4-((E)-2-tert-Butoxycarbonyl-vinyl)-3-methyl-benzoic Acid → (E)-3-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-acrylic Acid Tert-butyl Ester

HRID 220863Notes

Reaction equation

HRID 220863 reaction equation
[C:1]([O:5][C:6](/[CH:8]=[CH:9]/[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][C:11]=1[CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][N:21]1[C:30]2[NH:29][C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[NH:26][CH2:25][C:24]=2[CH:23]=[N:22]1>ClCCl.C(N(CC)CC)C.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6](=[O:7])/[CH:8]=[CH:9]/[C:10]1[CH:18]=[CH:17][C:13]([C:14]([N:26]2[CH2:25][C:24]3[CH:23]=[N:22][N:21]([CH3:20])[C:30]=3[NH:29][C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]2=3)=[O:16])=[CH:12][C:11]=1[CH3:19])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 575553374-((E)-2-tert-Butoxycarbonyl-vinyl)-3-methyl-benzoic AcidHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Product 1

HCID 136128393(E)-3-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-acrylic Acid Tert-butyl EsterYield 82%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

4-((E)-2-tert-Butoxycarbonyl-vinyl)-3-methyl-benzoic acid from Example E45.1 (1.1 g, 4.2 mmol) and 3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (720 mg, 3.6 mmol) were dissolved in dichloromethane (50 ml) and triethylamine (0.75 ml). DMAP (4.45 g, 3.6 mmol) and WSCD (1.36 g, 7.1 mmol) were added and the mixture was heated at re-flux for 2 days. The solution was diluted with di-chloromethane, washed with 0.3M KHSO4, saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; EtOAc) to yield the title compound (1.35 g, 82%).

Workup

  1. temperaturethe mixture was heated at re-flux for 2 days
  2. washwashed with 0.3M KHSO4, saturated NaHCO3
  3. dry with materialbrine, dried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (eluant; EtOAc)

Sources & evidence

ORD record
ord-16bd9a0d0a4f445ea59f5f580cf3d814
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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