Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[C:11]2[C:10]([C:12]([OH:14])=[O:13])=[CH:9][CH:8]=[CH:7][C:6]=2[NH:5][CH:4]=1)=[O:2].C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C)C=O.C(OCC)(=O)C.O>[CH:1]([C:3]1[C:11]2[C:10]([C:12]([O:14][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:13])=[CH:9][CH:8]=[CH:7][C:6]=2[NH:5][CH:4]=1)=[O:2]
Reactant: BrCc1ccccc1
Reactant: O=Cc1c[nH]c2cccc(C(=O)O)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: O=Cc1c[nH]c2cccc(C(=O)OCc3ccccc3)c12
Reaction time: 4 h
Yield: 90.3 %

Procedure:
To a suspension of 3-formylindole-4-carboxylic acid (390 mg) and potassium carbonate (285 mg) in N,N-dimethylformamide (10 ml) was added benzyl bromide (353 mg) at ambient temperature and the mixture was stirred for 4 hours. The resulting mixture was diluted with ethyl acetate and water, then the layers were separated. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residual solid was triturated with diethyl ether:n-hexane (1:6) to give benzyl 3-formylindole-4-carboxylate (520 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[Cl-].[Al+3].[Cl-].[Cl-].[Cl:13][C:14]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:15]=1[C:16](Cl)=[O:17].Cl>O>[Cl:13][C:14]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:15]=1[C:16]([C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[CH3:1])=[O:17]
Reactant: O=C(Cl)c1cc(Cl)ccc1Cl
Reactant: Cc1ccc(C)cc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Product: Cc1ccc(C)c(C(=O)c2cc(Cl)ccc2Cl)c1
Reaction time: 0.17 h
Yield: 94.2 %

Procedure:
To p-xylene (120 ml, 0.98 mol) was added aluminum chloride (32 g, 0.24 mol) at room temperature. To this mixture 2,5-dichlorobenzoyl chloride (30 g, 0.14 mol) was added slowly. The reaction was exothermic and hydrogen chloride evolved from the reddish solution. After the addition, the mixture was stirred for 10 min and then hydrolysed by slow addition of water. The aqueous layer was extracted with ether. The organic layer was combined with ethereal extract and washed with water, saturated sodium bicarbonate, brine, respectively, and then dried with magnesium sulfate. After the removal of solvent, the residue was recrystallized from methanol twice and then from hexane to give 36.8 g (92%) crystals (mp 58°-61° C.).
Reaction SMILES: C[O:2][C:3](=[O:29])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:14]=[C:15]3[C:20](=[C:21]([OH:23])[CH:22]=2)[O:19][C:18]([CH3:25])([CH3:24])[CH2:17][C:16]3([CH3:27])[CH3:26])=[CH:7][C:6]=1[F:28].[OH-].[K+]>CO>[F:28][C:6]1[CH:7]=[C:8]([C:11]#[C:12][C:13]2[CH:14]=[C:15]3[C:20](=[C:21]([OH:23])[CH:22]=2)[O:19][C:18]([CH3:25])([CH3:24])[CH2:17][C:16]3([CH3:26])[CH3:27])[CH:9]=[CH:10][C:5]=1[CH2:4][C:3]([OH:29])=[O:2]
Reactant: COC(=O)Cc1ccc(C#Cc2cc(O)c3c(c2)C(C)(C)CC(C)(C)O3)cc1F
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CC1(C)CC(C)(C)c2cc(C#Cc3ccc(CC(=O)O)c(F)c3)cc(O)c2O1
Temperature: 25 °C
Reaction time: 2 h
Yield: 69 %

