Lithium Hydroxide → 2-[(2-amino-2-oxoethyl)(3,4-dichlorophenyl)amino]-N-[(1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N-methylacetamide

HRID 2354434Notes

Reaction equation

HRID 2354434 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:15]([CH3:31])[C:16](=[O:30])[CH2:17][N:18]([CH2:27][C:28]#[N:29])[C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[Li+].[OH-].FC(F)(F)C(O)=[O:37]>O1CCCC1.O>[NH2:29][C:28](=[O:37])[CH2:27][N:18]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=1)[CH2:17][C:16]([N:15]([C@H:8]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)[CH3:31])=[O:30]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 59809668N1-[(1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(cyanomethyl)-N2-(3,4-dichlorophenyl)-N1-methylglycinamide

Product 1

HCID 574255432-[(2-amino-2-oxoethyl)(3,4-dichlorophenyl)amino]-N-[(1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N-methylacetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
77 °C

Procedure

N1-[(1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(cyanomethyl)-N2-(3,4-dichlorophenyl)-N1-methylglycinamide (6.1 g, crude) was dissolved in 25 mL of tetrahydrofuran and treated with a solution of LiOH (3.14 g, 74.9 mmol) suspended in 10.8 mL of water. The reaction was stirred vigorously and allowed to reflux at 77° C. for 24 hours before it was determined to be complete by LCMS (Eclipse XDB C18 (4.6×250 mm); trifluoroacetic acid: 1-99% B for 10 min, ES) Rt=7.8 min and m/e 543 [M+1]+. The solvent was removed by rotary evaporation and the crude residue was purified by silica gel chromatography (330 g Redisep column, silica, 40 um, 60 Å, 90 mL/min, A: methylene chloride, B: methanol, B: 0% for 5 min, 10% for 60 min; detection at 214 nm) to give 2-[(2-amino-2-oxoethyl)(3,4-dichlorophenyl)amino]-N-[(1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N-methylacetamide (2.82 g, 5.2 mmol). MS (ES) m/e 543 [M+H]+.

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customthe crude residue was purified by silica gel chromatography (330 g Redisep column, silica, 40 um, 60 Å, 90 mL/min
  3. wait10% for 60 min

Sources & evidence

ORD record
ord-245b27bdbb5649dd861528c572158236
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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