p-Toluenesulfonic acid monohydrate → 2-(4-((4-(((7R,8aS)-5,5-dimethyloctahydroindolizin-7-yl)amino)-5-fluoropyrimidin-2-yl)amino)-2-(trifluoromethyl)phenoxy)ethan-1-ol

HRID 633440Notes

Reaction equation

HRID 633440 reaction equation
[Si]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[C:19]([F:22])([F:21])[F:20])(C(C)(C)C)(C)C.Cl.Cl[C:25]1[N:30]=[C:29]([NH:31][C@@H:32]2[CH2:40][C@H:39]3[N:35]([CH2:36][CH2:37][CH2:38]3)[C:34]([CH3:42])([CH3:41])[CH2:33]2)[C:28]([F:43])=[CH:27][N:26]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CC(O)C>[CH3:41][C:34]1([CH3:42])[CH2:33][C@H:32]([NH:31][C:29]2[C:28]([F:43])=[CH:27][N:26]=[C:25]([NH:16][C:15]3[CH:17]=[CH:18][C:12]([O:11][CH2:10][CH2:9][OH:8])=[C:13]([C:19]([F:20])([F:21])[F:22])[CH:14]=3)[N:30]=2)[CH2:40][C@H:39]2[N:35]1[CH2:36][CH2:37][CH2:38]2

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 86704489(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine hydrochlorideHCID 867045324-(2-((Tert-butyldimethylsilyl)oxy)ethoxy)-3-(trifluoromethyl)aniline

Product 1

HCID 718113172-(4-((4-(((7R,8aS)-5,5-dimethyloctahydroindolizin-7-yl)amino)-5-fluoropyrimidin-2-yl)amino)-2-(trifluoromethyl)phenoxy)ethan-1-olYield 57.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

The general displacement procedure described herein was used with 4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-3-(trifluoromethyl)aniline (481 mg, 1.4 mmol), (7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine hydrochloride (480 mg, 1.4 mmol) and pTsOH.H2O (546 mg, 2.9 mmol) in IPA (10 mL) at reflux to give the product (387 mg, 56% yield) as a solid, after workup and purification by column chromatography on silica gel using DCM/2M NH3 in MeOH (1:0 to 9:1) as eluent.

Workup

  1. temperatureat reflux

Sources & evidence

ORD record
ord-038af05512a4439080176706d6210163
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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