Diisopropylethylamine → 1-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-butan-1-one

HRID 220918Notes

Reaction equation

HRID 220918 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1[CH:38]=[C:37]([C:39]([N:41]2[CH2:50][C:49]3[CH:48]=[N:47][N:46]([CH3:51])[C:45]=3[NH:44][C:43]3[CH:52]=[CH:53][CH:54]=[CH:55][C:42]2=3)=[O:40])[CH:36]=[CH:35][C:27]=1[O:28][CH2:29][CH2:30][CH2:31][C:32](O)=[O:33].Cl.Cl.[CH3:58][C:59]([CH3:69])([CH3:68])[CH2:60][CH2:61][N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1.CCN(C(C)C)C(C)C>ClCCl>[CH3:58][C:59]([CH3:69])([CH3:68])[CH2:60][CH2:61][N:62]1[CH2:63][CH2:64][N:65]([C:32](=[O:33])[CH2:31][CH2:30][CH2:29][O:28][C:27]2[CH:35]=[CH:36][C:37]([C:39]([N:41]3[CH2:50][C:49]4[CH:48]=[N:47][N:46]([CH3:51])[C:45]=4[NH:44][C:43]4[CH:52]=[CH:53][CH:54]=[CH:55][C:42]3=4)=[O:40])=[CH:38][C:26]=2[CH3:25])[CH2:66][CH2:67]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670538001-(3,3-Dimethyl-butyl)-piperazine dihydrochlorideHCID 1361284054-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-butyric Acid

Product 1

HCID 1361284431-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-butan-1-oneYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HBTU (101 mg, 0.27 mmol) was added to a solution of 4-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-butyric acid from E76.2 (71 mg, 0.17 mmol) and 1-(3,3-dimethyl-butyl)-piperazine dihydrochloride from Example E4 (54 mg, 0.22 mmol) in dichloromethane (10 ml) and DIEA (0.15 ml, 0.86 mmol). The mixture was stirred for 20 h at room temperature, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 6% methanol:94% dichloromethane) to give a white powder identified as the title compound (52 mg, 53%).

Workup

  1. washwashed with saturated NaHCO3
  2. dry with materialbrine, dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography on silica gel (eluant; 6% methanol:94% dichloromethane)
  5. customto give a white powder

Sources & evidence

ORD record
ord-38e49576219148ad8d5b087db97821d4
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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