Diisopropylethylamine → 1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic Acid 4-(1-benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzylamide

HRID 220988Notes

Reaction equation

HRID 220988 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]([CH3:39])([CH3:38])[CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][CH:32]([C:35]([OH:37])=O)[CH2:31][CH2:30]1.[NH2:40][CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]([N:50]2[CH2:59][CH2:58][C:57]3[N:56]=[C:55]([CH3:60])[N:54]([CH2:61][C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)[C:53]=3[C:52]3[CH:68]=[CH:69][CH:70]=[CH:71][C:51]2=3)=[O:49])=[CH:44][C:43]=1[CH3:72].CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:61]([N:54]1[C:53]2[C:52]3[CH:68]=[CH:69][CH:70]=[CH:71][C:51]=3[N:50]([C:48]([C:45]3[CH:46]=[CH:47][C:42]([CH2:41][NH:40][C:35]([CH:32]4[CH2:31][CH2:30][N:29]([CH2:28][CH2:27][C:26]([CH3:25])([CH3:39])[CH3:38])[CH2:34][CH2:33]4)=[O:37])=[C:43]([CH3:72])[CH:44]=3)=[O:49])[CH2:59][CH2:58][C:57]=2[N:56]=[C:55]1[CH3:60])[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 231123781-(3,3-Dimethylbutyl)piperidine-4-carboxylic acidHCID 57555234(4-Aminomethyl-3-methyl-phenyl)-(1-benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulen-6-yl)-methanone

Product 1

HCID 575552261-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic Acid 4-(1-benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzylamideYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HBTU (175 mg, 0.46 mmol) was added to a solution of 1-(3,3-dimethyl-butyl)-piperidine-4-carboxylic acid (86 mg, 0.34 mmol) in DMF (5 ml). The mixture was stirred at room temperature for 2 h then (4-aminomethyl-3-methyl-phenyl)-(1-benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulen-6-yl)-methanone from Example E121.2 (100 mg, 0.23 mmol) and DIEA (0.12 ml, 0.69 mmol) were added. The mixture was stirred at room temperature for 18 h then solvents were removed in vacuo and azeotroped with toluene. The residue was purified by flash chromatography on silica gel through an isolute (eluant; 5% methanol:95% dichloromethane then 10% methanol:90% dichloromethane) to give a yellow foam identified as the title compound (114 mg, 79%).

Workup

  1. stirringThe mixture was stirred at room temperature for 18 h
  2. customsolvents were removed in vacuo
  3. customazeotroped with toluene
  4. customThe residue was purified by flash chromatography on silica gel through an isolute (eluant
  5. custom5% methanol:95% dichloromethane then 10% methanol:90% dichloromethane) to give a yellow foam

Sources & evidence

ORD record
ord-3401d9e356f740b5b9115063605c63a5
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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