Diisopropylethylamine → 4-[4-(7,8-Dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carbonyl)-2-methyl-phenyl]-1-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-butan-1-one

HRID 220926

Reaction equation

HRID 220926 reaction equation
[CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:25])[CH2:12][CH2:13][CH2:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][C:16]=2[CH3:24])[CH2:7][CH2:6]1.[CH:28]1[C:33]2[NH:34][CH2:35][CH2:36][CH2:37][O:38][C:32]=2[CH:31]=[CH:30][CH:29]=1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.ClCCl>[CH:28]1[C:33]2[N:34]([C:19]([C:18]3[CH:22]=[CH:23][C:15]([CH2:14][CH2:13][CH2:12][C:11]([N:8]4[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][C:2]([CH3:1])([CH3:26])[CH3:27])[CH2:10][CH2:9]4)=[O:25])=[C:16]([CH3:24])[CH:17]=3)=[O:21])[CH2:35][CH2:36][CH2:37][O:38][C:32]=2[CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5777522,3,4,5-Tetrahydro-1,5-benzoxazepineHCID 575552274-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoic Acid

Product 1

HCID 575552614-[4-(7,8-Dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carbonyl)-2-methyl-phenyl]-1-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-butan-1-oneYield 10%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

WSCD (58 mg, 0.30 mmol) and DMAP (18 mg, 0.15 mmol) were added to a solution of 4-{4-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoic acid from Example E43 (55 mg, 0.15 mmol) and 6,7,8,9-tetrahydro-5-oxa-9-aza-benzocycloheptene (44 mg, 0.30 mmol) in di-chloromethane (3 ml) and DIEA (0.052 ml, 0.30 mmol). The mixture was heated at reflux for 5 days, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloro-methane) to give a white solid identified as the title compound (6 mg, 10%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 days
  3. washwashed with saturated NaHCO3
  4. dry with materialbrine, dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloro-methane)
  7. customto give a white solid

Sources & evidence

ORD record
ord-9527d21b65dd4993bc27f99d22b93031
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Linked notes

Loading…