Sodium Azide → N-cyclopropyl-4-{6-[(E)-(1-methyl-5-oxopyrrolidin-2-ylidene)methyl]-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}benzamide

HRID 925601Notes

Reaction equation

[CH:1]1([NH:4][C:5](=[O:34])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:16]4[CH:17]=[C:18]([C:26]#[C:27][CH2:28][CH2:29][C:30]([NH:32][CH3:33])=[O:31])[N:19]=[C:20]([NH:21][CH2:22][CH:23]([CH3:25])[CH3:24])[C:15]4=[N:14][CH:13]=3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[N-]=[N+]=[N-].[Na+]>CN1C(=O)CCC1.[Cu]I>[CH:1]1([NH:4][C:5](=[O:34])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:16]4[CH:17]=[C:18](/[CH:26]=[C:27]5/[N:32]([CH3:33])[C:30](=[O:31])[CH2:29][CH2:28]/5)[N:19]=[C:20]([NH:21][CH2:22][CH:23]([CH3:24])[CH3:25])[C:15]4=[N:14][CH:13]=3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 23 mg (0.05 mmol) N-cyclopropyl-4-{6-[5-(methylamino)-5-oxopent-1-yn-1-yl]-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}benzamide in 1.00 mL NMP were added 6.5 mg (0.1 mmol) sodium azide and 0.5 mg (0.003 mmol) copper(I)iodide and the mixture was heated at 160° C. for 30 min in a microwave tube. The mixture was filtered and purified by HPLC to yield 4.3 mg (19%) of the title compound. UPLC-MS: RT=1.08 min; m/z (ES+) 459.6 [MH+]; required MW=458.6. 1H-NMR (300 MHz, CDCl3): δ=7.91 (2H, d), 7.59 (4H, m), 7.39 (1H, s), 6.31 (1H, tr), 6.28 (1H, s), 3.45 (1H, m), 3.40 (2H, t), 2.95 (1H, m), 2.82 (3H, s), 2.56 (1H, m), 2.33 (1H, s), 2.05 (1H, m), 1.95 (1H, m), 1.05 (6H, d), 0.92 (2H, m), 0.66 (2H, m) ppm.

Workup

filtrationThe mixture was filtered
custompurified by HPLC

Sources & evidence

ORD record: ord-c9562beb1abf4634ae761b3393ec26a0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284317B2

Reaction notes

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