Sodium hydride → 1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 1514186Notes

Reaction equation

HRID 1514186 reaction equation
[OH:1][NH:2][C:3](=[NH:22])[C:4]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.[H-].[Na+].[C:25]([C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][C:36]=1[O:37][CH:38]([CH3:40])[CH3:39])[C:30](OC)=O)#[N:26]>C1COCC1>[C:25]([C:27]1[CH:28]=[C:29]([C:30]2[O:1][N:2]=[C:3]([C:4]3[C:14]4[CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10][CH2:9][C:8]=4[CH:7]=[CH:6][CH:5]=3)[N:22]=2)[CH:34]=[CH:35][C:36]=1[O:37][CH:38]([CH3:39])[CH3:40])#[N:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21956805Methyl 3-cyano-4-isopropoxybenzoateHCID 178451587HCID 178451587, compound

Product 1

HCID 575058821,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,1-Dimethylethyl 6-[(hydroxyamino)(imino)methyl]-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (Preparation 15) (360 mg, 1.179 mmol) was dissolved in THF (50 ml) and stirred with sodium hydride (60% dispersion in mineral oil, 51.9 mg, 1.297 mmol) under argon at room temperature for 30 minutes. Then methyl 3-cyano-4-[(1-methylethyl)oxy]benzoate (may be prepared as described in WO2005058848) (388 mg, 1.768 mmol) was added as a THF solution (5 ml) and the reaction heated at reflux temperature for 1.5 hours. The cooled reaction was evaporated and partitioned between DCM (100 ml) and water (100 ml). The water layer was washed with DCM (50 ml) and the combined DCM layers dried (hydrophobic frit) and evaporated. The product was isolated by silica chromatography (eluting with DCM) to give 1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (505 mg, 1.011 mmol, 86% yield) as a white foam. δH (400 MHz, CDCl3) 8.41 (1H, s), 8.33 (1H, dd), 7.7 (1H, dd), 7.31-7.25 (2H, m), 7.13 (1H, d), 4.80 (1H, sept), 3.63-3.62 (4H, m), 3.3-3.2 (2H, m), 2.95-3.05 (2H, m), 1.47 (6H, d), 1.43 (9H, br.s); MS (ES) C27H30N4O4 requires 474; found 475 [M+H]+.

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux temperature for 1.5 hours
  3. customThe cooled reaction
  4. customwas evaporated
  5. custompartitioned between DCM (100 ml) and water (100 ml)
  6. washThe water layer was washed with DCM (50 ml)
  7. dry with materialthe combined DCM layers dried (hydrophobic frit)
  8. customevaporated
  9. customThe product was isolated by silica chromatography (eluting with DCM)

Sources & evidence

ORD record
ord-444c0682a4e942a6ab29279d817ed8d2
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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