1-Hydroxybenzotriazole → HCID 44235271, compound

HRID 1093572Notes

Reaction equation

HRID 1093572 reaction equation
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([C:7]([NH:9][CH2:10][C:11]([OH:13])=O)=[O:8])=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.FC(F)(F)C(O)=O.[Br:58][C:59]1[CH:71]=[CH:70][CH:69]=[CH:68][C:60]=1[O:61][CH:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1>CN(C=O)C.O>[Br:58][C:59]1[CH:71]=[CH:70][CH:69]=[CH:68][C:60]=1[O:61][CH:62]1[CH2:67][CH2:66][N:65]([C:11](=[O:13])[CH2:10][NH:9][C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:6][CH:5]=2)=[O:8])[CH2:64][CH2:63]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2629432-((4-Phenylphenyl)formamido)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591525HCID 66591525, compound

Product 1

HCID 44235271HCID 44235271, compoundYield 24.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (0.08278 g, 0.00032 mol) in DMF (2 mL) was added, DIPEA (0.104 g, 0.00081 mol), HOBt (0.0437 g, 0.00032 mol) and EDCI.HCl (0.0619 g, 0.00032 mol) at ambient temperature. After 2 minutes 4-(2-bromo-phenoxy)-piperidine trifluoroacetate (0.1 g, 0.00027 mol) was added and the resulting mixture was stirred at the same temperature overnight. The reaction mixture was diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC [(column-Zorbax XDB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B), gradient: (Time): (% B)-0:50; 2:50; 5:80)]) to afford 0.033 g (22%) of biphenyl-4-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 493.1 (M+1)+, 98.35%, 1H NMR (DMSO-d6): δ 8.65 (t, 1H), 8.0 (d, 2H), 7.8 (m, 4H), 7.6 (dd, 1H), 7.52 (t, 2H), 7.4 (m, 2H), 7.24 (m, 1H), 6.95 (m, 1H), 4.8 (m, 1H), 4.3 (m, 2H), 3.7 (m, 2H), 3.55 (m, 2H), 1.9 (m, 2H), 1.7 (m, 2H).

Workup

  1. customat ambient temperature
  2. extractionthe product was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by preparative HPLC [(column-Zorbax XDB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B)

Sources & evidence

ORD record
ord-e9325b73234c48c7a61f11b7354e2dd7
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…