Water → HCID 123146761, compound

HRID 1509280Notes

Reaction equation

HRID 1509280 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+].[F:39][CH2:40][CH2:41]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]([CH2:41][CH2:40][F: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 24758Sodium hydrideHCID 69804Ethane, 1-fluoro-2-iodo-HCID 123453589HCID 123453589, compound

Product 1

HCID 123146761HCID 123146761, compoundYield 47%

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 (101 mg, 0.21 mmol) in dry DMF (1 ml) was added sodium hydride (12 mg, 0.32 mmol) and 1-fluoro-2-iodoethane (27 μl, 0.32 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 100% EtOAc in cyclohexane) to give the title compound (52 mg, 47%). 1H NMR (500 MHz, CDCl3): 7.62 (1H, s), 7.31-7.22 (7H, m), 7.16-7.14 (2H, m), 5.01 (1H, s), 4.75 (1H, br s), 4.74 (2H, dt), 4.07 (2H, dt), 3.92-3.88 (2H, m), 2.73 (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 (3×10 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 100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-1d98e0364d6b4edb9c8b937082ef483c
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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