Allyltributylstannane → 3-({6-chloro-2-fluoro-3-[(6-oxo-6,7-dihydro-1H-purin-1-yl)methyl]phenyl}oxy)-5-(2-propen-1-yl)benzonitrile

HRID 1875248Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([CH2:18][N:19]3[C:27](=[O:28])[C:26]4[NH:25][CH:24]=[N:23][C:22]=4[N:21]=[CH:20]3)[C:12]=2[F:29])[CH:9]=1)[C:5]#[N:6].[CH2:30]([Sn](CCCC)(CCCC)CCCC)[CH:31]=[CH2:32]>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>[Cl:17][C:16]1[C:11]([O:10][C:8]2[CH:7]=[C:4]([CH:3]=[C:2]([CH2:32][CH:31]=[CH2:30])[CH:9]=2)[C:5]#[N:6])=[C:12]([F:29])[C:13]([CH2:18][N:19]2[C:27](=[O:28])[C:26]3[NH:25][CH:24]=[N:23][C:22]=3[N:21]=[CH:20]2)=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 3-bromo-5-({6-chloro-2-fluoro-3-[(6-oxo-6,7-dihydro-1H-purin-1-yl)methyl]phenyl}oxy)benzonitrile (78 mg, 0.164 mmol), allyltri-n-butyltin (0.082 ml, 0.263 mmol) and tetrakis(triphenylphosphine)palladium(0) (18.99 mg, 0.016 mmol) was heated in a personal microwave reactor at 160° C. for 20 min. The mixture was filtrated and was purified with reverse phase HPLC to afford a white solid 3-({6-chloro-2-fluoro-3-[(6-oxo-6,7-dihydro-1H-purin-1-yl)methyl]phenyl}oxy)-5-(2-propen-1-yl)benzonitrile (20 mg, 27.9% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.41 (s, 1H) 8.06-8.20 (m, 1H) 7.35-7.52 (m, 1H) 7.23-7.32 (m, 1H) 7.18 (s, 1H) 7.12 (s, 1H) 5.79-5.98 (m, 1H) 5.27 (s, 2H) 5.02 (s, 1H) 3.38 (d, 2H). LC-MS (ES+) m/z 435.50, [M+1].

Workup

filtrationThe mixture was filtrated
customwas purified with reverse phase HPLC

Sources & evidence

ORD record: ord-3a176f8a735e4f29bcf965c9dd99e7b2
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304419B2

Reaction notes

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