反応 #9706

反応方程式

(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

収率 60.0%

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

収率 60.0%

溶媒

water

DMF

反応条件

後処理

1. 1
   その他was degassed
2. 2
   その他by bubbling a flow of nitrogen for 30 minutes
3. 3
   温度After the mixture was cooled to rt
4. 4
   温度the reaction mixture was heated at 85° C. under nitrogen for 3 h
5. 5
   温度The reaction mixture was cooled to rt
6. 6
   ろ過After the mixture was filtered through a pad of Celite®, 1 N HCl
7. 7
   workup.ADDITIONwas added to the filtrate
8. 8
   その他The solid that formed
9. 9
   ろ過was collected by filtration
10. 10
    workup.DISSOLUTIONdissolved in EtOAc (50 mL)
11. 11
    乾燥the resulting solution was dried over Na2SO4
12. 12
    その他Removal of solvent
13. 13
    その他drying in vacuo

実験手順

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.

出典