Triethylamine → 4-{3-[2-Fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-propyl}-piperazine-1-carboxylic Acid Tert-butyl Ester

HRID 220872Notes

Reaction equation

HRID 220872 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([OH:26])=O)=[CH:20][C:19]=2[F:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:35][N:36]1[C:45]2[NH:44][C:43]3[CH:46]=[CH:47][CH:48]=[CH:49][C:42]=3[NH:41][CH2:40][C:39]=2[CH:38]=[N:37]1>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:41]3[CH2:40][C:39]4[CH:38]=[N:37][N:36]([CH3:35])[C:45]=4[NH:44][C:43]4[CH:46]=[CH:47][CH:48]=[CH:49][C:42]3=4)=[O:26])=[CH:20][C:19]=2[F:27])[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 575552094-[3-(4-Carboxy-2-fluoro-phenoxy)-propyl]-piperazine-1-carboxylic Acid Tert-butyl EsterHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Product 1

HCID 1361283664-{3-[2-Fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-propyl}-piperazine-1-carboxylic Acid Tert-butyl EsterYield 48%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-[3-(4-carboxy-2-fluoro-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester from Example E39 (865 mg, 2.3 mmol) in dichloromethane (50 ml) was treated with triethylamine (to pH9), WSCD (865 mg, 4.5 mmol) and DMAP (276 mg, 2.3 mmol), and the mixture was stirred at room temperature for 10 min. 3-Methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (541 mg, 2.7 mmol) was added. The mixture was heated at reflux for 18 h then concentrated in vacuo. The residue was dissolved in EtOAc, washed with saturated NaHCO3 then brine and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 10% methanol:90% dichloromethane) to yield the title compound (615 mg, 48%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 18 h
  3. concentrationthen concentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc
  5. washwashed with saturated NaHCO3
  6. concentrationbrine and concentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (eluant; 10% methanol:90% dichloromethane)

Sources & evidence

ORD record
ord-8f47e631b5e74c508b429d9a3c8cc3d2
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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