Lithium Hydroxide → N-[4-Amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-succinamic acid

HRID 1714856Notes

Reaction equation

HRID 1714856 reaction equation
C[O:2][C:3](=[O:29])[CH2:4][CH2:5][C:6]([NH:8][C:9]1[N:14]=[C:13]([NH2:15])[C:12]([O:16][C:17]2[CH:22]=[C:21]([I:23])[C:20]([O:24][CH3:25])=[CH:19][C:18]=2[CH:26]([CH3:28])[CH3:27])=[CH:11][N:10]=1)=[O:7].[OH-].[Li+]>C1COCC1.O>[NH2:15][C:13]1[C:12]([O:16][C:17]2[CH:22]=[C:21]([I:23])[C:20]([O:24][CH3:25])=[CH:19][C:18]=2[CH:26]([CH3:27])[CH3:28])=[CH:11][N:10]=[C:9]([NH:8][C:6](=[O:7])[CH2:5][CH2:4][C:3]([OH:29])=[O:2])[N:14]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68510970Methyl 3-(5-(5-iodo-2-isopropyl-4-methoxyphenoxy)-4-aminopyrimidin-2-ylcarbamoyl)propanoate

Product 1

HCID 58826013N-[4-Amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-succinamic acidYield 7.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-succinamic acid methyl ester (0.54 g, 1.05 mmoles) in THF (20 ml) was added a solution of Lithium hydroxide (0.33 g, 13.8 mmoles) in water (10 ml). The mixture was stirred at room temperature for 4 hours, then concentrated under reduced pressure. The aqueous residue was pH adjusted to pH=8, washed with EtOAc, and lyophilized for 36 hours. The resulting solid was washed with 30% methanol in ethyl acetate, and filtered. The filtrate was evaporated and the residue was washed twice with dichloromethane, dissolved in water and pH adjusted pH=7 by addition of 0.5 N HCl aqueous solution. The resulting precipitate was recrystallized from water, and the crystals were washed with dichloromethane/ether to give 40 mg of N-[4-Amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-succinamic acid as a light yellow solid. MS (M+H)=501.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed with EtOAc
  3. waitlyophilized for 36 hours
  4. washThe resulting solid was washed with 30% methanol in ethyl acetate
  5. filtrationfiltered
  6. customThe filtrate was evaporated
  7. washthe residue was washed twice with dichloromethane
  8. dissolutiondissolved in water
  9. additionby addition of 0.5 N HCl aqueous solution
  10. customThe resulting precipitate was recrystallized from water
  11. washthe crystals were washed with dichloromethane/ether

Sources & evidence

ORD record
ord-2f0044da584c44cb83e137d829721e21
Source dataset
uspto-grants-2010_09
Patent number
US07799796B2

Reaction notes

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