Chlorosuccinimide → HCID 86608816, compound

HRID 2055577Notes

Reaction equation

HRID 2055577 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[OH:30])[CH:5]=[CH:6][C:7]=1[C@H:8]([NH:10][C:11]([C:13]1([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14]1)=[O:12])[CH3:9].[Cl:31]N1C(=O)CCC1=O>C(O)(=O)C>[Cl:31][C:27]1[CH:26]=[C:25]([F:29])[C:24]([OH:30])=[C:23]([C:4]2[CH:5]=[CH:6][C:7]([C@H:8]([NH:10][C:11]([C:13]3([NH:16][C:17](=[O:22])[C:18]([F:19])([F:21])[F:20])[CH2:15][CH2:14]3)=[O:12])[CH3:9])=[C:2]([F:1])[CH:3]=2)[CH:28]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 86608815HCID 86608815, compound

Product 1

HCID 86608816HCID 86608816, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of N-[(1R)-1-(3,3′-difluoro-2′-hydroxy-1,1′-biphenyl-4-yl)ethyl]-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide (125 mg, 0.292 mmol) in acetic acid (1 ml) was added N-chlorosuccinimide (39 mg, 0.292 mmol) and the solution was heated to 90 C for 2 h. After this time, the mixture was concentrated in vacuo and purified by column chromatography eluting with a 0-10% EtOAc/CH2Cl2 gradient to give N-[(1R)-1-(5′-chloro-3,3′-difluoro-2′-hydroxy-1,1′-biphenyl-4-yl)ethyl]-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide. Low resolution mass spectrometry: (M+H+)=462.9. 1H NMR (400 MHz, CDCl3) δ 7.26-7.34 (m, 3H), 7.12 (dd, 1H, J=9.9 and 2.4 Hz), 7.08 (s, 1H), 6.98 (s, 1H), 6.59 (d, 1H, J=8.6 Hz), 5.38-5.51 (br, 1H), 5.23 (quin, 1H, J=7.2 Hz), 1.55-1.70 (m, 2H), 1.52 (d, 3H, 7.2 Hz) and 1.08-1.21 (m, 2H) ppm.

Workup

  1. temperaturethe solution was heated to 90 C for 2 h
  2. concentrationAfter this time, the mixture was concentrated in vacuo
  3. custompurified by column chromatography
  4. washeluting with a 0-10% EtOAc/CH2Cl2 gradient

Sources & evidence

ORD record
ord-90f12ca5f78b40219fe4ee3f678485a0
Source dataset
uspto-grants-2008_02
Patent number
US07332499B2

Reaction notes

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