Water → HCID 123592920, compound

HRID 1509249Notes

Reaction equation

HRID 1509249 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:20][C:21]4[N:26]5[C:27](=[O:30])[NH:28][N:29]=[C:25]5[CH2:24][O:23][C:22]=4[N:31]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:46][C:47]#[N:48].O>CN(C=O)C>[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:20][C:21]4[N:26]5[C:27](=[O:30])[N:28]([CH2:46][C:47]#[N:48])[N:29]=[C:25]5[CH2:24][O:23][C:22]=4[N:31]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 123386190HCID 123386190, compound

Product 1

HCID 123592920HCID 123592920, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl(1-(4-(1-oxo-8-phenyl-2,4-dihydro-1H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazin-7-yl)phenyl)cyclobutyl)carbamate (70 mg, 0.14 mmol) in dry DMF (1 ml) was added potassium carbonate (57 mg, 0.41 mmol) and bromoacetonitrile (29 μl, 0.41 mmol) under nitrogen. The resulting mixture was stirred for 1 hour at room temperature. Water was added and the mixture was extracted with EtOAc (3×10 ml). The combined organic phases were dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 35% EtOAc in cyclohexane) to give the title compound (45 mg, 60%). 1H NMR (500 MHz, CDCl3): 8.43 (1H, s), 7.26-7.19 (7H,m), 7.14-7.12 (2H, m), 5.25 (2H, s), 4.96 (1H, br s), 4.72 (2H, s), 2.55-2.25 (4H, m), 2.10-2.03 (1H, m), 1.86-1.78 (1H, m), 1.44-1.15 (9H, br).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×10 ml)
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. concentrationconcentrated to dryness under reduced pressure
  4. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 35% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-ce396e4f35ef4cc8a42f76aa46d1a351
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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