Hydrogen Sulfide → 6-(3-Hydroxy-propoxy)-thionicotinamide

HRID 734432Notes

Reaction equation

HRID 734432 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=1.[SH2:14].C(NCC)C>CN(C=O)C>[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]([NH2:11])=[S:14])=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 402Hydrogen SulfideHCID 8021DiethylamineHCID 431521396-(3-Hydroxypropoxy)nicotinonitrile

Product 1

HCID 431521456-(3-Hydroxy-propoxy)-thionicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Through a solution of 6-(3-hydroxypropoxy)nicotinonitrile (Example 66, 16 g, 89.79 mmol) in DMF (450 mL) was passed H2S for 3 h at rt. The reaction mixture turned purple. Diethylamine (9.85 g, 134.69 mmol) was added slowly. The resultant dark green solution was heated at 60° C. for 2 h. The resulting mixture was concentrated under reduced pressure and purified by flash chromatography with a gradient of EtOAc in hexanes from 50 to 100%. The title compound was collected as a yellow solid (18.9 g, 98%). 1H NMR (400 MHz, acetone-d6) δ 8.98-8.87 (br, 2H), 8.80-8.79 (m, 1H), 8.29 (dd, 1H), 6.77 (dd, 1H), 4.48 (t, 2H), 3.74-3.68 (m, 3H), 1.99 (t, 2H). LC/MS m/z 213.2 (M+H)+; RT 0.50 min.

Workup

  1. customfor 3 h
  2. customat rt
  3. concentrationThe resulting mixture was concentrated under reduced pressure
  4. custompurified by flash chromatography with a gradient of EtOAc in hexanes from 50 to 100%
  5. customThe title compound was collected as a yellow solid (18.9 g, 98%)
  6. customRT 0.50 min.

Sources & evidence

ORD record
ord-f4d4cc5dfb654cbd95d5a8d542dc1ade
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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