Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([F:9])[CH:3]=1.[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:9][C:4]1[CH:3]=[C:2]([C:14]2[CH:13]=[CH:12][C:11]([F:10])=[CH:16][C:15]=2[F:17])[CH:7]=[CH:6][C:5]=1[NH2:8]
Reactant: Nc1ccc(Br)cc1F
Reactant: OB(O)c1ccc(F)cc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Nc1ccc(-c2ccc(F)cc2F)cc1F
Yield: 89.6 %

Procedure:
To a solution of 4-bromo-2-fluoro-phenylamine (190 mg, 1 mmol) and 2,4-difluorophenylboronic acid (240 mg, 1 mmol) in 2.5 ml of 1,2-dimethoxy-ethane was added tetrakis(triphenylphosphine)palladium(0) (110 mg, 0.1 mmol) and 0.5 ml of 2M sodium carbonate aqueous solution. The mixture was microwaved at 150° C. for 15 min. The solvents were evaporated and the residue was diluted with CH2Cl2 and filtered. The filtration was concentrated and purified on a flash chromatography column with 0-80% EtOAc/hexanes to give 3,2′,4′-trifluoro-biphenyl-4-ylamine as an off-white solid (200 mg, 90%). LRMS calcd for C12H8F3N (m/e) 223, obsd 224 (M+H).
Reaction SMILES: COC1C=CC=CC=1C(Cl)=O.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][N:18]=[C:17]2[O:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:42]([N:44]=[C:45]=[S:46])=[O:43]>C1(C)C=CC=CC=1.C(O)C>[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:42]([N:44]=[C:45]=[S:46])=[O:43].[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][N:18]=[C:17]2[O:26][C:27]1[CH:33]=[CH:32][C:30]([NH:31][C:45]([NH:44][C:42](=[O:43])[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[O:35][CH3:34])=[S:46])=[CH:29][CH:28]=1
Reactant: COc1cc2ncnc(Oc3ccc(N)cc3)c2cc1OC
Agent: COc1ccccc1C(=O)Cl
Agent: COc1ccccc1C(=O)N=C=S
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2ncnc(Oc3ccc(NC(=S)NC(=O)c4ccccc4OC)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 90%).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[C:4]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)=[N:3]1.[CH2:31](NN)C>>[CH2:1]([N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=2)[C:4]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)=[N:3]1)[CH3:31]
Reactant: CCNN
Reactant: Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ccccc4n3)cc2)n1
Product: CCn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ccccc4n3)cc2)n1

Procedure:
Following the procedure for the preparation of 2-[4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline but substituting ethyl hydrazine provided the title compound. 1H NMR (400 MHz, CDCl3) δ 8.35 (bs, 2H), 8.19 (d, J=8.3 Hz, 1H), 8.07 (d, J=9.1 Hz, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.73 (t, J=8.3 Hz, 1H), 7.67 (d, J=8.3 Hz, 2H), 7.62 (s, 1H), 7.55 (t, J=7.9 Hz, 1H), 7.37 (d, J=9.1 Hz, 2H), 7.21 (bs, 2H), 7.01 (d, J=8.7 Hz, 2H) 5.39 (s, 2H), 4.24 (q, J=7.5 Hz, 2H), 1.56 (t, J=7.5 Hz, 3H); MS: (M+H m/z=407.3).
Reaction SMILES: [C:1]([O:18][CH:19]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[C:20]([OH:22])=O)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[NH2:37][CH2:38][CH2:39][C:40]([NH:42][C@H:43]([C:47]([OH:49])=[O:48])[C@@H:44]([CH3:46])[OH:45])=[O:41]>>[C:1]([O:18][CH:19]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[C:20]([NH:37][CH2:38][CH2:39][C:40]([NH:42][C@H:43]([C:47]([OH:49])=[O:48])[C@@H:44]([CH3:46])[OH:45])=[O:41])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCC)C(=O)O
Reactant: C[C@@H](O)[C@H](NC(=O)CCN)C(=O)O
Product: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCC)C(=O)NCCC(=O)N[C@H](C(=O)O)[C@@H](C)O
Yield: 86 %

