1,1'-Carbonyldiimidazole → AR-A000002

HRID 2187485Notes

Reaction equation

HRID 2187485 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:28][C@@H:29]1[CH2:38][CH2:37][C:36]2[C:31](=[C:32]([N:40]3[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]3)[CH:33]=[CH:34][C:35]=2[CH3:39])[CH2:30]1>CN(C)C=O>[NH3:4].[CH3:39][C:35]1[CH:34]=[CH:33][C:32]([N:40]2[CH2:41][CH2:42][N:43]([CH3:46])[CH2:44][CH2:45]2)=[C:31]2[C:36]=1[CH2:37][CH2:38][C@@H:29]([NH:28][C:11](=[O:13])[C:10]1[CH:9]=[CH:8][C:7]([N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[CH:15][CH:14]=1)[CH2:30]2

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 3452784-(Morpholin-4-yl)benzoic acidHCID 53918832(2R)-5-Methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine

Product 2

HCID 222AmmoniaHCID 9846516AR-A000002Yield 146.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

4-Morpholinobenzoic acid (92 mg, 0.44 mmol) was dissolved in dry N,N-dimethylformamide (2 mL) and flushed with nitrogen. To the solution was added 1,1′-carbonyldiimidazole (76 mg, 0.47 mmol) and the reaction mixture was stirred at 75° C. for 1.5 h. The solution was cooled to room temperature and (R)-2-amino-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene (110 mg, 0.42 mmol), dissolved in dry N,N-dimethylformamide (2 mL) was added. The solution was stirred at room temperature for 30 h. The solvent was evaporated in vacuo giving 290 mg of a crude product. Purification by preparative TLC on silica gel using chloroform/methanol/conc. NH3 (95:5:0.5) as the eluent afforded 145 mg (73% yield) of the title compound as a white solid: mp >231° C. (dec); EIMS (70 eV) m/z (relative intensity) 448 (3, M+); [α]21D−60° (c 0.15, chloroform).

Workup

  1. customflushed with nitrogen
  2. temperatureThe solution was cooled to room temperature
  3. additionwas added
  4. stirringThe solution was stirred at room temperature for 30 h
  5. customThe solvent was evaporated in vacuo
  6. customgiving 290 mg of a crude product
  7. customPurification by preparative TLC on silica gel

Sources & evidence

ORD record
ord-2040669338fc40bf9f36a76e4e978d9f
Source dataset
uspto-grants-2002_06
Patent number
US06410532B1

Reaction notes

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