Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1([CH2:22][CH2:23][CH2:24][OH:25])[CH2:13][CH2:12][CH:11]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:30].CO>C1COCC1>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1([CH2:22][CH2:23][CH2:24][O:25][CH3:30])[CH2:13][CH2:12][CH:11]([O:14][Si:15]([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:17])[CH3:16])[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: CC(C)(C)OC(=O)NC1(CCCO)CCC(O[Si](C)(C)C(C)(C)C)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: COCCCC1(NC(=O)OC(C)(C)C)CCC(O[Si](C)(C)C(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
A solution of 250 mg (0.65 mmol) of [4-(tert-butyl-dimethyl-silanyloxy)-1-(3-hydroxy-propyl)-cyclohexyl]-carbamic acid tert-butyl ester (32) in 3 mL of THF was dropped into a suspension of 28.3 mg (0.71 mmol) of sodium hydride (60%) in 8 mL THF at 0° C. 120 μL (1.94 mmol) of iodomethane were added, and after stirring for 1 h at room temperature another 120 μL (1.94 mmol) of iodomethane were added. The reaction mixture was stirred for 14 h at room temperature, then 5 mL of methanol were added and the volatiles were removed in vacuo. Rt=2.32 min, 2.37 min (Method C). Detected mass: 402.3 (M+H+), 302.3 (M-Boc+H+).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[NH:11][C:12](=[O:19])[C:13]3[C:18]([C:9]=2[C:8]2[CH:7]=[C:6]([Cl:20])[CH:5]=[CH:4][C:3]1=2)=[CH:17][CH:16]=[CH:15][CH:14]=3.[H-].[Na+].[CH2:23](Br)[CH3:24]>>[CH2:23]([O:19][C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]2[C:8]3[CH:7]=[C:6]([Cl:20])[CH:5]=[CH:4][C:3]=3[N:2]([CH3:1])[C:10]=2[N:11]=1)[CH3:24]
Reactant: Cn1c2ccc(Cl)cc2c2c3ccccc3c(=O)[nH]c21
Reactant: CCBr
Agent: [H-]
Agent: [Na+]
Product: CCOc1nc2c(c3ccccc13)c1cc(Cl)ccc1n2C

Procedure:
5-Ethoxy-7-methyl-10-chloro-7H-indolo(2,3-c)isoquinoline (melting point 161°-163° C.) is prepared from 7-methyl-10-chloro-7H-indolo(2,3-c)isoquinolin-5(6H)-one, sodium hydride and ethyl bromide by the method described in Example 8.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.[C:16]([O:19][C@@H:20]1[C@@H:34]([O:35][C:36](=[O:38])[CH3:37])[C@H:33]([O:39][C:40](=[O:42])[CH3:41])[CH2:32][S:31][C@H:21]1[O:22][C:23]1[CH:28]=[C:27](Br)[CH:26]=[CH:25][C:24]=1[Cl:30])(=[O:18])[CH3:17]>>[C:16]([O:19][C@@H:20]1[C@@H:34]([O:35][C:36](=[O:38])[CH3:37])[C@H:33]([O:39][C:40](=[O:42])[CH3:41])[CH2:32][S:31][C@H:21]1[O:22][C:23]1[CH:28]=[C:27]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)[CH:26]=[CH:25][C:24]=1[Cl:30])(=[O:18])[CH3:17]
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cc(Br)ccc1Cl
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cc(-c2cnn(C)c2)ccc1Cl

Procedure:
By carrying out the operation analogously to example 87, starting from 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-2-chlorophenyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside obtained according to preparation X, the expected product is obtained and is reacted further without additional purification in order to obtain the nonacetylated xyloside.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[NH:11]1[CH:15]=[N:14][CH:13]=[N:12]1.C([O-])([O-])=O.[K+].[K+]>>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)=[N:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(F)nc1
Reactant: c1nc[nH]n1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: O=[N+]([O-])c1ccc(-n2cncn2)nc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
2-fluoro-5-nitropyridine (30 g, 18.9 mmol) was added to a stirred solution of 1H-1,2,4-triazole (1.566 g, 22.7 mmol) and K2CO3 (5.14 g, 37.8 mmol) and stirred for 16 hrs at 25° C. Reaction mass was diluted with ice cold water and stirred for 15 min. The solid obtained was filtered and dried under vacuum to afford the desired product. MS (ESI): m/z 192 (M+H).
Reaction SMILES: [CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH2:21])[N:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].[I:22]N1C(=O)CCC1=O>CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[C:20]([I:22])=[CH:19][N:18]=[C:17]([NH2:21])[N:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]
Reactant: O=C1CCC(=O)N1I
Reactant: CNC(=O)n1ccc2cc(Oc3ccnc(N)n3)ccc21
Solvent: CN(C)C=O
Product: CNC(=O)n1ccc2cc(Oc3nc(N)ncc3I)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.1 %

