(2,4-Dimethoxypyrimidin-5-yl)boronic acid → 4-[5-(3-Chloro-2-fluoro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-6-yl]-benzonitrile

HRID 2204365Notes

Reaction equation

Br[C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]2[CH:10]([C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=3)[N:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=3[F:21])[C:12](=[O:13])[C:4]=2[CH:3]=1.[CH3:30][O:31][C:32]1[N:37]=[C:36]([O:38][CH3:39])[C:35](B(O)O)=[CH:34][N:33]=1.BrC1N(C(C)C)C2C(C3C=CC(Cl)=CC=3)N(C3C=C(Cl)C=CC=3C)C(=O)C=2C=1.C(C1C=CC(OC)=C(B(O)O)C=1)#N>>[Cl:20][C:16]1[C:15]([F:21])=[C:14]([N:11]2[C:12](=[O:13])[C:4]3[CH:3]=[C:2]([C:35]4[C:36]([O:38][CH3:39])=[N:37][C:32]([O:31][CH3:30])=[N:33][CH:34]=4)[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]=3[CH:10]2[C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[CH:19]=[CH:18][CH:17]=1

Participants

Reactant 4

HCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acid

HCID 23005336(5-Cyano-2-Methoxyphenyl)Boronic Acid

HCID 867031692-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

HCID 867031704-[2-Bromo-5-(3-chloro-2-fluoro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-6-yl]-benzonitrile2×

Product 1

HCID 722040334-[5-(3-Chloro-2-fluoro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-6-yl]-benzonitrile

Procedure

The title compound was prepared in analogy to the procedure described for Example 17 but 4-[2-bromo-5-(3-chloro-2-fluoro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-6-yl]-benzonitrile (Intermediate I) and 2,4-dimethoxypyrimidine-5-boronic acid were used instead of 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one and 5-cyano-2-methoxyphenylboronic acid respectively. The reaction was performed at 75° C. for 2 h and the product was purified by flash chromatography. The title compound was obtained as a white solid. tR=5.27 min (HPLC 4); ESI-MS: tR=1.13 min, [M+H]+ 532/534 (LC-MS 1); 1H-NMR (d6-DMSO, 600 MHz): 8.31 (s, 1H), 7.82 (m, 2H), 7.47 (m, 2H), 7.39-7.46 (m, 2H), 7.18 (m, 1H), 6.51 (s, 1H), 6.40 (s, 1H), 3.95 (m, 1H), 3.94 (s, 3H), 3.90 (s, 3H), 1.31 (m, 3H), 0.43 (m, 3H).

Workup

customThe title compound was prepared in analogy to the procedure
customthe product was purified by flash chromatography

Sources & evidence

ORD record: ord-c299a545e7274785b3387c19b032cdff
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365576B2

Reaction notes

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