Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Se:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[CH2:10]=[O:11].C[OH:13]>O>[OH:11][CH2:10][N:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[Se:1](=[O:13])[CH2:2]1
Reactant: C=O
Reactant: c1ccc2[se]cnc2c1
Reactant: CO
Solvent: O
Product: O=[Se]1CN(CO)c2ccccc21
Temperature: 40 °C

Procedure:
2 grams (0.01 mol) of benzoselenazoline, 2 cm3 (0.02 mol) of aqueous formaldehyde solution and 2 cm3 of methanol are introduced into a ground-necked flask. The mixture is brought to reflux two hours. After cooling to 40° C. 20 cm3 of water are added. The mixture is allowed to cool and the product is drained, washed with water, dried and recrystallized in cyclohexane.
Reaction SMILES: O[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1N=[CH:9][CH:8]=[CH:7]2.N1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.O>C(O)C>[C:6]1([CH:7]=[CH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[CH:4][CH:3]=[CH:2][CH:11]=1
Reactant: Oc1cccc2cccnc12
Reactant: C1CCNCC1
Solvent: O
Solvent: CCO
Product: C(=Cc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 78 %

Procedure:
Complex II-1 was synthesized through a reaction in the ethanol solution of 8-hydroxyquinoline, 2,2′-diol-stilbene (L3) and GaCl3. First, a solution of 8-hydroxyquinoline (0.05M) and piperidine (0.05M) in 100 ml ethanol was added to a solution of GaCl3 (0.5M) in 10 ml ethanol very slowly with an intensive stirring. Then, a solution of L3 (0.01M) and piperidine (0.02M) in 500 ml ethanol was introduced slowly. The mixture was stirred for about 1 hour and cooled to room temperature and kept in dark for about 1 hour. A scarlet precipitate was formed when equivalent amount water was poured into the solution. The product was collected by filtration and washed with ethanol rapidly, then dried under an infrared lamp. The obtained product powder showed strong red fluorescence under an ultraviolet lamp. The materials were further purified by an improved train sublimation method. The L3 ligand was obtained by typical synthesis method of stilbene. The molecular structure of Complex II-I was supported by mass spectrum (MS) and element analysis.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:30])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[CH:16]=1)[C:11]([CH3:29])([CH3:28])[CH2:10]2)=[O:4].[OH-].[Na+].Cl>CO.O1CCCC1.O>[Cl:30][C:7]1[CH:8]=[C:9]2[C:14](=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=1)[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[CH:16]=1)[C:11]([CH3:29])([CH3:28])[CH2:10]2
Reactant: COC(=O)c1cc(Cl)cc2c1NC(c1cccc(N3CCN(C)CC3)c1)C(C)(C)C2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CN1CCN(c2cccc(C3Nc4c(cc(Cl)cc4C(=O)O)CC3(C)C)c2)CC1
Temperature: 70 °C
Reaction time: 6 h
Yield: 89.8 %