Procedure:
A solution of [2-fluoro-4-(8-hydroxy-2,2,4,4-tetramethyl-chroman-6-ylethynyl)-phenyl]-acetic acid methyl ester. (Intermediate 21, 0.037 g, 0.0493 mmol) in methanol (2 mL) and tetrahydrofaran (1 mL) was treated with a 2M solution of potassium hydroxide (2 mL, 4 mmol) and the resulting reaction mixture was stirred at ambient temperature for 2 h. The volatiles were evaporated in vacuo to a residue that was neutralized with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with water and brine, and dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product (0.024 g, 69%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7](Cl)=[O:8])([O-:3])=[O:2].[NH4+:17].[OH-]>C1COCC1>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([NH2:17])=[O:8])([O-:3])=[O:2]
Reactant: [NH4+]
Reactant: O=C(Cl)c1cc([N+](=O)[O-])cc(C(F)(F)F)c1
Agent: [OH-]
Solvent: C1CCOC1
Product: NC(=O)c1cc([N+](=O)[O-])cc(C(F)(F)F)c1
Temperature: 20 °C
Reaction time: 12 h
Yield: 82.5 %

Procedure:
To a mixture of 3-nitro-5-(trifluoromethyl)benzoyl chloride (1.8 g, 7.10 mmol) in THF (20 mL) was added NH4OH (2.96 mL, 21.30 mmol) at 20° C. The mixture was stirred at 20° C. for 12 h. LCMS showed the reaction was finished. The mixture was extracted with EA, washed with water, and concentrated to give 3-nitro-5-(trifluoromethyl)benzamide (1.5 g, 5.86 mmol, 83% yield): 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.62 (br.s, 2H), 8.53 (s, 1H), 7.93 (s., 1H). ES-LCMS m/z 235 (M+H).
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C@H:7]1[C@H:11]([C:12]([O:14]C)=[O:13])[O:10][C:9]([CH:29]([Br:31])[CH3:30])([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[C:21]([O:27][CH3:28])[C:22]=3[Br:26])[CH:17]=2)[O:8]1)=[O:6]>O.CO>[Br:31][C@H:29]([C:9]1([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[C:21]([O:27][CH3:28])[C:22]=3[Br:26])[CH:17]=2)[O:10][C@@H:11]([C:12]([OH:14])=[O:13])[C@H:7]([C:5]([OH:6])=[O:4])[O:8]1)[CH3:30]
Reactant: COC(=O)[C@@H]1OC(c2ccc3c(Br)c(OC)ccc3c2)(C(C)Br)O[C@H]1C(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1ccc2cc(C3([C@H](C)Br)O[C@@H](C(=O)O)[C@H](C(=O)O)O3)ccc2c1Br
Reaction time: 2 h

Procedure:
A solution of sodium hydroxide (5.32 g, 0.133 mol) in water (70 ml) was added dropwise in 1 hour, under stirring, to a solution of the diastereoisomer 3 (35.4 g, 0.665 mol) in methanol (250 ml) at 20° C. The reaction mixture was kept at 20° C. for 2 hours; then methanol was removed under reduced pressure mantaining the initial volume of the solution by addition of water. The aqueous solution, so obtained, was extracted with dichloromethane, acidified with conc HCl to pH 1, and extracted with diethylether (3×100 ml). The combined organic extracts were washed with water, anhydrified over sodium sulfate, filtered, and concentrated in vacuo. Crystallization of the residue from dichloromethane gave the pure 2-(1(S)-bromoethyl)-2-(5-bromo-6-methoxy-2-naphthyl)-1,3-dioxolane-4(R),5(R)-dicarboxylic acid (diastereoisomer 7).
Reaction SMILES: [NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH2:3]1.Br[CH:23]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:41](=[O:42])[C:40]2=[CH:43][CH:44]=[CH:45][CH:46]=[C:39]2[C:38]1=[O:47])[C:24]([O:26][CH2:27][CH3:28])=[O:25].C(N(CC)CC)C>C(#N)C>[CH2:27]([O:26][C:24]([C@H:23]([NH:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH2:3]1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:38](=[O:47])[C:39]2=[CH:46][CH:45]=[CH:44][CH:43]=[C:40]2[C:41]1=[O:42])=[O:25])[CH3:28]
Reactant: CCOC(=O)C(Br)CCCCCCCCN1C(=O)c2ccccc2C1=O
Reactant: CC(C)(C)OC(=O)CN1C(=O)[C@@H](N)CSc2ccccc21
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCOC(=O)[C@@H](CCCCCCCCN1C(=O)c2ccccc2C1=O)N[C@H]1CSc2ccccc2N(CC(=O)OC(C)(C)C)C1=O
Temperature: 80 °C
Yield: 25 %

