4-Bromobenzyl bromide → 10a-(4-Bromo-benzyl)-2-(3,5-dichloro-phenyl)-10,10a-dihydro-5H-imidazo[1,5-b]isoquinoline-1,3-dione

HRID 49987

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:21](=[O:22])[C@H:20]3[N:11]([CH2:12][C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[CH2:19]3)[C:10]2=[O:23])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Br:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1>C1COCC1>[Br:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][C:20]23[C:21](=[O:22])[N:9]([C:4]4[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=4)[C:10](=[O:23])[N:11]2[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[CH2:19]3)=[CH:27][CH:26]=1

Participants

Conditions

Temperature: -40 °C

Procedure

To a solution of (S)-2-(3,5-dichloro-phenyl)-10,10a-dihydro-5H-imidazo[1,5-b]isoquinoline-1,3-dione (100 mg) (0.1 mmol) (Prep. 22) in 2.5 mL of dry THF at −40° C. was added a 1 M solution of LIHMDS (0.5 mL) in THF. The reaction mixture was stirred for 15 min. at −40° C. and a solution of 4-bromobenzyl bromide (70 mg) in 1 mL of dry THF was added. The reaction mixture was stirred at −50 C. for 30 min., allowed to warm to RT, stirred overnight, then partitioned between brine and t-Bu methyl ether. The organic layer was dried over MgSO4, concentrated in vacuo, and the residue purified by HPLC to afford the above compound (34.5 mg). NMR (CDCl3, 200 MHz): 7.45 (2H, d), 7.25-7.35 (5H, m), 6.95-7.0 (4H, d+d), 5.15 (1H, d), 4.55 (1H, d), 3.25 (2H, s), 3.20 (1H, d), 2.95 (1H, d).

Workup

stirringThe reaction mixture was stirred at −50 C
waitfor 30 min.
temperatureto warm to RT
stirringstirred overnight
custompartitioned between brine and t-Bu methyl ether
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated in vacuo
customthe residue purified by HPLC

Sources & evidence

ORD record: ord-64015ac834f4426b8fbd73cf920b04bf
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06710064B2

Linked notes

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