Procedure:
To a stirred mixture solution of 6-chloro-3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (1.0 g, 2.4 mmol) in methanol (5.0 mL) and tetrahydrofuran (6.0 mL) was added 50% sodium hydroxide in water (2.0 mL). The reaction mixture was stirred at 70° C. for 6 hours. The mixture was neutralized with a 3 N aqueous hydrochloric acid solution and extracted with ethyl acetate (2×100 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 6-chloro-3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (892 mg, 90%) as a white solid: LC/MS m/e calcd for C23H28ClN3O2 (M+H)+: 414.95, observed: 414.1.
Reaction SMILES: CC1(C)[O:38][C@H:5]2[O:6][C@H:7]([CH2:15][N:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]4([C:36]5[C:27](=[CH:28][C:29]6[O:34][CH2:33][CH2:32][O:31][C:30]=6[CH:35]=5)[O:26][CH2:25]4)[C:17]3=[O:37])[C@@H:8]3[O:12]C(C)(C)[O:10][C@@H:9]3[C@H:4]2[O:3]1>FC(F)(F)C(O)=O>[O:37]=[C:17]1[C:18]2([C:36]3[C:27](=[CH:28][C:29]4[O:34][CH2:33][CH2:32][O:31][C:30]=4[CH:35]=3)[O:26][CH2:25]2)[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:16]1[CH2:15][C@H:7]1[O:6][CH:5]([OH:38])[C@H:4]([OH:3])[C@@H:9]([OH:10])[C@H:8]1[OH:12]
Reactant: CC1(C)O[C@H]2[C@@H](O1)[C@@H](CN1C(=O)C3(COc4cc5c(cc43)OCCO5)c3ccccc31)O[C@@H]1OC(C)(C)O[C@@H]12
Solvent: O=C(O)C(F)(F)F
Product: O=C1N(C[C@H]2OC(O)[C@H](O)[C@@H](O)[C@H]2O)c2ccccc2C12COc1cc3c(cc12)OCCO3
Temperature: 25 °C
Reaction time: 3 h
Yield: 6.6 %

Procedure:
1′-{[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4′,5′-d]pyran-5-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.45 g, 0.83 mmol) was suspended in 80% v/v aqueous trifluoroacetic acid (40 mL) and the reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was concentrated in vacuo and the residue recrystallized from ethanol to afford 6-deoxy-6-(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)-D-galactopyranose (0.025 g, 7%) as an off white solid: mp 122-126° C. (ethanol); 13C NMR (75 MHz, CDCl3) δ178.5, 155.2, 155.2, 155.1, 155.0, 144.5, 142.6, 142.2, 142.1, 138.0, 138.0, 132.3, 132.0, 129.0, 123.5, 123.4, 121.0, 120.9, 111.6, 111.4, 109.9, 109.7, 99.2, 92.7, 79.9, 64.4, 63.8, 60.4, 58.0, 21.0, 14.2; MS (ES+) m/z 480.0 (M+23).
Reaction SMILES: ClC1C=C(C=CC=1Cl)C([NH:7][CH2:8][C:9]([NH:11][C@@H:12]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)[CH2:13]1)=[O:10])=O.ClC1C=C(C=CC=1Cl)C(Cl)=[O:40]>>[NH2:7][CH2:8][C:9]([NH:11][C@@H:12]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:18][CH2:19][O:40][CH2:21][CH2:22]2)[CH2:13]1)=[O:10].[NH2:7][CH2:8][C:9]([NH:11][C@@H:12]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)[CH2:19][CH2:18]2)[CH2:13]1)=[O:10]
Reactant: COc1ccc(N2CCC(N3CC[C@@H](NC(=O)CNC(=O)c4ccc(Cl)c(Cl)c4)C3)CC2)cc1
Reactant: O=C(Cl)c1ccc(Cl)c(Cl)c1
Product: COc1ccc(N2CCC(N3CC[C@@H](NC(=O)CN)C3)CC2)cc1
Product: NCC(=O)N[C@@H]1CCN(C2CCOCC2)C1

