Cesium carbonate → HCID 86664065, compound

HRID 712367Notes

Reaction equation

HRID 712367 reaction equation
Cl[C:2]1[N:6]=[C:5]([N:7]2[CH2:12][CH2:11][C:10]([CH2:18][CH3:19])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9][CH2:8]2)[S:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:26]([NH:28][C:29]([NH:31][C:32]1[S:33][C:34]2[C:40]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=3)=[CH:39][C:38](B(O)O)=[CH:37][C:35]=2[N:36]=1)=[O:30])[CH3:27]>C1COCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:18]([C:10]1([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][CH2:12][N:7]([C:5]2[S:4][N:3]=[C:2]([C:38]3[CH:39]=[C:40]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=4)[C:34]4[S:33][C:32]([NH:31][C:29](=[O:30])[NH:28][CH2:26][CH3:27])=[N:36][C:35]=4[CH:37]=3)[N:6]=2)[CH2:8][CH2:9]1)[CH3:19]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 66977287Ethyl 1-(3-chloro-1,2,4-thiadiazol-5-yl)-4-ethylpiperidine-4-carboxylateHCID 727244832-(3-Ethylureido)-7-(pyridin-2-yl)benzothiazol-5-ylboronic acid

Product 1

HCID 86664065HCID 86664065, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

Ethyl 1-(3-chloro-1,2,4-thiadiazol-5-yl)-4-ethylpiperidine-4-carboxylate (110 mg, 0.35 mmol), cesium carbonate (285.6 mg, 0.88 mmol), Pd(dppf)2Cl2 (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 to give a black solid which was 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 the desired product as a brown solid. MS: 566.11 [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. customto give a black solid which
  9. customwas pre-absorbed onto silica
  10. custompurified by flash column chromatography (Biotage SP4 12 g, 2% MeOH/DCM-5% MeOH/DCM-8% MeOH/DCM)

Sources & evidence

ORD record
ord-e86ec6f965b14d2d90b41478271b850c
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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