Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][C:5](=[O:8])[CH2:4][CH2:3]1.F[B-](F)(F)F.[CH2:15]([O:17][CH+:18][O:19][CH2:20][CH3:21])[CH3:16]>>[CH2:15]([O:17][CH:18]([O:19][CH2:20][CH3:21])[CH:4]1[CH2:3][C:2]([CH3:9])([CH3:1])[CH2:7][CH2:6][C:5]1=[O:8])[CH3:16]
Reactant: CCO[CH+]OCC
Reactant: CC1(C)CCC(=O)CC1
Agent: F[B-](F)(F)F
Product: CCOC(OCC)C1CC(C)(C)CCC1=O

Procedure:
reacting 4,4-dimethylcyclohexanone, diethoxycarbenium fluoroborate and a fifth base to provide (2-(diethoxymethyl)-4,4-dimethylcyclohexanone and isolating or not isolating the 2-(diethoxymethyl)-4,4-dimethylcyclohexanone;
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH2:21][CH3:22])[CH:15]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)=[O:30])[CH:24]=1>>[CH2:21]([O:20][C:16]1[CH:15]=[C:14]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:29]([C:31]4[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=4)([C:25]4[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=4)[OH:30])[CH:3]=3)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=2)[CH:19]=[CH:18][CH:17]=1)[CH3:22]
Reactant: O=C(c1cccnc1)c1cccnc1
Reactant: CCOc1cccc(-c2cc(OC)nc3ccc(Br)cc23)c1
Product: CCOc1cccc(-c2cc(OC)nc3ccc(C(O)(c4cccnc4)c4cccnc4)cc23)c1
Yield: 41.2 %

Procedure:
Following the same procedure as that described in example 1E, 6-bromo-4-(3-ethoxy-phenyl)-2-methoxy-quinoline (400 mg, 1.11 mmol) and di-pyridin-3-yl-methanone (225 mg, 1.22 mmol) generated the title compound of 37A (212 mg, 41.2% yield).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl.C(=O)([O-])[O-].[K+].[K+].[F:23][CH2:24][CH2:25][CH2:26]I>C(#N)C.O>[F:23][CH2:24][CH2:25][CH2:26][N:13]1[CH2:14][CH2:15][N:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH2:11][CH2:12]1
Reactant: FCCCI
Reactant: O=[N+]([O-])c1cccc(N2CCNCC2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: O=[N+]([O-])c1cccc(N2CCN(CCCF)CC2)c1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a suspension of 1-(3-nitro-phenyl)-piperazine; hydrochloride (1.0 g, 4.1 mmol) and potassium carbonate (0.62 g, 4.5 mmol) in acetonitrile (10 mL) was added 1-fluoro-3-iodo-propane (0.85 g, 4.5 mmol) and was stirred at room temperature for 3 days. The mixture was poured into water (50 mL) and extracted with dichloromethane (3×20 mL). The combined organic layers were washed with saturated aqueous sodium chloride (10 mL), dried over magnesium sulfate, filtered and evaporated. 1-(3-Fluoro-propyl)-4-(3-nitro-phenyl)-piperazine was isolated as a viscous orange oil (0.886 g, 80%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.71 (s, 1H), 7.65 (d, J=8.2 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 7.18 (dd, J=8.3, 1.9 Hz, 1H), 4.54 (ddd, J=47.2, 5.9, 5.9 Hz, 2H), 3.32-3.27 (m, 4H), 2.65-2.60 (m, 4H), 2.55 (t, J=7.2 Hz, 2H), 2.00-1.85 (m, 2H). MS=268 (MH)+.
Reaction SMILES: [N+](C1C=C(S([CH2:13][C@@H:14]2[CH2:16][O:15]2)(=O)=O)C=CC=1)([O-])=O.[CH3:17][C:18]1[NH:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][C:21]=2[OH:27].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:17][C:18]1[NH:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][C:21]=2[O:27][CH2:13][C@@H:14]1[CH2:16][O:15]1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)C[C@@H]2CO2)c1
Reactant: Cc1cc2cccc(O)c2[nH]1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Cc1cc2cccc(OC[C@@H]3CO3)c2[nH]1
Temperature: 25 °C
Reaction time: 5 h
Yield: 59 %

