Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](=O)([O-])[O-].[Na+].[Na+].S(OC)(OC)(=O)=O.[OH:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]=[CH:22][C:23](=[O:25])[CH3:24])=[CH:17][C:16]=1[O:26][CH2:27][CH3:28]>CC(C)=O>[CH3:1][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]=[CH:22][C:23](=[O:25])[CH3:24])=[CH:17][C:16]=1[O:26][CH2:27][CH3:28]
Reactant: CCOc1cc(C=CC(C)=O)ccc1O
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: COS(=O)(=O)OC
Solvent: CC(C)=O
Product: CCOc1cc(C=CC(C)=O)ccc1OC
Yield: 65.1 %

Procedure:
Anhydrous sodium carbonate (3.98 g) and dimethyl sulfate (3.78 g, 30 mmol) were added to a solution of 4-(4-hydroxy-3-ethoxyphenyl)-3-buten-2-one (6.2 g, 30 mmol) in acetone (40 ml). The reaction mixture was stirred under refluxing for 8 hr. The precipitated yellow solid was filtered, washed with acetone, and then recrystallized from anhydrous ethanol to give 4.3 g of a yellow crystal, mp 95-96° C., yield 65.3%.
Reaction SMILES: [Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.OS(O)(=O)=O.[CH3:17][CH2:18]O>>[CH2:17]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([CH3:11])[C:2]([Cl:1])=[N:3][CH:4]=1)[CH3:18]
Reactant: CCO
Reactant: Cc1cc(C(=O)O)cnc1Cl
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cnc(Cl)c(C)c1
Temperature: 25 °C

Procedure:
A solution of 6-chloro-5-methyl-nicotinic acid (13.85 g, 80.75 mmol) in dry EtOH (200 mL) containing some drops of concentrated H2SO4 is stirred at reflux for 2 days. The solution is cooled to rt, the solvent evaporated, the residue dissolved in EA (200 mL) and washed with a solution of sat. aq. Na2CO3 (2×80 mL), 1M aq. KHSO4 (2×80 mL) and brine (50 mL). The org. phase is dried over MgSO4, filtered and evaporated to give 6-chloro-5-methyl-nicotinic acid ethyl ester (12.65 g) as a solid; LC-MS: tR=0.92 min; [M+1]+=200.10; 1H NMR (CDCl3) δ 1.43 (t, J=7.0 Hz, 3H), 2.46 (s, 3H), 4.43 (q, J=7.3 Hz, 2H), 8.16 (m, 1H), 8.84 (d, J=2.0 Hz, 1H).
Reaction SMILES: C[N:2]([CH:4]=[N:5][C:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([C:13]([N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][N:18]3[CH:26]=[CH:27][CH2:28][C:17]3=[CH:16]2)=[O:14])=[CH:9][CH:8]=1)C.C(O)(=O)C.[NH2:34]N>ClCCl>[CH:28]1[CH:27]=[CH:26][N:18]2[CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[N:15]([C:13]([C:10]3[CH:11]=[CH:12][C:7]([C:6]4[NH:34][N:2]=[CH:4][N:5]=4)=[CH:8][CH:9]=3)=[O:14])[CH2:16][C:17]=12
Reactant: NN
Reactant: CN(C)C=NC(=O)c1ccc(C(=O)N2C=C3CC=CN3Cc3ccccc32)cc1
Solvent: ClCCl
Solvent: CC(=O)O
Product: O=C(c1ccc(-c2ncn[nH]2)cc1)N1Cc2cccn2Cc2ccccc21
Yield: 42.4 %

