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]-piperidine-4-carboxylic acid

HRID 409451Notes

Reaction equation

HRID 409451 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[C:16]([N:18]3[CH2:22][C@@H:21]([N:23]([CH2:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=4)[C:24]4[N:29]=[CH:28][C:27]([C:30]5[CH:31]=[N:32][NH:33][CH:34]=5)=[CH:26][N:25]=4)[CH2:20][C@H:19]3[CH2:50][CH3:51])[C:15]([Cl:52])=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.[Li+].[OH-].Cl>CO>[F:49][C:46]([F:47])([F:48])[C:38]1[CH:37]=[C:36]([CH:41]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:39]=1)[CH2:35][N:23]([C:24]1[N:25]=[CH:26][C:27]([C:30]2[CH:34]=[N:33][NH:32][CH:31]=2)=[CH:28][N:29]=1)[C@@H:21]1[CH2:22][N:18]([C:16]2[C:15]([Cl:52])=[CH:14][N:13]=[C:12]([N:9]3[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]3)[N:17]=2)[C@H:19]([CH2:50][CH3:51])[CH2:20]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 866483941-[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]-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 596144111-[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]-piperidine-4-carboxylic acidYield 20%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 15 ml round-bottom flask is charged with 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]-piperidine-4-carboxylic acid ethyl ester, 2N LiOH (0.4 ml, 0.8 mmol) THF (0.5 ml) and MeOH (1 ml). The mixture is then stirred at rt for 1 hour. PH is adjusted to 6 using 1 N HCl and resulted solution is extracted with EtOAc. The organic layer is dried over Na2SO4 and removal of solvent, purification with reverse phase column 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]-piperidine-4-carboxylic acid (13 mg, 0.017 mmol, 20% for 3 steps).

Workup

  1. customresulted solution
  2. extractionis extracted with EtOAc
  3. dry with materialThe organic layer is dried over Na2SO4 and removal of solvent, purification with reverse phase column

Sources & evidence

ORD record
ord-443e7d23d1ce43e1976866b181876d0d
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

Loading…