Methanol → 3-(((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl)-5-tert-butylbenzoic acid

HRID 1171529Notes

Reaction equation

HRID 1171529 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]2[CH2:12][CH2:11][C@@H:10]([N:13]([CH:15]([CH3:17])[CH3:16])[CH3:14])[CH2:9][C@H:8]2[CH2:18][CH2:19][CH3:20])[C:3]1=[O:21].[C:22]([C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([C:35](OC)=[O:36])[CH:34]=1)[C:29]([OH:31])=[O:30])([CH3:25])([CH3:24])[CH3:23].[Li+].[OH-].CO>CN(C=O)C.C(O)(C(F)(F)F)=O.O>[CH:15]([N:13]([CH3:14])[C@@H:10]1[CH2:11][CH2:12][C@H:7]([N:4]2[CH2:5][CH2:6][C@H:2]([NH:1][C:35]([C:33]3[CH:32]=[C:28]([CH:27]=[C:26]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:34]=3)[C:29]([OH:31])=[O:30])=[O:36])[C:3]2=[O:21])[C@H:8]([CH2:18][CH2:19][CH3:20])[CH2:9]1)([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 121446585-tert-Butyl-isophthalic acid monomethyl esterHCID 68767742(S)-3-amino-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)pyrrolidin-2-one

Product 1

HCID 687659413-(((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl)-5-tert-butylbenzoic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

Following the method described in Example 2c, Step 4, (S)-3-amino-1-[(1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl]pyrrolidin-2-one (223 mg) was coupled with 3-tert-butyl-5-(methoxycarbonyl)benzoic acid (165 mg, see Preparation H6, Step 1) in 8 mL of DMF. After 14 h, 2 mL of this reaction mixture was removed and purified to provide Example 2ba. The remaining portion of the reaction mixture was charged successively with aq. LiOH (48 mg in 2 mL water) and MeOH (1 mL) before being stirred at RT for 14 h. The mixture was diluted with 2.0% TFA/water, filtered, and purified directly by RP-HPLC to afford the titled compound. MS found: (M+H)+=500.4.

Workup

  1. custom2 mL of this reaction mixture was removed
  2. custompurified
  3. customto provide Example 2ba
  4. filtrationfiltered
  5. custompurified directly by RP-HPLC

Sources & evidence

ORD record
ord-b32904377f454fb5a342dc7eef7eedff
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

Loading…