Sodium Hydroxide → (S)-1-(2-((R)-3-fluoropyrrolidin-1-yl)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one

HRID 539036Notes

Reaction equation

HRID 539036 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][N:14]2[CH2:18][C@H:17]([CH:19]([CH3:21])[CH3:20])[N:16]([C:22]3[CH:27]=[CH:26][N:25]4[N:28]=[CH:29][C:30]([C:31]5[CH:36]=[CH:35][C:34]([C:37]6[N:41]=[CH:40][N:39]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[N:38]=6)=[CH:33][CH:32]=5)=[C:24]4[N:23]=3)[C:15]2=[O:50])(=O)=O)=CC=1.Cl.[F:52][C@@H:53]1[CH2:57][CH2:56][NH:55][CH2:54]1.C(N(C(C)C)C(C)C)C.[OH-].[Na+]>CN(C=O)C>[F:52][C@@H:53]1[CH2:57][CH2:56][N:55]([CH2:12][CH2:13][N:14]2[CH2:18][C@H:17]([CH:19]([CH3:20])[CH3:21])[N:16]([C:22]3[CH:27]=[CH:26][N:25]4[N:28]=[CH:29][C:30]([C:31]5[CH:32]=[CH:33][C:34]([C:37]6[N:41]=[CH:40][N:39]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:47])([CH3:48])[CH3:49])[N:38]=6)=[CH:35][CH:36]=5)=[C:24]4[N:23]=3)[C:15]2=[O:50])[CH2:54]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 86667826(S)-2-(4-isopropyl-2-oxo-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-1-yl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 67034711(S)-1-(2-((R)-3-fluoropyrrolidin-1-yl)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-oneYield 40.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-(4-isopropyl-2-oxo-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-1-yl)ethyl 4-methylbenzenesulfonate (0.070 g, 0.098 mmol) in DMF was added (R)-3-fluoropyrrolidine hydrochloride (0.044 g, 0.49 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.13 g, 0.98 mmol) and the reaction stirred for 4 days at ambient temperature. The reaction was poured into 1N NaOH and the aqueous layer extracted into EtOAc. The organics were washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. The crude material was chromatographed using EtOAc to 3% MeOH/dichloromethane as eluent to yield (S)-1-(2-((R)-3-fluoropyrrolidin-1-yl)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one (0.025 g, 40%).

Workup

  1. extractionthe aqueous layer extracted into EtOAc
  2. washThe organics were washed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude material was chromatographed

Sources & evidence

ORD record
ord-e3f0cd8fac8944e3a332ba14e25a8bc7
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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