Diisopropylethylamine → 1-(4-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoyl)-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester

HRID 220925Notes

Reaction equation

HRID 220925 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](O)=[O:20])=[CH:17][C:16]=2[CH3:24])[CH2:7][CH2:6]1.[C:28]([O:32][C:33]([N:35]1[CH2:41][C:40]2[CH:42]=[CH:43][CH:44]=[CH:45][C:39]=2[NH:38][CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.ClCCl>[C:28]([O:32][C:33]([N:35]1[CH2:41][C:40]2[CH:42]=[CH:43][CH:44]=[CH:45][C:39]=2[N:38]([C:19](=[O:20])[C:18]2[CH:22]=[CH:23][C:15]([CH2:14][CH2:13][CH2:12][C:11]([N:8]3[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][C:2]([CH3:1])([CH3:27])[CH3:26])[CH2:6][CH2:7]3)=[O:25])=[C:16]([CH3:24])[CH:17]=2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27718261,2,3,5-Tetrahydro-benzo(e)(1,4)diazepine-4-carboxylic acid tert-butyl esterHCID 575552274-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoic Acid

Product 1

HCID 575553741-(4-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoyl)-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl esterYield 28%

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 1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester (73 mg, 0.30 mmol) in dichloromethane (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% dichloromethane) to yield the title compound (25 mg, 28%).

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% dichloromethane)

Sources & evidence

ORD record
ord-d197bf11323c4145b5fe71ac7c05d9a1
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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