1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 58921037, compound

HRID 1365538Notes

Reaction equation

HRID 1365538 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31](=[O:42])[NH:32][C@@H:33]2[CH2:38][CH2:37][CH2:36][CH2:35][C@@H:34]2[C:39]([OH:41])=O)([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.[NH2:43][CH2:44][CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31](=[O:42])[NH:32][C@@H:33]2[CH2:38][CH2:37][CH2:36][CH2:35][C@@H:34]2[C:39]([NH:43][CH2:44][CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48])=[O:41])([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:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 18614Methyl 4-aminobutanoateHCID 58920649HCID 58920649, compound

Product 1

HCID 58921037HCID 58921037, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (1S,2R)-2-(3-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)cyclohexanecarboxylic acid (11.6 mg, 0.019 mmol) and methyl 4-aminobutanoate (3.2 mg, 0.027 mmol) in CH2Cl2 (185 μL), was added EDCI (4.6 mg, 0.024 mmol) followed by DMAP (2.9 mg, 0.024 mmol) at room temperature. The reaction mixture was stirred at room temperature until starting material was consumed as indicated by HPLC analysis. The reaction mixture was concentrated to dryness and the resulting residue was taken up in MeOH and purified by preparative HPLC (Phenoma Luna AXIA 10A, C18; mobile phase: MeCN/H2O/TFA) to provide methyl 4-((1S,2R)-2-(3-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)cyclohexanecarboxamido)butanoate as white solid (7.1 mg, 53% yield). LC/MS RT=3.200 min; [M+H] 711.1 (LCMS Method 4), NMR: 500 MHz 1H (CDCl3) 8.19 ppm, 1 H, d, J=2.20 Hz; 7.57 ppm, 1 H, dd, J=8.25, 2.20 Hz; 7.04 ppm, 6 H, m; 6.99 ppm, 2 H, t, J=7.42 Hz; 6.79 ppm, 1 H, d, J=8.25 Hz; 6.52 ppm, 2 H, d, J=7.15 Hz; 6.18 ppm, 1 H, s; 5.78 ppm, 1 H, m; 4.28 ppm, 1 H, d, J=12.65 Hz; 3.87 ppm, 1 H, s; 3.61 ppm, 3 H, m; 3.47 ppm, 2 H, m; 3.40 ppm, 1 H, m; 2.40 ppm, 5 H, m; 1.58 ppm, 9 H, m.

Workup

  1. customwas consumed
  2. concentrationThe reaction mixture was concentrated to dryness
  3. custompurified by preparative HPLC (Phenoma Luna AXIA 10A, C18; mobile phase: MeCN/H2O/TFA)

Sources & evidence

ORD record
ord-fa85e4908fec463894682e8040cbe831
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

Loading…