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

HRID 78152Notes

Reaction equation

HRID 78152 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[S:32][CH:33]=[CH:34][N:35]=1>CN(C)C=O>[S:32]1[CH:33]=[CH:34][N:35]=[C:31]1[CH2:30][O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C:15]2[CH:14]=[C:13]([C:12]3[C:7]([NH2:6])=[N:8][C:9]([NH2:26])=[CH:10][CH:11]=3)[O:17][N:16]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 140908642-(Chloromethyl)-1,3-thiazoleHCID 592553274-(5-(2,6-Diamino-pyridine-3-yl)-isoxazol-3-ylmethyl)phenol

Product 1

HCID 592555083-(3-(4-(Thiazol-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 64%

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 (50 mg, 0.18 mmol) described in Manufacturing Example 18-1-1 was added a 5 N sodium hydroxide aqueous solution (35.4 μL, 0.18 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. To a suspension of this solid in N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-thiazole (28.4 mg, 0.21 mmol) described in manufacturing Example 88-1-2, which was stirred for 3 hours 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, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate) to obtain the title compound (43.0 mg, 64%).

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
  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 NH silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-bd9cc93042c8422eb086875cbd4cad58
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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