Procedure:
In 100 ml of acetonitrile are dissolved 1.7 g of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate and 2.4 g of ethyl 2-bromo-10-phthalimidodecanoate, and 0.75 g of triethylamine is added to the solution. The mixture is heated at 80° C. for 3 days, concentrated under reduced pressure, diluted with 100 ml of water and extracted with 150 ml of ethyl acetate. The ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting oily substance is separated and purified by silicagel column chromatography (hexane:ethyl acetate=3:1 - 2:1) to give from the first fraction 0.9 g of tert-butyl 3(R)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate as a colorless oil.
Reaction SMILES: I[C:2]1[O:3][C:4]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[CH:13]=[N:12][CH:11]=[CH:10]3)=[CH:5][N:6]=1.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH2:26])=[CH:21][CH:20]=1.CN1C(=O)CCC1.CO>C(Cl)Cl>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH:26][C:2]2[O:3][C:4]([C:7]3[CH:8]=[C:9]4[C:14](=[CH:15][CH:16]=3)[CH:13]=[N:12][CH:11]=[CH:10]4)=[CH:5][N:6]=2)=[CH:21][CH:20]=1
Reactant: COc1ccc(CN)cc1
Reactant: Ic1ncc(-c2ccc3cnccc3c2)o1
Solvent: CN1CCCC1=O
Solvent: ClCCl
Solvent: CO
Product: COc1ccc(CNc2ncc(-c3ccc4cnccc4c3)o2)cc1
Temperature: 165 °C
Yield: 136.3 %

Procedure:
A glass microwave reaction vessel was charged with 6-(2-iodooxazol-5-yl)isoquinoline (0.10 g, 310 μmol), (4-methoxyphenyl)methanamine (0.28 mL, 217 μmol) and NMP (2.00 mL). The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 165° C. for 10 minutes. The residual product was adsorbed onto a plug of silica gel and chromatographed through two stacked Redi-Sep® pre-packed silica gel column (12 g), eluting with a gradient of 1% to 10% of 2 M NH3.MeOH in DCM to provide N-(4-methoxybenzyl)-5-(isoquinolin-6-yl)oxazol-2-amine (98 mg, 95% yield). LCMS (API-ES) m/z (%): 332.1 (100%, M++H); 1H NMR (400 MHz, MeOH-d4) δ ppm 9.12 (s, 1H) 8.38 (d, J=5.87 Hz, 1H) 8.04 (d, J=8.80 Hz, 1H) 7.94 (s, 1H) 7.84 (dd, J=8.61, 1.56 Hz, 1H) 7.76 (d, J=5.87 Hz, 1H) 7.42 (s, 1H) 7.33 (d, J=8.80 Hz, 2H) 6.90 (d, J=8.61 Hz, 2H) 4.47 (s, 2H) 3.77 (s, 3H).
Reaction SMILES: [CH:1]([Si:4]([C:11]#[CH:12])([CH:8]([CH3:10])[CH3:9])[CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].Br[C:14]1[CH:15]=[C:16]([CH:19]=[O:20])[O:17][CH:18]=1.C(OCCCC)(C)=O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(OCC)(=O)C>[CH:8]([Si:4]([C:11]#[C:12][C:14]1[CH:15]=[C:16]([CH:19]=[O:20])[O:17][CH:18]=1)([CH:5]([CH3:6])[CH3:7])[CH:1]([CH3:3])[CH3:2])([CH3:10])[CH3:9]
Reactant: O=Cc1cc(Br)co1
Reactant: C#C[Si](C(C)C)(C(C)C)C(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCOC(C)=O
Solvent: CCCCOC(C)=O
Product: CC(C)[Si](C#Cc1coc(C=O)c1)(C(C)C)C(C)C
Reaction time: 2 h
Yield: 72 %