Procedure:
N1-Methyl-5-(2-amino-4-pyrimidyl)oxy-1H-1-indolecarboxamide (302 mg, 1.07 mmol) and N-iodosuccinimide (301 mg, 1.34 mmol) were dissolved in N,N-dimethylformamide (3.0 ml); and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with water and brine, and was dried over anhydrous magnesium sulfate. The solvent was distilled off; and the residue was purified by silica gel column chromatography (eluent; ethyl acetate:hexane=2:1) to yield the title compound as yellow crystals (224 mg, 0.547 mmol, 51%).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=1.[OH2:19]>>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=1)=[O:19]
Reactant: Nc1ccc(CSc2nc3ccccc3[nH]2)cn1
Reactant: O
Product: Nc1ccc(CS(=O)c2nc3ccccc3[nH]2)cn1

Procedure:
The title compound was prepared by the method of Example 85 using 1.0 g (3.9 mmole) of 5-[(1H-benzimidazol-2-ylthio)methyl]-2-pyridinamine (see Example 110) instead of 6-[(1H-benzimidazol-2-ylthio)methyl]-2-pyridinamine. Structure assignment was supported by the nmr and infrared spectra and by elemental analysis. Analysis. Calc'd. for C13H12N4SO*¼ H2O: C, 56.40; H, 4.55; N, 20.24; S, 11.58. Found: C, 56.35; H, 4.46; N, 20.25; S, 11.66.
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:24])[NH:5][C:6]1[S:7][C:8]([C:12]2[CH:13]=[CH:14][C:15]([O:22][CH3:23])=[C:16]([S:18](Cl)(=[O:20])=[O:19])[CH:17]=2)=[C:9]([CH3:11])[N:10]=1)[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[CH2:31]([CH2:33][NH2:34])[OH:32].O>O1CCOCC1.C(Cl)Cl.CO.C(OC(=O)C)C>[CH2:1]([NH:3][C:4](=[O:24])[NH:5][C:6]1[S:7][C:8]([C:12]2[CH:13]=[CH:14][C:15]([O:22][CH3:23])=[C:16]([S:18]([NH:34][CH2:33][CH2:31][OH:32])(=[O:20])=[O:19])[CH:17]=2)=[C:9]([CH3:11])[N:10]=1)[CH3:2]
Reactant: NCCO
Reactant: CCNC(=O)Nc1nc(C)c(-c2ccc(OC)c(S(=O)(=O)Cl)c2)s1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: CCNC(=O)Nc1nc(C)c(-c2ccc(OC)c(S(=O)(=O)NCCO)c2)s1
Reaction time: 2 h

Procedure:
To 5-[2-(3-Ethyl-ureido)-4-methyl-thiazol-5-yl]-2-methoxy benzenesulfonylchloride (Example 28d) (0.2 g, 0.514 mmol) in dioxane (10 ml) is added 2M Na2CO3 (0.515 ml) followed by ethanolamine (0.031 ml, 0.514 mmol). After 2 hours at room temperature, the reaction mixture is poured into water (150 ml)/ethylacetate (50 ml) and sonicated. The layers are separated then the aqueous layer is extracted with ethyl acetate (3×50 ml). The combined organic layers are dried over MgSO4, filtered and concentrated to afford a sticky oil which is dissolved in a minimum amount of DCM/methanol and dried at reduced pressure to afford 5-[2-(3-ethyl-ureido)-4-methyl-thiazol-5-yl]-N-(2-hydroxy-ethyl)-2-methoxy-benzenesulfonamide as a yellow foam.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]=[C:15]([CH2:18][NH2:19])[S:16][CH:17]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1.[CH2:20]([C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][CH:23]=1)[CH3:21]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]=[C:15]([CH2:18][NH:19][C:29]([NH:28][C:25]3[CH:26]=[CH:27][C:22]([CH2:20][CH3:21])=[CH:23][CH:24]=3)=[O:30])[S:16][CH:17]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1
Reactant: NCc1nc(C(=O)NCCc2cccc(Cl)c2)cs1
Reactant: CCc1ccc(N=C=O)cc1
Solvent: CN(C)C=O
Product: CCc1ccc(NC(=O)NCc2nc(C(=O)NCCc3cccc(Cl)c3)cs2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 44.4 %

