Dimethylformamide → HCID 178461890, compound

HRID 1397691Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[C:8]([C@@H:18]([NH:20][C:21]1[N:29]=[CH:28][N:27]=[C:26]3[C:22]=1[N:23]=[CH:24][NH:25]3)[CH3:19])=[CH:7]2.[CH3:30][N:31](C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[C-]#N.[Zn+2]>[N:29]1[C:21]([NH:20][C@H:18]([C:8]2[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:10][C:11]3[C:6]([CH:7]=2)=[CH:5][CH:4]=[CH:3][C:2]=3[C:30]#[N:31])[CH3:19])=[C:22]2[C:26]([NH:25][CH:24]=[N:23]2)=[N:27][CH:28]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of N—((S)-1-(8-chloro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (80 mg, 0.2 mmol), Pd(PPh3)4 (23 mg, 0.1 eq) and Zn(CN)2 (117 mg, 5.0 eq) in DMF (5 mL) was purged with N2 for 5 min before heating to 130° C. After 3 h, LCMS showed formation of trace amount of 2. The reaction was then heated to 165° C. over night. After cool to rt, the reaction was filtered through Celite™ and purified by reverse HPLC (MeCN/H2O, 0.1% TFA) to give a white solid. 1H-NMR (400 Hz, DMSO-d6) δ 8.83 (s, 1H), 8.72 (s, 1H), 8.52 (s, 1H), 8.42-8.37 (m, 3H), 8.14 (d, J=8.0 Hz, 1H), 8.08 (t, J=8.0 Hz, 1H), 7.79 (t, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 6.24 (s, 1H), 1.72 (d, J=8.0 Hz, 3H). Mass Spectrum (ESD m/e=393 (M+1).

Workup

customwas purged with N2 for 5 min
temperatureThe reaction was then heated to 165° C. over night
temperatureAfter cool to rt
filtrationthe reaction was filtered through Celite™
custompurified by reverse HPLC (MeCN/H2O, 0.1% TFA)
customto give a white solid

Sources & evidence

ORD record: ord-2a3b65e57b864a7f865116084a3cb6eb
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901135B2

Reaction notes

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