Cesium carbonate → HCID 67951109, compound

HRID 923639Notes

Reaction equation

HRID 923639 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]2[S:9][NH:10][C:11](=[O:12])[C:3]=12.C(N(C(C)C)CC)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:29][C:30]([O:32][CH3:33])=[O:31]>C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]2[S:9][N:10]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[C:11](=[O:12])[C:3]=12

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 173760Isothiazolo(5,4-b)pyridin-3(2H)-one, 4,6-dimethyl-

Product 1

HCID 67951109HCID 67951109, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To enhance the selectivity of N-alkylation over O-alkylation, pyridinothiazolone 4 (500 mg, 2.77 mmol) was suspended in CH2Cl2 (20 mL) containing of diisopropylethylamine (DIEA, 1.5 mL, 8.61 mmol) and Cs2CO3 (700 mg, 3.07 mmol). Methyl 2-bromoacetate (900 mg, 5.88 mmol) was then added at room temperature. The mixture was stirred for 5 h, concentrated under reduced pressure, and purified by chromatography on a silica gel column with elution of EtOAc/hexane (1:4) to give the title compound 7 (360 mg, 55% yield) accompanied by an O-alkylation side product (7%). Compound 7: C11H12N2O3S; white solid; mp 89-91° C.; IR vmax (neat) 2928, 1766, 1728, 1664, 1561, 1523, 1435, 1375, 1324, 1210 cm−1; 1H NMR (400 MHz, CDCl3) δ 6.92 (1H, s), 4.54 (2H, s), 3.76 (3H, s), 2.70 (3H, s), 2.57 (3H, s); 13C NMR (100 MHz, CDCl3) δ 167.4, 164.3, 162.6, 162.3, 149.6, 122.4, 113.8, 52.8, 44.2, 24.9, 17.8; ESI-HRMS calcd for C11H13N2O3S: 253.0647. found: m/z 253.0657 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by chromatography on a silica gel column with elution of EtOAc/hexane (1:4)

Sources & evidence

ORD record
ord-e36d1f706a024314bacc3cc7f37db3ad
Source dataset
uspto-grants-2016_03
Patent number
US09278982B2

Reaction notes

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