Tetrahydro-4H-pyran-4-ol → tert-butyl 4-(2-{4-[2-chloro-7-(tetrahydro-2H-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(trifluoromethyl)phenoxy}ethyl)piperidine-1-carboxylate

HRID 522280Notes

Reaction equation

HRID 522280 reaction equation
C(C=P(CCCC)(CCCC)CCCC)#N.[Cl:17][C:18]1[N:19]=[C:20]([C:27]2[CH:48]=[CH:47][C:30]([O:31][CH2:32][CH2:33][CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[C:29]([C:49]([F:52])([F:51])[F:50])[CH:28]=2)[C:21]2[CH:26]=[CH:25][NH:24][C:22]=2[N:23]=1.[O:53]1[CH2:58][CH2:57][CH:56](O)[CH2:55][CH2:54]1>C1(C)C=CC=CC=1>[Cl:17][C:18]1[N:19]=[C:20]([C:27]2[CH:48]=[CH:47][C:30]([O:31][CH2:32][CH2:33][CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:45])([CH3:44])[CH3:46])=[O:41])[CH2:36][CH2:35]3)=[C:29]([C:49]([F:50])([F:51])[F:52])[CH:28]=2)[C:21]2[CH:26]=[CH:25][N:24]([CH:56]3[CH2:57][CH2:58][O:53][CH2:54][CH2:55]3)[C:22]=2[N:23]=1

Participants

5

Reactant 3

HCID 74956Tetrahydro-4H-pyran-4-olHCID 4622928CyanomethylenetributylphosphoraneHCID 90065716tert-butyl 4-{2-[4-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate

Product 1

HCID 117899579tert-butyl 4-(2-{4-[2-chloro-7-(tetrahydro-2H-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(trifluoromethyl)phenoxy}ethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Cyanomethylenetributylphosphorane (1.1 mL) was added to a mixture of tert-butyl 4-{2-[4-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate (1.0 g), tetrahydro-2H-pyran-4-ol (0.36 mL), and toluene (30 mL) at room temperature in a nitrogen atmosphere, and the reaction mixture was stirred overnight while heating to reflux. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=67:33 to 33:67), whereby tert-butyl 4-(2-{4-[2-chloro-7-(tetrahydro-2H-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(trifluoromethyl)phenoxy}ethyl)piperidine-1-carboxylate (1.04 g) was obtained as a yellow amorphous material.

Workup

  1. temperaturewhile heating to reflux
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=67:33 to 33:67)

Sources & evidence

ORD record
ord-85753d2c72584525ae71437546368700
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

Loading…