Toluene → 2-(Methylthio)ethyl methyl(5-(pyridin-3-yl)-1,3,4-thiadiazol-2-yl)carbamate

HRID 1404703Notes

Reaction equation

HRID 1404703 reaction equation
[CH3:1][S:2][CH2:3][CH2:4][OH:5].[C:6](Cl)(Cl)=[O:7].C1(C)C=CC=CC=1.[CH3:17][NH:18][C:19]1[S:20][C:21]([C:24]2[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=2)=[N:22][N:23]=1>CN(C)C1C=CN=CC=1.ClCCCl.C(=O)(O)[O-].[Na+]>[CH3:17][N:18]([C:19]1[S:20][C:21]([C:24]2[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=2)=[N:22][N:23]=1)[C:6](=[O:7])[O:5][CH2:4][CH2:3][S:2][CH3:1]

Participants

8

Reactant 4

HCID 1140TolueneHCID 6371PhosgeneHCID 789252-(Methylthio)ethanolHCID 6488196N-methyl-5-(pyridin-3-yl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 666132842-(Methylthio)ethyl methyl(5-(pyridin-3-yl)-1,3,4-thiadiazol-2-yl)carbamateYield 79%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
23 °C

Procedure

2-Methylthioethanol (100 μL, 1.2 mmol, 1.5 equiv) was added to a stirred 20% solution of phosgene in toluene (1.2 mL, 2.3 mmol, 3.0 equiv) at 0° C. The resulting colorless solution was allowed to warm to 23° C. and stirred for 1.5 h. The reaction mixture was concentrated by rotary evaporation. The residue was added to a stirred suspension of N-methyl-5-(pyridin-3-yl)-1,3,4-thiadiazol-2-amine (150 mg, 0.78 mmol, 1.0 equiv) and 4-dimethylaminopyridine (190 mg, 1.6 mmol, 2.0 equiv) in 1,2-dichloroethane (7.8 mL) at 23° C. The resulting yellow solution was heated to 75° C. for 18 h. The cooled reaction mixture was diluted with a saturated solution of sodium bicarbonate (50 mL) and extracted with ethyl acetate (3×40 mL). The combined organic layers were dried (MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by silica gel column chromatography (ethyl acetate) to afford the title compound as a white powder (190 mg, 79%): mp 126-128° C.; IR (KBr thin film) 3044 (w), 2958 (w), 2910 (w), 1700 (s), 1572 (w) cm−1; 1H NMR (300 MHz, CDCl3) δ 9.12 (br s, 1H), 8.70 (d, J=5 Hz, 1H), 8.27 (dt, J=8, 2 Hz, 1H), 7.42 (dd, J=8, 5 Hz, 1H), 4.51 (t, J=7 Hz, 2H), 3.75 (s, 3H), 2.87 (t, J=7 Hz, 2H), 2.21 (s, 3H); ESIMS m/z 311 ([M+H]+). Compounds 14, 15, and 16 were prepared as described in Example 12.

Workup

  1. concentrationThe reaction mixture was concentrated by rotary evaporation
  2. temperatureThe resulting yellow solution was heated to 75° C. for 18 h
  3. customThe cooled reaction mixture
  4. extractionextracted with ethyl acetate (3×40 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4), gravity
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-e5e71a6dbe3446f8b8c3dfb321a52416
Source dataset
uspto-grants-2014_12
Patent number
US08912338B2

Reaction notes

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