Water → HCID 123483116, compound

HRID 1509275Notes

Reaction equation

HRID 1509275 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:20][C:21]4[NH:27][C:26](=[O:28])[CH2:25][CH2:24][NH:23][C:22]=4[N:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:39]I.O>CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[CH:20][C:21]4[N:27]([CH3:39])[C:26](=[O:28])[CH2:25][CH2:24][NH:23][C:22]=4[N:29]=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 6328Methyl iodideHCID 24758Sodium hydrideHCID 123453589HCID 123453589, compound

Product 1

HCID 123483116HCID 123483116, compoundYield 38.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-8-phenyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-b][1,4]diazepin-7-yl)phenyl)cyclobutyl)carbamate (53 mg, 0.11 mmol) in dry DMF (1 ml) was added sodium hydride (4.4 mg, 0.11 mmol) and methyliodide (6.9 μl, 0.11 mmol) under nitrogen. The resulting mixture was stirred for 1 hour at room temperature. Water was added and the mixture was extracted with EtOAc (3×15 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 57% EtOAc in cyclohexane) to give the title compound (21 mg, 38%). 1H NMR (500 MHz, CDCl3): 7.39 (1H, s), 7.27-7.23 (7H, m), 7.16-7.14 (2H, m), 5.04 (1H, s), 4.91 (1H, br s), 3.88 (2H, br s), 3.39 (3H, s), 2.74 (2H, t), 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 (3×15 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 57% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-494bbafce1fb41d492e36d375f3c1c1f
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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