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

HRID 921772노트

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HRID 921772 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
105 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-fa9e0f842459426394974752fe025555
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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