4-Methyl-5-(2-hydroxyethyl)thiazole → HCID 57664411, compound

HRID 656644Notes

Reaction equation

HRID 656644 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[CH2:7][CH2:8][OH:9].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:20]1([NH:23][C:24]([C:26]2[S:39][C:29]3=[N:30][C:31](S(C)=O)=[C:32]([Cl:35])[C:33]([CH3:34])=[C:28]3[C:27]=2[NH2:40])=[O:25])[CH2:22][CH2:21]1>C1COCC1>[CH:20]1([NH:23][C:24]([C:26]2[S:39][C:29]3=[N:30][C:31]([O:9][CH2:8][CH2:7][C:6]4[S:5][CH:4]=[N:3][C:2]=4[CH3:1])=[C:32]([Cl:35])[C:33]([CH3:34])=[C:28]3[C:27]=2[NH2:40])=[O:25])[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 11364-Methyl-5-(2-hydroxyethyl)thiazoleHCID 2733832Lithium HexamethyldisilazideHCID 576644203-Amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

Product 1

HCID 57664411HCID 57664411, compoundYield 25.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-methyl-5-thiazole-ethanol (0.375 g, 2.62 mmol) in THF (1 ml) at room temperature is added dropwise a solution of lithium bis(trimethylsilyl)amide (11.0M in hexanes)(1.74 ml, 1.74 mmol). The reaction mixture is stirred for 15 minutes and then is treated with 3-amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (0.300 g, 0.872 mmol). The reaction mixture is stirred at room temperature for 18 hours, then quenched by the addition of water (5 ml). The mixture is partitioned between water and EtOAc (40 ml each). Five ml of 1 N HCl is added, and the layers are shaken and separated. The aqueous layer is extracted with EtOAc (50 ml) and the combined organic layers are dried (anhydrous magnesium sulfate), filtered, concentrated, and flashed (1:2 hexane:EtOAc) to give the title compound as a pale yellow solid (0.094 g, 25%). Mass (m/z): 423.1 (M++1), 421.1 (M+−1).

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 18 hours
  2. customquenched by the addition of water (5 ml)
  3. customThe mixture is partitioned between water and EtOAc (40 ml each)
  4. additionFive ml of 1 N HCl is added
  5. stirringthe layers are shaken
  6. customseparated
  7. extractionThe aqueous layer is extracted with EtOAc (50 ml)
  8. dry with materialthe combined organic layers are dried (anhydrous magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-316b4bb42d7b4a6b864b0fd70f95f4b3
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

Loading…