Procedure:
A mixture of N-(dimethylaminomethylene)-4-(5H,1 H-pyrrolo[2,1-c][1,4]-benzodiazepine-10-carbonyl)-benzamide (1.0 g) from Example 46, glacial acetic acid (15 ml), and anhydrous hydrazine (0.16 g) was refluxed for 15 hours and the volatiles removed in vacuo. Saturated aqueous sodium bicarbonate solution was added and the resultant solid was recovered by filtration. The solid was refluxed for 4 hours and the volatiles removed in vacuo to give a solid. The solid was dissolved in dichloromethane and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a steam bath with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield the title compound (0.39 g), m.p. 225-227° C.; MS, m/z: 355 (M)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][NH2:11].[C:12]([C:14](C#N)=[C:15]([C:18]#[N:19])[C:16]#[N:17])#[N:13]>C(O)C>[NH2:19][C:18]1[N:10]([C:3]2[C:2]([Cl:1])=[CH:7][C:6]([Cl:8])=[CH:5][C:4]=2[Cl:9])[N:11]=[C:14]([C:12]#[N:13])[C:15]=1[C:16]#[N:17]
Reactant: NNc1c(Cl)cc(Cl)cc1Cl
Reactant: N#CC(C#N)=C(C#N)C#N
Solvent: CCO
Product: N#Cc1nn(-c2c(Cl)cc(Cl)cc2Cl)c(N)c1C#N
Yield: 41.7 %

Procedure:
A mixture of 2,4,6-trichlorophenylhydrazine (21.1 g) and tetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for 15 minutes. The reaction mixture was cooled and the solid precipitate was filtered off and washed with diethyl ether to give 5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl) pyrazole (13 g), as a buff colored solid, m.p. 267°-271° C.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:3]=1[C:4](O)=[O:5].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:23]2[N:24]=[CH:25]C=CC=2N=N1.C(N(CC)CC)C.CNC>ClCCl>[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:3]=1[C:4]([N:24]([CH3:25])[CH3:23])=[O:5]
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: Nc1ccc(I)cc1C(=O)O
Agent: CNC
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN(C)C(=O)c1cc(I)ccc1N
Reaction time: 0.08 h
Yield: 98 %

Procedure:
2-Amino-5-iodobenzoic acid (5.0 g, 19 mmol) was dissolved in dichloromethane (100 mL). O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (7.9 g, 21 mmol) and triethyl amine (2.1 g, 21 mmol) were added with magnetic stirring. After 5 min., dimethyl amine (2 N in THF, 19 mL, 38 mmol) was added and the resulting solution was stirred overnight. The reaction solution was washed with aqueous saturated sodium chloride and concentrated. The residue was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane to afford 2-amino-5-iodo-N,N-dimethyl-benzamide (5.4 g, 98% yield) as yellow solids. MS: m/z 291 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([CH3:10])[CH3:9])[N:5]=[C:4]([NH:12][CH:13]([CH:23]2[CH2:25][CH2:24]2)[CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH:31]=O)=[CH:29][CH:28]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[N:1][C:2]2[N:7]=[C:6]([C:8]([F:11])([CH3:9])[CH3:10])[N:5]=[C:4]([NH:12][CH:13]([CH:23]3[CH2:24][CH2:25]3)[CH2:14][CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:3]=2)=[CH:29][CH:28]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: CC(C)(F)c1nc(N)nc(NC(CCCc2ccccc2)C2CC2)n1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(F)c1nc(N=Cc2ccc(Cl)cc2)nc(NC(CCCc2ccccc2)C2CC2)n1

Procedure:
A mixture of 2.5 g (7.28 mmol) of 2-amino-4-(1-fluoro-1-methylethyl)-6-(1-cyclopropyl-4-phenyl-1-butylamino)-1,3,5-triazine, 1.08 g (7.70 mmol) of p-chlorobenzaldehyde and 100 mg of p-toluenesulfonic acid in 80 ml of toluene are boiled for 10 hours in a water separator. When cold, all volatile constituents are distilled. The crude product is purified by column chromatography (eluent:toluene/ethyl acetate=85:15). This gives 3.0 g (89% of theory) of 2-(4-chloro-6-benzylideneamino)-4-(1-fluoro-1-methylethyl-)-6-(1-cyclopropyl-4-phenyl-1-butylamino)-1,3,5-triazine as colorless oil.
Reaction SMILES: F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[O:13]1[C:17]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[O:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C>[O:13]1[C:17]2([CH2:22][CH2:21][N:20]([C:2]3[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=3)[CH2:19][CH2:18]2)[O:16][CH2:15][CH2:14]1
Reactant: C1CC2(CCN1)OCCO2
Reactant: CCOC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CCOC(=O)c1ccc(N2CCC3(CC2)OCCO3)cc1
Temperature: 100 °C

