Cesium fluoride → 2-(((2S,3R)-1-(2-Fluoro-6-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

HRID 61195Notes

Reaction equation

[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25](I)[C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([CH3:12])[C@H:7]1[CH2:13][N:14]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]1=[O:24])=[O:5].C([Sn](CCCC)(CCCC)[C:35]1[N:40]=[CH:39][CH:38]=[CH:37][N:36]=1)CCC.[F-].[Cs+]>CN(C=O)C.[Cu]I.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>[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([C:35]2[N:40]=[CH:39][CH:38]=[CH:37][N:36]=2)[C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([CH3:12])[C@H:7]1[CH2:13][N:14]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]1=[O:24])=[O:5]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-(((2S,3R)-1-(2-fluoro-6-iodobenzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione (0.6 g, 1.185 mmol), 2-(tributylstannyl)pyrimidine (0.437 g, 1.185 mmol), CsF (0.36 g, 2.37 mmol), CuI (0.023 g, 0.119 mmol) and Pd(PPh3)4 (0.14 g, 0.119 mmol) in DMF (5 mL) was degassed and heated at 100° C. for 16 h. The solvent was removed in vacuo to obtain the crude which was purified by silica gel chromatography (0˜100% EtOAc/hexanes) to yield the title compound as a white solid. MS (ESI) 459 (M+H).

Workup

customwas degassed
customThe solvent was removed in vacuo
customto obtain the crude which
customwas purified by silica gel chromatography (0˜100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-77b5c0b57b524353a8b81e99afa17583
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440982B2

Reaction notes

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