2,4-Dibromo-1,3-thiazole → 4-((4-Bromothiazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104957Notes

Reaction equation

Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1.[Li]CCCC.[CH2:13]([O:15][C:16]1[CH:17]=[C:18]([O:33][CH:34]([CH3:36])[CH3:35])[C:19]([F:32])=[C:20]([CH:31]=1)/[CH:21]=[N:22]/[C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1)[CH3:14]>C1COCC1>[Br:7][C:5]1[N:6]=[C:2]([N:22]([CH2:21][C:20]2[CH:31]=[C:16]([O:15][CH2:13][CH3:14])[CH:17]=[C:18]([O:33][CH:34]([CH3:36])[CH3:35])[C:19]=2[F:32])[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[S:3][CH:4]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2,4-dibromothiazole (100 mg, 0.412 mmol) in 2 mL THF was added BuLi (1.6 M in THF, 283 μL, 0.453 mmol). The mixture was stirred at −78° C. for 15 min, then a solution of Intermediate 7.3 (134 mg, 0.412 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at −78° C. for 30 min, was allowed to warm to rt, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient) followed by preparative HPLC purification to afford 39 mg of Intermediate 16.1.

Workup

stirringThe mixture was stirred at −78° C. for 30 min
temperatureto warm to rt
customwas quenched with sat. NH4Cl
additionThe mixture was diluted with EtOAc
washwashed with H2O and brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)
customfollowed by preparative HPLC purification

Sources & evidence

ORD record: ord-09466bdbd88546ce8cb51f4629933834
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576098B2

Reaction notes

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