Procedure:
Triisopropylsilylacetylene (9.0 mL) was added dropwise to a mixture of 4-bromofuran-2-carbaldehyde (2.0 g), PdCl2(PPh3)2 (0.40 g), CuI (0.22 g), TEA (7.9 mL) and AcOBu (20 mL) at 110 to 120° C. over the course of 6 hours in a nitrogen atmosphere, and then the mixture was stirred for 2 hours. After the reaction mixture was allowed to cool, ethyl acetate (50 mL), OH type silica gel (1.0 g), cellpure (1.2 g) and activated carbon (20 mg) were added. The insolubles were filtered out, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with hexane/ethyl acetate=100/0→65/35) to obtain 4-[(triisopropylsilanyl)ethynyl]furan-2-carbaldehyde (black oil) (2.3 g, 72%).
Reaction SMILES: [CH2:1]([NH:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[CH2:10]=O>>[CH3:10][N:5]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:1][CH2:2][CH2:3][CH3:4]
Reactant: CCCCNCCCC
Reactant: C=O
Product: CCCCN(C)CCCC
Yield: 95.8 %

Procedure:
In a similar manner to Example 1, 258.5 g (2.0 mol) of di-n-butylamine and 330.2 g (3.2 mol) of formaldehyde (29.1%) are reacted in a 1 l autoclave; a maximum pressure of 3.2 MPa is established at a temperature of 120° C. After the crude amine (aqueous and organic phase) has been degassed at a maximum temperature of 80° C., the water is removed on a water separator. The remaining organic phase is subsequently fractionally distilled. 274.6 g of N-methyldi-n-butylamine having a purity of 99.6% are isolated, corresponding to a yield of 95.6% of theory.
Reaction SMILES: Br.Br[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[CH2:10]([O:12][C:13](=[S:15])[SH:14])[CH3:11].[K].O=O.[OH-].[Na+]>C(O)C>[C:13]([S:15][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)(=[S:14])[O:12][CH2:10][CH3:11]
Reactant: CCOC(=S)S
Reactant: BrCc1ccccn1
Agent: Br
Agent: O=O
Agent: [K]
Solvent: CCO
Product: CCOC(=S)SCc1ccccn1
Temperature: 25 °C

Procedure:
1.00 g (3.9 mmol) of 2-(bromomethyl)pyridine hydrobromide and 0.36 g (3.9 mmol) of O-ethyldithiocarbonic acid, potassium salt were combined in a 50 ml round bottom flask with 20 ml of 100% ethanol. The reaction vessel was sealed with a rubber septum and oxygen was removed by several freeze-pump-thaw cycles. The reaction mixture was then warmed to room temperature and allowed to stir under positive nitrogen pressure. A white precipitate was observed after the first few minutes of the reaction. The reaction was allowed to stir for an additional 20 hours. 20 mL of 0.5M aqueous sodium hydroxide was then added causing the reaction mixture to become homogenous and take on a red color. Extraction with hexane after addition of an additional 20 ml of the sodium hydroxide solution yielded a fluorescent yellow-green solution. Hexane was removed and the residue was passed over a silica column (ethyl acetate as the elluent). The final product appears as a yellow-green liquid and fluoresces blue when exposed to long wavelength ultra-violet light. Yield=0.342 g (39%). 1H NMR (CDCl3) δ=1.212 (t, 3 H), δ=4.353 (s, 2 H), δ=4.47 (q, 2 H), δ=7.002 (t, 1 H), δ=7.234 (d, 1 H), δ=7.466 (t, 1 H), δ=8.377 (d, 1 H). 13C NMR (CDCl3) δ=13.929, δ=42.135, δ=70.358, δ=122.494 (CH), δ=123.424 (CH), δ=136.777 (CH), δ=149.660 (CH), δ=156.152 (C), δ=213.730 (C═S).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[CH2:13][CH2:12][NH:11][CH2:10][C:9]=3[C:14](=[O:16])[O:15][C:4]=2[CH:3]=1.C(N(CC)CC)C.Cl[CH2:25][CH2:26][N:27]1[CH2:34][CH:33]2[CH2:35][CH:29]([CH2:30][CH2:31][CH2:32]2)[CH2:28]1>>[CH:33]12[CH2:35][CH:29]([CH2:30][CH2:31][CH2:32]1)[CH2:28][N:27]([CH2:26][CH2:25][N:11]1[CH2:12][CH2:13][C:8]3[C:5]4[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][C:4]=4[O:15][C:14](=[O:16])[C:9]=3[CH2:10]1)[CH2:34]2
Reactant: Cc1ccc2c3c(c(=O)oc2c1)CNCC3
Reactant: ClCCN1CC2CCCC(C2)C1
Solvent: CCN(CC)CC
Product: Cc1ccc2c3c(c(=O)oc2c1)CN(CCN1CC2CCCC(C2)C1)CC3
Reaction time: 72 h
Yield: 70.2 %