Procedure:
Ethyl 4-fluorobenzoate (36.16 g, 215 mmol), 1,4-dioxa-8-azaspiro[4.5]decane (35.40 g, 247 mmol), and potassium carbonate (29.72 g, 215 mmol) were added to N,N-dimethylacetamide (500 mL) and heated to 100° C. for 16 hours. The solution was cooled, filtered, added to 2M HCl and extracted with 50% ethyl acetate (in hexanes). The organics were washed with water, brine, and dried on anhydrous sodium sulfate. The solution was concentrated and purified by flash column chromatography on silica gel with 20% ethyl acetate (in hexanes) increasing to 30% ethyl acetate (in hexanes).
Reaction SMILES: [CH:1]1([N:7]([CH:31]([CH3:33])[CH3:32])[C:8](=[O:30])[C:9]2[CH:14]=[CH:13][C:12]([CH:15](O)[C:16]3[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=3)=[C:11]([CH3:29])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>CCO.S(=O)(=O)(O)O.[Pd].C(OCC)(=O)C>[CH:1]1([N:7]([CH:31]([CH3:33])[CH3:32])[C:8](=[O:30])[C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]3[CH:17]=[C:18]([O:26][CH3:27])[C:19]([O:24][CH3:25])=[C:20]([O:22][CH3:23])[CH:21]=3)=[C:11]([CH3:29])[CH:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COc1cc(C(O)c2ccc(C(=O)N(C(C)C)C3CCCCC3)cc2C)cc(OC)c1OC
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: CCO
Solvent: CCOC(C)=O
Product: COc1cc(Cc2ccc(C(=O)N(C(C)C)C3CCCCC3)cc2C)cc(OC)c1OC

Procedure:
The compound of Example 47 (800 mg, 1.81 mmol) in EtOH (20 mL) containing concentrated sulfuric acid (4 drops) is hydrogenated at 60 psi and room temperature using 5% Pd/C as catalyst. The catalyst is filtered and the filtrate concentrated in vacuo to give the crude product. The crude product is dissolved in ethyl acetate and washed twice with aqueous NaHO3 solution and then with saturated aqueous NaCl solution. After drying (Na2SO4) the organic layer is filtered and concentrated in vacuo. Purification to give the title compound is carried out by chromatography of the residue on silica gel using mixtures of ethyl acetate and hexane as the eluents.
Reaction SMILES: [C:1]([C:4]1[C:17]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3[O:18]C)[C:8]=2[C:7]2[O:20][CH2:21][O:22][C:6]=2[CH:5]=1)([OH:3])=[O:2].Cl.N1C=CC=CC=1>Cl>[C:1]([C:4]1[C:17]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3[OH:18])[C:8]=2[C:7]2[O:20][CH2:21][O:22][C:6]=2[CH:5]=1)([OH:3])=[O:2]
Reactant: COc1cccc2c1ccc1c(C(=O)O)cc3c(c12)OCO3
Agent: Cl
Solvent: c1ccncc1
Product: O=C(O)c1cc2c(c3c1ccc1c(O)cccc13)OCO2

