Acetic Acid → tert-butyl 3-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]pyrrolidine-1-carboxylate

HRID 1821880Notes

Reaction equation

HRID 1821880 reaction equation
[C:1]1([C:7]([C:9]2[NH:17][C:12]3=[CH:13][N:14]=[CH:15][CH:16]=[C:11]3[CH:10]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:18][O:19][CH:20]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]1.C(O)(=O)C>C(O)(C)C>[C:1]1([C:7](=[N:18][O:19][CH:20]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]2)[C:9]2[NH:17][C:12]3=[CH:13][N:14]=[CH:15][CH:16]=[C:11]3[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 19691331Tert-butyl 3-(aminooxy)pyrrolidine-1-carboxylateHCID 57893467phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone

Product 1

HCID 136386506tert-butyl 3-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]pyrrolidine-1-carboxylateYield 32.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a mixture of phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone (Example 35) (90 mg, 0.40 mmol) and tert-butyl 3-(aminooxy)pyrrolidine-1-carboxylate (Reference Example 9) (82 mg, 0.40 mmol) in isopropanol (6 mL) was added 4 Å molecular sieves. The pH of the solution was adjusted to pH 4-5 with glacial acetic acid. The reaction mixture was heated to reflux. After 3 days, the reaction mixture was cooled to ambient temperature. The mixture was filtered through a pad of diatomaceous earth and the filtrate was concentrated under reduced pressure. Purification by column chromatography (silica gel, 9.75:0.25 CH2Cl2/MeOH to 9.5:0.5 CH2Cl2/MeOH) followed by ion-exchange chromatography (SCX-2, 1:3 7 N NH4OH in MeOH/MeOH) gave tert-butyl 3-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]pyrrolidine-1-carboxylate (52.3 mg, 32%) as a mixture of isomers: mp 80-82° C.; 1H NMR (500 MHz, DMSO-d6) major isomer δ 1.37-1.39 (9H, m), 2.08-2.10 (2H, m), 3.13-3.17 (1H, m), 3.31-3.50 (3H, m), 4.92 (1H, br s), 6.23 (1H, s), 7.41-7.53 (6H, m), 8.08 (1H, d, J=5.4 Hz), 8.79 (1H, s), 11.85 (1H, s); ESI MS m/z 407 [C23H26N4O3+H]+; HPLC (Method A) 85.8% (AUC), tR=18.0 min.

Workup

  1. additionwas added 4 Å molecular sieves
  2. temperatureThe reaction mixture was heated to reflux
  3. filtrationThe mixture was filtered through a pad of diatomaceous earth
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customPurification by column chromatography (silica gel, 9.75:0.25 CH2Cl2/MeOH to 9.5:0.5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-40ed9b291aa64077adaec1c60fb74258
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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