Cyanogen Bromide → HCID 58381242, compound

HRID 1025801Notes

Reaction equation

HRID 1025801 reaction equation
[CH3:1][C:2]([CH3:31])([CH3:30])[CH:3]([C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][NH2:27])=[O:25])=[CH:22][CH:21]=1)[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:12][CH3:13])=[CH:6][CH:5]=1.C(=O)(O)[O-].[Na+].[N:37]#[C:38]Br.C(=O)(O)[O-].[Na+].[Cl-].[Na+].O>O1CCOCC1.O.O.O1CCOCC1>[CH3:31][C:2]([CH3:30])([CH3:1])[CH:3]([C:20]1[CH:21]=[CH:22][C:23]([C:24]2[O:25][C:38]([NH2:37])=[N:27][N:26]=2)=[CH:28][CH:29]=1)[C:4]1[CH:5]=[CH:6][C:7]([O:10][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:12][CH3:13])=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 58381244HCID 58381244, compoundHCID 129703874Sodium hydrogencarbonate brine

Product 1

HCID 58381242HCID 58381242, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
5 °C

Procedure

Crude 3d (40.0 mg, 0.0967 mmol) was suspended in dioxane/water (1.3 mL of a 3:1 mixture) and cooled to approximately 5° C. A solution of aqueous sodium bicarbonate (22.0 mg, 0.237 mmol) in water (150 μL) was added followed by a solution of cyanogen bromide (15.0 mg, 0.142 mmol) in dioxane (100 μL). After 5 min, the reaction mixture was warmed to ambient temperature and aged for approximately 1 h. The reaction mixture was poured into saturated aqueous sodium bicarbonate/brine (1:1) and extracted twice with DCM. The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (isocratic elution; 80% EtOAc/hexanes as eluent) afforded the title compound 3e. m/z (ES) 443 (M)+. 1HNMR (500 MHz, CDCl3): δ 1H NMR (500 MHz, CDCl3) δ 8.61 (t, 1H, J==2.6 Hz), 7.79 (d, 2H, J=8.8 Hz), 7.66 (m, 1H), 7.48 (d, 2H, J=8.7 Hz), 7.40 (d, 1H, J=7.7 Hz), 7.25 (d, 2H, J=8.7 Hz), 7.20 (m, 1H), 6.81 (d, 2H, J=8.7 Hz), 5.5-5.8 (bs, 2H), 5.18 (t, 1H, J=6.9 Hz), 3.67 (s, 1H), 2.0 (m, 2H), 1.05 (t, 3H, J=7.3 Hz), 1.0 (s, 9H).

Workup

  1. temperaturethe reaction mixture was warmed to ambient temperature and aged for approximately 1 h
  2. extractionextracted twice with DCM
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude residue by flash chromatography on silica gel (isocratic elution; 80% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-db8c05cacef84121a6bbf7021fea7da2
Source dataset
uspto-grants-2014_05
Patent number
US08729104B2

Reaction notes

Loading…