Diisopropylethylamine → 1-(4-[1,3]Dioxolan-2-yl-piperidin-1-yl)-3-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propan-1-one

HRID 220879Notes

Reaction equation

HRID 220879 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:25]1[CH2:29][CH2:28][O:27][CH:26]1[CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.[CH3:36][C:37]1[CH:42]=[C:41]([C:43]([N:45]2[CH2:54][C:53]3[CH:52]=[N:51][N:50]([CH3:55])[C:49]=3[NH:48][C:47]3[CH:56]=[CH:57][CH:58]=[CH:59][C:46]2=3)=[O:44])[CH:40]=[CH:39][C:38]=1[CH2:60][CH2:61][C:62](O)=[O:63].CCN(C(C)C)C(C)C>ClCCl>[O:25]1[CH2:29][CH2:28][O:27][CH:26]1[CH:30]1[CH2:35][CH2:34][N:33]([C:62](=[O:63])[CH2:61][CH2:60][C:38]2[CH:39]=[CH:40][C:41]([C:43]([N:45]3[CH2:54][C:53]4[CH:52]=[N:51][N:50]([CH3:55])[C:49]=4[NH:48][C:47]4[CH:56]=[CH:57][CH:58]=[CH:59][C:46]3=4)=[O:44])=[CH:42][C:37]=2[CH3:36])[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 127257254-(1,3-Dioxolan-2-yl)piperidineHCID 1361283543-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionic Acid

Product 1

HCID 1361283771-(4-[1,3]Dioxolan-2-yl-piperidin-1-yl)-3-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propan-1-oneYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

HBTU (327 mg, 0.86 mmol) was added to a solution of 4-[1,3]dioxolan-2-yl-piperidine from Example E33 (143 mg, 0.91 mmol) and 3-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionic acid from Example E45 (320 mg, 0.82 mmol) in dichloromethane (20 ml) and DIEA (0.7 ml, 4.02 mmol) and the mixture was stirred for 20 h at room temperature. Dichloromethane was added and the solution was washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 4% methanol:96% dichloro-methane to 8% methanol:92% dichloromethane) to give a white solid identified as the title compound (359 mg, 83%).

Workup

  1. washthe solution was washed with saturated NaHCO3
  2. dry with materialbrine, dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography on silica gel (eluant; 4% methanol:96% dichloro-methane to 8% methanol:92% dichloromethane)
  5. customto give a white solid

Sources & evidence

ORD record
ord-6b92ee27981445be8f327309078db5d3
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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