Ethanolamine → 2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo [b][1,4]diazepin-2-yl]-phenyl}-4-methyl-thiazole-5-carboxylic Acid (2-hydroxy-ethyl)-amide

HRID 1745789Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:28]=[CH:27][C:11]3[N:12]=[C:13]([C:18]4[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=4)[C:21]([NH2:23])=[S:22])[CH2:14][C:15](=[O:17])[NH:16][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.Cl[CH2:30][C:31](=O)[CH2:32][C:33]([O:35]CC)=O.[NH2:39][CH2:40][CH2:41][OH:42]>C(O)C>[OH:42][CH2:41][CH2:40][NH:39][C:33]([C:32]1[S:22][C:21]([C:20]2[CH:24]=[CH:25][CH:26]=[C:18]([C:13]3[CH2:14][C:15](=[O:17])[NH:16][C:10]4[CH:9]=[C:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH:28]=[CH:27][C:11]=4[N:12]=3)[CH:19]=2)=[N:23][C:31]=1[CH3:30])=[O:35]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture 3-[7-(4-fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamide (Example 149) (78 mg, 0.2 mmol) and ethyl 4-chloro-3-oxo-butanoate (164 mg, 1.0 mmol) in ethanol (4 mL) was heated at reflux for 24 h. The solution was cooled to 0° C. and stirred for 0.5 h. The crystals were isolated by filtration and subsequently suspended in 2-amino-ethanol (4 mL). The mixture was stirred at 70° C. for 4 h, cooled to 23° C., and partitioned between ethyl acetate and H2O. The organic layer was dried over Na2SO4 and evaporated in vacuum and the residue was triturated with ethyl acetate to give the title compound as light yellow solid (37 mg).

Workup

temperatureat reflux for 24 h
customThe crystals were isolated by filtration
stirringThe mixture was stirred at 70° C. for 4 h
temperaturecooled to 23° C.
custompartitioned between ethyl acetate and H2O
dry with materialThe organic layer was dried over Na2SO4
customevaporated in vacuum
customthe residue was triturated with ethyl acetate

Sources & evidence

ORD record: ord-aa7fd9668a6a4818bdc9e6be4ae653ef
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07018998B2

Reaction notes

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