Triethylamine → N-[4-(2-Dimethylaminoethyl)-3,4-dihydro-3-methyl-2H-1,4-benzoxazin-6-yl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide

HRID 1292027Notes

Reaction equation

HRID 1292027 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]=[C:11]([CH3:13])[O:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][CH:15]=1.S(Cl)(Cl)=O.[NH2:27][C:28]1[CH:29]=[CH:30][C:31]2[O:36][CH2:35][CH:34]([CH3:37])[N:33]([CH2:38][CH2:39][N:40]([CH3:42])[CH3:41])[C:32]=2[CH:43]=1.C(N(CC)CC)C>ClCCl>[CH3:41][N:40]([CH3:42])[CH2:39][CH2:38][N:33]1[C:32]2[CH:43]=[C:28]([NH:27][C:20]([C:17]3[CH:16]=[CH:15][C:14]([C:3]4[CH:4]=[CH:5][C:6]([C:8]5[N:12]=[C:11]([CH3:13])[O:10][N:9]=5)=[CH:7][C:2]=4[CH3:1])=[CH:19][CH:18]=3)=[O:21])[CH:29]=[CH:30][C:31]=2[O:36][CH2:35][CH:34]1[CH3:37]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 111301684-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]benzoic AcidHCID 189140836-amino-3,4-dihydro-4-(2-dimethylaminoethyl)-3-methyl-2H-1,4-benzoxazine

Product 1

HCID 18914091N-[4-(2-Dimethylaminoethyl)-3,4-dihydro-3-methyl-2H-1,4-benzoxazin-6-yl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamideYield 54.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid (EP 0533268A1) (77 mg, 0.26 mmol) was treated with thionyl chloride (5 ml) and the mixture heated under reflux under Ar for 1 hour, then concentrated in vacuo to afford a yellow solid. This was dissolved in dichloromethane (5 ml) and treated with a solution of 6-amino-3,4-dihydro-4-(2-dimethylaminoethyl)-3-methyl-2H-1,4-benzoxazine (D14, 61.7 mg, 0.26 mmol) and triethylamine (0.11 ml, 0.78 inmol) in dichloromethane (10 ml). The reaction mixture was stirred at room temperature under Ar for 24 hours, then washed with brine/saturated potassium carbonate solution (30 ml of a 1:1 solution). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo to afford a brown oil. This was chromatographed on SiO2, eluting with 0-8% methanol/dichloromethane to afford the title compound as a light yellow oil (72.2 mg, 54%).

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux under Ar for 1 hour
  3. concentrationconcentrated in vacuo
  4. customto afford a yellow solid
  5. washwashed with brine/saturated potassium carbonate solution (30 ml of a 1:1 solution)
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto afford a brown oil
  10. customThis was chromatographed on SiO2
  11. washeluting with 0-8% methanol/dichloromethane

Sources & evidence

ORD record
ord-a7f58dde311a4fb292bb758ff95ea4ec
Source dataset
uspto-grants-1998_05
Patent number
US05756496

Reaction notes

Loading…