Procedure:
1.0 g. 1-carboxy-3,4-methylenedioxy-8-methoxyphenanthrene is melted with 2.0 g. pyridine hydrochloride in an oil bath at 170° C. and maintained at this temperature for 1 hour while gassing with nitrogen. After cooling, the solidified mass is taken up with 10 liters 5% hydrochloric acid and extracted three times with 10 liter amounts of chloroform. The extracts are combined, washed neutral with water and dried by filtering through silanised filter paper (Whatman 1 PS). After evaporation of the solvent at 30° C. on a rotary evaporator, the mixture of starting material and hydrolysate is esterified for separation by boiling under reflux for 3 hours with a mixture of 2.5 liters methanol and 0.1 liter concentrated sulphuric acid. The reaction mixture is then poured into 10 liters of water and the aqueous methanolic phase shaken out three times with 10 liter amounts of diisopropyl ether. The organic solvent, after having been washed several times with water, is extracted with 10 liters of sodium hydroxide solution, the methyl ester of the 8-methoxy compound remaining in the organic phase, whereas the 8-hydroxy compound is transferred into the aqueous phase, with simultaneous hydrolysis of the ester. After washing with fresh diisopropyl ether, the alkaline phase is acidified and shaken out several times with chloroform. The chloroform solution is dried over phase separation paper (Whatman 1 PS) and the solvent stripped off on a rotary evaporator, 1-carboxy-3,4-methylenedioxy-8-hydroxyphenanthrene remaining behind in solid form as a thin layer chromatographically-uniform compound.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]1[N:13]=[C:12]([NH2:14])[N:11]2[N:15]=[C:16]([C:18]3[O:19][CH:20]=[CH:21][CH:22]=3)[N:17]=[C:10]2[N:9]=1.[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][N:5]2[CH2:6][CH:1]3[CH2:7][CH:4]2[CH2:3][N:2]3[C:8]2[N:13]=[C:12]([NH2:14])[N:11]3[N:15]=[C:16]([C:18]4[O:19][CH:20]=[CH:21][CH:22]=4)[N:17]=[C:10]3[N:9]=2)=[CH:26][CH:25]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: Nc1nc(N2CC3CC2CN3)nc2nc(-c3ccco3)nn12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: Nc1nc(N2CC3CC2CN3Cc2ccc(F)cc2)nc2nc(-c3ccco3)nn12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
5-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (0.25 mmol; see Example 13(a) above) was dissolved in 4 mL of CH2Cl2 along with 1.2 eq of 4-fluorobenzaldehyde and 2 eq of sodium triacetoxyborohydride. The reaction mixture was stirred at room temperature for 18 hours. It was then concentrated and purified by preparative HPLC to afford the title compound. 1H NMR (400 Hz, DMSO-d6) δ 8.20 (brs, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.00 (d, J=3.6 Hz, 1H), 7.2-7.4 (m, 4H), 6.60 (dd, J=3.6, 1.0 Hz, 1H), 6.30 (s, 1H), 4.80 (brs, 2H), 4.20-4.30 (m, 8H). MS m/z: 407 [M+H]+.
Reaction SMILES: [Na].[Cl:2][C:3]1[CH:28]=[CH:27][C:6]([C:7]([C:9]2[N:13]([CH2:14][CH2:15][CH:16]3[C:21](=[O:22])[O:20][C:19](C)(C)[O:18][C:17]3=[O:25])[C:12]([Cl:26])=[CH:11][CH:10]=2)=[O:8])=[CH:5][CH:4]=1.[CH3:29]O>Cl>[Cl:2][C:3]1[CH:28]=[CH:27][C:6]([C:7]([C:9]2[N:13]([CH2:14][CH2:15][CH:16]([C:21]([O:20][CH3:19])=[O:22])[C:17]([O:18][CH3:29])=[O:25])[C:12]([Cl:26])=[CH:11][CH:10]=2)=[O:8])=[CH:5][CH:4]=1
Reactant: CC1(C)OC(=O)C(CCn2c(Cl)ccc2C(=O)c2ccc(Cl)cc2)C(=O)O1
Reactant: CO
Agent: Cl
Agent: [Na]
Product: COC(=O)C(CCn1c(Cl)ccc1C(=O)c1ccc(Cl)cc1)C(=O)OC
Temperature: 0 °C
Reaction time: 3 h

