반응 #9706

반응 방정식

(1R,2R)-2-(4-bromobenzoyl)cyclopentanecarboxylic acid

Cs2CO3

N-(4-iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine

bis(pinacolato)diboron

KOAc

→

desired product

수율 60.0%

(1R,2R)-2-({4′-[(6-Chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

수율 60.0%

용매

water

DMF

반응 조건

후처리

1. 1
   기타was degassed
2. 2
   기타by bubbling a flow of nitrogen for 30 minutes
3. 3
   온도After the mixture was cooled to rt
4. 4
   온도the reaction mixture was heated at 85° C. under nitrogen for 3 h
5. 5
   온도The reaction mixture was cooled to rt
6. 6
   여과After the mixture was filtered through a pad of Celite®, 1 N HCl
7. 7
   workup.ADDITIONwas added to the filtrate
8. 8
   기타The solid that formed
9. 9
   여과was collected by filtration
10. 10
    workup.DISSOLUTIONdissolved in EtOAc (50 mL)
11. 11
    건조the resulting solution was dried over Na2SO4
12. 12
    기타Removal of solvent
13. 13
    기타drying in vacuo

실험 절차

A suspension of N-(4-iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine (200 mg, 0.49 mmol), bis(pinacolato)diboron (130 mg, 0.52 mmol), KOAc (150 mg, 1.48 mmol), and PdCl2(dppf) (30 mg, 0.04 mmol) in DMF (5.0 mL) was degassed by bubbling a flow of nitrogen for 30 minutes. The reaction mixture was heated under nitrogen at 85° C. for 3 h. After the mixture was cooled to rt, (1R,2R)-2-(4-bromobenzoyl)cyclopentanecarboxylic acid (140 mg, 0.49 mmol, >99% ee), Cs2CO3 (400 mg, 1.23 mmol) and PdCl2(dppf) (30 mg, 0.04 mmol) were added, and the reaction mixture was heated at 85° C. under nitrogen for 3 h. TLC analysis showed little starting materials remaining. The reaction mixture was cooled to rt, and diluted with water (50 mL). After the mixture was filtered through a pad of Celite®, 1 N HCl was added to the filtrate to adjust the acidity to pH<3. The solid that formed was collected by filtration, then dissolved in EtOAc (50 mL), and the resulting solution was dried over Na2SO4. Removal of solvent and drying in vacuo provided the desired product (120 mg, 60%, >99% ee). LC-MS m/z 495.3 (MH+), retention time 4.01 min.

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