Triethylamine → 1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic Acid 2-methyl-4-(2-methyl-4,5-dihydro-1-oxa-3,6-diaza-benzo[e]azulene-6-carbonyl)-benzylamide

HRID 220985Notes

Reaction equation

HRID 220985 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:21][CH2:20][C:19]3[N:18]=[C:17]([CH3:22])[O:16][C:15]=3[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]2=3)=[O:11])=[CH:6][C:5]=1[CH3:27].C(N(CC)CC)C.[CH3:35][C:36]([CH3:49])([CH3:48])[CH2:37][CH2:38][N:39]1[CH2:44][CH2:43][CH:42]([C:45](O)=[O:46])[CH2:41][CH2:40]1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:27][C:5]1[CH:6]=[C:7]([C:10]([N:12]2[CH2:21][CH2:20][C:19]3[N:18]=[C:17]([CH3:22])[O:16][C:15]=3[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]2=3)=[O:11])[CH:8]=[CH:9][C:4]=1[CH2:3][NH:2][C:45]([CH:42]1[CH2:43][CH2:44][N:39]([CH2:38][CH2:37][C:36]([CH3:49])([CH3:48])[CH3:35])[CH2:40][CH2:41]1)=[O:46]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2733179PyBroPHCID 231123781-(3,3-Dimethylbutyl)piperidine-4-carboxylic acidHCID 67287214(4-Aminomethyl-3-methyl-phenyl)-(2-methyl-4,5-dihydro-1-oxa-3,6-diaza-benzo[e]azulen-6-yl)-methanone Hydrochloride

Product 1

HCID 116423921-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic Acid 2-methyl-4-(2-methyl-4,5-dihydro-1-oxa-3,6-diaza-benzo[e]azulene-6-carbonyl)-benzylamideYield 69%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-Aminomethyl-3-methyl-phenyl)-(2-methyl-4,5-dihydro-1-oxa-3,6-diaza-benzo[e]azulen-6-yl)-methanone hydrochloride from Example E119.2 (89 mg, 0.225 mmol) was dissolved in dichloromethane (10 ml) and triethylamine (to pH9) at room temperature. 1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid (53 mg, 0.25 mmol), DMAP (27 mg, 0.225 mmol) and PyBroP (165 mg, 0.36 mmol) were added and the mixture was heated at reflux for 18 h. The solution was diluted with EtOAc, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 1% 35% ammonia:9% methanol:90% dichloro-methane) to give a white solid identified as the title compound (84 mg, 69%).

Workup

  1. customat room temperature
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 18 h
  4. washwashed with saturated NaHCO3
  5. dry with materialbrine, dried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (eluant; 1% 35% ammonia:9% methanol:90% dichloro-methane)
  8. customto give a white solid

Sources & evidence

ORD record
ord-821226f5468f4ed8b752227fa022459e
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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