4-(Morpholin-4-yl)benzoic acid → AR-A000002

HRID 1274948Notes

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.[NH2:16][C@@H:17]1[CH2:26][CH2:25][C:24]2[C:19](=[C:20]([N:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)[CH:21]=[CH:22][C:23]=2[CH3:27])[CH2:18]1>CN(C)C=O>[NH3:4].[CH3:27][C:23]1[CH:22]=[CH:21][C:20]([N:28]2[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]2)=[C:19]2[C:24]=1[CH2:25][CH2:26][C@@H:17]([NH:16][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)[CH2:18]2

Participants

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

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

Sources & evidence

ORD record: ord-1a1f9205c8104570b96f24a785250dbc
Source dataset: uspto-grants-2000_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06159972

Reaction notes

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