Imidazole → HCID 67336416, compound

HRID 1892192Notes

Reaction equation

HRID 1892192 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([NH:12][C:13]2[N:14]=[CH:15][C:16]3[CH2:17][C:18](=[O:32])[NH:19][C:20]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=4[C:22]=3[N:23]=2)[C:8]([CH3:11])=[N:9][CH:10]=1.N1C=CN=C1.[Si:38](Cl)([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]>C1COCC1>[Si:38]([O:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([NH:12][C:13]2[N:14]=[CH:15][C:16]3[CH2:17][C:18](=[O:32])[NH:19][C:20]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=4[C:22]=3[N:23]=2)[C:8]([CH3:11])=[N:9][CH:10]=1)([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67336441HCID 67336441, compound

Product 1

HCID 67336416HCID 67336416, compoundYield 51.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{[5-(3-hydroxypropyl)-2-methylpyridin-3-yl]amino}-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (0.25 g, 0.564 mmol) in THF (10 ml) were added imidazole (0.077 g, 1.13 mmol) and tert-butyldimethylsilyl chloride (0.10 g, 0.676 mmol). The reaction mixture was allowed to stir overnight at rt and was then concentrated. Water (10 ml) and saturated NaHCO3 (10 ml) were added. The resulting mixture was allowed to stir for 1 h at rt. The mixture was extracted with EtOAc (2×30 mL). The organic solutions were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 2-{[5-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-2-methylpyridin-3-yl]amino}-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (0.16 g, 0.29 mmol, 51%).

Workup

  1. concentrationwas then concentrated
  2. additionWater (10 ml) and saturated NaHCO3 (10 ml) were added
  3. stirringto stir for 1 h at rt
  4. extractionThe mixture was extracted with EtOAc (2×30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ec2514904e6342f287eddeec79f1ec77
Source dataset
uspto-grants-2013_08
Patent number
US08507667B2

Reaction notes

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