Procedure:
The title compound was synthesized in similar fashion to 3,4-dichloro-N-[2-({(3R)-1-[1-(4-methoxyphenyl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl)benzamide, substituting 3-(trifluoromethoxy)benzoyl chloride for 3,4-dichlorobenzoylchloride, as well as 2-amino-N-[(3R)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]acetamide for 2-amino-N-{(3R)-1-[1-(4-methoxyphenyl)piperidin-4-yl]pyrrolidin-3-yl}acetamide, and was isolated as a white solid. 1H-NMR (CDCl3) δ: 1.40-1.78 (m, 5H), 2.12-2.36 (m, 3H), 2.62 (d, J=5.4 Hz, 2H), 2.83 (m, 1H), 2.94 (m, 1H), 3.33 (m, 2H), 3.91 (m, 2H), 4.06 (d, J=5.4 Hz, 2H), 4.39 (m, 1H), 7.16 (d, J=7.8 Hz, 1H), 7.30 (m, 1H), 7.40 (t, J=8.0 Hz, 1H), 7.70 (m, 1H). MS m/z: 416 (M+1).
Reaction SMILES: [C:1]1([CH3:17])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[C:14]2[C:10]([CH2:11][C:12](=[O:16])[NH:13]2)=[CH:9][CH:8]=1.[C:18]([O:27][CH2:28][CH3:29])(OCC)(OCC)[CH2:19][CH3:20].C(O[C:34](=[O:36])[CH3:35])(=O)C>>[C:34]([N:13]1[C:14]2[C:10](=[CH:9][CH:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[CH3:17])[CH:15]=2)[C:11](=[C:18]([O:27][CH2:28][CH3:29])[C:19]2[CH:20]=[CH:3][CH:2]=[CH:1][CH:6]=2)[C:12]1=[O:16])(=[O:36])[CH3:35]
Reactant: CCOC(CC)(OCC)OCC
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccccc1-c1ccc2c(c1)NC(=O)C2
Product: CCOC(=C1C(=O)N(C(C)=O)c2cc(-c3ccccc3C)ccc21)c1ccccc1

Procedure:
Prepared from 6-(2-tolyl)-2-indolinone, triethyl orthopropionate and acetic anhydride
Reaction SMILES: Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].N1C=CC=CC=1.[CH3:14][CH:15]([CH2:18][CH3:19])[CH2:16][OH:17]>ClCCl>[C:2](=[O:3])([O:17][CH2:16][CH:15]([CH3:14])[CH2:18][CH3:19])[O:4][CH:5]([Cl:7])[CH3:6]
Reactant: CCC(C)CO
Reactant: CC(Cl)OC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCC(C)COC(=O)OC(C)Cl
Temperature: 0 °C

Procedure:
In 70 ml of dichloromethane are dissolved 13 ml of 2-methyl-1-butanol and 17 g of 1-chloroethyl chloroformate, and the solution is cooled to 0° C. With stirring, a solution of 9.6 ml of pyridine in 30 ml of dichloromethane is added dropwise, and the mixture is stirred for 30 minutes. The salt precipitate is collected by filtration and the filtrate is washed with two 200-ml portions of water and dried over anhydrous sodium sulfate. The solvent is then distilled off under reduced pressure and the residue is further distilled under reduced pressure to give 12.5 g of 1-chloroethyl 2-methylbutyl carbonate.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:7]([OH:9])=O)=[CH:4][NH:5][CH:6]=1.Cl.[CH2:11]([O:13][C:14](=[O:18])[CH2:15][CH2:16][NH2:17])[CH3:12].C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl>[CH3:1][C:2]1[C:3]([C:7]([NH:17][CH2:16][CH2:15][C:14]([O:13][CH2:11][CH3:12])=[O:18])=[O:9])=[CH:4][NH:5][CH:6]=1
Reactant: CCOC(=O)CCN
Reactant: Cc1c[nH]cc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)CCNC(=O)c1c[nH]cc1C
Yield: 43.1 %