Procedure:
2-Aminomethyl-thiazole-4-carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide (50 mg, 0.17 mmol) was dissolved in DMF (1 mL). 4-Ethyl phenylisocyanate (0.05 mL, 0.34 mmol) was added and the reaction mixture stirred at ambient temperature for 20 hours. The crude product was concentrated in vacuo. The product was purified by column chromatography (silica, 5% MeOH in DCM) to give a white solid (33.4 mg, 44%). 1H NMR (400 MHz, CD3OD): 8.07 (s, 1H), 7.26 (m, 4H), 7.19 (m, 2H), 7.11 (m, 2H), 4.66 (s, 2H), 3.60 (t, 2H), 2.90 (t, 2H), 2.58 (q, 2H), 1.20 (t, 3H); MS (ESI-LCMS) for C22H24C1N4O2S: 443 (MH+).
Reaction SMILES: O1CCCOB1[C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[C:9]#[N:10].Br[C:16]1[CH:22]=[C:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:20]=[CH:19][C:17]=1[NH2:18].C(=O)([O-])[O-].[K+].[K+].CCO>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:23]([C:21]1[CH:22]=[CH:16][C:17]2[C:19](=[C:7]3[C:8](=[C:9]([NH2:10])[N:18]=2)[CH:11]=[CH:12][CH:13]=[CH:14]3)[CH:20]=1)[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCc1ccc(N)c(Br)c1
Reactant: N#Cc1ccccc1B1OCCCO1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCCCCCc1ccc2nc(N)c3ccccc3c2c1
Yield: 39.8 %

Procedure:
13.1 g (69.8 mmol) 2-(1,3,2-dioxaborinan-2-yl)benzonitrile, 16.3 g (63.4 mmol) 2-bromo-4-hexylaniline, 1.62 g (1.40 mmol) tetrakis(triphenylphosphine) palladium(0), and 23.6 g (171 mmol) potassium carbonate where refluxed in 250 ml toluene and 100 ml EtOH under N2 atmosphere for 20 hours. HPLC and TLC revealed almost complete consumption of the aniline. The reaction mixture was cooled and passed through a filter. The solids were washed with ethyl acetate to remove organics from the collected base. The filtrate was then evaporated down and dried on silica. The sample was purified using silica gel chromatography with 100% ethyl acetate as the eluent. The product fractions were then evaporated down to a minimal amount and hexanes added to crystallize the product as off white solids (7.05 g, 39.8% yield, GC-MS confirmed).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH2:16][CH:17]2[CH2:21][CH2:20][O:19][CH2:18]2)[C:12]([O:14]C)=[O:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[OH-].[Na+].Cl>CO>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]([CH2:16][CH:17]2[CH2:21][CH2:20][O:19][CH2:18]2)[C:12]([OH:14])=[O:13])=[CH:9][CH:10]=1)(=[O:4])=[O:3]
Reactant: COC(=O)C(CC1CCOC1)c1ccc(S(C)(=O)=O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CS(=O)(=O)c1ccc(C(CC2CCOC2)C(=O)O)cc1
Temperature: 50 °C
Reaction time: 16 h
Yield: 90.5 %

Procedure:
To a solution of methyl 2-[4-(methylsulfonyl)phenyl]-3-(tetrahydrofuran-3-yl)propanoate (3.61 g) in a mixed solvent of methanol (46 mL) was added 2M aqueous sodium hydroxide solution (11.6 mL), and the mixture was stirred at 50° C. for 16 hr. The reaction mixture was acidified with 6M hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (3.12 g, 90%) as colorless crystals.
Reaction SMILES: [C@@H:1]([NH:5][C:6]1[C:7]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([O:18]C)=[O:17])=[CH:11][CH:10]=2)([CH2:3][CH3:4])[CH3:2].[H-].[Na+].I[CH3:30]>O1CCCC1>[C@@H:1]([N:5]([CH3:30])[C:6]1[C:7]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)([CH2:3][CH3:4])[CH3:2]
Reactant: CI
Reactant: CC[C@H](C)Nc1nc2cc(C(=O)OC)ccc2nc1-c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC[C@H](C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 44.5 %

