Tetrahydrofuran → HCID 42611238, compound

HRID 81662Notes

Reaction equation

HRID 81662 reaction equation
[BH4-].[Na+].O1CCCC1.[Cl:8][C:9]1[CH:10]=[C:11]([O:33][CH2:34][CH:35]=[O:36])[CH:12]=[N:13][C:14]=1[O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][N:20]=[C:19]2[NH:26][C:27]1[CH:31]=[CH:30][N:29]([CH3:32])[N:28]=1>O>[Cl:8][C:9]1[CH:10]=[C:11]([O:33][CH2:34][CH2:35][OH:36])[CH:12]=[N:13][C:14]=1[O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][N:20]=[C:19]2[NH:26][C:27]1[CH:31]=[CH:30][N:29]([CH3:32])[N:28]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 86645901{[5-chloro-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}acetaldehyde

Product 1

HCID 42611238HCID 42611238, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

With cooling with ice, sodium borohydride (9 mg, 0.25 mmol) was added to a tetrahydrofuran (3 ml)/water (0.3 ml) mixed solution containing {[5-chloro-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}acetaldehyde obtained in Example 1, and the reaction solution was stirred for 15 minutes. Saturated saline water was added to the reaction solution, extracted with chloroform/methanol (9:1), the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Biotage, chloroform:methanol=100:4 to 100:5) and reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC), and the obtained solid was recrystallized from ethyl acetate to obtain the entitled compound (19 mg) as a white solid.

Workup

  1. additionmixed solution
  2. extractionextracted with chloroform/methanol (9:1)
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (Biotage, chloroform:methanol=100:4 to 100:5) and reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC)
  6. customthe obtained solid was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-dc38d8d77a6d4c049b7c7984c1e21382
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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