Procedure:
Using 7.63 g (60 mmol) of 4-methyl-3-pyrrolecarboxylic acid, 15.4 g (100 mmol) of β-alanine ethyl ester hydrochloride, 14 ml (100 mmol) of triethylamine, 17.3 g (90 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 100 ml of methylene chloride, 5.80 g of the title compound were obtained in a similar manner as in Example 2 (yield: 26%).
Reaction SMILES: [NH2:1][C:2]1[N:26]=[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:12]=[CH:13][C:14]([F:25])=[C:15]([NH:17]C(=O)OC(C)(C)C)[CH:16]=3)=[CH:9][N:4]2[N:3]=1.[CH:27]1([C:30](Cl)=[O:31])[CH2:29][CH2:28]1.FC(F)(F)C(O)=O>CN(C)C(=O)C>[NH2:17][C:15]1[CH:16]=[C:11]([CH:12]=[CH:13][C:14]=1[F:25])[O:10][C:8]1[CH:7]=[CH:6][C:5]2[N:4]([N:3]=[C:2]([NH:1][C:30]([CH:27]3[CH2:29][CH2:28]3)=[O:31])[N:26]=2)[CH:9]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(Oc2ccc3nc(N)nn3c2)ccc1F
Reactant: O=C(Cl)C1CC1
Solvent: O=C(O)C(F)(F)F
Solvent: CC(=O)N(C)C
Product: Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)nn3c2)ccc1F
Yield: 77.2 %

Procedure:
In the same manner as in Example 66-2 and using tert-butyl {5-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-2-fluorophenyl}carbamate (8.99 g, 25.0 mmol), cyclopropanecarbonyl chloride (3.82 mL, 42.0 mmol), N,N-dimethylacetamide (60 mL) and trifluoroacetic acid (50 mL) as starting materials, the title compound (6.32 g, 77%) was obtained as a white solid.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=2[C:14]2[C:15]3[N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:21]([CH3:31])=[C:20]([C:32](O)=[O:33])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:3][CH2:2]1.[NH2:35][C@H:36]1[C@H:40]([OH:41])[CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]1>>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=2[C:14]2[C:15]3[N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:29])([CH3:28])[CH3:30])[C:21]([CH3:31])=[C:20]([C:32]([NH:35][C@H:36]4[C@H:40]([OH:41])[CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]4)=[O:33])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:3][CH2:2]1
Reactant: COc1ccc(-c2ncnc3c(C(=O)O)c(C)n(COCC[Si](C)(C)C)c23)c(OCC2CC2)c1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](N)[C@H](O)C1
Product: COc1ccc(-c2ncnc3c(C(=O)N[C@@H]4CN(C(=O)OC(C)(C)C)C[C@H]4O)c(C)n(COCC[Si](C)(C)C)c23)c(OCC2CC2)c1

Procedure:
Starting from 4-[2-(cyclopropylmethoxy)-4-methoxyphenyl]-6-methyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (example D.c5) and commercially available tert-butyl(3R*,4R*)-3-amino-4-hydroxy-pyrrolidine-1-carboxylate the title compound is obtained as colorless foam.
Reaction SMILES: [H-].[Na+].[CH3:3][S:4]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH2:11][CH2:10]2)(=[O:6])=[O:5].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[C:34](Cl)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.[Cl-].[Na+].O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[C:34]([N:12]3[C:13]4[C:9](=[CH:8][C:7]([S:4]([CH3:3])(=[O:6])=[O:5])=[CH:15][CH:14]=4)[CH2:10][CH2:11]3)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]
Reactant: CS(=O)(=O)c1ccc2c(c1)CCN2
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2cc(Cl)ncn2)CC1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCc4cc(S(C)(=O)=O)ccc43)ncn2)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 40.3 %

Procedure:
To a suspension of sodium hydride (0.25 g, 2 eq) in 10 mL of DMF, was added 5-methanesulfonyl-2,3-dihydro-1H-indole (0.63 g, 1 eq). The mixture was stirred at room temperature for 10 minutes then 3a (1 g, 3.19 mmol) was added. The resulting mixture was heated up to 80° C. for 18 h. The reaction mixture was then allowed to cool down to room temperature and brine (200 mL) was added. The solution was extracted with DCM twice (200 mL then 50 mL). The combined extracts were washed with brine (2×50 mL), dried over magnesium sulfate and filtered. The solvent was removed under vacuum to give an oil which was purified by column chromatography (elution with 10-100% ethyl acetate and 0.1% TEA in hexanes) to give 0.61 g of 4a (40% yield), LCMS 475.2 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[OH-].[K+].[CH3:13]I>CO.C(OCC)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:13])=[CH:4][CH:3]=1
Reactant: CI
Reactant: Brc1ccc2cn[nH]c2c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CCOCC
Product: Cn1ncc2ccc(Br)cc21