Procedure:
Prepared by the method described for Example 13 from 1,2,3,4-tetrahydro-8-methyl-5H-[1]benzopyrano[3,4-c]pyridin-5-one (3.0 g, 0.014 moles), triethylamine (4.2 ml, 0.030 moles), and 3-(2-chloroethyl)-3-azabicyclo[3.3.1]nonane (3.3 g, 0.015 moles). The reflux time is 72 hours. Recrystallization from ethanol gave the product (3.6 g), mp 150°-152° C.
Reaction SMILES: [CH:1]1([C:8](=O)[CH:9]([C:15]2[C:20]([F:21])=[CH:19][C:18]([F:22])=[CH:17][C:16]=2[F:23])[C:10]([O:12]CC)=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[N:26]1[CH:31]=[CH:30][N:29]=[CH:28][C:27]=1[C:32]([NH2:34])=[NH:33]>C(N(CCCC)CCCC)CCC>[CH:1]1([C:8]2[N:34]=[C:32]([C:27]3[CH:28]=[N:29][CH:30]=[CH:31][N:26]=3)[N:33]=[C:10]([OH:12])[C:9]=2[C:15]2[C:16]([F:23])=[CH:17][C:18]([F:22])=[CH:19][C:20]=2[F:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: N=C(N)c1cnccn1
Reactant: CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F
Agent: Cl
Solvent: CCCCN(CCCC)CCCC
Product: Oc1nc(-c2cnccn2)nc(C2CCCCCC2)c1-c1c(F)cc(F)cc1F
Temperature: 160 °C
Reaction time: 4 h

Procedure:
A mixture of ethyl 3-cycloheptyl-3-oxo-2-(2,4,6-trifluorophenyl)propanoate (649 mg, 1.9 mmol) and 2-pyrazinecarboxamidine hydrochloride (452 mg, 2.85 mmol) in 1.5 mL of tributylamine is stirred under nitrogen atmosphere at 160° C. for 4 h. The mixture is cooled to room temperature and the excess of tributylamine is decanted off. The residue is washed with hexanes and chromatographed over silica gel, eluting with 10% methanol in ethyl acetate. Concentration provides 6-cycloheptyl-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)pyrimidin-4-ol as a light yellow solid. MS: m/z 401.2 (M+H).
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[Cl-:6].[Cl-].[Cl-].[Cl-].[Zr+4:10]>C(OCC)C>[Cl-:6].[Cl-:6].[CH3:4][C:3]1[CH:4]=[CH:3][C:2]([CH:1]2[CH2:4][CH:3]3[C:2](=[CH:3][CH:4]=[CH:1][CH2:2]3)[CH:1]2[Zr+2:10])=[CH:1][CH:2]=1
Reactant: [Zr+4]
Reactant: [Li]CCCC
Agent: [Cl-]
Solvent: CCOCC
Product: Cc1ccc(C2CC3CC=CC=C3C2[Zr+2])cc1

Procedure:
In this case the procedure of Example I was used except 0.476 mmol of 2-(para-methylphenyl) tetrahydroindenyl, 0.52 mmol of butyllithium, and 0.242 of zirconium tetrachloride, and 4 ml of diethylether were employed. The solid was identified as bis(2-para-methylphenyl) tetrahydroindenyl zirconium dichloride.
Reaction SMILES: [CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][O:4][C:5]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:6]=1/[CH:13]=[CH:14]/[C:15]1[N:16]=[C:17]2[N:21]([C:22]=1[C:23](O)=[O:24])[CH:20]=[CH:19][S:18]2.[F:28][C:29]([F:37])([F:36])[C:30]1[N:31]=[C:32]([NH2:35])[S:33][CH:34]=1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl.CN(C=O)C>[CH3:26][C:2]([CH3:1])([CH3:27])[CH2:3][O:4][C:5]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:6]=1/[CH:13]=[CH:14]/[C:15]1[N:16]=[C:17]2[N:21]([C:22]=1[C:23]([NH:35][C:32]1[S:33][CH:34]=[C:30]([C:29]([F:37])([F:36])[F:28])[N:31]=1)=[O:24])[CH:20]=[CH:19][S:18]2
Reactant: Nc1nc(C(F)(F)F)cs1
Reactant: COc1cccc(/C=C/c2nc3sccn3c2C(=O)O)c1OCC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1cccc(/C=C/c2nc3sccn3c2C(=O)Nc2nc(C(F)(F)F)cs2)c1OCC(C)(C)C