Procedure:
A mixture of (2S)-2{[(3-nitrophenyl)sulfonyl]methyl}oxirane (39 mg, 0.15 mmol), 2-methyl-1H-indol-7-ol (15 mg, 0.1 mmol), caesium carbonate (Cs2CO3) (65 mg, 0.2 mmol) in DMF (1.5 mL) was kept on stirring at room temperature for 5 h. The reaction mixture was partitioned between ethylacetate and water, organic layer dried over sodium sulphate (Na2SO4), filtered and concentrated. The residue was purified by silica gel flash chromatography to give subtitled compound (12 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12](=[O:18])[N:13]([CH3:17])[CH2:14][CH2:15][CH3:16])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH:19]([O:21]CCCC)=[CH2:20].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]([C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12](=[O:18])[N:13]([CH3:17])[CH2:14][CH2:15][CH3:16])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])(=[O:21])[CH3:20]
Reactant: C=COCCCC
Reactant: CCCN(C)C(=O)c1cc(Br)cc(C(=O)OC)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Product: CCCN(C)C(=O)c1cc(C(C)=O)cc(C(=O)OC)c1
Temperature: 122 °C
Yield: 63.1 %

Procedure:
A mixture of methyl 3-bromo-5-(methyl(propyl)carbamoyl)benzoate (314 mg, 1.0 mmol), 1-(vinyloxy)butane (200.4 mg, 0.26 mL, 2.0 mmol), palladium acetate (6.68 mg, 0.030 mmol), DPPP (27.2 mg, 0.066 mmol) and potassium carbonate (166 mg, 1.2 mmol) in DMF (2.5 mL) and H2O (0.3 mL) in a Smith process vial was heated at 122° C. in microwave for 3 h. The reaction mixture was cooled down to RT and hydrolyzed by addition of 5% HCl slowly. The reaction mixture was worked up by extraction with ethyl acetate and concentration under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (175 mg, 63% yield): HPLC retention time: 1.58 min (method A). MS (ESI) (M+H)+ 278.19.
Reaction SMILES: O[C:2]1([CH3:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[CH3:11][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]=1
Reactant: CC1(O)CCc2ccccc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC1=CCc2ccccc21
Yield: 67 %

Procedure:
A solution of 24.64 (0.166 mol) of 1-hydroxy-1-methyl-2,3-dihydro-1H-indene and 0.30 g of p-toluenesulphonic acid monohydrate in 300 ml of toluene was heated to reflux for 3 h with water being collected by means of a Dean Stark trap. The reaction mixture was cooled, washed with water (3×100 ml), then with saturated sodium chloride solution (100 ml), dried (K2CO3) and evaporated in vacuo to leave an orange oil. This was vacuum distilled to yield 14.57 g (67%) of the title product as a colourless oil, b.p. 32°-35° C./0.3 mm of Hg. NMR δ(CDCl3) 2.17 (3H, m), 3.31 (2H, m), 6.20 (1H, m), 7.16-7.35 (3H, m), 7.45 (1H, m).
Reaction SMILES: [O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.I[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(O)CO>[Cu]I.CCCCCC.C(OCC)(=O)C.CC(O)C>[C:17]1([N:13]2[CH2:14][CH2:15][N:10]([CH3:9])[CH2:11][CH2:12]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CN1CCNCC1
Reactant: Ic1ccccc1
Agent: [Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: CC(C)O
Product: CN1CCN(c2ccccc2)CC1
Yield: 70.9 %

