Triethylamine → 1-[(2,4-Difluorophenyl)methyl]pyrrolo[2,3-c]pyridine-5-carbohydroxamic acid

HRID 2377050Notes

Reaction equation

HRID 2377050 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14](O)=[O:15])[CH:13]=[C:8]2[CH:7]=[CH:6]1.F[P-](F)(F)(F)(F)F.[N:29]1([O:38]C(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.Cl.NO>CN(C=O)C>[F:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([NH:29][OH:38])=[O:15])[CH:13]=[C:8]2[CH:7]=[CH:6]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218922121-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid

Product 1

HCID 99483631-[(2,4-Difluorophenyl)methyl]pyrrolo[2,3-c]pyridine-5-carbohydroxamic acidYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid (0.15 g, 0.52 mmol) in DMF (10 mL) were added O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU; 0.20 g, 0.52 mmol), triethylamine (0.15 mL, 1.05 mmol), and hydroxylamine hydrochloride (0.036 g, 0.52 mmol). The resulting mixture was stirred for 16 hours at ambient temperature. It was quenched with water (30 mL) and extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water (2×30 mL), dried over sodium sulfate, concentrated in vacuo and purified by preparative HPLC to provide the title compound as a white powder (0.075 g, 48% yield). 1H NMR (DMSO-d6) δ ppm 11.14 (s, 1H), 8.92 (s, 1H), 8.85 (s, 1H), 8.21 (s, 1H), 7.78 (s, 1H), 7.26-7.38 (m, 2H), 7.08 (t, 1H, J=8.3 Hz), 6.71 (d, 1H, J=3.0 Hz), 5.64 (s, 2H). LCMS (API-ES, M+H+): 304.1 HRMS (M+H): 304.0886; cal: 304.0898 with C15H12N3O2F2. HPLC: 98% purity.

Workup

  1. customIt was quenched with water (30 mL)
  2. extractionextracted with ethyl acetate (3×30 mL)
  3. washThe combined organic extracts were washed with water (2×30 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-0e3b83180d6c42c49e99786104c3c47b
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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