1,2-Dichloroethane → 1,1-Dimethylethyl 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 1514208Notes

Reaction equation

HRID 1514208 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13])[C:5]([OH:7])=O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.O[NH:30][C:31](=[NH:50])[C:32]1[CH:49]=[CH:48][C:35]2[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH2:40][C:34]=2[CH:33]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:30]=[C:31]([C:32]3[CH:49]=[CH:48][C:35]4[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[O:42])[CH2:39][CH2:40][C:34]=4[CH:33]=3)[N:50]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178451593HCID 178451593, compound

Product 1

HCID 594034491,1-Dimethylethyl 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylateYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (Preparation 6) (1.406 g, 6.55 mmol) in DMF was added HOBT (1.103 g, 7.20 mmol) and EDC (1.381 g, 7.20 mmol), the resultant solution was stirred under argon for 10 mins at room temp. 1,1-dimethylethyl 7-[(hydroxyamino)(imino)methyl]-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (Preparation 41)(2 g, 6.55 mmol) was then added to the reaction mixture and the solution heated at 80° C. overnight. The solvent was removed in vacuo and the residue dissolved in methanol for purification by Biotage Horizon, reverse phase cartridge, eluting 5-100% acetonitrile in water. The product containing fractions (last 5) were concentrated in vacuo to yield the title compound as a yellow oil (950 mg, 1.87 mmol, 29% yield). δH (d6DMSO, 400 MHz): 8.19 (1H, d), 8.11 (1H, dd), 7.83-7.89 (2H, m), 7.45 (1H, d), 7.37 (1H, d), 4.89 (1H, sept), 3.50 (4H, br.s), 2.96 (4H, br.s), 1.41 (9H, s), 1.36 (6H, d). MS (ES): C26H3035ClN3O4 requires 483; found 384 [M+H−100]+.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in methanol for purification by Biotage Horizon, reverse phase cartridge
  3. washeluting 5-100% acetonitrile in water
  4. additionThe product containing fractions (last 5)
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-bcffb24844964f8780d417bc0174a2cb
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

Loading…