Procedure:
6-Bromoindazole (400 mg) was dissolved in methanol (10 mL). To this solution, potassium hydroxide (450 mg) was added followed by methyl iodide (0.50 mL) and the mixture was refluxed for 2.5 h. The reaction was cooled, diluted with diethyl ether, washed with water, brine, dried and concentrated. The product 6-bromo-1-methylindazole (160 mg) was separated from its isomer by Combiflash.
Reaction SMILES: [CH3:1][N:2]1[C@H:16]2[C@@H:6]([C:7]3[CH:8]=[C:9]([N+:18]([O-:20])=[O:19])[CH:10]=[C:11]4[C:17]=3[C@H:14]([CH2:15]2)[CH2:13][NH:12]4)[CH2:5][C@H:4]([NH:21][C:22](=[O:28])[N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:3]1.F[B-](F)(F)F.[CH3:34][S+:35](C)SC.N>O1CCCC1>[CH3:1][N:2]1[C@H:16]2[C@@H:6]([C:7]3[CH:8]=[C:9]([N+:18]([O-:20])=[O:19])[CH:10]=[C:11]4[C:17]=3[C@H:14]([CH2:15]2)[CH2:13][N:12]4[S:35][CH3:34])[CH2:5][C@H:4]([NH:21][C:22](=[O:28])[N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:3]1
Reactant: CS[S+](C)C
Reactant: CCN(CC)C(=O)N[C@H]1C[C@@H]2c3cc([N+](=O)[O-])cc4c3[C@@H](CN4)C[C@H]2N(C)C1
Agent: F[B-](F)(F)F
Agent: N
Solvent: C1CCOC1
Product: CCN(CC)C(=O)N[C@H]1C[C@@H]2c3cc([N+](=O)[O-])cc4c3[C@H](C[C@H]2N(C)C1)CN4SC
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 64.6 %

Procedure:
Under argon, 38 mg (0.1 mmol) of 3-(2,3β-dihydro-6-methyl-13-nitro-8α-ergolinyl)-1,1-diethylurea in 2 ml of absolute, freshly distilled tetrahydrofuran is combined with 47 mg (0.24 mmol) of dimethylmethylthiosulfonium fluoroborate, and the mixture is agitated for 20 minutes at room temperature. For working-up purposes, the batch is poured on 10 ml of ice and rendered alkaline with 25% strength ammonia solution. The organic phase is extracted repeatedly with methylene chloride. The extracts are dried over magnesium sulfate and concentrated. The crude product is purified over a preparative silica gel plate with methylene chloride/methanol 9:1 as the eluent, thus obtaining 28 mg of 3-(2,3β-dihydro-6-methyl-1-methylthio-13-nitro-8α-ergolinyl)-1,1-diethylurea.
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]1([C:13]2([CH2:19][CH:20]=O)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:22][CH2:23][O:24][C:25]([CH3:27])=[O:26]>C1COCC1>[C:7]1([C:13]2([CH2:19]/[CH:20]=[CH:27]/[C:25]([O:24][CH2:23][CH3:22])=[O:26])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CCOC(C)=O
Reactant: O=CCC1(c2ccccc2)CCCCC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)/C=C/CC1(c2ccccc2)CCCCC1
Reaction time: 0.5 h