Procedure:
The general procedure under argon was followed using copper(I) iodide (10 mg, 0.05 mmol), K3PO4 (425 mg, 2.00 mmol), N-(methyl)piperazine (166 μL, 1.50 mmol), iodobenzene (112 μL, 1.00 mmol), ethylene glycol (111 μL, 2.00 mmol) and 2-propanol (1.0 mL). Column chromatography using a solvent mixture (hexane/ethyl acetate=20/1, Rf=0.1) afforded N-phenyl-N′-(methyl)piperazine (125 mg, 71% isolated yield) as colorless liquid. The spectral data (1H NMR) matched with the literature references and GC analysis indicated >95% purity.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[NH:11][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([NH2:22])[CH:18]=3)[N:13]=2)=[CH:4][CH:3]=1.[CH:23]([N:26]=[C:27]=[O:28])([CH3:25])[CH3:24]>>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[NH:11][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([NH:22][C:27]([NH:26][CH:23]([CH3:25])[CH3:24])=[O:28])[CH:18]=3)[N:13]=2)=[CH:4][CH:3]=1
Reactant: Nc1ccc2nc(NC3CCc4ccc(F)cc43)ccc2c1
Reactant: CC(C)N=C=O
Product: CC(C)NC(=O)Nc1ccc2nc(NC3CCc4ccc(F)cc43)ccc2c1

Procedure:
The title compound was prepared in accordance with the general method described in example 3 from rac-N2-(6-fluoro-indan-1-yl)-quinoline-2,6-diamine and isopropyl isocyanate; MS: m/e=379.4 (M+H+).
Reaction SMILES: [N+]([O-])([O-])=[O:2].[Sr+2].[N+]([O-])([O-])=[O:7].[O-2:10].[La+3:11].[O-2].[O-2].[La+3]>O.O.O.O.O.O.O.[N+]([O-])([O-])=O.[Ni+2].[N+]([O-])([O-])=O.O.O.O.O.O.O.[N+]([O-])([O-])=O.[Co+2].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[Fe+2].[N+]([O-])([O-])=O>[OH-:2].[La+3:11].[OH-:7].[OH-:10].[O-2:2].[La+3:11].[O-2:2].[O-2:2].[La+3:11]
Reactant: O=[N+]([O-])[O-]
Agent: [Co+2]
Agent: [Fe+2]
Agent: [Ni+2]
Solvent: O
Product: [OH-]

Procedure:
21.6 g (0.102) of strontium nitrate was dissolved in about 60 ml of distilled water, and this solution was poured over 32.26 g (0.099 mole) lanthanum oxide in a 150 cm3 beaker and left to react. Meanwhile 27.92 g nickel nitrate hexahydrate (0.096 mole) and 55.1 g (0.189 mole) cobalt nitrate hexahydrate and 6.06 g (0.015 mole) iron nitrate nanohydrate were dissolved in about 140 cm3 distilled water. The slurry of lanthanum hydroxide in strontium nitrate solution, resulting from reaction of lanthanum oxide with water was then quantitatively blended under vigorous stirring into the solution of nickel and cobalt nitrates. The resulting mixture was further vigorously stirred for about one hour until pourable homogeneous dark green suspension of insoluble metal hydroxides was obtained. This mixture was then further processed by spray-freezing, freeze-drying, dry-milling for about one hour of the freeze-dried agglomerates, and calcination as described in the example 1. The specific surface area of the resulting powder was 9.5 m2 /g. This powder has been further processed by wet (water suspension) milling, addition of colloidal silica to the suspension, and depositing the perovskite powder slurry on pretreated alumina pellets. The loading of perovskite powder was 7.5%, and the catalyst showed a good catalytic activity for methane combustion (FIG. 3) as well as for toluene oxidation. In preparing 0.3 mole La0.66 Sr0.34 Ni0.32 Co0.63 Fe0.05 O3, 0.819 mole (corresponding to 16.8 liters) NOx were produced, e.g. 2.73 mole NOx /1 mole perovskite powder.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][NH2:9])=[CH:4][CH:3]=1.[I:10][C:11]1[CH:12]=[C:13]([CH:27]=[CH:28][CH:29]=1)[C:14]([C:16](=[CH:19]NC1C=CC=CC=1)[C:17]#[N:18])=[O:15]>C(O)C.CCCCCC>[NH2:18][C:17]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:9]=[CH:19][C:16]=1[C:14](=[O:15])[C:13]1[CH:27]=[CH:28][CH:29]=[C:11]([I:10])[CH:12]=1
Reactant: NNc1ccc(F)cc1
Reactant: N#CC(=CNc1ccccc1)C(=O)c1cccc(I)c1
Solvent: CCO
Solvent: CCCCCC
Product: Nc1c(C(=O)c2cccc(I)c2)cnn1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.4 %

