تفاعل #9706

معادلة التفاعل

(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

المردود 60.0%

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

المردود 60.0%

المذيبات

water

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىwas degassed
2. 2
   أخرىby bubbling a flow of nitrogen for 30 minutes
3. 3
   درجة الحرارةAfter the mixture was cooled to rt
4. 4
   درجة الحرارةthe reaction mixture was heated at 85° C. under nitrogen for 3 h
5. 5
   درجة الحرارةThe reaction mixture was cooled to rt
6. 6
   ترشيحAfter the mixture was filtered through a pad of Celite®, 1 N HCl
7. 7
   workup.ADDITIONwas added to the filtrate
8. 8
   أخرىThe solid that formed
9. 9
   ترشيحwas collected by filtration
10. 10
    workup.DISSOLUTIONdissolved in EtOAc (50 mL)
11. 11
    تجفيفthe resulting solution was dried over Na2SO4
12. 12
    أخرىRemoval of solvent
13. 13
    أخرىdrying in vacuo

الإجراء التجريبي

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.

المصدر