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

HRID 220970Notes

Reaction equation

HRID 220970 reaction equation
[C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].Cl.[NH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([N:18]2[CH2:27][C:26]3[CH:25]=[N:24][N:23]([CH3:28])[C:22]=3[NH:21][C:20]3[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:19]2=3)=[O:17])=[CH:12][C:11]=1[Cl:34].CC1C=C2N=C3C(=NC(NC3=O)=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(O)=O)C2=CC=1C.[Na+]>ClCCl.C(N(CC)CC)C.CCOC(C)=O>[Cl:34][C:11]1[CH:12]=[C:13]([C:16]([N:18]2[CH2:27][C:26]3[CH:25]=[N:24][N:23]([CH3:28])[C:22]=3[NH:21][C:20]3[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:19]2=3)=[O:17])[CH:14]=[CH:15][C:10]=1[CH2:9][NH:8][C:1](=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

7

Reactant 3

HCID 62325Isobutyryl chlorideHCID 23666409Riboflavin sodium phosphate2×HCID 136346649(4-Aminomethyl-3-chloro-phenyl)-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Hydrochloride

Product 1

HCID 135736064N-[2-Chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-isobutyramideYield 40%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Isobutyryl chloride (46 mg, 0.4 mmol) was added to a solution of (4-aminomethyl-3-chloro-phenyl)-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride from Example E106.2 (161 mg, 0.4 mmol) in dichloromethane (10 ml) and triethylamine (to pH9) at room temperature. The mixture was stirred for 18 h, diluted with EtOAc, 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 (75 mg, 40%).

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 solid

Sources & evidence

ORD record
ord-da4075677e194c8bbf4a635746eef687
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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