Iodine → 4-(5-fluoro-2-methoxyphenyl)-2-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 1522008Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:27][CH3:28])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[N:14]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:15]=[C:16]([C:17]#[N:18])[C:9]=23)[CH:7]=1.C([N-]C(C)C)(C)C.[Li+].[I:37]I>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:27][CH3:28])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[N:14]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:26])[CH3:25])[C:15]([I:37])=[C:16]([C:17]#[N:18])[C:9]=23)[CH:7]=1

Participants

Conditions

Temperature: -75 °C

Procedure

A solution of Example 248B (0.7 g, 1.76 mmol) in tetrahydrofuran (50 mL) was cooled to −75° C. and treated dropwise with 2N lithium diisopropylamide in tetrahydrofuran (1.7 mL, 3.40 mmol). The mixture was stirred at −75° C. for 30 minutes and iodine (0.85 g, 3.52 mmol) in 2.5 mL tetrahydrofuran was added. The mixture was slowly brought to room temperature and quenched with aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (twice). The organic layers were concentrated and purified by column chromatography (Combi Flash Rf) (silica gel, 30% ethyl acetate in hexane) to afford the title compound. MS (ESI+) m/z 524 (M+H)+.

Workup

customwas slowly brought to room temperature
customquenched with aqueous ammonium chloride (100 mL)
extractionextracted with ethyl acetate (twice)
concentrationThe organic layers were concentrated
custompurified by column chromatography (Combi Flash Rf) (silica gel, 30% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-cb38fa9446e24e90a1338f83bad414b5
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073922B2

Reaction notes

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