Piperidin-4-ol → 1-[2-((3,5-bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-one

HRID 409445Notes

Reaction equation

HRID 409445 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:6][N:7]([C@H:21]1[CH2:25][C@@H:24]([CH2:26][CH3:27])[N:23]([C:28]2[C:33]([Cl:34])=[CH:32][N:31]=[C:30](Cl)[N:29]=2)[CH2:22]1)[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:18][CH2:17][N:16]([CH3:19])[C:15]2=[O:20])=[CH:10][N:9]=1.[NH:45]1[CH2:50][CH2:49][CH:48]([OH:51])[CH2:47][CH2:46]1>CC(O)C>[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:36]=[C:37]([C:39]([F:40])([F:42])[F:41])[CH:38]=1)[CH2:6][N:7]([C@H:21]1[CH2:25][C@@H:24]([CH2:26][CH3:27])[N:23]([C:28]2[C:33]([Cl:34])=[CH:32][N:31]=[C:30]([N:45]3[CH2:50][CH2:49][CH:48]([OH:51])[CH2:47][CH2:46]3)[N:29]=2)[CH2:22]1)[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:18][CH2:17][N:16]([CH3:19])[C:15]2=[O:20])=[CH:10][N:9]=1

Participants

4

Reactant 2

HCID 79341Piperidin-4-olHCID 596143571-(2-{(3,5-bis-trifluoromethyl-benzyl)-[(3S,5R)-1-(2,5-dichloro-pyrimidin-4-yl)-5-ethyl-pyrrolidin-3-yl]-amino}-pyrimidin-5-yl)-3-methyl-imidazolidin-2-one

Product 1

HCID 596144061-[2-((3,5-bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-oneYield 79%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 1-(2-{(3,5-bis-trifluoromethyl-benzyl)-[(3S,5R)-1-(2,5-dichloro-pyrimidin-4-yl)-5-ethyl-pyrrolidin-3-yl]-amino}-pyrimidin-5-yl)-3-methyl-imidazolidin-2-one (30 mg, 0.05 mmol) in i-PrOH (1 mL) is added piperidin-4-ol (23 mg, 0.23 mmol). The reaction mixture is stirred at 80° C. for 12 hours. After removal of solvent, the mixture is washed with brine and extracted with EtOAc. The combined organic layer is dried over MgSO4 then concentrated under reduced pressure to give 1-[2-((3,5-bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-one (26 mg, 79%) after purification by silica gel column chromatography (eluent: EtOAc:MeOH=20:1).

Workup

  1. customAfter removal of solvent
  2. washthe mixture is washed with brine
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic layer is dried over MgSO4
  5. concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record
ord-d3d95d7d80bc41009227db7524faa293
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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