Methyl Isocyanate → 4-[2-[4-(3-Bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-yl)-1-piperazinyl]-2-oxoethyl]-N-methyl-1-piperidinecarboxamide

HRID 47350Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:32])[CH2:25][CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH2:20][CH2:19]3)[C:5]2=[N:6][CH:7]=1.[CH3:33][N:34]=[C:35]=[O:36]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:19][CH2:20][N:21]([C:24](=[O:32])[CH2:25][CH:26]4[CH2:31][CH2:30][N:29]([C:35]([NH:34][CH3:33])=[O:36])[CH2:28][CH2:27]4)[CH2:22][CH2:23]3)[C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 25 °C

Procedure

1-(3-Bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-4-[(4-piperidinyl)acetyl]piperazine (Preparative Example 10) (500 mg, 0.9 mmoles) was dissolved in anhydrous dichloromethane (5 ml) and methyl isocyanate (220.3 mg, 3.6 mmoles) was added. The mixture was stirred under argon at 25° C. for 47 h. Additional methyl isocyanate (110.15 mg, 1.8 mmoles) was added and the reaction was stirred for a total of 144 h. The solution was heated at 74° C. for 5 h and the stirred at 25° C. for an additional 24 h. The solution was chromatographed on silica gel using 2% (10% conc. NH4OH in methanol)dichloromethane as the eluant to give 438.9 mg of the title compound (Yield: 79%).

Workup

stirringthe reaction was stirred for a total of 144 h
temperatureThe solution was heated at 74° C. for 5 h
stirringthe stirred at 25° C. for an additional 24 h
customThe solution was chromatographed on silica gel using 2% (10% conc. NH4OH in methanol)dichloromethane as the eluant

Sources & evidence

ORD record: ord-088a5fdd65324df1b490dea75610fb21
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06699872B2

Reaction notes

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