Thiosemicarbazide → 5-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine
Reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11](O)=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[NH2:14][NH:15][C:16]([NH2:18])=[S:17]>P(Cl)(Cl)(Cl)=O>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:17][C:16]([NH2:18])=[N:15][N:14]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
Commercially available isoquinoline-6-carboxylic acid (15.4 g, 89 mmol) and thiosemicarbazide (12.2 g, 133 mmol) were mixed in 150 ml phosphorus oxychloride. The mixture was heated at 80° C. for 60 hours. After removing the excess phosphorus oxychloride via rotatory evaporation at a reduced pressure, the remaining residue was mixed with ice water and the pH increased to pH 12 with KOH. After filtration and washing with water, a yellow amorphous solid 1a was obtained as the crude product (17 g, y (yield)=85%). It was used directly for next step. A pure sample of the product was obtained by subjecting the crude product to a silica gel column chromatography with a gradient of 1-5% 2M NH3 methanol solution in dichloromethane as the eluent. 1H NMR (400 MHz, DMSO-d6): δ 7.73 (s, 2H), 8.02 (d, J=6 Hz, 1H), 8.27 (m, 2H), 8.38 (s, 1H), 8.66 (d, J=6 Hz, 1H), 9.45 (s, 1H). MS (API-ES) m/z (%): 229 (100%, M++1).
Workup
- customAfter removing the excess phosphorus oxychloride
- customvia rotatory evaporation at a reduced pressure
- additionthe remaining residue was mixed with ice water
- temperaturethe pH increased to pH 12 with KOH
- filtrationAfter filtration
- washwashing with water
Sources & evidence
- ORD record
- ord-04a288dc105a4107858003a01479ba9f
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07354944B2
Reaction notes
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