1-Methylpiperazine → HCID 69318372, compound

HRID 2053750Notes

Reaction equation

HRID 2053750 reaction equation
[CH3:1][C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]=1[C:8]1[CH:32]=[CH:31][C:11]([C:12]([N:14]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[CH2:18][N:17]3[C:25]([C:28]([OH:30])=O)=[CH:26][CH:27]=[C:16]3[CH2:15]2)=[O:13])=[CH:10][CH:9]=1.C(Cl)(=O)C(Cl)=O.[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C(N(CC)C(C)C)(C)C>ClCCl.C(OCC)(=O)C.CN(C)C=O>[CH3:1][C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]([C:12]([N:14]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[CH2:18][N:17]3[C:25]([C:28]([N:43]4[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]4)=[O:30])=[CH:26][CH:27]=[C:16]3[CH2:15]2)=[O:13])=[CH:31][CH:32]=1

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 69313753HCID 69313753, compound

Product 1

HCID 69318372HCID 69318372, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

10-[4-(2-Methyl-cyclohex-1-enyl)-benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step F (0.0510 g, 0.120 mmol) and oxalyl chloride (0.011mL, 0.126 mmol) were combined in anhydrous dichloromethane (1.2 mL) followed by dropwise addition of N,N-dimethylformamide (0.0003 mL, 0.0036 mmol). The reaction was refluxed for 3 hours, then the solvent was removed and the residue dried in vacuo. The crude acid chloride thus prepared was combined with N-methylpiperazine (0.0146 mL, 0.132 mmol) and N,N-diisopropylethyl amine (0.025 mL, 0.144 mmol) in anhydrous dichloromethane (1.2 mL). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with 5% methanol in chloroform to afford the title compound (0.025 g) as a white solid from a mixture of diethyl ether and hexane,

Workup

  1. temperatureThe reaction was refluxed for 3 hours
  2. customthe solvent was removed
  3. customthe residue dried in vacuo
  4. customThe crude acid chloride thus prepared
  5. washwashed with saturated sodium bicarbonate and brine
  6. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography on silica gel
  10. washeluting with 5% methanol in chloroform

Sources & evidence

ORD record
ord-b6df985e65a84f64bc5977e5b24d5dd9
Source dataset
uspto-grants-2008_02
Patent number
US07326700B2

Reaction notes

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