HCID 14901692, compound → HCID 71735151, compound

HRID 717079Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH3:15])=[C:4]([CH:12]=[CH:13][CH:14]=1)[C:5]([N:7]([CH2:10][CH3:11])CC)=[O:6].[Li]CCCC.C(C1[CH:39]=[CH:38][C:26]([C:27]([NH:29][CH2:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[O:28])=[CH:25][CH:24]=1)#N>C1COCC1>[Cl:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:4]2[C:3]=1[CH:15]=[C:10]([C:11]1[CH:39]=[CH:38][C:26]([C:27]([NH:29][CH2:30][CH:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[O:28])=[CH:25][CH:24]=1)[NH:7][C:5]2=[O:6]

Participants

Conditions

Temperature: -78 °C

Procedure

3-Chloro-N,N-diethyl-2-methyl-benzamide (150 mg, 0.66 mmol) was dissolved in anhydrous THF (2 mL) under N2 and cooled to −78° C. n-BuLi (2.5M in n-hexanes, 558 μL, 1.39 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 30 minutes. 4-Cyano-N-(1-methyl-piperidin-4-ylmethyl)-benzamide (180 mg, 0.66 mmol) in anhydrous THF (2 mL) was added dropwise to the reaction mixture and stirred at −78° C. continued for 1 h. The reaction mixture was poured into ice/water, allowed to warm to RT and extracted with CH2Cl2 (×3) and the organic phase dried (MgSO4). The solution was filtered and concentrated in vacuo. The crude material was purified by reverse phase preparative HPLC-MS to afford 4-(5-chloro-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(1-methyl-piperidin-4-ylmethyl)-benzamide as a white solid (37 mg, 13%).

Workup

additionwas added dropwise
stirringstirred at −78° C.
waitcontinued for 1 h
temperatureto warm to RT
extractionextracted with CH2Cl2 (×3)
dry with materialthe organic phase dried (MgSO4)
filtrationThe solution was filtered
concentrationconcentrated in vacuo
customThe crude material was purified by reverse phase preparative HPLC-MS

Sources & evidence

ORD record: ord-cf924d25813e4e2da0a4834f9aca1324
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193689B2

Reaction notes

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