Procedure:
The title compound was prepared according to the general procedure (Method B) by coupling Intermediate 3 (200 mg, 0.517 mmol) with 4-(trifluoromethyl)-1,3-thiazol-2-amine (105 mg, 0.621 mmol) in the presence of EDCI hydrochloride (198 mg, 1.035 mmol) and DMAP (95 mg, 0.776 mmol) in a mixture of DCM and DMF (4:1, 5 mL) to give 114 mg of the product as a pale yellow solid; 1H NMR (300 MHz, DMSO-d6) δ 1.01 (s, 9H), 3.56 (s, 2H), 3.80 (s, 3H), 6.98-6.99 (m, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.34 (d, J=7.8 Hz, 1H), 7.43-7.48 (m, 2H), 7.85 (d, J=16.2 Hz, 1H), 8.05-8.09 (m, 2H), 12.97 (br s, 1H); ESI-MS (m/z) 535.20 (M−H)−.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([N+:17]([O-])=O)=[C:5]([OH:16])[CH:6]=[CH:7][C:8]=1[NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH3:2].FC(F)(F)C(NC1C=CC=CC=1O)=O>CO.[Pd]>[NH2:17][C:4]1[C:3]([CH2:1][CH3:2])=[C:8]([NH:9][C:10](=[O:15])[C:11]([F:12])([F:13])[F:14])[CH:7]=[CH:6][C:5]=1[OH:16]
Reactant: CCc1c(NC(=O)C(F)(F)F)ccc(O)c1[N+](=O)[O-]
Agent: [Pd]
Agent: O=C(Nc1ccccc1O)C(F)(F)F
Solvent: CO
Product: CCc1c(NC(=O)C(F)(F)F)ccc(O)c1N

Procedure:
To a solution of 3-ethyl-2-nitro-4-trifluoroacetamidophenol (18.21 mmol) and 10% palladium-on-carbon (0.45 g) in methanol (100 mL) is shaken under an atmosphere of hydrogen (50 psi) for three hours. The mixture is filtered through Celite and concentrated under reduced pressure to yield 2-amino-3-ethyl. trifluoroacetamidophenol.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]1[C:10](=[O:11])[CH2:9][N:8]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[CH:14][C:13]=2[N+:21]([O-])=O)[S:7]1(=[O:25])=[O:24]>CO.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]1[C:10](=[O:11])[CH2:9][N:8]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][C:13]=2[NH2:21])[S:7]1(=[O:25])=[O:24]
Reactant: COc1ccc(CN2C(=O)CN(c3ccc([N+](=O)[O-])cc3[N+](=O)[O-])S2(=O)=O)c(OC)c1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1ccc(CN2C(=O)CN(c3ccc(N)cc3N)S2(=O)=O)c(OC)c1
Reaction time: 1 h

