Acetic Acid → HCID 58777639, compound

HRID 1435318Notes

Reaction equation

HRID 1435318 reaction equation
[NH2:1][C:2]1[C:7]([C:8](=[O:18])[C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[O:16][CH3:17])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:25][CH2:24][N:23]([S:26]([CH2:29][CH2:30][CH2:31][O:32]C(=O)C)(=[O:28])=[O:27])[CH2:22][CH2:21]2)[N:3]=1.[OH-].[K+].C(O)C.C(O)(=O)C>O>[NH2:1][C:2]1[C:7]([C:8]([C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[O:16][CH3:17])=[O:18])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:25][CH2:24][N:23]([S:26]([CH2:29][CH2:30][CH2:31][OH:32])(=[O:28])=[O:27])[CH2:22][CH2:21]2)[N:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 702EthanolHCID 14797Potassium HydroxideHCID 58777653HCID 58777653, compound

Product 1

HCID 58777639HCID 58777639, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

A suspension of acetic acid 3-[4-[4-amino-5-(5-fluoro-2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-sulfonyl]-propyl ester (25 mg, 0.049 mmol, Example 274) in a solution of potassium hydroxide (50 mg, 0.9 mmol), water (1 mL) and ethanol (6 mL) was stirred at 25° C. for 1 hour. The solution was cooled, acidified with acetic acid and reduced in volume to 2 mL. This was diluted with water and the product extracted into methylene chloride. After washing with water, the organic layer was separated and dried (Na2SO4). The residue was purified by silica gel chromatography (ethyl acetate) and crystallized from methylene chloride/hexane to give [4-amino-2-[1-(3-hydroxy-propane-1-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone as a white solid (12 mg, 50% yield). HRMS, observed: 468.1716; Calcd for (M+H)+: 468.1712

Workup

  1. temperatureThe solution was cooled
  2. extractionthe product extracted into methylene chloride
  3. washAfter washing with water
  4. customthe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. customThe residue was purified by silica gel chromatography (ethyl acetate)
  7. customcrystallized from methylene chloride/hexane

Sources & evidence

ORD record
ord-b7d52746de614d2da8390c521a595bab
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

Loading…