Lithium Hydroxide → (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid

HRID 63748Notes

Reaction equation

HRID 63748 reaction equation
C([O:4][C:5](=[O:38])[C@@H:6]([NH:25][C:26](=[O:37])[C:27]1[C:32]([F:33])=[CH:31][C:30]([CH2:34][NH2:35])=[CH:29][C:28]=1[F:36])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=2[CH3:20])=[CH:10][CH:9]=1)CC.[OH-].[Li+].C(O)(C(F)(F)F)=O>C1COCC1.O>[NH2:35][CH2:34][C:30]1[CH:29]=[C:28]([F:36])[C:27]([C:26]([NH:25][C@@H:6]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=3[CH3:20])=[CH:12][CH:13]=2)[C:5]([OH:38])=[O:4])=[O:37])=[C:32]([F:33])[CH:31]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 86691355HCID 86691355, compound

Product 1

HCID 86691354(S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acidYield 96.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester (508 mg, 0.96 mmol) in THF (10 mL) was added a solution of lithium hydroxide (240 mg, 10 mmol) in water (2 mL) at room temperature. The mixture was stirred for 15 h at which time TLC analysis indicated the absence of starting material. Then, the THF was removed under reduced pressure and the residue was diluted with water (100 mL) and the mixture was acidified with TFA. The crude product was purified by HPLC to afford 450 mg (78% yield) of (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid as a TFA salt as a white solid. ES-LRMS m/e calcd for C24H24F2N4O5 (M+H)+ 487, found 487.

Workup

  1. customThen, the THF was removed under reduced pressure
  2. additionthe residue was diluted with water (100 mL)
  3. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-87b410a735684971b6d7dd97f7954313
Source dataset
uspto-grants-2016_09
Patent number
US09447035B2

Reaction notes

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