Dichloromethane → 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride

HRID 1514261Notes

Reaction equation

HRID 1514261 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:28]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].FC(F)(F)C(O)=O.C(Cl)[Cl:44]>>[ClH:44].[CH3:12][CH:10]([O:9][C:8]1[CH:7]=[CH:6][C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:28]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)[N:14]=2)=[CH:4][C:3]=1[C:1]#[N:2])[CH3:11]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 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-carboxylate

Product 1

HCID 684658932-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochlorideYield 100%

Procedure

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 (Preparation 16) (505 mg, 1.064 mmol) was dissolved in DCM (40 ml) and treated with trifluoroacetic acid (4 ml, 51.9 mmol). The resulting mixture was heated at reflux for 1 hour then evaporated. The resulting residue was partitioned between DCM (20 ml) and 2N NaOH (20 ml). The DCM layer was collected, dried (hydrophobic frit) and evaporated. The free-base was dissolved in 4M HCl in dioxane and evaporated to give the HCl salt, 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride (438 mg, 1.066 mmol, 100% yield) as an off-white powder. δH (400 MHz, CDCl3) 10.15 (1H, br.s), 8.39 (1H, s), 8.33-8.31 (1H, m), 7.75-7.85 (1H, m), 7.45-7.3 (2H, m), 7.14 (1H, d), 4.84-4.76 (1H, m), 3.90-3.30 (8H, m) 1.48 (6H, d); MS (ES) C22H22N4O2 requires 374; found 375 [M+H]+.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 1 hour
  3. customthen evaporated
  4. customThe resulting residue was partitioned between DCM (20 ml) and 2N NaOH (20 ml)
  5. customThe DCM layer was collected
  6. customdried (hydrophobic frit)
  7. customevaporated
  8. dissolutionThe free-base was dissolved in 4M HCl in dioxane
  9. customevaporated

Sources & evidence

ORD record
ord-20f552d70cd642f682ada337833e0598
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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