N,N,N',N'-Tetramethylethylenediamine → [2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-thiazol-4-yl-methanol

HRID 746614Notes

Reaction equation

Br[C:2]1[C:3]2[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=2[S:5][C:6]=1[CH2:7][CH2:8][N:9]([CH3:11])[CH3:10].CN(CCN(C)C)C.[Li]CCCC.[S:29]1[CH:33]=[C:32]([CH:34]=[O:35])[N:31]=[CH:30]1>C1(C)C=CC=CC=1.ClCCl>[CH3:10][N:9]([CH3:11])[CH2:8][CH2:7][C:6]1[S:5][C:4]2[CH:12]=[CH:13][CH:14]=[CH:15][C:3]=2[C:2]=1[CH:34]([C:32]1[N:31]=[CH:30][S:29][CH:33]=1)[OH:35]

Participants

Conditions

Temperature: -78 °C

Procedure

To a cooled (−78° C.) solution of [2-(3-bromo-benzo[b]thiophen-2-yl)-ethyl]-dimethyl-amine (200 mg, 0.7 mmol) in anhydrous toluene (8 mL), TMEDA (110 uL, 0.7 mmol) was added followed by nBuLi (0.47 mL, 0.75 mmol, 1.6M in hexanes). The mixture was stirred for 40 min at −78° C. and a solution of thiazole-4-carbaldehyde (0.32 g, 2.8 mmol) in dichloromethane (1 mL) was added. The mixture was stirred for 16 hrs during which the temperature reached room temperature. The reaction was quenched with water, the resulting mixture was basified by the addition of NH4OH and extracted with EtOAc. The combined organic layers were concentrated and subjected to mass triggered preparative HPLC to afford [2-(2-dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-thiazol-4-yl-methanol (Compound 14-1) (200 mg). MH+=318.8.

Workup

additionwas added
stirringThe mixture was stirred for 16 hrs during which the temperature
customreached room temperature
customThe reaction was quenched with water
additionthe resulting mixture was basified by the addition of NH4OH
extractionextracted with EtOAc
concentrationThe combined organic layers were concentrated

Sources & evidence

ORD record: ord-83c5772ecd16421aa16fecfe741b0bd7
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07393865B2

Reaction notes

Loading…