Procedure:
To a solution of (S)-methyl 3-(sec-butylamino)-2-(4-fluorophenyl)quinoxaline-6-carboxylate (280.0 mg, 0.79 mmol) in tetrahydrofuran (30 mL) was added sodium hydride (127 mg, 3.17 mmol) and stirred for 1 h at room temperature. Subsequently, iodomethane (570 mg, 3.97 mmol) was added and stirred overnight at room temperature. The reaction was concentrated in vacuo and then quenched by the addition of water (20 mL), adjusted to pH 5 with hydrochloric acid (1N). The solids were collected by filtration to afford (S)-3-(sec-butyl(methyl)amino)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid as a yellow solid (124.3 mg, 44%).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][C@@H:25]([CH3:28])[CH2:26][CH3:27])=[O:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1>[Pd].C(OCC)(=O)C>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][C@@H:25]([CH3:28])[CH2:26][CH3:27])=[O:22])=[CH:17][CH:16]=2)=[CH:13][CH:14]=1
Reactant: CC[C@H](C)COC(=O)c1ccc(-c2ccc(OCc3ccccc3)cc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC[C@H](C)COC(=O)c1ccc(-c2ccc(O)cc2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 85.1 %

Procedure:
In a 125-ml Parr bomb equipped with a magnetic stirrer were placed 960 mg (S)-2-methyl-1-butyl 4-benzyloxy-4'-biphenylcarboxylate, 200 mg 5% palladium on carbon, and 50 ml ethyl acetate. The bomb was purged with argon and pressurized with 500 psi hydrogen. After stirring at room temperature for one day, thin layer chromatographic analysis showed that considerable starting material remained. An additional 200 mg 5% palladium on carbon was carefully added, and the bomb was re-pressurized with 500 psi hydrogen. After stirring for one more day, TLC analysis showed that the reaction was complete. The reaction mixture was filtered through Celite and the solids were washed thoroughly with ethyl acetate. Evaporation of the solvent yielded white crystals which were recrystallized from hexanes at low temperature to yield 0.62 g (85%) of product, mp 111.5°14 113° C., whose structure was confirmed by infrared, nuclear magnetic resonance, and mass spectral analyses, as follows. ##STR28##
Reaction SMILES: O[CH:2]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14].[OH-].[Li+:23].P([O-])([O-:27])([S-])=S.[S]>>[OH:27][CH:12]([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:13]([O-:15])=[O:14].[Li+:23]
Reactant: CCCCCCC(O)CCCCCCCCCCC(=O)O
Reactant: [O-]P([O-])(=S)[S-]
Agent: [Li+]
Agent: [OH-]
Agent: [S]
Product: CCCCCCCCCCCCCCCCC(O)C(=O)[O-]
Temperature: 98.88888888888889 °C

Procedure:
A lithium hydroxystearate grease thickener was prepared by saponification of a mixture containing 12-hydroxystearic acid (8%) and the glyceride thereof (9%) with lithium hydroxide in a mineral oil vehicle (ISO 150 viscosity grade of a 70/30 mixture of naphthenic and paraffinic stocks) at about 350° F. in a closed contactor. After depressuring and dehydration of the thickener in an open kettle sufficient mineral oil was added to reduce the thickener content to about 9.0%. After cooling to 210° F., a typical grease additive package, consisting of an amine antioxidant, phenolic antioxidant, metallic dithiophosphate, sulfur-containing metal deactivator and nitrogen containing antirust additives, was added. The dropping point of this base grease was 201° C.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[Br:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH:13](CC(C)C)[C:14](Cl)=[O:15]>C(=S)=S>[Br:5][C:6]1([CH2:6][CH:7]([CH3:12])[CH3:8])[CH:11]=[CH:10][CH:9]=[C:8]2[CH:7]1[CH2:12][CH2:13][C:14]2=[O:15]
Reactant: CC(C)CC(Cc1ccccc1Br)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: CC(C)CC1(Br)C=CC=C2C(=O)CCC21
Reaction time: 1 h
Yield: 209.6 %

