HCID 86613594, compound → HCID 86613593, compound

HRID 1365548Notes

Reaction equation

HRID 1365548 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]([C@H:33]2[CH2:37][C:36]([F:39])([F:38])[CH2:35][N:34]2C(OC(C)(C)C)=O)=[O:32])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]([C@H:33]2[CH2:37][C:36]([F:38])([F:39])[CH2:35][NH:34]2)=[O:32])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:25])[F:26])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1

Participants

3

Reactant 1

HCID 86613594HCID 86613594, compound

Product 1

HCID 86613593HCID 86613593, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

(R)-tert-butyl 2-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamoyl)-4,4-difluoropyrrolidine-1-carboxylate (33.9 mg, 0.05 mmol) was dissolved in a solution of TFA/CH2Cl2 (2 mL/2 mL) and the reaction mixture was stirred overnight. The solvent was removed and the residue dissolved in MeOH and purified by preparative HPLC (Phenoma Luna AXIA 100A, C18; mobile phase: MeCN/H2O/TFA) to yield (R)-N-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-4,4-difluoropyrrolidine-2-carboxamide as a white solid (22.4 mg, 78% yield). LC/MS RT=3.876 min; [M+H]=576.2 (LCMS Method 3). NMR: 500 MHz 1H (CDCl3); 8.35 ppm, 1H, d, J=5 Hz;, 7.79 ppm, 1H, m; 7.38 ppm, 1H, d, J=10 Hz; 7.17 ppm, 1H, m; 7.04 ppm, 4H, m; 6.89 ppm, 1H, m; 6.51 ppm, 1H, d, J=5 Hz; 6.21 ppm, 1H; m; 4.56 ppm, 1H′ t, J=9 Hz; 4.19 ppm, 1H, d, J=13 Hz; 3.84 ppm, 1H, d, J=13 Hz; 3.60 ppm, 2H′ t, J=12 Hz; 2.68 ppm, 1H, m; 2.22 ppm, 1H, m.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue dissolved in MeOH
  3. custompurified by preparative HPLC (Phenoma Luna AXIA 100A, C18; mobile phase: MeCN/H2O/TFA)

Sources & evidence

ORD record
ord-d954f0ff0bd24926ba31ddd3aac574b1
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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