Potassium Hydroxide → 5-(3-Methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine

HRID 899408Notes

Reaction equation

HRID 899408 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11](O)=O)[CH:9]=2)[NH:4][N:3]=1.[NH2:14][NH:15][C:16]([NH2:18])=[S:17].[OH-].[K+]>>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:17][C:16]([NH2:18])=[N:15][N:14]=3)[CH:9]=2)[NH:4][N:3]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 2723789ThiosemicarbazideHCID 178434289HCID 178434289, compound

Product 1

HCID 1784342715-(3-Methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amineYield 53%

Conditions

Temperature
90 °C

Procedure

To a round bottom flash equipped with an overhead stir motor was added 80 g of polyphosphoric acid. The flask was heated to 90° C. and a finely ground mixture of 3-methyl-1H-indazole-5-carboxlic acid 4e (8.0 g, 45.5 mmol) and thiosemicarbazide (4.1 g (45.4 mmol) was slowly added over a period of 30 min. The resulting mixture was stirred for 24 hr. At this point 200 ml of ice water was added to the solution, and the pH of the resulting mixture was adjusted to 7.0 using solid KOH. A precipitate was formed in the process. The precipitate was isolated by filtration, washed sequentially with water and ether, and dried at reduced pressure, affording 5-(3-Methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-ylamine (4f) (5.50 g, 53% yield) as a tan colored solid. 1H 400 MHz NMR (d6 DMSO), 2.54 (3 H, s), 3.17 (1H, s), 7.54 (1H, d, J=8.0 Hz), 7.83 (1H, t, J=8.0 Hz), 8.06 (1H, s). MS (API-ES) m/z (%): 232 (100%, M++H).

Workup

  1. customTo a round bottom flash equipped with an overhead
  2. additionwas slowly added over a period of 30 min
  3. stirringThe resulting mixture was stirred for 24 hr
  4. customA precipitate was formed in the process
  5. customThe precipitate was isolated by filtration
  6. washwashed sequentially with water and ether
  7. customdried at reduced pressure

Sources & evidence

ORD record
ord-b77a8ebc03d34ef99fb35969fb8daf0e
Source dataset
uspto-grants-2008_04
Patent number
US07354944B2

Reaction notes

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