Cyclopropanecarbonyl chloride → Cyclopropanecarboxylic Acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide

HRID 220956Notes

Reaction equation

HRID 220956 reaction equation
CCN(C(C)C)C(C)C.[CH:10]1([C:13](Cl)=[O:14])[CH2:12][CH2:11]1.Cl.[NH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([N:27]2[CH2:36][C:35]3[CH:34]=[N:33][N:32]([CH3:37])[C:31]=3[NH:30][C:29]3[CH:38]=[C:39]([CH3:42])[CH:40]=[CH:41][C:28]2=3)=[O:26])=[CH:21][C:20]=1[F:43]>ClCCl>[CH3:37][N:32]1[C:31]2[NH:30][C:29]3[CH:38]=[C:39]([CH3:42])[CH:40]=[CH:41][C:28]=3[N:27]([C:25]([C:22]3[CH:23]=[CH:24][C:19]([CH2:18][NH:17][C:13]([CH:10]4[CH2:12][CH2:11]4)=[O:14])=[C:20]([F:43])[CH:21]=3)=[O:26])[CH2:36][C:35]=2[CH:34]=[N:33]1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 135736009(4-Aminomethyl-3-fluoro-phenyl)-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Hydrochloride

Product 1

HCID 136128374Cyclopropanecarboxylic Acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamideYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DIEA (0.08 ml, 0.46 mmol) and cyclopropanecarbonyl chloride (0.013 ml, 0.14 mmol) were added to a solution of (4-aminomethyl-3-fluoro-phenyl)-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride from Example E98.2 (57 mg, 0.14 mmol) in dichloromethane (10 ml) at 0° C. The mixture was stirred for 90 min at room temperature then diluted with dichloromethane, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane) to give a white solid identified as the title compound (33 mg, 54%).

Workup

  1. washwashed with saturated NaHCO3
  2. dry with materialbrine, dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane)
  5. customto give a white solid

Sources & evidence

ORD record
ord-36eb15bf9aaf439d94a328742c49450c
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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