5-Cyclopropyl-1,3,4-thiadiazol-2-amine → N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-((1-methyl-2-oxopyrrolidin-3-yl)oxy)benzamide

HRID 75966Notes

Reaction equation

HRID 75966 reaction equation
Cl.CN(C)CCCN=C=NCC.COCC(OC1C=C(C=C(OC2C=CC(C3OC(C)=NN=3)=CC=2)C=1)C(O)=O)C.[CH3:41][C:42]1[O:46][C:45]([C:47]2[CH:70]=[CH:69][C:50]([O:51][C:52]3[CH:53]=[C:54]([CH:58]=[C:59]([O:61][CH:62]4[CH2:66][CH2:65][N:64]([CH3:67])[C:63]4=[O:68])[CH:60]=3)[C:55]([OH:57])=O)=[CH:49][CH:48]=2)=[N:44][N:43]=1.[CH:71]1([C:74]2[S:78][C:77]([NH2:79])=[N:76][N:75]=2)[CH2:73][CH2:72]1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:71]1([C:74]2[S:78][C:77]([NH:79][C:55](=[O:57])[C:54]3[CH:58]=[C:59]([O:61][CH:62]4[CH2:66][CH2:65][N:64]([CH3:67])[C:63]4=[O:68])[CH:60]=[C:52]([O:51][C:50]4[CH:69]=[CH:70][C:47]([C:45]5[O:46][C:42]([CH3:41])=[N:43][N:44]=5)=[CH:48][CH:49]=4)[CH:53]=3)=[N:76][N:75]=2)[CH2:73][CH2:72]1

Participants

7

Reactant 4

HCID 7170215-Cyclopropyl-1,3,4-thiadiazol-2-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 669719313-(1-Methoxypropan-2-yloxy)-5-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)benzoic acidHCID 669722263-(4-(5-Methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-(1-methyl-2-oxo pyrrolidin-3-yloxy)benzoic acid

Product 1

HCID 50915017N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-((1-methyl-2-oxopyrrolidin-3-yl)oxy)benzamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(Dimethylamino)pyridine (DMAP) (0.149 g), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI.HCl) (0.524 g) were added to a solution of 3-(1-methoxypropan-2-yloxy)-5-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)benzoic acid (0.5 g) (Intermediate 1) in dry DCM under nitrogen at 0-5° C. 5-cyclopropyl-1,3,4-thiadiazol-2-amine (0.134 g) was added and the mixture was stirred for 16 h at room temperature. It was diluted with commercially available DCM. Organic phase was washed with dil HCl, saturated solution of NaHCO3, Water, brine, dried over Na2SO4, filtered and concentrated in vacuo to get the crude residue. The residue was chromatographed using silica gel as stationary phase and MeOH: CHCl3 gradient as mobile phase up to yield the product (0.3 g) as a white solid.

Workup

  1. washOrganic phase was washed with dil HCl, saturated solution of NaHCO3, Water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto get the crude residue
  6. customThe residue was chromatographed

Sources & evidence

ORD record
ord-5dc8da72b0f6415589ad4acaf86fc52c
Source dataset
uspto-grants-2014_09
Patent number
US08835469B2

Reaction notes

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