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

HRID 1477103Notes

Reaction equation

HRID 1477103 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

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].

Workup

  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

Sources & evidence

ORD record
ord-62fd3af02f0447dc86a0b9f2bea2dbcf
Source dataset
uspto-grants-2016_08
Patent number
US09403763B2

Reaction notes

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