Procedure:
A mixture of the title C compound, 2-(2,4-dimethoxybenzyl)-5-(2,4-dinitrophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (200 mg, 4.42 mmol) in 20 mL of MeOH/EtOAc (3:1) and 10% palladium on carbon (100 mg) is shaken under hydrogen atmosphere at 40 psi for 1 h. The catalyst is removed by filtration and the solvents are evaporated to afford 2-(2,4-dimethoxy-benzyl)-5-(2,4-diaminophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one as a brown solid: [M+1]+=393.
Reaction SMILES: [CH2:1]([N:8]1[CH2:26][CH2:25][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)[N:14]=[C:15]([OH:16])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:27][C:28]([F:38])([F:37])[C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Br)=[CH:31][CH:30]=1>>[CH2:1]([N:8]1[CH2:26][CH2:25][C:11]2[N:12]=[C:13]([C:17]3[CH:18]=[C:19]([Cl:24])[CH:20]=[C:21]([Cl:23])[CH:22]=3)[N:14]=[C:15]([O:16][CH2:33][C:32]3[CH:31]=[CH:30][C:29]([C:28]([F:27])([F:37])[F:38])=[CH:36][CH:35]=3)[C:10]=2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1nc(-c2cc(Cl)cc(Cl)c2)nc2c1CN(Cc1ccccc1)CC2
Reactant: FC(F)(F)c1ccc(CBr)cc1
Product: FC(F)(F)c1ccc(COc2nc(-c3cc(Cl)cc(Cl)c3)nc3c2CN(Cc2ccccc2)CC3)cc1

Procedure:
The title compound was prepared from 6-benzyl-2-(3,5-dichloro-phenyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ol (which was obtained in Intermediate 7) and 4-(trifluoromethyl)benzyl bromide according to Method A; LC retention time 3.49 min; MS: m/z (ESI) 544 (M+H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][C:8]1[CH:23]=[CH:22][C:11]([C:12]([O:14]CC2C=CC=CC=2)=[O:13])=[CH:10][CH:9]=1>C(O)C.[Pd]>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][C:8]1[CH:23]=[CH:22][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=1
Reactant: O=C(OCc1ccccc1)c1ccc(Oc2ccccn2)cc1
Agent: [Pd]
Solvent: CCO
Product: O=C(O)c1ccc(Oc2ccccn2)cc1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To a solution of benzyl 4-(pyridin-2-yloxy)benzoate (24.8 g, 81.5 mmol) in ethanol (300 ml) was added 10% palladium/carbon (containing water by 50%) (2.0 g), and the mixture was stirred overnight under a hydrogen stream at 80° C. The reaction solution was filtered with celite and the filtrate was concentrated. The residue was recrystallized from ethanol to give the objective substance (14.1 g, 80%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH:4]([CH2:9][C@H:10]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:11]([O:13][CH3:14])=[O:12])[C:5](OC)=[O:6].CCN(CC)CC.O>C1COCC1>[C:19]([O:18][C:16]([NH:15][C@@H:10]([CH2:9][CH:4]1[CH2:3][CH2:2][NH:1][C:5]1=[O:6])[C:11]([O:13][CH3:14])=[O:12])=[O:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: COC(=O)C(CCN)C[C@H](NC(=O)OC(C)(C)C)C(=O)OC
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)[C@H](CC1CCNC1=O)NC(=O)OC(C)(C)C
Temperature: 60 °C
Reaction time: 8 h
Yield: 60 %

Procedure:
To a solution of (4S)-dimethyl 2-(2-aminoethyl)-4-((tert-butoxycarbonyl)amino)pentanedioate (crude) in THF (20 mL) was added Et3N (20 mL). The reaction mixture was stirred at 60° C. overnight and then cooled to ambient temperature. Water (50 mL) was added and the resulting mixture was extracted with methylene chloride (100 mL×2). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (heptanes/EtOAc=1:1) to afford (2S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(2-oxopyrrolidin-3-yl)propanoate (5.5 g, 60% yield over two steps) as a light brown oil.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.[C:12](Cl)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>ClCCl.C(N(CC)CC)C>[C:12]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1ccc2c(c1)CCC2=O
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc2c(c1)CCC2=O)c1ccccc1

Procedure:
5-Aminoindan-1-one (2.5 g) was reacted with benzoyl chloride (2.63 g) in dichloromethane and triethylamine to give 5-benzamidoindan-1-one which was reacted with benzaldehyde in a similar manner to Example 7a) to give N-(2-benzylidene-1-oxoindan-5-yl)benzamide which was reacted with hydrogen peroxide in a similar manner to Example 7b) to give an intermediate which was reacted with hydrazine hydrate in a similar manner to Example 7c) to give -(3N-phenyl-1,4-dihydroindeno[1,2-c]pyrazol-6-yl)benzamide, m.p. 271° C., after chromatography of the reaction mixture.