p-Toluenesulfonic acid monohydrate → HCID 86704537, compound

HRID 633447Notes

Reaction equation

HRID 633447 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[CH3:19])(C(C)(C)C)(C)C.Cl.Cl[C:22]1[N:27]=[C:26]([NH:28][C@@H:29]2[CH2:37][C@H:36]3[N:32]([CH2:33][CH2:34][CH2:35]3)[C:31]([CH3:39])([CH3:38])[CH2:30]2)[C:25]([F:40])=[CH:24][N:23]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CC(O)C>[CH3:38][C:31]1([CH3:39])[CH2:30][C@H:29]([NH:28][C:26]2[C:25]([F:40])=[CH:24][N:23]=[C:22]([NH:16][C:15]3[CH:17]=[CH:18][C:12]([O:11][CH2:10][CH2:9][OH:8])=[C:13]([CH3:19])[CH:14]=3)[N:27]=2)[CH2:37][C@H:36]2[N:32]1[CH2:33][CH2:34][CH2:35]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 86704538HCID 86704538, compound

Product 1

HCID 86704537HCID 86704537, compoundYield 59.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

The general displacement procedure described herein was used with 4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-3-methylaniline (563 mg, 2.0 mmol), (7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine hydrochloride (478 mg, 1.4 mmol) and pTsOH.H2O (544 mg, 2.9 mmol) in IPA (10 mL) at reflux to give the product (360 mg, 59% 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-7049c15a194641919241d1767b602d67
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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