Procedure:
The 5-(4-chlorobenzoyl)-2-chloro-1-[2-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)ethyl]pyrrole sodium salt from Example 3A was dissolved in methanol saturated with hydrogen chloride (30 ml) and stirred at 0° C. for three hours. The solution was diluted with methanol (30 ml) and allowed to warm to room temperature, and was then stirred for another four hours. The solvent was then evaporated under reduced pressure at 10°-20° C. The residue was partitioned between ether and water (150 ml+150 ml), and the water was extracted with ether (2×150 ml). The combined ether extracts were dried over anhydrous sodium sulfate and evaporated to dryness. The residue was chromatographed on Florisil® (50 g/g mixture), eluting the product with hexane/ethyl acetate, 7:3. The product so obtained (1.912 g, 68%) was a colorless crystalline solid, which was recrystallized from dichloromethane/hexane to afford 5-(4-chlorobenzoyl)-2-chloro-1-[3,3-di(methoxycarbonyl)propyl]pyrrole, having the following properties:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:17]=[N:18][C:19]4[N:20]([N:30]=[CH:31][C:32]=4[C:33](O)=[O:34])[C:21]=3[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[CH:24]=3)=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH2:36]([S:38]([NH2:41])(=[O:40])=[O:39])[CH3:37]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:17]=[N:18][C:19]4[N:20]([N:30]=[CH:31][C:32]=4[C:33]([NH:41][S:38]([CH2:36][CH3:37])(=[O:40])=[O:39])=[O:34])[C:21]=3[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[CH:24]=3)=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: CCS(N)(=O)=O
Reactant: Cc1cccc(Nc2c(C(=O)N3CCC(c4ccc(F)cc4)CC3)cnc3c(C(=O)O)cnn23)c1
Product: CCS(=O)(=O)NC(=O)c1cnn2c(Nc3cccc(C)c3)c(C(=O)N3CCC(c4ccc(F)cc4)CC3)cnc12
Yield: 35.4 %

Procedure:
In the same manner as in Example 1, step 6 and using 6-[4-(4-fluorophenyl)piperidine-1-carbonyl]-7-(3-methylphenylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.05 g, 0.11 mmol) obtained in step 2 and ethanesulfonamide (0.070 g, 0.64 mmol), the title compound (0.022 g, 37%) was obtained.
Reaction SMILES: Br[CH2:2][CH2:3][CH:4]=[CH2:5].[N:6]1([C:17](=[O:18])[C:16]2[NH:15][CH:14]=[N:13][C:12]=2[N:10]([CH3:11])[C:8]1=[O:9])[CH3:7].[Na]>CN(C)C=O>[CH3:7][N:6]1[C:17](=[O:18])[C:16]2[N:15]([CH2:2][CH2:3][CH:4]=[CH2:5])[CH:14]=[N:13][C:12]=2[N:10]([CH3:11])[C:8]1=[O:9]
Reactant: C=CCCBr
Reactant: Cn1c(=O)c2[nH]cnc2n(C)c1=O
Agent: [Na]
Solvent: CN(C)C=O
Product: C=CCCn1cnc2c1c(=O)n(C)c(=O)n2C
Reaction time: 7 h

