HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Tetrahydrofuran → 3-(3-(4-(5-Fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 640382
Notes
Print preview

Reaction equation

HRID 640382 reaction equation
O1CCCC1.[NH2:6][C:7]1[C:12]([C:13]2[O:17][N:16]=[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[CH:14]=2)=[CH:11][CH:10]=[C:9]([NH2:26])[N:8]=1.[OH-].[Na+].Cl[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][N:32]=1>CN(C)C=O>[F:37][C:34]1[CH:35]=[CH:36][C:31]([CH2:30][O:25][C:22]2[CH:23]=[CH:24][C:19]([CH2:18][C:15]3[CH:14]=[C:13]([C:12]4[C:7]([NH2:6])=[N:8][C:9]([NH2:26])=[CH:10][CH:11]=4)[O:17][N:16]=3)=[CH:20][CH:21]=2)=[N:32][CH:33]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 216980592-(Chloromethyl)-5-fluoropyridineHCID 592553274-(5-(2,6-Diamino-pyridine-3-yl)-isoxazol-3-ylmethyl)phenol

Product 1

HCID 592555053-(3-(4-(5-Fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 67%

Reagents, catalysts & solvents

1
HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a tetrahydrofuran (3 mL) solution of 4-(5-(2,6-diamino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (25.5 mg, 0.09 mmol) described in Manufacturing Example 18-1-1 was added a 5 N sodium hydroxide aqueous solution (18.1 μL, 0.09 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction solution was concentrated under a reduced pressure, which gave a white solid. An N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-5-fluoro-pyridine (13.2 mg, 0.09 mmol) described in manufacturing Example 41-1-2 was added to a suspension of this solid in N,N-dimethylformamide (1 mL), which was stirred for 1 hour at 60° C. The reaction mixture was cooled to room temperature and then partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (23.6 mg, 67%) as a ditrifluoroacetic acid salt.

Workup

  1. dissolutionwas dissolved
  2. customby irradiating ultrasonic wave for 1 minute
  3. concentrationThe reaction solution was concentrated under a reduced pressure, which
  4. customgave a white solid
  5. temperatureThe reaction mixture was cooled to room temperature
  6. custompartitioned into water and ethyl acetate
  7. customThe organic layer was separated
  8. washwashed with water and saturated aqueous sodium chloride solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under a reduced pressure
  12. customThe residue was purified by reverse-phase high performance liquid chromatography (
  13. additioncontaining 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-99f8cc71899c412db216074d7f7f8e24
Source dataset
uspto-grants-2010_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07691882B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes