Dichloromethane → phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone O-(3-aminopropyl)oxime hydrochloride

HRID 1821874Notes

Reaction equation

HRID 1821874 reaction equation
[C:1]1([C:7](=[N:17][O:18][CH2:19][CH2:20][CH2:21][NH:22]C(=O)OC(C)(C)C)[C:8]2[NH:16][C:11]3=[CH:12][N:13]=[CH:14][CH:15]=[C:10]3[CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O.C(Cl)[Cl:38]>>[ClH:38].[NH2:22][CH2:21][CH2:20][CH2:19][O:18][N:17]=[C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]1[NH:16][C:11]2=[CH:12][N:13]=[CH:14][CH:15]=[C:10]2[CH:9]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 136366032tert-butyl 3-[[[phenyl (1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]propylcarbamate

Product 1

HCID 136366085phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone O-(3-aminopropyl)oxime hydrochloride

Procedure

tert-Butyl 3-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]propylcarbamate (Example 76) (60 mg, 0.15 mmol) was dissolved in methylene chloride (4 mL) and trifluoroacetic acid (1 mL) was added. The reaction mixture was stirred for 1 h. The solvents were removed under vacuum and the residue was dissolved in ethyl acetate. Saturated sodium bicarbonate solution was added and the mixture was stirred for 10 min. The layers were separated and the aqueous layer extracted with ethyl acetate (2×). The combined organic extracts were washed with water and brine, dried over sodium sulfate, and concentrated to an oil. The oil was dissolved in ethyl acetate (4 mL), 2 M ethereal hydrogen chloride (0.2 mL) was added and the precipitate formed. Removal of the solvents and drying under vacuum produced phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone O-(3-aminopropyl)oxime hydrochloride, a mixture of isomers (39 mg, 71%) as an off-white solid: mp 168-174° C. dec.; 1H NMR (500 MHz, CD3OD) δ2.02-2.31 (2H, m), 2.98-3.27 (2H, m), 4.47-4.59 (2H, m), 6.75 (0.24H, s) 7.12 (0.76H, s), 7.47-7.59 (5H, m), 8.05-8.27 (2H, m), 8.96 (0.24H, s), 9.13 (0.76H, br s); ESI MS m/z 295 [C17H18N4O+H]+; HPLC (Method A) 91.5% (AUC), tR=14.0 min.

Workup

  1. customThe solvents were removed under vacuum
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. additionSaturated sodium bicarbonate solution was added
  4. stirringthe mixture was stirred for 10 min
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted with ethyl acetate (2×)
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to an oil
  10. dissolutionThe oil was dissolved in ethyl acetate (4 mL)
  11. addition2 M ethereal hydrogen chloride (0.2 mL) was added
  12. customthe precipitate formed
  13. customRemoval of the solvents
  14. customdrying under vacuum

Sources & evidence

ORD record
ord-98baa90fd54f4a37876a72a592b4e506
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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