Procedure:
A mixture of 4-fluorophenylhydrazine (26.6 g, 211 mmol) and 2-(3-iodobenzoyl)-3-phenylaminoacrylonitrile (79 g, 211 mmol) in ethanol (400 ml) was heated at reflux under a nitrogen atmosphere. After 30 minutes, the reaction mixture was cooled to room temperature, diluted with hexane to give 5-amino-4-(3-iodobenzoyl)-1-(4-fluorophenyl)pyrazole (75.1 g) as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[CH3:24])[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[N:11]=1.[CH:25]1([C:30](Cl)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1>CN(C)C(=O)C>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:21]=[CH:22][C:23]([CH3:24])=[C:2]([NH:1][C:30]([CH:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)=[O:31])[CH:3]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1
Reactant: O=C(Cl)C1CCCC1
Reactant: Cc1ccc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)cc1N
Solvent: CC(=O)N(C)C
Product: Cc1ccc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)cc1NC(=O)C1CCCC1
Yield: 45.8 %

Procedure:
Using N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.62 mmol), N,N-dimethylacetamide (3.0 mL) and cyclopentanecarbonyl chloride (90 μL, 0.74 mmol), and in the same manner as in Example 120, the title compound (119 mg, 46%) was obtained as a white powder.
Reaction SMILES: C(O[C:6](=O)[N:7](C)[C@@H:8]([C:20](=[O:35])[N:21]([CH3:34])[C@@H:22]([C:30](=[O:33])[NH:31][CH3:32])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1)(C)(C)C.FC(F)(F)C(O)=O.O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:34][N:21]([C@@H:22]([C:30](=[O:33])[NH:31][CH3:32])[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:20](=[O:35])[C@H:8]([NH:7][CH3:6])[CH2:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1
Reactant: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1cccc2ccccc12)N(C)C(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: O
Product: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1cccc2ccccc12)NC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 104.3 %

Procedure:
Methyl-((1R)-1-(methyl-((1R)-1-methylcarbamoyl-2-phenylethyl)carbamoyl)-2-(1-naphthyl)ethyl)carbamic acid tert butyl ester (0.77 g; 1.52 mmol) was dissolved in methylene chloride (4 mL) and trifluoroacetic acid (4 mL) was added. The reaction mixture was stirred for 30 min at room temperature. Water (5 mL) and methylene chloride (5 mL) were added. An aqueous solution of sodium hydrogen carbonate was added until pH 8. The organic phase was extracted with methylene chloride (3×10 mL) and dried (magnesium sulfate). The solvent was removed in vacuo to afford 0.64 g of (2R)-N-methyl-2-methylamino-N-((1R)-1-methylcarbamoyl-2-phenylethyl)-3-(1-naphthyl)propionamide.
Reaction SMILES: N[C@@H](CC1C=CC(OC[CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25](F)=[CH:24][CH:23]=3)[O:19][C:20]=2[CH3:21])=CC=1)C(O)=O.C[O:30][C:31](=[O:49])[C@H:32]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][CH:43]=1)[NH:33]C(OC(C)(C)C)=O.CC1OC(C2C=CC=CC=2)=NC=1CO>>[NH2:33][C@@H:32]([CH2:41][C:42]1[CH:43]=[CH:44][C:45]([O:48][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[O:19][C:20]=2[CH3:21])=[CH:46][CH:47]=1)[C:31]([OH:49])=[O:30]
Reactant: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C
Reactant: Cc1oc(-c2ccc(F)cc2)nc1CCOc1ccc(C[C@H](N)C(=O)O)cc1
Agent: Cc1oc(-c2ccccc2)nc1CO
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(C[C@H](N)C(=O)O)cc1

