Potassium Carbonate → 4-(5-Bromo-2-((quinolin-2-ylthio)methyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

HRID 1772717Notes

Reaction equation

HRID 1772717 reaction equation
[Br:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11]O)[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[N:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:42]=[CH:41][C:40]=1[SH:49]>ClCCl.O>[Br:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][S:49][C:40]3[CH:41]=[CH:42][C:43]4[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=4)[N:39]=3)[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 117727888(5-Bromo-8-morpholinoimidazo[1,2-a]pyrazin-2-yl)methanolHCID 178418736HCID 178418736, compound

Product 1

HCID 1177279734-(5-Bromo-2-((quinolin-2-ylthio)methyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of compound 1e (10 g, 30.45 mmol) and DIPEA (10.23 g, 79.30 mmol) in dichloromethane (200 mL) was cooled in an ice bath and MsCl (7.3 g, 63.48 mmol) was added dropwise. Upon complete addition, the reaction mixture was stirred for 3 h at room temperature and concentrated under reduced pressure. To the residue was added CH3CN (150 mL), followed by potassium carbonate (6.57 g, 47.6 mmol) and quinoline-2-thiol (5.62 g, 34.9 mmol). The resulting mixture was stirred overnight at 60° C. and allowed to cool to rt. Water (300 mL) was then added. The solids were collected by filtration. The crude product was recrystallized from DCM/ethyl ether (1:2 v/v) to obtain compound 78a as a white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C20H18BrN5OS: 457.1 (M+H). found: 457.0

Workup

  1. additionUpon complete addition
  2. concentrationconcentrated under reduced pressure
  3. additionTo the residue was added CH3CN (150 mL)
  4. stirringThe resulting mixture was stirred overnight at 60° C.
  5. temperatureto cool to rt
  6. filtrationThe solids were collected by filtration
  7. customThe crude product was recrystallized from DCM/ethyl ether (1:2 v/v)

Sources & evidence

ORD record
ord-f4bc388c1d7f499db07259da2a5f8aed
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

Loading…