Sodium hydride → 1,1-Dimethylethyl 7-{5-[3-cyano-4-(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 1514216Notes

Reaction equation

HRID 1514216 reaction equation
[OH:1][NH:2][C:3](=[NH:22])[C:4]1[CH:21]=[CH:20][C:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12][C:6]=2[CH:5]=1.[H-].[Na+].[C:25]([C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][C:36]=1[O:37][CH3:38])[C:30](OC)=O)#[N:26]>C1COCC1.O.C(OC(=O)C)C>[C:25]([C:27]1[CH:28]=[C:29]([C:30]2[O:1][N:2]=[C:3]([C:4]3[CH:21]=[CH:20][C:7]4[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH2:11][CH2:12][C:6]=4[CH:5]=3)[N:22]=2)[CH:34]=[CH:35][C:36]=1[O:37][CH3:38])#[N:26]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 2801011Methyl 3-cyano-4-methoxybenzoateHCID 178451593HCID 178451593, compound

Product 1

HCID 684667951,1-Dimethylethyl 7-{5-[3-cyano-4-(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylateYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

1,1-Dimethylethyl 7-[(hydroxyamino)(imino)methyl]-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (Preparation 41) (240 mg, 0.785 mmol) was added to a suspension of sodium hydride (60% dispersion in mineral oil) (23.01 mg, 0.575 mmol) in THF (5 ml) at room temperature (note slight effervescence). The resultant mixture was stirred at room temperature for 30 mins, methyl 3-cyano-4-(methyloxy)benzoate (100 mg, 0.523 mmol) was then added and the reaction mixture was heated to reflux (75° C.) for 45 mins. The reaction mixture was diluted with water and ethylacetate and the layers partitioned, solid was present in the bi-phasic mixture so this was transferred to a conical flask and stirred at room temperature for 2 h at room temperature. The mixture was then partitioned and the organic layer concentrated in vacuo. to yield the title compound (280 mg, 0.502 mmol, 96% yield) as a yellow oil. MS (ES): C25H26N4O4 requires 447; no mass ion present. 1H NMR (400 MHz, CDCl3) δ 1H, d (8.44), 1H, dd (8.38), 2H, m (7.89-7.95), 1H, m (7.35-7.42), 1H, m (7.13-7.17), 3H, s (4.06), 4H, m (3.50-3.66), 4H, m (2.87-3.06), 9H, s (1.50).

Workup

  1. temperaturethe reaction mixture was heated
  2. customthe layers partitioned
  3. customthis was transferred to a conical flask
  4. customThe mixture was then partitioned
  5. concentrationthe organic layer concentrated in vacuo

Sources & evidence

ORD record
ord-c39c16ed24054fdcbbd035e204002cd3
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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