DD287715A5 - PROCESS FOR SYNTHESIS OF SUBSTITUTED 3- (N-ARYL-CARBAMOYL) -BZW. 3- (N-cycloalkyl-carbamoyl) -2-methylthio-3,4-dihydroquinazolines - Google Patents

Abstract

The invention relates to a novel process for the preparation of the hitherto unknown alkyl-, aryl- or halogen-substituted * or * of the general formula III, which are of importance as intermediates for the synthesis of potentially biologically active preparations. The preparation is carried out by reacting substituted * of the general formula I with aryl or cycloalkyl isocyanates of the general formula II in anhydrous toluene. {Synthesis process; * Aryl or cycloalkyl isocyanates; Solvents toluene; aryl-, alkyl- or halogen-substituted * intermediates for biological preparations}

Description

Application blot of the invention

The invention relates to a method for the synthesis of substituted 3- (N-aryl-carbamoyl) or 3- (N-cycloalkyl-carbamoyl) -2-methylthiü-3,4-dihydroquinazolines, which are for the preparation of potentially biologically active preparations as organic chemical intermediates are used.

Characteristic of the known technical solutions

The inventively described 3- (N-aryl-carbamoyl) or a-IN-cycloalkyl-carbamoyD ^ -methylthio-S ^ - dihydroquinazolines of the general formula III are unknown. Described are N-aryl-carbamoyl-substituted hydantoins, which, however, have a andoren basic body; (US 4080473 from 21.3.1978; C07 C127 / 22) and were obtained using dlpolaraprotischen solvents and triethylamine in the boiling heat. The described title compounds can not be prepared by the known process or in insufficient yields,

Object of the invention

The aim of the invention is, on the basis of readily available starting materials, an economically favorable process for the preparation of potentially biologically active substituted 3- (N-aryl-carbamoyl) or 3- (N-cycloalkyl-carbamoyl) -2-methylthio-3,4 to find dihydroquinazolines, since such compounds have not been synthesized. The process found is generally applicable and suitable for the synthesis of N-substituted carbamoyl derivatives of 2-methylthio-3,4-dihydroquinazolines.

Explanation of the essence of the invention

The technical object of the invention is an economically favorable and simple process for the synthesis of previously inaccessible aryl, alkyl or halogen-substituted 3- {N-aryl-carbamoyl) or S-IN-cycloalkyl-carbamoyU ^ -methylthio-3 To develop 4-dihydroquinazolines of the general formula III, which are used; readily available starting materials in one step at high Ausboute is feasible.

According to the invention, this is achieved in that an alkyl, aryl or halogen-substituted 2-methylthio-3,4-dihydroquinazoline of general formula I with aryl or cycloalkyl isocyanates of general formula II, wherein R ^{2 is} preferably phenyl, naphth 1-yl, 2-chlorophenyl, 3,4-dichlorophenyl or cyclohexyl mean, is reacted in an inert solvent (primarily toluene) at its own boiling point. The reaction time is 10 hours.

The isolation of the formed substituted 3- (N-aryl-carbamoyl) or 3- (N-cycloalkylcarbamoyl) -2-methylthio-3,4-dihydroquinazolines takes place directly from the reaction mixture by suction of the resulting solid.

The crystalline reaction products are obtained in high purity.

The starting materials used were those 2-methylthiochiazolin derivatives which can be prepared by a process protected by patent law (WP 251974), where R ¹ can be assigned to hydrogen, methyl, chlorine or bromine.

¹ -HCO

II

III

R '

a H b H C H d Cl e Cl f Cl Ausführungsbelsplsle

R ²

3,4-dichlorophenyl

cyclohexyl

Naphth-1-yl

Naphth-1-yl

phenyl

cyclohexyl

Belsplel 13- | N- (2,4-dichlorophenyl) carbamoyl-2-methylthio-4-phenyl-3,4-dihydroquinazoline (Ilia) 0.01 mol of 2-methylthio-4-phenyl-3,4-dihydroquinazoline are disclosed in US Pat Toluene dissolved with slight warming. Then the

Addition of 0.01 mol of 2,4-dichlorophenyl isocyanate. The reaction solution is heated at reflux for 10 hours. The one in the heat

resulting solid is filtered off and rinsed with toluene.

Yield: 48% of theory

F: 265-267 "C

Example 2

3- (N-Cyclohexylcarbamoyl) -2-methylthio-4-phenyl-3,4-dihydrochlorazoline (HIb)

Analogously to Example 1 from 2-methylthio-4-phenyl-3,4-dihydroquinazoline with cyclohexylisocyanate Yield: 62% of theory

Q: 220-222 ⁰ C

Example 3

2-methylthio-3- [N- (naphth-1-yl) carbamoyl-4-phenyl-3,4-dihydroquinazolin (lllci

Analogously to Example 1 from 2-methylthio-4-phenyl-3,4-dihydroquinazoline with naphth-1-ylisocyanate. Yield: 56% of theory

F: 297-299 ⁰ C

Example 4

6-Chloro-2-methylcili-3- (N- (naphth-1-yl) carbamoyl] -4-phenyl-3,4-dihydroquinazoline (IIID)

Analogous to Example 1 ause-chloro-methylthio ^ -phenyl-S.-l-dihydroquinazoline with naphth-1-yl isocyanate. Yield: 49% of theory

Q: 269-271 ⁰ C

Example 5

e-chloro-methylthio-S-IN-phenyl-carbamyl-D-phenyl-S, -dihydroquinazoline (IIe)

Analogously to Example 1 from B-chloro-methylthio 4-phenyl-3,4-dihydroquinazoline with phenyl isocyanate. Yield: 53% of theory

Q: 241-242 ⁰ C

Example β6-Chloro -? - (N-cyclohoxyl-carbamoyl) -2-methylthio-4-phenyl-3,4-dihydroquinazoline (IIIf)

Analogously to Example 1 from e-chloro ^ -Meihylthio ^ -phenyl-SAdihydrochinazolin with cyclohexyl isocyanate. Yield: 58% of theory

F: 217-219 ⁰ C '

Claims (6)

1. A process for the synthesis of alkyl, aryl or halogen-substituted 3- (N-aryl-carbamoyl) or 3- (N-CyClOaIlCyI-carbamoyl) -2-methyl-thio-3,4-dihydroquinazolinen of the general formula III , characterized by reacting substituted 2-methylthio-3,4-dihydroquinazolines of the general formula I with aryl or cycloalkyl isocyanates. 2. The method according to claim 1, characterized in that are used as starting materials 2-methylthio-3,4-dihydroquinazolines, in the general formula I for R ^{1 is} hydrogen, halogen or alkyl. 3. The method according to claim!, Characterized in that the reaction is carried out by lOstündiges heating in dor boiling heat of the solvent. 4. The method according to claim 1, characterized in that one carries out the reaction in an inert, anhydrous solvent, primarily toluene. 5. The method according to claim 1, characterized in that the aryl »zw. Cycloalkyl isocyanates find commercial form and the products are obtained in high purity. 6. The method according to claim 1, characterized in that the resulting, reaction products ι correspond to the general III ^ sleeve III, wherein R ^{1 is} the same meaning as in formula I assign.