Cesium carbonate → Tert-butyl (2-chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)(4-methoxybenzyl)carbamate

HRID 921772ノート

反応式

HRID 921772 の反応式
[NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]2)[CH2:2]1.Br[C:13]1[C:14]([Cl:40])=[C:15]([N:23]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:16]=[C:17]([O:19][CH:20]([F:22])[F:21])[CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:40][C:14]1[C:13]([N:1]2[CH2:4][CH:3]([N:5]3[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]3)[CH2:2]2)=[CH:18][C:17]([O:19][CH:20]([F:22])[F:21])=[CH:16][C:15]=1[N:23]([CH2:31][C:32]1[CH:33]=[CH:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=1)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 206598001-(Azetidin-3-yl)-4-methylpiperazineHCID 117925637Tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)(4-methoxybenzyl)carbamate

生成物 1

HCID 117926182Tert-butyl (2-chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)(4-methoxybenzyl)carbamate収率 61.7%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
105 °C

実験手順

1-(Azetidin-3-yl)-4-methylpiperazine (95 mg, 0.609 mmol), tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)(4-methoxybenzyl)carbamate (300 mg, 0.609 mmol), cesium carbonate (397 mg, 1,218 mmol), Pd2(dba)3 (27.9 mg, 0.030 mmol) and BINAP (56.9 mg, 0.091 mmol) were suspended in toluene (6088 μl) at room temperature. The reaction was degassed under vacuum and backfilled with N2 (4 times), and then heated to 105° C. for 4 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc, filtered through celite and concentrated. Column chromatography (24 g SiO2, 0 to 10% CH3OH—CH2Cl2 gradient elution) afforded tert-butyl (2-chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)(4-methoxybenzyl)carbamate (213.1 mg).

後処理

  1. customThe reaction was degassed under vacuum
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture was diluted with EtOAc
  4. filtrationfiltered through celite and
  5. concentrationconcentrated
  6. washColumn chromatography (24 g SiO2, 0 to 10% CH3OH—CH2Cl2 gradient elution)

出典と根拠

ORDレコード
ord-fa9e0f842459426394974752fe025555
出典データセット
uspto-grants-2016_03
特許番号
US09273057B2

反応ノート

読み込み中…