Lithium hydroxide, monohydrate → (S)-2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoic acid

HRID 1752393Notes

Reaction equation

HRID 1752393 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:7]=[C:6]([NH:24][C@@H:25]([CH3:30])[C:26]([O:28]C)=[O:27])[CH:5]=1)(=[O:3])[NH2:2].O[Li].O>C1COCC1.O>[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:7]=[C:6]([NH:24][C@@H:25]([CH3:30])[C:26]([OH:28])=[O:27])[CH:5]=1)(=[O:3])[NH2:2]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71283440(S)-methyl 2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoate

Product 1

HCID 71283615(S)-2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoic acidYield 41%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of the (S)-methyl 2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoate (0.123 g, 0.300 mmol) in 5:1 THF/water (5 mL) was added LiOH.H2O (0.025 g, 0.60 mmol). After stirring 3 days, the reaction was quenched with 1N aqueous HCl (0.60 mL). The mixture was evaporated in vacuo then chromatographed using reverse-phase HPLC with a 40-100% acetonitrile in water (+0.1% TFA) gradient. The product fractions were pooled and concentrated to give a solid suspension. After cooling, the solid precipitate was filtered, rinsed with water and dried under vacuum at 50° C. to give (S)-2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoic acid as a white powder (0.049 g, 0.12 mmol, 41% yield). 1H NMR (400 MHz, DMSO-d6): 12.57 (1H, s), 8.50 (2H, d, J=8.8 Hz), 8.29 (1H, s), 8.12 (1H, d, J=6.1 Hz), 7.76 (1H, s), 7.31-7.24 (2H, m), 7.18-7.12 (2H, m), 7.07 (1H, s), 7.03 (2H, d, J=8.8 Hz), 4.56 (1H, m), 1.44 (3H, d, J=7.5 Hz). LC/MS: m/z=397.1 [M+H]+.

Workup

  1. customthe reaction was quenched with 1N aqueous HCl (0.60 mL)
  2. customThe mixture was evaporated in vacuo
  3. customthen chromatographed
  4. concentrationconcentrated
  5. customto give a solid suspension
  6. temperatureAfter cooling
  7. filtrationthe solid precipitate was filtered
  8. washrinsed with water
  9. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-d5a0fddda44b419eb04a44f49cf83d6e
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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