1,4-Dimercapto-2,3-butanediol → N-{6-[(6-ethoxy[1,2,4]triazolo[4,3-b]pyridazin-3-yl)sulphanyl]-1,3-benzothiazol-2-yl}-3-methoxypropanamide

HRID 633510Notes

Reaction equation

HRID 633510 reaction equation
SCC(C(CS)O)O.[CH3:9][O:10][CH2:11][CH2:12][C:13]([NH:15][C:16]1[S:17][C:18]2[CH:24]=[C:23]([S:25][C:26]#[N:27])[CH:22]=[CH:21][C:19]=2[N:20]=1)=[O:14].ClC1N2[N:34]=[C:35]([O:38][CH2:39][CH3:40])[CH:36]=[CH:37][C:32]2=[N:31][N:30]=1>O.C(O)C.O1CCCC1.P([O-])(O)(O)=O.[K+]>[CH2:39]([O:38][C:35]1[CH:36]=[CH:37][C:32]2[N:27]([C:26]([S:25][C:23]3[CH:22]=[CH:21][C:19]4[N:20]=[C:16]([NH:15][C:13](=[O:14])[CH2:12][CH2:11][O:10][CH3:9])[S:17][C:18]=4[CH:24]=3)=[N:30][N:31]=2)[N:34]=1)[CH3:40]

Participants

8

Reactant 3

HCID 190011,4-Dimercapto-2,3-butanediolHCID 675245223-Chloro-6-ethoxy[1,2,4]triazolo[4,3-b]pyridazineHCID 866478972-[(3-Methoxypropanoyl)amino]-1,3-benzothiazol-6-ylthiocyanate

Product 1

HCID 86647896N-{6-[(6-ethoxy[1,2,4]triazolo[4,3-b]pyridazin-3-yl)sulphanyl]-1,3-benzothiazol-2-yl}-3-methoxypropanamideYield 41.2%

Reagents, catalysts & solvents 4

HCID 516951Monobasic potassium phosphateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

7 mg of potassium dihydrogen phosphate in 0.2 cm3 of water and 699 mg of DL-dithiothreitol are added to a degassed solution of 443 mg of 2-[(3-methoxypropanoyl)amino]-1,3-benzothiazol-6-yl thiocyanate in 10 cm3 of ethanol and 10 cm3 of tetrahydrofuran. The reaction is heated at 80° C. for 15 min and then 301 mg of 3-chloro-6-ethoxy[1,2,4]triazolo[4,3-b]pyridazine are added and the reaction is heated for a further 24 h. The reaction medium is then evaporated to dryness under reduced pressure. The residue is taken up in 20 cm3 of ethanol and 57 mg of sodium borohydride are added and the mixture is then brought to reflux for 18 h. The reaction medium is concentrated under reduced pressure. The residue is chromatographed by solid deposit on Biotage Quad 12/25 (KP-SIL, 60 A; 32-63 μm), elution being carried out with a gradient of 100% dichloromethane to 97/3 dichloromethane/methanol. 268 mg of N-{6-[(6-ethoxy[1,2,4]triazolo[4,3-b]pyridazin-3-yl)sulphanyl]-1,3-benzothiazol-2-yl}-3-methoxypropanamide are thus obtained in the form of a white powder, the characteristics of which are as follows:

Workup

  1. temperaturethe reaction is heated for a further 24 h
  2. customThe reaction medium is then evaporated to dryness under reduced pressure
  3. addition57 mg of sodium borohydride are added
  4. temperatureto reflux for 18 h
  5. concentrationThe reaction medium is concentrated under reduced pressure
  6. customThe residue is chromatographed by solid deposit on Biotage Quad 12/25 (KP-SIL, 60 A
  7. wash32-63 μm), elution

Sources & evidence

ORD record
ord-a0efa041a9014c74b0476de56198ebb6
Source dataset
uspto-grants-2016_04
Patent number
US09321777B2

Reaction notes

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