Benzothiazole → 4-(Benzo[d]thiazol-2-yl(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104948Notes

Reaction equation

[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Li]CCCC.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([O:35][CH:36]([CH3:38])[CH3:37])[C:21]([F:34])=[C:22]([CH:33]=1)/[CH:23]=[N:24]/[C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1)[CH3:16]>C1COCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:24]([CH2:23][C:22]1[CH:33]=[C:18]([O:17][CH2:15][CH3:16])[CH:19]=[C:20]([O:35][CH:36]([CH3:38])[CH3:37])[C:21]=1[F:34])[C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of benzothiazole (61.9 mg, 0.458 mmol) in 2 mL THF at −78° C. was added 1.6 M solution of BuLi in THF (315 μL, 0.504 mmol). The mixture was stirred at −78° C. for 45 min, then a solution of Intermediate 7.3 (149 mg, 0.458 mmol) in 0.5 mL THF was added dropwise. The mixture was stirred and allowed to warm to rt overnight, 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 50% EtOAc/hexanes gradient) to afford 90 mg of Intermediate 7.4 as a white solid.

Workup

stirringThe mixture was stirred
temperatureto warm to rt overnight
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 50% EtOAc/hexanes gradient)

Sources & evidence

ORD record: ord-5b91879fcf2842bc87e613742167ebbb
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576098B2

Reaction notes

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