Triethylamine → 4-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-butyric Acid Tert-butyl Ester

HRID 220916Notes

Reaction equation

HRID 220916 reaction equation
[C:1]([O:5][C:6]([CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][C:13]=1[CH3:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][N:23]1[C:32]2[NH:31][C:30]3[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=3[NH:28][CH2:27][C:26]=2[CH:25]=[N:24]1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[C:1]([O:5][C:6](=[O:7])[CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([N:28]2[CH2:27][C:26]3[CH:25]=[N:24][N:23]([CH3:22])[C:32]=3[NH:31][C:30]3[CH:33]=[CH:34][CH:35]=[CH:36][C:29]2=3)=[O:18])=[CH:14][C:13]=1[CH3:21])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 575552384-(3-tert-Butoxycarbonyl-propoxy)-3-methyl-benzoic AcidHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Product 1

HCID 1361283964-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-butyric Acid Tert-butyl EsterYield 18%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

WSCD (391 mg, 2.06 mmol) and DMAP (133 mg, 1.09 mmol) were added to a solution of 4-(3-tert-butoxycarbonyl-propoxy)-3-methyl-benzoic acid from Example E42 (275 mg, 0.94 mmol) and 3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (191 mg, 0.95 mmol) in dichloromethane (30 ml) and triethylamine (0.28 ml, 2.01 mmol). The mixture was heated at reflux for 72 h, 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 (80 mg, 18%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 72 h
  3. washwashed with 0.3M KHSO4, saturated NaHCO3
  4. dry with materialbrine, dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel (eluant; EtOAc)

Sources & evidence

ORD record
ord-48c8ce4757cc4cd38e3baa444c5dff97
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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