Ammonia → 1-(6-{[6-(4-Fluorophenyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-[2-(morpholin-4-yl)ethyl]urea

HRID 1035780Notes

Reaction equation

HRID 1035780 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([S:17][C:18]4[CH:38]=[CH:37][C:21]5[N:22]=[C:23]([NH:25][C:26]([NH:28][CH2:29][CH2:30][N:31]6[CH2:36][CH2:35][O:34][CH2:33][CH2:32]6)=[O:27])[S:24][C:20]=5[CH:19]=4)=[N:15][N:16]=3)[N:13]=2)=[CH:4][CH:3]=1.N>C(O)(=O)C.[Zn]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][C:11]3[N:12]([C:14]([S:17][C:18]4[CH:38]=[CH:37][C:21]5[N:22]=[C:23]([NH:25][C:26]([NH:28][CH2:29][CH2:30][N:31]6[CH2:36][CH2:35][O:34][CH2:33][CH2:32]6)=[O:27])[S:24][C:20]=5[CH:19]=4)=[N:15][N:16]=3)[N:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 222AmmoniaHCID 25182860Sar-125844

Product 1

HCID 425988921-(6-{[6-(4-Fluorophenyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-[2-(morpholin-4-yl)ethyl]ureaYield 22.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 176Acetic AcidSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 209 mg of 1-(6-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-(2-morpholin-4-ylethyl)urea and 241 mg of zinc in 7 cm3 of acetic acid is stirred at 20° C. for 1.5 h and then heated at 50° C. for 3.5 h. 241 mg of zinc are again added and the mixture is again left for 1 h at 50° C. After stirring overnight at 20° C., aqueous ammonia is added so that the reaction mixture changes to an alkaline pH. This mixture is extracted with ethyl acetate. The organic phase is washed with a saturated solution of sodium bicarbonate and then with brine and is then dried with magnesium sulphate and evaporated to dryness under vacuum. The residue is purified by chromatography on a Merck cartridge of 25 g of silica 15-40 μm by solid deposit, elution being carried out with a 9/1 mixture of dichloromethane/(dichloromethane:38/methanol:17/aqueous ammonia:2). 48 mg of 1-(6-{[6-(4-fluorophenyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-[2-(morpholin-4-yl)ethyl]urea are thus obtained in the form of a white solid, the characteristics of which are as follows:

Workup

  1. temperatureheated at 50° C. for 3.5 h
  2. waitthe mixture is again left for 1 h at 50° C
  3. stirringAfter stirring overnight at 20° C.
  4. extractionThis mixture is extracted with ethyl acetate
  5. washThe organic phase is washed with a saturated solution of sodium bicarbonate
  6. dry with materialwith brine and is then dried with magnesium sulphate
  7. customevaporated to dryness under vacuum
  8. customThe residue is purified by chromatography on a Merck cartridge of 25 g of silica 15-40 μm by solid deposit, elution
  9. additionbeing carried out with a 9/1 mixture of dichloromethane/(dichloromethane:38/methanol:17/aqueous ammonia:2)

Sources & evidence

ORD record
ord-6bec203cd488419abc0503715e55f261
Source dataset
uspto-grants-2013_10
Patent number
US08546393B2

Reaction notes

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