Procedure:
Amino acid Intermediate 54 was prepared as described for the preparation of Intermediate 46. From 187 mg of N-(Boc)-L-Tyrosine methyl ester and 120 mg of Intermediate 8D (with DIAD replacing DEAD) was prepared 116 mg (53% overall yield) of the title compound as a solid. 1H NMR (DMSO-d6, 300 MHz) δ7.89-7.85 (m, 2H), 7.43-7.36 (m, 3H), 7.12 (d, 2H, J=8.5), 6.9 (d, 2H, J=8.5), 4.9 (s, 2H), 3.63 (m, 1H), 3.0 (dd, 1H, J=14.4, 4.5), 2.85 (dd, 1H, J=14.4, 8.1), 2.37 (s, 3H); low resolution MS (ES+)m/e 353.07 (MH+).
Reaction SMILES: [C:1]([C:3]1[NH:17][C:16]2[C:18]3[C:4]=1[CH2:5][C@@H:6]1[C@@H:11]([C:12]=3[CH:13]=[CH:14][CH:15]=2)[CH2:10][C@H:9]([NH:19][C:20](=[O:26])[N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH2:8][N:7]1[CH3:27])#[CH:2]>C(O)C.[Ni]>[CH2:1]([C:3]1[NH:17][C:16]2[C:18]3[C:4]=1[CH2:5][C@@H:6]1[C@@H:11]([C:12]=3[CH:13]=[CH:14][CH:15]=2)[CH2:10][C@H:9]([NH:19][C:20](=[O:26])[N:21]([CH2:22][CH3:23])[CH2:24][CH3:25])[CH2:8][N:7]1[CH3:27])[CH3:2]
Reactant: C#Cc1[nH]c2cccc3c2c1C[C@@H]1[C@@H]3C[C@H](NC(=O)N(CC)CC)CN1C
Agent: [Ni]
Solvent: CCO
Product: CCc1[nH]c2cccc3c2c1C[C@@H]1[C@@H]3C[C@H](NC(=O)N(CC)CC)CN1C
Yield: 384.4 %

Procedure:
At room temperature and under normal pressure, 140 mg (0.084 mmol) of 3-(2-ethynyl-6-methyl-8α-ergolinyl)-1,1-diethylurea is hydrogenated in 20 ml of ethanol after addition of 0.1 g of Raney nickel within 45 minutes. After the catalyst has been removed by filtration and the solution has been concentrated, the product is recrystallized from ethanol/hexane, yielding 119 mg of 3-(2-ethyl-6-methyl-8α-ergolinyl)-1,1-diethylurea (84%), mp 165°-168° C.,
Reaction SMILES: [CH3:1][O:2][C:3]1[C:16]2[C:7](=[C:8]3[CH:18]([OH:19])[CH:17]([OH:20])[C:15]=2[C:14]2[C:9]3=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:6]([O:21][CH3:22])=[CH:5][CH:4]=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>C(O)(=O)C>[CH3:22][O:21][C:6]1[C:7]2[C:16](=[C:15]([CH:17]=[O:20])[C:14]3[C:9]([C:8]=2[CH:18]=[O:19])=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:3]([O:2][CH3:1])=[CH:4][CH:5]=1
Reactant: COc1ccc(OC)c2c3c4ccccc4c(c12)C(O)C3O
Agent: CC(=O)[O-]
Agent: [Pb+4]
Solvent: CC(=O)O
Product: COc1ccc(OC)c2c(C=O)c3ccccc3c(C=O)c12
Reaction time: 2 h

