1,1'-Carbonyldiimidazole → (S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-4-(4-benzylpiperazin-1-yl)benzamide

HRID 433912Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:35][C@H:36]1[CH2:41][C:40]2[C:42]([N:46]3[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]3)=[CH:43][CH:44]=[CH:45][C:39]=2[O:38][CH2:37]1>CN(C)C=O>[CH3:52][N:49]1[CH2:50][CH2:51][N:46]([C:42]2[C:40]3[CH2:41][C@H:36]([NH:35][C:18](=[O:19])[C:17]4[CH:21]=[CH:22][C:14]([N:11]5[CH2:10][CH2:9][N:8]([CH2:1][C:2]6[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=6)[CH2:13][CH2:12]5)=[CH:15][CH:16]=4)[CH2:37][O:38][C:39]=3[CH:45]=[CH:44][CH:43]=2)[CH2:47][CH2:48]1

Participants

Conditions

Temperature: 75 °C

Procedure

A suspension of 4-(4-benzylpiperazin-1-yl)benzoic acid (1.3 g, 4.2 mmol) and 1,1′-carbonyldiimidazole (740 mg, 4.2 mmol) in N,N-dimethylformamide (30 mL) was heated to 75° C. for 1.5 h. The reaction mixture was cooled to 50° C. and a solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4 dihydro-2H-1-benzopyran (1.0 g, 4.0 mmol) was added. The solution was stirred at 50° C. for 20 h and the solvent was evaporated in vacuo giving 3.5 g of a crude product. Purification by chromatography on a silica gel column using chloroform/methanol/concentrated ammonia 95:5:0.5 as the eluent gave 1.7 g (80% yield) 25 of the title compound as a pale yellow solid: mp sinters >85° C.; TSPMS m/z (relative intensity) 526 (100, M+1); [α]22D−130° (c 1.0, chloroform).

Workup

temperatureThe reaction mixture was cooled to 50° C.
customthe solvent was evaporated in vacuo
customgiving 3.5 g of a crude product
customPurification by chromatography on a silica gel column

Sources & evidence

ORD record: ord-4351a17e260f4dd2bf30487296a82509
Source dataset: uspto-grants-2003_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06670359B2

Reaction notes

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