Compounds, compositions and methods for cancer treatment

A method of preparing compound 1, said method comprising the steps of

• reacting a compound of formula (IV)
• with pure morpholine at elevated temperatures, or with morpholine and a base, optionally in a polar aprotic solvent, at reflux temperature, to obtain Compound (V)
• which then is reacted with a strong base, in a polar aprotic solvent at low temperatures followed by addition of (C1-C4-alkyl)bromoacetate or (C1-C4-alkyl)chloroacetate neat or in a polar aprotic solvent,
• allowing the mixture to warm up from initial −78° C. to RT, optionally isolating the crude product, and then adding either hydrazine or hydrazine hydrate in a polar protic organic solvent under reflux temperature to obtain the racemic compound 1c
• and subsequently performing a separation of enantiomers of Compound 1c to obtain Compound 1 and Compound (1a)
• whereby optionally compound (1a) is converted into the racemic compound (1c) which could then be separated again in order to obtain Compound 1 and less of the initial amount of compound 1a isolated from the enantiomeric separation.

A method for the preparation of Compound 1 whereby compound (IV)

• is reacted with strong base in a polar aprotic solvent at low temperatures −78° to −60° C., followed by addition of (C1-C4-alkyl)bromoacetate or (C1-C4-alkyl)chloroacetate neat or in a polar aprotic solvent allowing the mixture to warm up from initial −78° C. to RT, optionally isolating the crude product, and then adding either hydrazine or hydrazine hydrate in a polar protic organic solvent under reflux temperature to produce compound (VII)
• and further allowing compound (VII) to react with pure morpholine at elevated temperatures, or with morpholine and a base in a polar aprotic solvent at reflux temperature to obtain Compound 1c
• and subsequently performing a separation of enantiomers of Compound 1c to obtain Compound 1 and Compound (1a)
• whereby optionally compound 1a is converted into racemic material which could then be separated in order to obtain Compound 1 and less of the initial amount of compound 1a.