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

HRID 1468171Notes

Reaction equation

HRID 1468171 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([CH2:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18](O)=[O:19])=[N:11][N:10]=2)=[CH:5][CH:4]=1)#[N:2].C(N(CC)C(C)C)(C)C.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+]>CC(N(C)C)=O.O.C(Cl)CCl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:13][C:12]([CH2:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([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:19])=[N:11][N:10]=2)=[CH:7][CH:8]=1)#[N:2]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 675078233-[5-(4-Cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-benzoic acidHCID 86672750(S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide

Product 1

HCID 569668943-[5-(4-cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-N-((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamideYield 16.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Dissolve 3-[5-(4-cyano-phenyl)-[1,3,4]-thiadiazol-2-ylmethyl]-benzoic acid (0.13 g, 0.28 mmol) in 3 mL of dimethylacetamide. Add N,N-diisopropylethyl amine (0.17 mL, 0.95 mmol), of 7-aza-hydroxybenzotriazole (0.05 g, 0.37 mmol) and EDC (0.07, (0.36 mmol). Stir the mixture at room temperature for 1 h and add (S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide (0.14 g, 0.35 mmol) in one portion. Heat the mixture at 60° C. for 15 h. Cool to room temperature and dilute with H2O. Add a saturated 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 material by preparative reverse phase HPLC (CH3CN:H2O with 0.1% trifluoroacetic acid) to give 0.025 g, 14% yield of 3-[5-(4-cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-N—((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide as a solid. MS, ES+ 543.62 (M+H), rt 1.50 min.

Workup

  1. temperatureHeat the mixture at 60° C. for 15 h
  2. temperatureCool to room temperature
  3. customto precipitate from solution
  4. customCollect the solid
  5. filtrationby filtration
  6. washwash with H2O
  7. customdry on the filter pad
  8. customPurify the material by preparative reverse phase HPLC (CH3CN:H2O with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-d71a11601a8d402681f26f2b28b2ac08
Source dataset
uspto-grants-2015_04
Patent number
US09000154B2

Reaction notes

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