Procedure:
To a solution of triethyl phosphonoacetate (0.601 mL, 3.00 mmol) in THF (10 mL) at 0° C. was added 1 M potassium tert-butoxide (3.00 mL, 3.00 mmol) in THF dropwise and the mixture was stirred for 30 mins at the same temp. Then a solution of 2-(1-phenylcyclohexyl)acetaldehyde (405 mg, 2.0 mmol) in 4 ml of THF was added dropwise and the mixture was stirred for 0.5 hrs at 0° C. and for 1.5 hrs at room temp. It was added to EtOAc and washed with water (2×) and saturated NH4Cl. It was dried over Na2SO4 and evaporated to give an oily residue. It was purified by Combiflash (80 g silica gel) eluting with 5:95 EtOAc-hexane to give (E)-ethyl 4-(1-phenylcyclohexyl)but-2-enoate (213.7 mg). 1H NMR (400 MHz, CCl3D) δ ppm 7.27-7.37 (4H, m), 7.15-7.23 (1H, m), 6.60 (1H, ddd, J=15.49, 7.91, 7.80 Hz), 5.66 (1H, dt, J=15.60, 1.32 Hz), 4.12 (2H, q, J=7.18 Hz), 2.39 (2H, dd, J=7.80, 1.21 Hz), 2.11 (2H, dd, J=13.07, 5.60 Hz), 1.33-1.66 (8H, m), 1.24 (3H, t, J=7.18 Hz).
Reaction SMILES: N1C2C(=CC=CC=2)C(C(=O)[CH2:11][C:12]2([OH:29])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=3)[N:14]([CH2:22][CH2:23][CH2:24][N:25]=[N+:26]=[N-:27])[C:13]2=[O:28])=C1.N(CCCN1C2C(=CC(C)=CC=2)C(=O)C1=O)=[N+]=[N-].[CH3:49][O:50][C:51]1[N:56]=[C:55]([C:57](=[O:59])C)[CH:54]=[CH:53][CH:52]=1>>[N:25]([CH2:24][CH2:23][CH2:22][N:14]1[C:15]2[C:20](=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[C:12]([OH:29])([CH2:11][C:57]([C:55]2[CH:54]=[CH:53][CH:52]=[C:51]([O:50][CH3:49])[N:56]=2)=[O:59])[C:13]1=[O:28])=[N+:26]=[N-:27]
Reactant: Cc1ccc2c(c1)C(O)(CC(=O)c1c[nH]c3ccccc13)C(=O)N2CCCN=[N+]=[N-]
Reactant: COc1cccc(C(C)=O)n1
Agent: Cc1ccc2c(c1)C(=O)C(=O)N2CCCN=[N+]=[N-]
Product: COc1cccc(C(=O)CC2(O)C(=O)N(CCCN=[N+]=[N-])c3ccc(C)cc32)n1

Procedure:
This compound was made in a similar manner to 3-(2-(1H-indol-3-yl)-2-oxoethyl)-1-(3-azidopropyl)-3-hydroxy-5-methylindolin-2-one using 1-(3-azidopropyl)-5-methylindoline-2,3-dione and 1-(6-methoxypyridin-2-yl)ethanone (commercially available from Fisher Scientific).
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].C(N(C(C)C)C(C)C)C.C1(C)C=CC(S(O[CH2:31][CH2:32][CH:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[O:35][CH2:34]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:31][CH2:32][CH:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[O:35][CH2:34]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)OCCC2COc3ccccc3C2)cc1
Reactant: CCOC(=O)C1CCNCC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C1CCN(CCC2COc3ccccc3C2)CC1
Reaction time: 16 h
Yield: 97.1 %