Procedure:
13.9 g of 4-bromo-but-1-ene are reacted with 20.2 g of sodium theophylline in 200 ml of dimethyl-formamide at 120° C. with stirring for approximately 6 to 8 hours until the reaction is complete as indicated by thin-layer chromatography. The solvent is then removed under reduced pressure. The residue is dissolved at 20° C. in 100 ml of methylene chloride, separated from insoluble sodium bromide and purified through a column packed with neutral aluminum oxide to remove small quantities of dark-coloured accompanying substances. Melting point: 110° C. (acetone); yield: 21.6 g (91% of theory relative to the starting material used). After thin-layer chromatography on Merck DC finished plates of silica gel 60 F254 with benzene/acetone (6:4) as eluent, the product has an Rf value of 0.54; and with nitromethane/benzene/pyridine (20:10:3) as eluent, an Rf value of 0.65. Utra-violet light was used as indicator, the pyridine of the eluent having, however, to be removed at 50° C. under reduced pressure because of its property to extinguish fluorescence.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:16](=[O:23])[CH2:17][N:18]1[CH:22]=[N:21][CH:20]=[N:19]1.[C:24]([Mg]Br)#[C:25][CH3:26]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=2)[CH:5]=[CH:4][C:3]=1[C:16]([OH:23])([C:24]#[C:25][CH3:26])[CH2:17][N:18]1[CH:22]=[N:21][CH:20]=[N:19]1
Reactant: O=C(Cn1cncn1)c1ccc(Oc2ccc(Cl)cc2)cc1Cl
Reactant: CC#C[Mg]Br
Solvent: C1CCOC1
Product: CC#CC(O)(Cn1cncn1)c1ccc(Oc2ccc(Cl)cc2)cc1Cl
Reaction time: 1 h

Procedure:
To a solution of the above-mentioned ethanone (75.5 g, 216.8 mmol) dissolved in THF (450 mL) was added a solution of LaCl3.2LiCl (395.9 mL, 0.6 M in THF) at room temperature and stirred for 1 hour. The resulting solution was added dropwise to 1-propynylmagnesium bromide (650.5 mL, 0.5M in THF) at room temperature. After 1 hour at room temperature, the resulting mixture was quenched with a 10% aqueous solution of HCl and extracted with MTBE. The organic phase was washed with brine, dried and evaporated. The crude compound was stirred in a solution of MTBE/diisopropylether and filtrated to eliminate the starting material. The mother liquors were evaporated and purified on silica gel to give the title compound as a beige solid (31.1 g, HPLC-MS2 Rt=1.15 min, masse=388, m.p=137° C.).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:8][CH:7]=1.[CH2:23]([NH:26][CH2:27][CH2:28][CH3:29])[CH2:24][CH3:25].Cl>>[CH2:23]([N:26]([CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:8][CH:7]=1)[CH2:27][CH2:28][CH3:29])[CH2:24][CH3:25]
Reactant: CCCNCCC
Reactant: ClCCCOc1ccc(/C=C/c2nc3ccccc3o2)cc1
Agent: Cl
Product: CCCN(CCC)CCCOc1ccc(/C=C/c2nc3ccccc3o2)cc1
Yield: 40 %

Procedure:
The title compound was prepared as described in Example 8 starting with (C) of Example 8 (2.0 g, 6.4 mmol) and using dipropylamine in place of dibutylamine to produce 1.2 g (40% yield) of the title compound as the HCl salt, mp 172°-173° C. IR(KBr): 3400, 1600 cm-1. MS: 379(MH+). 1H NMR (CDCl3): δ 8.48-6.95 (m, 10H), 4.19 (t, J=5.1 Hz, 2H), 3.21 (m, 6H), 2.49-0.91 (m, 12H).
Reaction SMILES: NC1C2C(=O)C=C(C(OCC)=O)[O:11]C=2C=CC=1.[CH2:18]([S:20]([C:22]1[C:31]2[C:26](=[C:27]([CH2:40][CH2:41][CH3:42])[C:28]3[O:35][C:34]([C:36]([O-:38])=[O:37])=[CH:33][C:32](=[O:39])[C:29]=3[CH:30]=2)[N:25]=[C:24]([C:43]([O-:45])=[O:44])[CH:23]=1)=[O:21])[CH3:19].[Na+:46].[Na+]>>[CH2:18]([S:20]([C:22]1[C:31]2[C:26](=[C:27]([CH2:40][CH2:41][CH3:42])[C:28]3[O:35][C:34]([C:36]([O-:38])=[O:37])=[CH:33][C:32](=[O:39])[C:29]=3[CH:30]=2)[N:25]=[C:24]([C:43]([O-:45])=[O:44])[CH:23]=1)(=[O:11])=[O:21])[CH3:19].[Na+:46].[Na+:46]
Reactant: CCOC(=O)c1cc(=O)c2c(N)cccc2o1
Reactant: CCCc1c2nc(C(=O)[O-])cc(S(=O)CC)c2cc2c(=O)cc(C(=O)[O-])oc12
Agent: [Na+]
Product: CCCc1c2nc(C(=O)[O-])cc(S(=O)(=O)CC)c2cc2c(=O)cc(C(=O)[O-])oc12

