Trifluoroacetic acid → n1-[1-(4-Biphenylyl)-2-(1-pyrrolidinyl)ethyl]-n2-(3,4-dichlorophenyl)-n1-methyl-n2-[2-(methyloxy)ethyl]glycinamide

HRID 2114374Notes

Reaction equation

HRID 2114374 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:14][CH2:15][O:16][CH3:17])[CH2:10][C:11]([OH:13])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[Li].[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH3:20].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2N=N1.F[C:54](F)(F)[C:55](O)=O.C[C:61]#[N:62].O>CN(C=O)C>[C:55]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:54]=[CH:6][C:7]([CH:20]([N:62]([CH3:61])[C:11](=[O:13])[CH2:10][N:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:14][CH2:15][O:16][CH3:17])[CH2:19][N:21]2[CH2:24][CH2:25][CH2:23][CH2:22]2)=[CH:2][CH:3]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 3028194LithiumHCID 18373917Acetonitrile--water (1/1)HCID 57418671HCID 57418671, compound

Product 1

HCID 59809621n1-[1-(4-Biphenylyl)-2-(1-pyrrolidinyl)ethyl]-n2-(3,4-dichlorophenyl)-n1-methyl-n2-[2-(methyloxy)ethyl]glycinamideYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(3,4-dichlorophenyl)-N-[2-(methyloxy)ethyl]glycine, lithium salt (100 mg, 0.35 mmol) [1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (98 mg, 0.35 mmol), triethylamine (73 uL, 0.53 mmol), and (1H-1,2,3-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (BOP Reagent, 186 mg, 0.42 mmol) were added in that order to a 4 mL screw capped vial that contained 1 mL of anhydrous DMF. The reaction mixture was stirred for 20 hours at room temperature, after which time HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) showed that the reaction was complete. The solvent was removed under vacuum and the residue was dissolved in 2 mL of DMSO, filtered through a 0.2 um PTFE Acrodisk, and purified by reverse-phase HPLC (Xterra Prep RP, 30×150 mm, 35 mL/min, A: acetonitrile B: water (adjusted to pH 10 with NH40H), A: 35 to 99% over 14 min, UV detection at 214 nm) to give the title compound (117 mg, 0.216 mmol, 61%) as a white solid. MS (ES) m/e 540 [M+H]+.

Workup

  1. customcapped vial
  2. customThe solvent was removed under vacuum
  3. dissolutionthe residue was dissolved in 2 mL of DMSO
  4. filtrationfiltered through a 0.2 um PTFE Acrodisk
  5. custompurified by reverse-phase HPLC (Xterra Prep RP, 30×150 mm, 35 mL/min
  6. waitA: acetonitrile B: water (adjusted to pH 10 with NH40H), A: 35 to 99% over 14 min

Sources & evidence

ORD record
ord-7e787e440b1e4cf0b063cf00abcece10
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

Loading…