Reaktion #356692

Reaktionsgleichung

Methanol

2,3-difluorophenylacetyl chloride

[4-(1H-pyrrolo[2,3-]pyridin-5-yl)-cyclohexyl]-carbamic acid tert-butyl ester

AlCl3

CH2Cl

3-[4-(2,3-Dichloro-phenyl)-isoxazol-5-yl]-1H-pyrrolo[2, 3-b]pyridine

→

1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ]-2-(2,3-difluoro-phenyl)-ethanone

Ausbeute 70.5%

Lösungsmittel

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.WAITAfter 1 hr
3. 3
   Sonstigethe reaction was evaporated
4. 4
   Sonstigethe resulting residue purified by flash chromatography

Vorschrift

A solution of 2,3-difluorophenylacetyl chloride (1.0 mmol) in CH2Cl 2(3 ml) was added dropwise to a mixture of [4-(1H-pyrrolo[2,3-]pyridin-5-yl)-cyclohexyl]-carbamic acid tert-butyl ester (280 mg, 0.88 mmol) and AlCl3 (612 mg, 4.6 mmol) in CH2Cl2(15 ml) at 0° C. After the addition, the reaction was stirred for 1.5 hrs at 0° C. Methanol (5 ml) was added to the reaction. After 1 hr. the reaction was evaporated and the resulting residue purified by flash chromatography to afford 1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ]-2-(2,3-difluoro-phenyl)-ethanone (229 mg) in 70.5% yield. LC-MS: m/e=370.3 (M+H), 368.4 (M−H). After the treatment of the above cyclohexylamine (220 mg, 0.60 mmol) with 37% formaldehyde (2 ml) and formic acid (4 ml) at 80° C. for 15 h, pure 2-(2,3-Difluoro-phenyl)-1-[5-(4-dimethylamino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone was obtained by FC (167 mg) in 70.1% yield. LC-MS: m/e: 398.4 (M+H), 396.4 (M−H).

Quelle