Triethylamine → HCID 57597222, compound

HRID 1786946Notes

Reaction equation

HRID 1786946 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[NH:25][C:24]([C:26]4[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=4)=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][C:12]([CH3:15])=[CH:13][CH:14]=1.C(N(CC)CC)C.C(N1C=CN=C1)(N1C=CN=C1)=O.[BH4-].[Na+]>O1CCCC1.O.CO>[CH3:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[NH:25][C:24]([C:26]4[CH:27]=[CH:28][C:29]([CH2:30][OH:31])=[CH:33][CH:34]=4)=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][C:12]([CH3:15])=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 57597162HCID 57597162, compound

Product 1

HCID 57597222HCID 57597222, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]benzoic acid (122 mg) in tetrahydrofuran (10 mL) was added triethylamine (30.5 mg) and, after stirring at room temperature for 10 min, 1,1′-carbonyldiimidazole (49 mg) was added, and the mixture was stirred at room temperature for 13 hrs. Under ice-cooling, sodium borohydride (28 mg) was added, and methanol (2.5 mL) was further added. After stirring under ice-cooling for 2 hrs, water (1.5 mL) was added, and tetrahydrofuran and methanol were evaporated under reduced pressure. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (30 mL)-tetrahydrofuran (15 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (15 mL)-tetrahydrofuran (5 mL). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (eluent, ethyl acetate:methanol=99:1→9:1). The object fraction was concentrated under reduced pressure. The residue was recrystallized from methanol-ethyl acetate to give the title compound (65 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 13 hrs
  2. temperatureUnder ice-cooling
  3. stirringAfter stirring under ice-
  4. temperaturecooling for 2 hrs
  5. customtetrahydrofuran and methanol were evaporated under reduced pressure
  6. additionWater (20 mL) was added
  7. extractionthe mixture was extracted with ethyl acetate (30 mL)-tetrahydrofuran (15 mL)
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (15 mL)-tetrahydrofuran (5 mL)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationAfter concentration under reduced pressure
  12. concentrationThe object fraction was concentrated under reduced pressure
  13. customThe residue was recrystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-819695785614457faa55f55bf57bc999
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

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