Diisopropylethylamine → 3-[5-(4-cyano-phenyl)-1,3,4-oxadiazol-2-ylmethyl]-N-((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide

HRID 1468168Notes

Reaction equation

HRID 1468168 reaction equation
C(N(CC)C(C)C)(C)C.[C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:22][C:21]([CH2:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([OH:29])=O)=[N:20][N:19]=2)=[CH:14][CH:13]=1)#[N:11].Br.Br.[N:35]1([C@H:41]2[CH2:50][CH2:49][C:44]3[N:45]=[C:46]([NH2:48])[S:47][C:43]=3[CH2:42]2)[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C(=O)(O)[O-].[Na+]>CN(C)C(=O)C.O.C(Cl)CCl>[C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:22][C:21]([CH2:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([NH:48][C:46]3[S:47][C:43]4[CH2:42][C@@H:41]([N:35]5[CH2:36][CH2:37][O:38][CH2:39][CH2:40]5)[CH2:50][CH2:49][C:44]=4[N:45]=3)=[O:29])=[N:20][N:19]=2)=[CH:14][CH:13]=1)#[N:11]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 675076033-[5-(4-Cyano-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-benzoic acidHCID 86672750(S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide

Product 1

HCID 569666713-[5-(4-cyano-phenyl)-1,3,4-oxadiazol-2-ylmethyl]-N-((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamideYield 15.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Add N,N-diisopropylethyl amine (0.17 mL, 0.95 mmol), 7-aza-hydroxybenzotriazole (0.040 g, 0.29 mmol) and EDC (0.06 g (0.31 mmol) to a solution of 3-[5-(4-cyano-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-benzoic acid (0.106 g, 0.24 mmol) in 3 mL of N,N-dimethylacetamide. Stir the mixture at room temperature for 1 h then add (S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide (0.12 g, 0.30 mmol) in one portion and heat overnight at 60° C. Cool the reaction mixture to room temperature and dilute with H2O. Add an aqueous solution of sodium bicarbonate until the pH of the solution is alkaline causing a solid to precipitate from solution. Collect the solid by filtration, wash with H2O and dry on the filter pad. Purify the isolated material by preparative reverse phase HPLC to give 0.02 g, 13% yield of 3-[5-(4-cyano-phenyl)-1,3,4-oxadiazol-2-ylmethyl]-N—((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide as a white powder. MS, ES+ 527.67 (M+H), rt 1.24 min.

Workup

  1. temperatureCool the reaction mixture to room temperature
  2. customto precipitate from solution
  3. customCollect the solid
  4. filtrationby filtration
  5. washwash with H2O
  6. customdry on the filter pad
  7. customPurify the isolated material by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-aa71b0fca0a04fcfb4e7088e9f04683c
Source dataset
uspto-grants-2015_04
Patent number
US09000154B2

Reaction notes

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