1,2-Dichloroethane → N'-formyl-2-methyl-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanehydrazide

HRID 410614Notes

Reaction equation

HRID 410614 reaction equation
[CH3:1][C:2]([C:7]1[S:8][C:9]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=3)[CH:15]=[C:14]([CH3:29])[CH:13]=2)=[CH:10][N:11]=1)([CH3:6])[C:3]([OH:5])=O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH:44]([NH:46][NH2:47])=[O:45].CCN(C(C)C)C(C)C>O.O1CCOCC1>[CH:44]([NH:46][NH:47][C:3](=[O:5])[C:2]([CH3:1])([C:7]1[S:8][C:9]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[N:24]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:22]=[CH:21][N:20]=3)[CH:15]=[C:14]([CH3:29])[CH:13]=2)=[CH:10][N:11]=1)[CH3:6])=[O:45]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 12229HydrazinecarboxaldehydeHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 672489222-Methyl-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoic acid

Product 1

HCID 67431912N'-formyl-2-methyl-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanehydrazideYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

The product from Step 1 (HCl salt, 187 mg, 0.408 mmol), HOBT (125 mg, 0.815 mmol), and EDC (156 mg, 0.815 mmol) were combined with dioxane (5 mL) and stirred for 5 min at room temperature. Formic acid hydrazide (73 mg, 1.223 mmol) and DIEA (105 mg, 0.815 mmol) were subsequently added. The reaction was stirred overnight at room temperature. The reaction was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. Column chromatography on silica (50-100% EtOAc/hexanes) afforded N′-formyl-2-methyl-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanehydrazide (87 mg, 46%) as a colorless solid. MS ESI: [M+H]+ m/z 465.0.

Workup

  1. stirringThe reaction was stirred overnight at room temperature
  2. extractionextracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-f8ffb3ec510c4981aabfbd25b9025d7b
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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