Hydrochloric Acid → 1-[4-((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidin-4-ol

HRID 409448Notes

Reaction equation

HRID 409448 reaction equation
[F:1][C:2]([F:54])([F:53])[C:3]1[CH:4]=[C:5]([CH:46]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:48]=1)[CH2:6][N:7]([C:29]1[N:34]=[CH:33][C:32]([C:35]2[CH:36]=[N:37][N:38](C3CCCCO3)[CH:39]=2)=[CH:31][N:30]=1)[C@@H:8]1[CH2:12][N:11]([C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[C:15]([N:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)[N:14]=2)[C@H:10]([CH2:27][CH3:28])[CH2:9]1.Cl.CO.C([O-])(O)=O.[Na+]>ClCCl>[F:54][C:2]([F:1])([F:53])[C:3]1[CH:4]=[C:5]([CH:46]=[C:47]([C:49]([F:50])([F:52])[F:51])[CH:48]=1)[CH2:6][N:7]([C:29]1[N:30]=[CH:31][C:32]([C:35]2[CH:39]=[N:38][NH:37][CH:36]=2)=[CH:33][N:34]=1)[C@@H:8]1[CH2:12][N:11]([C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[C:15]([N:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)[N:14]=2)[C@H:10]([CH2:27][CH3:28])[CH2:9]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 516892Sodium BicarbonateHCID 866483931-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidin-4-ol

Product 1

HCID 596143881-[4-((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidin-4-olYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 25 ml round-bottom flask is charged with 1-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidin-4-ol (0.15 mmol), 1N HCl (0.8 ml, 0.8 mmol) and MeOH (2 ml). The mixture is then heated to 60 degree for 30 minutes. After cooling down to rt, sat. NaHCO3 and dichloromethane are added, then organic layer is collected. Removal of solvent and purification with reverse phase column chromatography give 1-[4-((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidin-4-ol (11.3 mg, 0.015 mmol, 10% for 2 steps).

Workup

  1. temperatureThe mixture is then heated to 60 degree for 30 minutes
  2. customorganic layer is collected
  3. customRemoval of solvent and purification with reverse phase column chromatography

Sources & evidence

ORD record
ord-29640ceca4de4da6a0307fdc22338349
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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