Procedure:
Starting from 2-hexadecanoyloxyhexadecanoic acid (200 mg) prepared by the method described in Preparation 7 and N-β-alanyl-L-threonine (190 mg), N-[N-(2-hexadecanoyloxyhexadecanoyl)-β-alanyl]-L-threonine (230 mg) was obtained as crystals according to a similar manner to that of Example 6.
Reaction SMILES: [CH3:1][NH2:2].CO.[CH:5]([C:7]1[NH:8][C:9]2[C:14]([C:15]=1[C:16]#[N:17])=[CH:13][CH:12]=[CH:11][CH:10]=2)=O.[BH4-].[Na+]>O>[CH3:1][NH:2][CH2:5][C:7]1[NH:8][C:9]2[C:14]([C:15]=1[C:16]#[N:17])=[CH:13][CH:12]=[CH:11][CH:10]=2
Reactant: CN
Reactant: N#Cc1c(C=O)[nH]c2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CNCc1[nH]c2ccccc2c1C#N
Temperature: 0 °C
Reaction time: 5 h
Yield: 75.3 %

Procedure:
Methylamine (6.2 mL, 49.4 mmol, 33% in EtOH) was added to a MeOH (50 mL) solution of 2-formyl-1H-indole-3-carbonitrile (2.80 g, 16.5 mmol) at 0° C. Upon stirring for 5 h at 0° C., NaBH4 (740 mg, 19.8 mmol) was added to the solution and the stirring was continued for 16 h. The mixture was diluted with water, extracted with methylene chloride; the organic layer was dried and evaporated. The crude residue was subjected to chromatography (1-5% MeOH in methylene chloride). The desired fractions were collected and concentrated; the residue was recrystallized from a methylene chloride/hexane mixture to afford the title compound (2.30 g, 75%). 1H NMR (300 MHz, DMSO-d6, δ): 7.54 (m, 1H), 7.48 (m 1H), 7.21 (m, 2H), 3.93 (s, 2H), 2.31 (s, 3H). MS (ESI): m/e 186 (M+H)+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].C1(N2CCC3C(=CC(O)=CC=3)C2=O)CCCC1.BrC[C:26]1[CH:27]=[C:28]([B:32]([OH:34])[OH:33])[CH:29]=[CH:30][CH:31]=1>CC(C)=O>[C:28]1([B:32]([OH:34])[OH:33])[CH:29]=[CH:30][CH:31]=[CH:26][CH:27]=1
Reactant: OB(O)c1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: O=C1c2cc(O)ccc2CCN1C1CCCC1
Agent: [K+]
Solvent: CC(C)=O
Product: OB(O)c1ccccc1
Temperature: 60 °C
Reaction time: 1 h
Yield: 215.3 %

Procedure:
Potassium carbonate (0.166 g, 1.2 mmol) was added to a solution of 2-cyclopentyl-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (0.235 g, 1 mmol) and 3-(bromomethyl)phenylboronic acid (0.257 g, 1.2 mmol) in acetone (10 mL). After stirring for 1 h at 60° C., the reaction mixture was cooled to room temperature and filtered and the filtrate was evaporated under reduced pressure to give crude 34(2-cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)phenylboronic acid as a colorless solid (0.315 g, 85%). The crude product was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (s, 2H), 7.83 (s, 1H), 7.73-7.68 (m, 2H), 7.56 (s, 1H), 7.47 (d, 1H, J=7.8 Hz), 7.32 (t, 1H, J=7.8 Hz), 7.04 (d, 1H, J=8.7 Hz), 5.25 (s, 2H), 4.85-4.81 (m, 1H), 2.01-1.98 (m, 2H), 1.75-1.59 (m, 6H). LC-MS (ESI) Calcd for C19H20BNO4S [M+H]+: 370.12. Found: 369.90.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH:11]1([SH:16])[CH2:15][CH2:14][CH2:13][CH2:12]1.Br[CH2:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=1>C1COCC1>[CH:11]1([S:16][CH2:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: N#Cc1ccc(CBr)cc1
Reactant: SC1CCCC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: N#Cc1ccc(CSC2CCCC2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Add sodium bis(trimethylsilyl)amide (20 mL, 40 mmol, 2M solution in THF) to a solution of cyclopentanethiol (4.3 mL, 40 mmol) in anhydrous THF (100 mL) and stir at room temperature under nitrogen for 1 h. Add 4-bromomethyl-benzonitrile (7.85 g, 40 mmol) and stir the mixture for 24 h at room temperature. Reduce solvent in vacuo and wash with saturated aqueous NaHCO3. Extract with DCM (50 mL), wash organic phase with brine (50 mL) and dry over MgSO4 to obtain a light yellow oil suitable for use without additional purification. GC-MS m/z: 217 (M+).
Reaction SMILES: C[O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:5]=1.CO.C(O)C.[OH-].[K+]>O>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:27])=[O:2])=[CH:5][C:6]=1[O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: CCCCCCCCCCCCCCOc1cc(C(=O)OC)ccc1OC
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: CO
Product: CCCCCCCCCCCCCCOc1cc(C(=O)O)ccc1OC
Yield: 81.3 %

