(1R,2S)-(+)-cis-1-Amino-2-indanol → N-(4-chloro-3-fluoro-phenyl)-N'-[(1R,2S)-2-hydroxyindan-1-yl]oxamide

HRID 1477103노트

반응식

HRID 1477103 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[C:10]([O:12]CC)=O)=[CH:4][C:3]=1[F:16].[NH2:17][C@@H:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][C@@H:19]1[OH:27]>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[C:10]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2[OH:27])=[O:12])=[CH:4][C:3]=1[F:16]

참가 물질

4

반응물 2

HCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 57523348Ethyl 2-(4-chloro-3-fluorophenylamino)-2-oxoacetate

생성물 1

HCID 46198987N-(4-chloro-3-fluoro-phenyl)-N'-[(1R,2S)-2-hydroxyindan-1-yl]oxamide수율 83%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

To a solution containing ethyl 2-(4-chloro-3-fluorophenylamino)-2-oxoacetate (1) (1.73 g, 7.05 mmol) in 20 mL dioxane in a round-bottom flask was added (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol (1.16 g, 7.76 mmol) and both a stir bar and a reflux condenser were equipped. The reaction was heated to reflux for 72 hours and then allowed to cool to room temperature. The crude reaction mixture was concentrated in vacuo. The solid was collected by filtration with a 1:1 mixture of hexanes and dichloromethane to give 2.04 g (83%) of TK-II-103 as an off-white flakey solid; [α]29D=−112.1° (c=0.48, DMSO): 1H NMR (500 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.36 (d, J=8.7 Hz, 1H), 7.97, (dd, J=2, 11.7 Hz, 1H), 7.77, (d, J=8.8 Hz, 1H), 7.59, (t, J=8.7 Hz, 1H), 7.28-7.18, (m, 4H), 5.46, (d, J=4.9 Hz, 1H), 5.25, (dd, J=5.2, 8.6 Hz, 1H), 4.52, (dd, J=4.6, 8.6 Hz, 1H), 3.14, (dd, J=4.9, 16.2 Hz, 1H), 2.88, (d, J=16.1 Hz, 1H); 13C NMR (125 MHz, DMSO-d6) δ 159.3, 158.8, 156.8, (d, JCF=242.5 Hz), 141.0, 140.8, 138.2, (d, JCF=10 Hz), 131.6, 127.7, 126.5, 125.0, 124.1, 117.5 (d, JCF=2.9 Hz), 114.5 (d, JCF=17.5 Hz), 108.6, (d, JCF=25 Hz), 71.6, 56.9. HRMS (ES+) m/z 371.0572 [(M+Na)+; calcd for C17H14ClFN2O3: 371.0575].

후처리

  1. customboth a stir bar and a reflux condenser were equipped
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 72 hours
  4. customThe crude reaction mixture
  5. concentrationwas concentrated in vacuo
  6. filtrationThe solid was collected by filtration with a 1:1 mixture of hexanes and dichloromethane

출처 및 근거

ORD 기록
ord-62fd3af02f0447dc86a0b9f2bea2dbcf
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403763B2

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