3'-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile → 3'-[7-(Tert-butyldimethylsilanyloxymethyl)imidazo[1,2-a]pyrimidin-3-yl]biphenyl-2-carbonitrile
Reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([CH2:11][O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[N:10][C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([C:34]3[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:31]=[CH:32][CH:33]=2)O1>>[Si:13]([O:12][CH2:11][C:9]1[CH:8]=[CH:7][N:6]2[C:2]([C:32]3[CH:31]=[C:30]([C:34]4[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH:29]=[CH:28][CH:33]=3)=[CH:3][N:4]=[C:5]2[N:10]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]Participants
Procedure
3-Bromo-7-(tert-butyldimethylsilanyloxymethyl)imidazo[1,2-a]pyrimidine (1.37 g, 4.00 mmol) was coupled with 3′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile as described in Example 1 to give 3′-[7-(tert-butyldimethylsilanyloxymethyl)imidazo[1,2-a]pyrimidin-3-yl]biphenyl-2-carbonitrile as a yellow solid. This solid was suspended in methanol (25 ml) and treated with conc. hydrochloric acid (1 ml) and left to stir at ambient temperature for 5 min. The solution was loaded onto a cartridge of strong cation-exchange resin, eluting with methanol then with 10% conc. ammonia in methanol. The basic fractions were concentrated in vacuo and the residue purified further by chromatography on silica gel. Elution with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (2-5%) afforded 3′-(7-hydroxymethylimidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile (587 mg, 45%) as a yellow powder: δH (400 MHz, CDCl3) 1.90 (1H, s), 4.88 (2H, s), 6.91 (1H, d, J 7), 7.51 (1H, td, J 8 and 1), 7.57-7.73 (5H, m), 7.77 (1H, dd, J 1 and 1), 7.82 (1H, dd, J 8 and 1), 7.89 (1H, s), 8.94 (1H, d, J 7); m/z (ES+) 327 (M++H).
Sources & evidence
- ORD record
- ord-d64a9cd118f94f74abfbc929ce86fb89
- Source dataset
- uspto-grants-2003_11
- Patent number
- US06642229B2
Reaction notes
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