Propionyl chloride → N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-propionamide

HRID 220963Notes

Reaction equation

HRID 220963 reaction equation
CCN(C(C)C)C(C)C.[C:10](Cl)(=[O:13])[CH2:11][CH3:12].Cl.[NH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([N:26]2[CH2:35][C:34]3[CH:33]=[N:32][N:31]([CH3:36])[C:30]=3[NH:29][C:28]3[CH:37]=[C:38]([Cl:41])[CH:39]=[CH:40][C:27]2=3)=[O:25])=[CH:20][C:19]=1[F:42].C1C(N=NC2C(=O)N(C3C=CC(S([O-])(=O)=O)=CC=3)N=C2C([O-])=O)=CC=C(S([O-])(=O)=O)C=1.[Na+].[Na+].[Na+]>ClCCl>[Cl:41][C:38]1[CH:39]=[CH:40][C:27]2[N:26]([C:24]([C:21]3[CH:22]=[CH:23][C:18]([CH2:17][NH:16][C:10](=[O:13])[CH2:11][CH3:12])=[C:19]([F:42])[CH:20]=3)=[O:25])[CH2:35][C:34]3[CH:33]=[N:32][N:31]([CH3:36])[C:30]=3[NH:29][C:28]=2[CH:37]=1

Participants

6

Reactant 4

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 164825Tartrazine2×HCID 136346648(4-Aminomethyl-3-fluoro-phenyl)-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Hydrochloride

Product 1

HCID 135736058N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-propionamideYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIEA (0.27 ml, 1.56 mmol) and propionyl chloride (0.048 ml, 0.55 mmol) were added to a solution of (4-aminomethyl-3-fluoro-phenyl)-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride from Example E102.2 (220 mg, 0.52 mmol) in dichloromethane (6 ml) at room temperature. The mixture was stirred for 2 h, 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 powder identified as the title compound (129 mg, 56%).

Workup

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

Sources & evidence

ORD record
ord-0552e0f9143141ccb789dd7f56509a01
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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