Procedure:
A 500-ml four-necked round flask equipped with a stirrer, a Dimroth condenser, a dropping funnel, a thermometer and a NaOH trap was charged with 20.33 g (152.5 mmol) of anhydrous aluminum chloride and 70 ml of carbon disulfide. To the mixture was added dropwise a solution containing 40.2 g (132.6 mmol) of the above-obtained 3-(2-bromophenyl)-2-i-butylpropionic acid chloride dissolved in 50 ml of carbon disulfide under a nitrogen atmosphere while cooling with ice bath. After the addition was completed, the temperature in the flask was elevated to room temperature, and the mixture was stirred for 1 hour. Then, the reaction mixture was quenched by pouring onto 200 ml of ice water, which was then extracted with 100 ml of ether three times. The combined organic phase was washed with 100 ml of a saturated aqueous solution of sodium bicarbonate, and then 100 ml of a saturated NaCl aq., followed by dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to give 37.4 g of the desired product as an orange liquid. This ketone was used in the next reaction without further purification.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:20][CH2:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1.[NH:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([NH:39][C:40]3[C:49]4[C:44](=[CH:45][C:46](O)=[C:47]([O:50][CH3:51])[CH:48]=4)[N:43]=[CH:42][C:41]=3[C:53]#[N:54])[CH:37]=2)[CH2:32][CH2:31]1.CCOC(/N=N/C(OCC)=O)=O.Cl.C(=O)(O)[O-].[Na+]>O.O1CCCC1.C(Cl)(Cl)Cl>[NH:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([NH:39][C:40]3[C:49]4[C:44](=[CH:45][C:46]([O:20][CH2:21][CH2:22][CH2:23][C:24]5[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=5)=[C:47]([O:50][CH3:51])[CH:48]=4)[N:43]=[CH:42][C:41]=3[C:53]#[N:54])[CH:37]=2)[CH2:32][CH2:31]1
Reactant: OCCCc1ccncc1
Reactant: COc1cc2c(Nc3ccc4c(c3)NCC4)c(C#N)cnc2cc1O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: Cl
Agent: O=C([O-])O
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: C1CCOC1
Product: COc1cc2c(Nc3ccc4c(c3)NCC4)c(C#N)cnc2cc1OCCCc1ccncc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a 0° C. solution consisting of 2 ml of chloroform, 1 ml of tetrahydrofurane, 167 mg (0.64 mM) of triphenyl phosphine, 52 μl (0.40 mM) of 4-hydroxypropylpyridine and 107 mg (0.32 mM) of the 4-(2,3-dihydro-1H-indol-6-ylamino)-7-hydroxy-6-methoxy-quinoline-3-carbonitrile, was slowly added 101 μL (0.64 mM) of DEAD. The reaction was allowed to run at 0° C. for 15 min and then allowed to warm to room temperature. The heterogeneous solution was allowed to stir at room temperature for 7 hour. TCL and ES MS showed no signs of product formation. An additional 1 ml of chloroform and 500 mL of tetrahydrofurane was added and the reaction was refluxed for 14 hours. Once again no signs of product formation were seen. The volume of the reaction was reduced to 1 ml by heating and then brought up to 4 ml by addition of tetrahydrofurane. Once the reaction had cooled to room temperature, and additional 80 mg (0.32 mM) of triphenyl phosphine, 25 μl (0.20 mM) of 4-hydroxypropylpyridine was added followed by the slow addition of 50 μL (0.32 mM) of DEAD. The reaction quickly turned to a clear brown solution. After six hours at room temperature, TLC and the mass spectrum showed the reaction was complete. To the reaction mixture was added 10 ml of 1N HCl followed by 20 ml of water. The solution was extracted five time with 25 ml portions of chloroform. The water layer was allowed to stand for three hours at room temperature and the resulting brown solid was isolated by filtration. The filtrate was treated with solid sodium bicarbonate until a yellow solid fell from solution. The precipitate was isolated and washed with excess water followed by 1 ml of diethyl ether and dried under vacuum at 80° C. to give 57 mg of 4-(2,3-dihydro-1H-indol-6-ylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-quinoline-3-carbonitrile as a yellow solid: mass spectrum (electrospray, m/e): 452.3 M+H, 226.7 M+2H/2, mp=100-105° C.
Reaction SMILES: [CH2:1]1[C:14]2[C:5](=[N:6][C:7]3[C:12]([C:13]=2[NH2:15])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:4][CH2:3][CH2:2]1.N1CCOCC1.[C:22]([C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1)#[N:23]>C1(C)C=CC=CC=1>[C:22]([C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[N:15][C:13]2[C:12]3[C:7]([N:6]=[C:5]4[C:14]=2[CH2:1][CH2:2][CH2:3][CH2:4]4)=[CH:8][CH:9]=[CH:10][CH:11]=3)=[CH:26][CH:25]=1)#[N:23]
Reactant: N#Cc1ccc(C=O)cc1
Reactant: Nc1c2c(nc3ccccc13)CCCC2
Solvent: Cc1ccccc1
Solvent: C1COCCN1
Product: N#Cc1ccc(C=Nc2c3c(nc4ccccc24)CCCC3)cc1
Yield: 45.8 %

