Imidazole → tert-butyl(1-(4-(1-((1H-imidazol-5-yl)methyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate

HRID 1509162Notes

Reaction equation

HRID 1509162 reaction equation
[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[NH:3]1.[H-].[Na+].Cl.Cl[CH2:40][C:41]1[NH:45][CH:44]=[N:43][CH:42]=1.N1C=CN=C1>CN(C=O)C>[C:31]([O:30][C:29](=[O:35])[NH:28][C:24]1([C:21]2[CH:22]=[CH:23][C:18]([C:9]3[C:10]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[CH:11][C:4]4[N:3]([CH2:40][C:41]5[NH:45][CH:44]=[N:43][CH:42]=5)[C:2](=[O:1])[CH2:7][O:6][C:5]=4[N:8]=3)=[CH:19][CH:20]=2)[CH2:25][CH2:26][CH2:27]1)([CH3:32])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 24758Sodium hydride2×HCID 217324Imidazole, 4-chloromethyl-, hydrochlorideHCID 67256382HCID 67256382, compound

Product 1

HCID 123965594tert-butyl(1-(4-(1-((1H-imidazol-5-yl)methyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamateYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a round bottom flask was added tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (150 mg, 0.318 mmol) in DMF (Volume: 8 ml) to give a brown solution.sodium hydride (30.5 mg, 0.763 mmol) and 5-(chloromethyl)-1H-imidazole hydrochloride salt (58.4 mg, 0.501 mmol) was added. The resulting mixture was stirred at room temperature for 2 h. further sodium hydride (15.2 mg) and imidazole (29 mg) were added and the resulting mixture stirred for another hour. The reaction mixture was concentrated to dryness. The residue was partitioned between ethyl acetate (35 ml) and water (30 ml). The organic phase was separated and washed with water (2×25 ml), brine and concentrated. The residue was purified by column (biotage 25 g) to give product (14 mg). LCMS (Method A) RT=4.58 min, M+H+=552.1.

Workup

  1. customto give a brown solution
  2. additionwere added
  3. concentrationThe reaction mixture was concentrated to dryness
  4. customThe residue was partitioned between ethyl acetate (35 ml) and water (30 ml)
  5. customThe organic phase was separated
  6. washwashed with water (2×25 ml), brine
  7. concentrationconcentrated
  8. customThe residue was purified by column (biotage 25 g)

Sources & evidence

ORD record
ord-3c380b64155d4dabac91fe80c89ec6df
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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