Procedure:
First 3.76 g (24 mmol) of piperidine-4-carboxylic acid ethyl ester and then 3.1 g (24 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.98 g (12 mmol) of 3-[2-(p-toluenesulphonyloxy)ethyl]chroman in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction by shaking is carried out with diethyl ether. The combined organic phases are extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 3.8 g (100%) of crude product are obtained which are chromatographed on 200 g of silica gel (0.040-0.063 mm) using ethyl acetate as the eluant. 3.7 g (97.3%) of 1-[2-(chroman-3-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester are then obtained in the form of a colourless oil. The 1-[2-chroman-3-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester hydrochloride produced thereform using hydrochloric acid in diethyl ether crystallises from ethanol/diethyl ether and melts at 182°-186°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH2:9][CH2:8][C:7]=2[CH:20]=1.Cl[C:22]1[N:27]=[CH:26][N:25]=[C:24]([C:28]([N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32][CH:31]2[CH2:39][CH3:40])=[O:29])[CH:23]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:39]([CH:31]1[CH2:32][C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:30]1[C:28]([C:24]1[N:25]=[CH:26][N:27]=[C:22]([N:17]2[CH2:18][CH2:19][CH:14]([N:10]3[CH2:9][CH2:8][C:7]4[CH:20]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=4[NH:12][C:11]3=[O:13])[CH2:15][CH2:16]2)[CH:23]=1)=[O:29])[CH3:40]
Reactant: CCC1Cc2ccccc2N1C(=O)c1cc(Cl)ncn1
Reactant: COc1ccc2c(c1)CCN(C1CCNCC1)C(=O)N2
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCC1Cc2ccccc2N1C(=O)c1cc(N2CCC(N3CCc4cc(OC)ccc4NC3=O)CC2)ncn1

Procedure:
110 mg (0.40 mmol) 7-methoxy-3-piperidin-4-yl-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, 103 mg (0.36 mmol) (6-chloro-pyrimidin-4-yl)-(2-ethyl-2,3-dihydro-indol-1-yl)-methanone and 0.14 mL (0.80 mmol) DIPEA in 3.0 mL DMF were stirred overnight at RT. Then the reaction mixture was purified by preparative HPLC-MS. The product-containing fractions were combined, the organic solvent was evaporated down and the residue was neutralised with 1N aqueous sodium hydroxide solution. The precipitate formed was suction filtered, washed with water and dried under HV.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[N:6][C:5]([C:9]#[N:10])=[C:4]([C:11]#[N:12])[N:3]=1.[C:13]([NH2:17])([CH3:16])([CH3:15])[CH3:14].O>O1CCCC1>[Cl:8][C:7]1[C:2]([NH:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[N:3][C:4]([C:11]#[N:12])=[C:5]([C:9]#[N:10])[N:6]=1
Reactant: CC(C)(C)N
Reactant: N#Cc1nc(Cl)c(Cl)nc1C#N
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)Nc1nc(C#N)c(C#N)nc1Cl
Reaction time: 2 h
Yield: 76.4 %

Procedure:
5.0 g (0.025 mol) of 2,3-dichloro-5,6-dicyanopyrazine was dissolved in 50 ml of dry tetrahydrofuran, and 25 ml of a dry tetrahydrofuran solution containing 3.7 g (0.050 mol) of tert-butylamine was dropwise added thereto at a temperature of from -15°to 0° C. After completion of the dropwise addition, the mixture was stirred for 2 hours, and the reaction solution was poured into 500 ml of water. The precipitated solid was collected by filtration and recrystallized from toluene to obtain 4.5 g of slightly yellow crystals (yield: 76.4%, melting point: 174°-176° C.).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11](=O)[CH2:12]Cl)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH2:15][C:16]([NH2:18])=[S:17]>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:15]=[C:16]([NH2:18])[S:17][CH:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: NC(N)=S
Reactant: O=C(CCl)c1c[nH]c2ncc(Br)cc12
Solvent: CCO
Product: Nc1nc(-c2c[nH]c3ncc(Br)cc23)cs1
Yield: 98.5 %

Procedure:
A solution 1-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-chloro-ethanone (0.32 g, 1.17 mmol) and thio urea (0.097 g, 1.28 mmol) in ethanol (4 mL) was stirred at 80° C. for 1.5 hours. The resulting precipitate was filtered, washed with MeOH, and dried under vacuum to give 4-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-ylamine (0.34 g, 99% yield).