Nitrogen → (S)-3-(4-(5-Methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-((1-methyl-2-oxopyrrolidin-3-yl)oxy)-N-(thiazol-2-yl)benzamide

HRID 75975Notes

Reaction equation

HRID 75975 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:30]=[CH:29][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][CH:22]4[CH2:26][CH2:25][N:24]([CH3:27])[C:23]4=[O:28])[CH:20]=3)[C:15]([OH:17])=O)=[CH:9][CH:8]=2)=[N:4][N:3]=1.N#N.Cl.CN(C)CCCN=C=NCC.[NH2:45][C:46]1[S:47][CH:48]=[CH:49][N:50]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@H:22]4[CH2:26][CH2:25][N:24]([CH3:27])[C:23]4=[O:28])[CH:20]=3)[C:15]([NH:45][C:46]3[S:47][CH:48]=[CH:49][N:50]=3)=[O:17])=[CH:29][CH:30]=2)=[N:4][N:3]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 21552-AminothiazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 669722263-(4-(5-Methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-(1-methyl-2-oxo pyrrolidin-3-yloxy)benzoic acid2×

Product 1

HCID 49855240(S)-3-(4-(5-Methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-((1-methyl-2-oxopyrrolidin-3-yl)oxy)-N-(thiazol-2-yl)benzamideYield 83.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of S-(+3-[4-(5-Methyl-1,3,4-oxadiazol-2-yl)phenoxy]-5-[(1-methyl-2-oxo-pyrrolidin-3-yl)oxy]benzoic acid (3.5 g) (Intermediate 13) in dry DCM in single necked round bottomed flask fitted with stop cock with N2(g) balloon, 4-(dimethylamino)pyridine (2.24 g) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI. HCl) (3.3 g) were added at room temperature. After stirring at the same temperature for 15 min, 2-aminothiazole (0.94 g) was added and stirring was continued for 16 h. Progress of reaction was monitored by TLC. After completion, reaction mixture was diluted with DCM (200 mL), washed with dil HCl (20 mL, 0.05 N), saturated sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulphate, filtered and concentrated under vacuum to get crude brown solid (3.5 g). The crude brown solid was purified by solvent trituration.

Workup

  1. additionwere added at room temperature
  2. stirringstirring
  3. waitwas continued for 16 h
  4. customProgress of reaction
  5. customAfter completion, reaction mixture
  6. washwashed with dil HCl (20 mL, 0.05 N), saturated sodium bicarbonate solution, water and brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-165fa4908cfd4bebab0166bbc843f79e
Source dataset
uspto-grants-2014_09
Patent number
US08835469B2

Reaction notes

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