Procedure:
The product (ii) of section (a) above was hydrolysed in the same manner as in (b) above to afford the sub-title compound (0.12 g).
Reaction SMILES: [C:1]1([N:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+].CN([CH:30]=[O:31])C>>[C:14]1([N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:13]=[CH:12][C:11]([CH:30]=[O:31])=[CH:10][CH:9]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CN(C)C=O
Reactant: c1ccc(N(c2ccccc2)c2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O=P(Cl)(Cl)Cl
Product: O=Cc1ccc(N(c2ccccc2)c2ccccc2)cc1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 84 %

Procedure:
Triphenyl amine (98.32 g, 0.393 mol) is suspended in DMF (280 ml). Phosphorus oxychloride (66.24 g, 0.432 mol) is added dropwise to it over a 30-minutes period without external cooling. After stirring for one more hour, the reaction is heated to 80° C. (bath temperature) for 2½ hours. After cooling to room temperature, the reaction is slowly poured onto ice-cold water (8 liters) with vigorous stirring. After 30 minutes, aqueous sodium hydroxide (5 N, 250 ml) is added to the reaction, and stirring is continued for one hour. The obtained precipitate is filtered off, washed with water (2 liters), then with methanol (2 liters) and dried to give 4-diphenylaminobenzaldehyde as a beige solid (90.47 g, 0.331 mol, 84%), which is used in the next step without further purification.
Reaction SMILES: [CH2:1]([N:4]1[CH:13]2[C:8]3=[C:9]([C:22]([OH:27])=[C:23]([O:25][CH3:26])[CH:24]=[C:7]3[CH2:6][CH2:5]1)[C:10]1[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[CH:14][C:11]=1[CH2:12]2)[CH:2]=[CH2:3].[C:28]1(C)C=CC=CC=1.CN(C)C=O.[OH-].C1([N+](C)(C)C)C=CC=CC=1>CO>[CH2:1]([N:4]1[CH:13]2[C:8]3=[C:9]([C:22]([O:27][CH3:28])=[C:23]([O:25][CH3:26])[CH:24]=[C:7]3[CH2:6][CH2:5]1)[C:10]1[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[CH:14][C:11]=1[CH2:12]2)[CH:2]=[CH2:3]
Reactant: C=CCN1CCc2cc(OC)c(O)c3c2C1Cc1cc(OC)c(OC)cc1-3
Reactant: Cc1ccccc1
Agent: C[N+](C)(C)c1ccccc1
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: C=CCN1CCc2cc(OC)c(OC)c3c2C1Cc1cc(OC)c(OC)cc1-3

Procedure:
4.5 g. (12.2 mmol) (+)-6-Allyl-5,6,6a,7-tetrahydro-1-hydroxy-2,9,10-trimethoxy-4H-dibenzo(de,g)quinoline are reacted in 230 ml. of a mixture of toluene and dimethylformamide (9:1 v/v) with 20 ml. of a 1N solution of phenyltrimethylammonium hydroxide in methanol as described in Variant 1. After appropriate working up, there is obtained (+)-6-allyl-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-4H-dibenzo(de,g)quinoline, which is identical in every respect to the product obtained according to Variant 1. [α]DRT (hydrochloride): +117.7° (c=0.5, methanol).