Procedure:
The title compound is prepared by the procedure of Example 32 using 60 g of product from Example 41, 480 ml methyl alcohol, 190 ml of ethyl alcohol, 28.5 ml of water and 26.7 g of potassium hydroxide. The residue is recrystallized from chloroform/hexane to give 47 g of the desired product as white crystals.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.ClC1C=CC=C(C=O)C=1[S:20][C:21]1[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([N:31]2[CH2:36][CH2:35][N:34]([C:37](=[O:39])[CH3:38])[CH2:33][CH2:32]2)=[O:30])=[CH:23][C:22]=1[Cl:40].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([S:20][C:21]3[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([N:31]4[CH2:32][CH2:33][N:34]([C:37](=[O:39])[CH3:38])[CH2:35][CH2:36]4)=[O:30])=[CH:23][C:22]=3[Cl:40])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1
Reactant: CC(=O)N1CCN(C(=O)/C=C/c2ccc(Sc3c(Cl)cccc3C=O)c(Cl)c2)CC1
Reactant: Ic1ccc2[nH]ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)N1CCN(C(=O)/C=C/c2ccc(Sc3ccc4[nH]ccc4c3)c(Cl)c2)CC1
Temperature: 120 °C

Procedure:
To a stirred solution of 5-iodoindole (255 mg, 1.05 mmol) in 5.0 mL of anhydrous DMF was added the potassium thiolate (457 mg, 1.26 mmol) from Example 65B, followed by K2CO3 (174 mg, 1.26 mmol), and cuprous iodide (20 mg, 0.11 mmol). The resulting mixture was then heated at 120° C. for overnight. The reaction mixture was then allowed to cool to ambient temperature and poured into water. The aqueous mixture was extracted twice with 25 mL of ethyl acetate. The combined organic layer was then washed with water and brine, dried over Na2SO4, filtered, concentrated on a rotavap under reduced pressure. The crude product was purified using Gilson Preparative HPLC as described in Example 38B to give the title compound (115 mg, 25% based on the iodide) as a light-brown solid. 1H NMR (d6-DMSO, 300 MHz) δ 2.03 (s, 3H), 3.40-3.78 (m, 8H), 6.5.1 (d, J=8.4 Hz, 1H), 6.53 (s, 1H), 7.23 (dd, J=2.1, 8.4 Hz, 1H), 7.27 (d, J=15.6 Hz, 1H), 7.39 (d, J=15.6 Hz, 1H), 7.41 (dd, J=1.8, 8.4 Hz, 1H), 7.49 (t, J=2.7 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.85 (d, J=1.8 Hz, 1H), 7.99 (d, J=1.8 Hz, 1H). MS (APCI+) (M+NH4)+ at m/z 440, 442. Anal. Calcd for C23H22ClN3O2S.0.53 CH2Cl2: C, 58.28; H, 4.79; N, 8.66. Found: C, 58.31; H, 4.93; N, 8.65.
Reaction SMILES: [CH:1]12[CH2:13][CH2:12][CH:8]([CH2:9][NH:10][CH2:11]1)[C:7]1[C:2]2=[CH:3][C:4]([NH:14][C:15]2[N:20]=[C:19]([NH:21][C@@H:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]3[NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[C:18]([Cl:33])=[CH:17][N:16]=2)=[CH:5][CH:6]=1.C(N(CC)CC)C.[C:41](Cl)(=[O:43])[CH3:42]>ClCCl>[C:41]([N:10]1[CH2:11][CH:1]2[CH2:13][CH2:12][CH:8]([C:7]3[C:2]2=[CH:3][C:4]([NH:14][C:15]2[N:20]=[C:19]([NH:21][C@@H:22]4[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]4[NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[C:18]([Cl:33])=[CH:17][N:16]=2)=[CH:5][CH:6]=3)[CH2:9]1)(=[O:43])[CH3:42]
Reactant: CC(=O)Cl
Reactant: CS(=O)(=O)N[C@@H]1CCCC[C@H]1Nc1nc(Nc2ccc3c(c2)C2CCC3CNC2)ncc1Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N1CC2CCC(C1)c1cc(Nc3ncc(Cl)c(N[C@@H]4CCCC[C@H]4NS(C)(=O)=O)n3)ccc12
Reaction time: 0.5 h

