Tetrahydrofuran → HCID 25120535, compound

HRID 1893464Notes

Reaction equation

HRID 1893464 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[C:7]2[N:8]([C:20](C=O)=[CH:21][N:22]=2)[C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2.[CH3:25][NH:26][C:27]([NH2:29])=[O:28].[BH4-].[Na+].O1CCC[CH2:33]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[C:7]2[N:8]([C:20]([CH2:25][NH:26][C:27]([NH:29][CH3:33])=[O:28])=[CH:21][N:22]=2)[C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([F:17])([F:18])[F:19])=[CH:11][CH:10]=2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11719MethylureaHCID 4311764Sodium borohydrideHCID 25120537HCID 25120537, compound

Product 1

HCID 25120535HCID 25120535, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Conditions

Temperature
35 °C

Procedure

To a solution of 4-[(3-hydroxypropyl)amino]-7-(trifluoromethyl)imidazo[1,2-a]quinoxaline-1-carbaldehyde (35 mg, 0.10 mmol) in anhydrous tetrahydrofuran (190 μL) under Argon were added titanium(IV) isopropoxide (50 μL, 0.17 mmol) and N-methylurea (9 mg, 0.11 mmol). After 5 h at room temperature, sodium borohydride (2.2 mg, 0.05 mmol) was added at 0° C. and the solution was stirred at 35° C. overnight. The mixture was allowed to cool to room temperature, quenched with water (formation of a precipitate) and concentrated. The residue was triturated in ethyl acetate and water, filtrated and rinsed with ethyl acetate and water. The filtrate was washed with a saturated aqueous solution of ammonium chloride and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and evaporated. The crude product was purified by preparative TLC (silica gel, dichloromethane/methanol 9/1) to afford the title compound (27 mg, 69%) as a pale yellow solid.

Workup

  1. temperatureto cool to room temperature
  2. customquenched with water (formation of a precipitate) and
  3. concentrationconcentrated
  4. customThe residue was triturated in ethyl acetate
  5. filtrationwater, filtrated
  6. washrinsed with ethyl acetate and water
  7. washThe filtrate was washed with a saturated aqueous solution of ammonium chloride
  8. extractionextracted twice with ethyl acetate
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product was purified by preparative TLC (silica gel, dichloromethane/methanol 9/1)

Sources & evidence

ORD record
ord-ff48867ba33b493290990a2342d22c99
Source dataset
uspto-grants-2013_08
Patent number
US08513250B2

Reaction notes

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