Procedure:
A mixture of isomers of 1,4-dimethoxy-11,12-dihydroxy-9,10-ethano-anthracene weighing 10 g. is dissolved in 150 ml. of glacial acetic acid at 50° C. and treated portionwise with 30 g. of lead tetraacetate. After 2 hours at 50° C., the solution is filtered to remove insoluble materials and cooled yielding orange crystals, which are filtered, washed with glacial acetic acid and dried, m.p. 208°-212° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([S:13][C:14]([F:17])([F:16])[F:15])=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[Br:18]Br>C(Cl)(Cl)Cl>[Br:18][C:12]1[CH:11]=[C:10]([S:13][C:14]([F:15])([F:17])[F:16])[NH:9][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1
Reactant: FC(F)(F)Sc1ccc(-c2ccc(Cl)cc2)[nH]1
Reactant: BrBr
Solvent: ClC(Cl)Cl
Product: FC(F)(F)Sc1cc(Br)c(-c2ccc(Cl)cc2)[nH]1
Reaction time: 2 h
Yield: 80.2 %

Procedure:
A solution of 2-(p-chlorophenyl)-5-[(trifluoromethyl)thio]pyrrole (1.94 g, 0.00699 mol) in chloroform is cooled, treated with a solution of bromine (1.16 g, 0.00699 mol) in chloroform, stirred for two hours, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a dark syrup. Flash chromatography of the syrup using silica gel and a 1:10 ethyl acetate/hexanes solution gives the title product as a pink syrup (2.0 g) which is identified by 1HNMR and 13CNMR spectral analyses.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]2[N:13]([CH2:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[C:12]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:11]=3[N:10]=2)=[C:6]([OH:8])[CH:7]=1.[CH3:27][O:28][C:29](=[O:39])[C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37]Br)=[CH:32][CH:31]=1>>[CH3:27][O:28][C:29](=[O:39])[C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][O:8][C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[C:9]2[N:13]([CH2:14][CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]3)[C:12]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:11]=3[N:10]=2)=[CH:32][CH:31]=1
Reactant: Oc1cc(Cl)ccc1-c1nc2cc(F)c(F)cc2n1CC1CCCCC1
Reactant: COC(=O)c1ccc(CCBr)cc1
Product: COC(=O)c1ccc(CCOc2cc(Cl)ccc2-c2nc3cc(F)c(F)cc3n2CC2CCCCC2)cc1

Procedure:
The title compound was prepared in analogy to Example 5, intermediate a, from 5-chloro-2-(1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazol-2-yl)-phenol (Example 19, intermediate a) and 4-(2-bromo-ethyl)-benzoic acid methyl ester (CAS Reg. No. 136333-97-6). Colorless sticky solid (42%). MS (Turbo Spray): m/z=539.3 (M+H).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1Br)([CH3:3])[CH3:2].C([Li])CCC.[CH2:18]([N:20]([CH2:24][CH3:25])[C:21](Cl)=[O:22])[CH3:19]>C(OCC)C>[CH:1]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[C:21]([N:20]([CH2:24][CH3:25])[CH2:18][CH3:19])=[O:22])([CH3:3])[CH3:2]
Reactant: COc1ccc(Br)c(C(C)C)c1
Reactant: CCN(CC)C(=O)Cl
Agent: [Li]CCCC
Solvent: CCOCC
Product: CCN(CC)C(=O)c1ccc(OC)cc1C(C)C
Temperature: 0 °C
Reaction time: 5 h
Yield: 79.3 %

