Diisopropylethylamine → 4-[(Cyclopropyl-{3-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionyl}-amino)-methyl]-piperidine-1-carboxylic Acid Tert-butyl Ester

HRID 220938Notes

Reaction equation

HRID 220938 reaction equation
C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1[CH:31]=[C:30]([C:32]([N:34]2[CH2:43][C:42]3[CH:41]=[N:40][N:39]([CH3:44])[C:38]=3[NH:37][C:36]3[CH:45]=[CH:46][CH:47]=[CH:48][C:35]2=3)=[O:33])[CH:29]=[CH:28][C:27]=1[CH2:49][CH2:50][C:51](O)=[O:52].[C:54]([O:58][C:59]([N:61]1[CH2:66][CH2:65][CH:64]([CH2:67][NH:68][CH:69]2[CH2:71][CH2:70]2)[CH2:63][CH2:62]1)=[O:60])([CH3:57])([CH3:56])[CH3:55].CCN(C(C)C)C(C)C>ClCCl.CCOC(C)=O>[C:54]([O:58][C:59]([N:61]1[CH2:66][CH2:65][CH:64]([CH2:67][N:68]([CH:69]2[CH2:70][CH2:71]2)[C:51](=[O:52])[CH2:50][CH2:49][C:27]2[CH:28]=[CH:29][C:30]([C:32]([N:34]3[CH2:43][C:42]4[CH:41]=[N:40][N:39]([CH3:44])[C:38]=4[NH:37][C:36]4[CH:45]=[CH:46][CH:47]=[CH:48][C:35]3=4)=[O:33])=[CH:31][C:26]=2[CH3:25])[CH2:63][CH2:62]1)=[O:60])([CH3:57])([CH3:55])[CH3:56]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 16641216tert-Butyl 4-((cyclopropylamino)methyl)piperidine-1-carboxylateHCID 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 1361283784-[(Cyclopropyl-{3-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionyl}-amino)-methyl]-piperidine-1-carboxylic Acid Tert-butyl EsterYield 73%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

PyBroP (238 mg, 0.51 mmol) was added to a solution of 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 (200 mg, 0.51 mmol) and 4-cyclopropylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester (130 mg, 0.51 mmol) in dichloromethane (10 ml) and DIEA (0.18 ml, 1.02 mmol). The mixture was stirred for 4 days at room temperature, diluted with EtOAc, washed with 5% KHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 5% methanol:95% dichloromethane) to yield the title compound (235 mg, 73%).

Workup

  1. washwashed with 5% KHCO3
  2. dry with materialbrine, dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography on silica gel (eluant; 5% methanol:95% dichloromethane)

Sources & evidence

ORD record
ord-7fd767d147774ffd8ff3fc2f95609466
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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