Triethylamine → N-{[1-(4-Bromobenzyl)pyrrolidin-3-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

HRID 2066834Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:27]([CH3:29])[CH3:28])[C:6]2[O:10][C:9]([C:11]3[CH:25]=[CH:24][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:23][CH2:22][NH:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:26]=1)#[N:2].C(N(CC)CC)C.[Br:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44]Br)=[CH:40][CH:39]=1>CO>[Br:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44][N:21]2[CH2:22][CH2:23][CH:19]([CH2:18][NH:17][C:15](=[O:16])[C:14]3[CH:13]=[CH:12][C:11]([C:9]4[O:10][C:6]5[C:5]([CH:27]([CH3:29])[CH3:28])=[CH:4][C:3]([C:1]#[N:2])=[CH:26][C:7]=5[N:8]=4)=[CH:25][CH:24]=3)[CH2:20]2)=[CH:40][CH:39]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(pyrrolidin-3-ylmethyl)benzamide (78 mg) in 2 ml of methanol was added 558 μl of triethylamine and 50 mg of 1-bromo-4-(bromomethyl)benzene. The solution was heated to 150° C. via microwave for 30 min, cooled, and purified via column chromatography on a Biotage Horizon 40M column eluting with 1 column volume of 100% hexanes, followed by a gradient of 0 to 100% ethyl acetate in hexanes over 10 column volumes, followed by 6 column volumes at 100% ethyl acetate to provide the title compound (75 mg, 68%). Mass spectrum (ESI) 559.0 (M+2). 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=8.5 Hz, 2H), 7.96 (s, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.52 (s, 1H), 7.42 (d, J=8.2 Hz, 2H), 7.16 (d, J=8.2 Hz, 2H), 3.52 (m, 3H), 2.98 (td, J=9.1, 2.9, 1H), 2.76 (d, J=9.6 Hz, 1H), 2.58 (m, 2H), 2.32 (m, 1H), 2.14 (m, 1H), 1.68 (m, 1H), 1.48 (d, J=6.8 Hz, 6H).

Workup

temperaturecooled
custompurified via column chromatography on a Biotage Horizon 40M column
washeluting with 1 column volume of 100% hexanes

Sources & evidence

ORD record: ord-9838d8d136c44174b5ac932eea718275
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293721B2

Reaction notes

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