Procedure:
To a solution of 40.0 g (0.174 mol) of 2-isopropyl-4-methoxybromobenzene in 600 ml of diethyl ether at 0° C. was added 103.68 ml (0.175 mol) of a 1.69M solution of butyl lithium in diethyl ether. When the addition was complete the solution was cooled to 0° C. for one hour and stirred for an additional five hours at ambient temperature, then recooled to -78° C. and treated with a solution of 23.68 g (0.175 mol) of N,N-diethylcarbamyl chloride in 80 ml of diethyl ether. The resulting solution was stirred for about 12 hours while the reaction temperature was allowed to rise and then quenched with saturated ammonium chloride solution. The aqueous and organic layers were separated, the aqueous layer back extracted with ethyl acetate and the combined organic extracts washed once with brine, then dried and the solution taken to dryness to give a crude product which was flash chromatographed on silica gel, eluting with 30% ethyl acetate/hexane to give 34.4 g (79%) of 2-isopropyl-4-methoxy-N,N-diethylbenzamide as an oil which was used as such in the next step without further purification. The oil can be distilled, if desired, and boils at 123-129/0.2-0.3 mm.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:35][CH2:36][CH2:37][CH3:38])[N:14]([CH2:15][CH2:16][CH2:17][N:18]([CH2:23][C:24]3[CH:25]=[C:26]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[CH:27]=[CH:28][CH:29]=3)[CH2:19][CH2:20][CH2:21]O)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.S(Cl)([Cl:41])=O>C(Cl)Cl>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:35][CH2:36][CH2:37][CH3:38])[N:14]([CH2:15][CH2:16][CH2:17][N:18]([CH2:23][C:24]3[CH:25]=[C:26]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[CH:27]=[CH:28][CH:29]=3)[CH2:19][CH2:20][CH2:21][Cl:41])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1
Reactant: CCCCc1nc2c(N)nc3ccccc3c2n1CCCN(CCCO)Cc1cccc(CC(=O)OC)c1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CCCCc1nc2c(N)nc3ccccc3c2n1CCCN(CCCCl)Cc1cccc(CC(=O)OC)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of the product from step (viii) (2.43 g) and thionyl chloride (10 mL) in DCM (30 mL) was stirred at rt for 4 h then evaporated under reduced pressure to give the subtitle compound. Used crude in next step.
Reaction SMILES: C[O-].[Na+].[CH3:4][C:5]1[N:6]=[C:7]2[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][N:8]2[C:9](=[O:11])[CH:10]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[CH:22]=O>CO>[CH3:16][C:15]1[C:7]2=[N:6][C:5]([CH:4]=[CH:22][C:21]3[CH:24]=[C:25]([O:29][CH3:30])[C:26]([O:27][CH3:28])=[C:19]([O:18][CH3:17])[CH:20]=3)=[CH:10][C:9](=[O:11])[N:8]2[CH:12]=[CH:13][CH:14]=1
Reactant: COc1cc(C=O)cc(OC)c1OC
Reactant: Cc1cc(=O)n2cccc(C)c2n1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(C=Cc2cc(=O)n3cccc(C)c3n2)cc(OC)c1OC
Yield: 21.5 %

Procedure:
To a solution of 2.2g of sodium methoxide in 100ml of absolute methanol is added 3.5g of 2,9-dimethyl-4H-pyrido-[1,2-a]pyrimidin-4-one, followed by 4.0g of 3,4,5-trimethoxybenzaldehyde. The mixture is stirred and heated under reflux for 28 hours. A crystalline solid separates and this is colled and filtered. The solid consists of a mixture of colorless and yellow crystals that are separated manually to give 1.52g of a pale yellow solid, melting point 208° - 210°C. The yellow solid is recrystallized from 35ml of methoxyethanol to yield 1.22g of the title compound, melting point 212°-214°C.
Reaction SMILES: CS(Cl)(=O)=O.[Br:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH:9]=[CH:10][N+:11]([O-])=[CH:12]2.C(C[NH2:21])O>N1C=CC=CC=1>[Br:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH:9]=[CH:10][N:11]=[C:12]2[NH2:21]
Reactant: [O-][n+]1ccc2c(Br)cccc2c1
Reactant: NCCO
Agent: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: Nc1nccc2c(Br)cccc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
3.2 47 μl (0.61 mmol) of methanesulfonyl chloride is added dropwise with ice-cooling to a suspension of 112.0 mg (0.50 mmol) of 5-bromoisoquinoline 2-oxide in 0.48 ml of pyridine. The reaction mixture is stirred at room temperature for 18 hours. 685 μl of ethanolamine are then added dropwise with ice-cooling, and the mixture is stirred at room temperature for a further 4 hours. The reaction mixture is poured into ice-water and stirred for 30 minutes. The precipitate formed is filtered off with suction, washed with water and dried in vacuo: 5-bromoisoquinolin-1-ylamine as yellow crystals; HPLC/MS: 1.26 min, [M+H] 223/225.