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

HRID 2427391

反応式

HRID 2427391 の反応式
I[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][C:11]3[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:12]=3[N:13]=2)=[C:4]([F:19])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:44]1[CH:59]=[CH:58][C:47]([C:48]([C@@H:50]2[CH2:54][CH2:53][CH2:52][C@H:51]2[C:55]([OH:57])=[O:56])=[O:49])=[CH:46][CH:45]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.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]>[Cl:18][C:16]1[CH:15]=[CH:14][C:12]2[N:13]=[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([C:44]4[CH:45]=[CH:46][C:47]([C:48]([C@@H:50]5[CH2:54][CH2:53][CH2:52][C@H:51]5[C:55]([OH:57])=[O:56])=[O:49])=[CH:58][CH:59]=4)=[CH:3][C:4]=3[F:19])[S:10][C:11]=2[CH:17]=1

参加物

9

反応物 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 23549251trans-2-(4-Bromobenzoyl)cyclopentanecarboxylic acidHCID 23549325N-(4-Iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine

生成物 1

HCID 11466071(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%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

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.

後処理

  1. customwas degassed
  2. customby bubbling a flow of nitrogen for 30 minutes
  3. temperatureAfter the mixture was cooled to rt
  4. temperaturethe reaction mixture was heated at 85° C. under nitrogen for 3 h
  5. temperatureThe reaction mixture was cooled to rt
  6. filtrationAfter the mixture was filtered through a pad of Celite®, 1 N HCl
  7. additionwas added to the filtrate
  8. customThe solid that formed
  9. filtrationwas collected by filtration
  10. dissolutiondissolved in EtOAc (50 mL)
  11. dry with materialthe resulting solution was dried over Na2SO4
  12. customRemoval of solvent
  13. customdrying in vacuo

出典と根拠

ORDレコード
ord-1adf009dffe94df0a7c1630dce504dad
出典データセット
uspto-grants-2011_06
特許番号
US07968576B2

関連ノート

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