Procedure:
1,2,3,4-Tetrahydro-9-acridinamine (3.2 g) was refluxed in 300 ml of toluene containing morpholine (2.8 g) and 4-cyanobenzaldehyde (2.60 g). After twenty-four (24) hours the reaction mixture was concentrated and purified by flash chromatography. Fractions containing the product were concentrated and recrytallized from CH2Cl2 /pentane to give 2.30 g of product, m.p. 204°-205° C.
Reaction SMILES: Br[CH:2]([CH2:5][CH3:6])[CH2:3][CH3:4].[O:7]=[CH:8][C:9]1[CH:17]=[CH:16][C:14]([OH:15])=[C:11]([O:12][CH3:13])[CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>CCO>[CH3:13][O:12][C:11]1[CH:10]=[C:9]([CH:17]=[CH:16][C:14]=1[O:15][CH:2]([CH2:5][CH3:6])[CH2:3][CH3:4])[CH:8]=[O:7]
Reactant: CCC(Br)CC
Reactant: COc1cc(C=O)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCC(CC)Oc1ccc(C=O)cc1OC
Yield: 47 %

Procedure:
3-Bromopentane (1.2 mL, 9.9 mmol) was added to a suspension of vanillin (1.0 g, 6.6 mmol), potassium carbonate (2.7 g, 20 mmol) in EtOH (10 mL) and treated according to Procedure 3. The crude product was purified by flash chromatography with 10% EtOAc/petrol as eluent to give 3-methoxy-4-(pent-3-yloxy)benzaldehyde (0.69 g, 47%) as a pale yellow oil; δH (400 MHz, CDCl3) 0.96 (t, J=7.2 Hz, 6H, CH3), 1.73 (m, 4H, CH2), 3.88 (s, 3H, OCH3), 4.23 (m, 1H, OCH), 6.94 (d, J5,6=8.0 Hz, 1H, H5), 7.40 (s, 1H, H2), 7.41 (d, J5,6=8.0 Hz, 1H, H6), 9.81 (s, 1H, CHO); δC (100 MHz, CDCl3) 9.6, 26.1, 56.0, 81.9, 109.8, 113.1, 126.5, 129.7, 150.5, 154.0, 190.7; vmax 1133, 1263, 1504, 1582, 1682, 2967 cm−1.
Reaction SMILES: C([N:8]1[CH2:15][CH2:14][CH:13]2[CH:9]1[CH:10]([CH3:16])[NH:11][CH2:12]2)C1C=CC=CC=1>C(O)C.[Pd]>[CH3:16][CH:10]1[CH:9]2[CH:13]([CH2:14][CH2:15][NH:8]2)[CH2:12][NH:11]1
Reactant: CC1NCC2CCN(Cc3ccccc3)C21
Agent: [Pd]
Solvent: CCO
Product: CC1NCC2CCNC21

Procedure:
7.8 g (36 mmol) of 2-benzyl-8-methyl-2,7-diazabicyclo[3.3.0]octane in 200 ml of ethanol are hydrogenated on 2 g of palladium/active carbon (10% Pd) at 100° C. and 100 bar. The catalyst is filtered off with suction, the filtrate is concentrated, and the residue is distilled. The distillate crystallises.
Reaction SMILES: C(OCC)C.[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([CH3:17])[CH:11]=[CH:10]2.C([Li])CCC.[CH3:23][C:24]([CH3:26])=[O:25]>O>[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([CH2:17][C:24]([CH3:26])([OH:25])[CH3:23])[CH:11]=[CH:10]2
Reactant: Cc1ccc2cc(Br)ccc2n1
Reactant: CC(C)=O
Agent: [Li]CCCC
Solvent: O
Solvent: CCOCC
Product: CC(C)(O)Cc1ccc2cc(Br)ccc2n1
Reaction time: 0.08 h

Procedure:
20 ml of diethylether was added to 2.22 g of 6-bromoquinaldine, and 3.76 ml of 2.66 M normal butyl lithium was dropped thereto at −78° C. The obtained suspension was stirred for 5 min, 2 ml of anhydrous acetone was added and the mixture was further stirred for 10 min, and water was added. The products were extracted with ethyl acetate, organic layer was dried with anhydrous sodium sulfated and the solvents were distilled outunder reduced pressure. The obtained residues were separated and purified by silicagel colum chromatography (hexane:ethyl acetate=2:1) to obtain 1.14 g of the above compound.