Reaktion #510176

Reaktionsgleichung

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid

4-(tert-Butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid

Intermediate 1

4-(tert-Butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid

(R)-1-(4-chlorophenyl)ethanamine

DIPEA

→

(R)-4-amino-N-(1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

Ausbeute 52.9%

Lösungsmittel

DMA

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe crude product was purified by ion exchange chromatography
2. 2
   WaschenThe desired product was eluted from the column
3. 3
   Sonstigewere evaporated to dryness
4. 4
   workup.ADDITIONThe crude material was treated with a 10% solution of TFA in DCM (5 mL)
5. 5
   workup.STIRRINGstirred at room temperature
6. 6
   SonstigeThe crude product was purified by ion exchange chromatography
7. 7
   WaschenThe desired product was eluted from the column
8. 8
   Sonstigewere evaporated to dryness
9. 9
   SonstigeThe crude product was purified by preparative LCMS
10. 10
    workup.ADDITIONFractions containing the desired compound
11. 11
    Sonstigewere evaporated to dryness

Vorschrift

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.418 g, 1.10 mmol) was added in one portion to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (0.361 g, 1 mmol), (R)-1-(4-chlorophenyl)ethanamine (0.156 g, 1.00 mmol) and DIPEA (0.524 mL, 3.00 mmol) in DMA (10 mL) at 25° C. under nitrogen. The resulting solution was stirred at 60° C. for 4 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7N ammonia/MeOH and pure fractions were evaporated to dryness. The crude material was treated with a 10% solution of TFA in DCM (5 mL) and stirred at room temperature. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7N ammonia/MeOH and pure fractions were evaporated to dryness. The crude product was purified by preparative LCMS using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (R)-4-amino-N-(1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (0.211 g, 52.9%) as a white solid.

Quelle