of 2-(aminooxy)ethanol (184 mg, 2.39 mmol) in dry THF (2 mL) was added and the reaction mixture stirred overnight at room temperature. The reaction solvent was then removed under reduced pressure and the resulting residue partitioned between EtOAc (50 mL) and saturated NaHCO3 solution (50 mL). The EtOAc layer was then dried (Na2SO4), the solvent removed under reduced pressure, and the resulting oil purified by column chromatography on silica gel (50% EtOAc/hexanes) to give 3,4-difluoro-2-[[2-fluoro-4-(3-methoxy-1-propynyl)phenyl]amino]-N-(2-hydroxyethoxy)benzamide as a white solid (165 mg, 71%); mp (EtOAc/Et2O) 121-123° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.84 (br s, 1 H), 8.85 (br s, 1 H), 7.46-7.38 (m, 1 H), 7.32 (dd, J=12.1, 1.7 Hz, 1 H), 7.29-7.21 (m, 1 H), 7.14 (dd, J=8.4, 1.6 Hz, 1 H), 6.79 (td, J=8.8, 4.7 Hz, 1 H), 4.74 (br s, 1 H), 4.30 (s, 2 H), 3.84 (t, J=4.8 Hz, 2 H), 3.56 (t, J=4.9 Hz, 2 H), 3.32 (s, 3 H). Anal. Calcd for C19H17F3N2O4: C, 57.9; H, 4.4; N, 7.1. Found C, 57.9; H, 4.3; N, 7.0.

Workup

  1. customThe reaction solvent was then removed under reduced pressure
  2. customthe resulting residue partitioned between EtOAc (50 mL) and saturated NaHCO3 solution (50 mL)
  3. dry with materialThe EtOAc layer was then dried (Na2SO4)
  4. customthe solvent removed under reduced pressure
  5. customthe resulting oil purified by column chromatography on silica gel (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1f4ec704429a435a8c03bdc55ef86a6e
Source dataset
uspto-grants-2004_08
Patent number
US06770778B2

Reaction notes

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