2-Bromobenzonitrile → 7-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,1'-isoindol]-3'-amine

HRID 1409505Notes

Reaction equation

C([Li])CCC.Br[C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[C:9]#[N:10].[Br:15][C:16]1[CH:17]=[C:18]2[C:29](=[CH:30][CH:31]=1)[O:28][C:21]1[C:22]([F:27])=[N:23][C:24]([Cl:26])=[CH:25][C:20]=1[C:19]2=[N:32]S(C(C)(C)C)=O>C1COCC1>[Br:15][C:16]1[CH:17]=[C:18]2[C:19]3([C:11]4[C:8](=[CH:7][CH:14]=[CH:13][CH:12]=4)[C:9]([NH2:10])=[N:32]3)[C:20]3[CH:25]=[C:24]([Cl:26])[N:23]=[C:22]([F:27])[C:21]=3[O:28][C:29]2=[CH:30][CH:31]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of n-butyllithium (1.6 M in hexane, 0.75 mL, 1.2 mmol, Aldrich) was added dropwise to a solution of 2-bromobenzonitrile (219 mg, 1.2 mmol, Oakwood Products) in THF (30 mL) at −78° C. under nitrogen atmosphere. The reaction mixture was allowed to stir for 5 min at −78° C. Subsequently, a solution of N-(7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-ylidene)-2-methylpropane-2-sulfinamide (400 mg, 0.93 mmol, step 1) in THF (30 mL) was added. After 5 min, the reaction mixture was quenched with aqueous, saturated solution of NH4Cl and EtOAc was added. The organic phase was separated and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (55-100% EtOAc/hexanes) to afford the title compound as a yellow solid. MS m/z=431.9 [M+H]+. Calculated for C19H10BrClFN3O: 430.7.

Workup

waitAfter 5 min
customthe reaction mixture was quenched with aqueous, saturated solution of NH4Cl and EtOAc
additionwas added
customThe organic phase was separated
dry with materialdried over MgSO4
customThe solvent was removed under reduced pressure
customthe residue was purified by flash chromatography on silica gel (55-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-4e5bfd54534643e4acde9c0ea850b394
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921363B2

Reaction notes

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