Cesium carbonate → 1-[5-(3-Chloro-1,2,4-thiadiazol-5-yl)-7-(pyridin-2-yl)-1,3-benzothiazol-2-yl]-3-ethylurea

HRID 712369Notes

Reaction equation

HRID 712369 reaction equation
[Cl:1][C:2]1[N:6]=[C:5](Cl)[S:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:14]([NH:16][C:17]([NH:19][C:20]1[S:21][C:22]2[C:28]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)=[CH:27][C:26](B(O)O)=[CH:25][C:23]=2[N:24]=1)=[O:18])[CH3:15]>C1COCC1.O>[Cl:1][C:2]1[N:6]=[C:5]([C:26]2[CH:27]=[C:28]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:22]3[S:21][C:20]([NH:19][C:17]([NH:16][CH2:14][CH3:15])=[O:18])=[N:24][C:23]=3[CH:25]=2)[S:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2725055Dichloro-1,2,4-thiadiazoleHCID 72724483HCID 72724483, compound

Product 1

HCID 866640671-[5-(3-Chloro-1,2,4-thiadiazol-5-yl)-7-(pyridin-2-yl)-1,3-benzothiazol-2-yl]-3-ethylurea

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

3,5-dichloro-1,2,4-thiadiazole (50 mg, 0.32 mmol), Cesium carbonate (285.6 mg, 0.88 mmol), Pd(dppf)2C12 (20 mg, 0.03 mmol) and {2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}boronic acid (100 mg, 0.29 mmol) was suspended in a mixture of THF (9 mL) and water (1 mL) and heated in the microwave at 110° C. for 50 min. The reaction mixture was concentrated in vacuo and the residue partitioned between 10% IPA/DCM (10 mL) and water (10 mL). The organic layer was separated and the aqueous extracted with further 10% IPA/DCM (3×10 mL), the organic layers were combined, dried (MgSO4), filtered and concentrated, then pre-absorbed onto silica and purified by flash column chromatography (Biotage SP4 12 g, 2% MeoH/DCM-5% MeoH/DCM-8% MeOH/DCM) to give 1-[5-(3-chloro-1,2,4-thiadiazol-5-yl)-7-(pyridin-2-yl)-1,3-benzothiazol-2-yl]-3-ethylurea as a brown solid. (100 mg, 81%) MS: 416.92 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between 10% IPA/DCM (10 mL) and water (10 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous extracted with further 10% IPA/DCM (3×10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompre-absorbed onto silica
  9. custompurified by flash column chromatography (Biotage SP4 12 g, 2% MeoH/DCM-5% MeoH/DCM-8% MeOH/DCM)

Sources & evidence

ORD record
ord-8198744b7248480c9320c396b3dff307
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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