Procedure:
N-{(1R,2R)-2-[2-(10-Aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (35 mg, 0.0713 mmol) was placed in dichloromethane (3 mL) and triethylamine (21.6 mg, 0.214 mmol, 30.0 μL, 3.0 eq) was added followed by acetyl chloride (6.67 mg, 0.0856 mmol, 6.04 μL, 1.2 eq). The reaction was stirred for 30 minutes and then concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-6% MeOH/CH2Cl2 as the eluting solvent to obtain N-{(1R,2R)-2-[2-(10-acetyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a white foam as a mixture of diastereomers (32.88 mg, 86%). LCMS (m/e) 533 (M+1); 1H-NMR (CDCl3, 400 MHz) mixture of diasteromers δ 7.90 (s, 1H), 7.50-7.23 (m, 1H), 7.20-6.80 (m, 2H), 5.80-5.40 (m, 2H), 4.38-4.07 (m, 1H), 4.00-3.70 (m, 2H), 3.70-3.52 (m, 1H), 3.50-3.30 (m, 1H), 3.30-3.00 (m, 4H), 2.79 (s, 3H), 2.30-1.20 (m, 14H).
Reaction SMILES: C(C(CCCC)CO[C:6](=O)[CH2:7][CH2:8][S:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]1[CH:20]=[CH:21][N:22]=[C:15]1[CH:14]=[CH:13]2)C.FC1[N:34]=[C:33]([C:35]2([C:41]#[N:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH:32]=CC=1>CN(C=O)C>[CH:20]1[N:16]2[C:17]3[C:12]([CH:13]=[CH:14][C:15]2=[N:22][CH:21]=1)=[CH:11][C:10]([S:9][C:8]1[N:34]=[C:33]([C:35]2([C:41]#[N:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH:32]=[CH:6][CH:7]=1)=[CH:19][CH:18]=3
Reactant: N#CC1(c2cccc(F)n2)CCOCC1
Reactant: CCCCC(CC)COC(=O)CCSc1ccc2c(ccc3nccn32)c1
Solvent: CN(C)C=O
Product: N#CC1(c2cccc(Sc3ccc4c(ccc5nccn54)c3)n2)CCOCC1
Temperature: 90 °C

Procedure:
1i (261 mg, 0.6 mmol) and 4-(6-Fluoro-pyridin-2-yl)-tetrahydro-pyran-4-carbonitrile (1j, 123 mg, 0.6 mmol) were dissolved in DMF and degassed with N2 for 10 minutes. Potassium tert-butoxide (81 mg, 0.72 μmmol) was added, and the mixture was degassed with N2 for an additional 10 minutes. The reaction was heated to 90° C. for 24 hours, then cooled to room temperature. The solution was diluted with EtOAc and water, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the residue was purified by silica gel chromatography to obtain the desired product, 1k.
Reaction SMILES: S([O-])([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]C)(=O)=O.[OH2:18]>>[CH:8]([CH:7]=[CH:6][C:5]([OH:4])=[O:18])=[CH:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CCCCCCCCCCCCOS(=O)(=O)[O-]
Reactant: O
Product: O=C(O)C=CC=Cc1ccccc1
Temperature: 80 °C

Procedure:
A 2 l reactor with stirrer and reflux condenser was charged with 433 g of deionized water, and 3 grams of lauryl sulfate (30% strength solution), this initial charge then being heated to 80° C. with stirring under a nitrogen atmosphere.
Reaction SMILES: [Mg].C(OCC)C.[CH2:7](Br)[C:8]#[CH:9].[C:11]1(=[O:16])[CH2:15][CH2:14][CH2:13][CH2:12]1>O1CCCC1.Cl[Hg]Cl>[CH2:9]([C:11]1([OH:16])[CH2:15][CH2:14][CH2:13][CH2:12]1)[C:8]#[CH:7]
Reactant: O=C1CCCC1
Reactant: C#CCBr
Agent: Cl[Hg]Cl
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Product: C#CCC1(O)CCCC1
Temperature: 25 °C
Yield: 54.1 %

Procedure:
Magnesium turnings (350 mg, 14.4 mmol) and HgCl2 (16 mg, 0.659 mmol) were stirred with 20 mL of anhydrous diethyl ether in a 100-mL round bottom flask. Propargyl bromide (80% in xylene, 2.5 mL, 13.2 mmol) was added. The mixture was stirred for 30 min at room temperature before cyclopentanone (1.0 g, 11.9 mmol) was added in 4.0 mL tetrahydrofuran. The resulting mixture was refluxed for 2 h, then allowed to cool to room temperature, and quenched with saturated aqueous ammonium chloride (15 mL). The biphasic mixture was extracted with ethyl (50 mL) and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuuo. The residue was purified by flash chromatograph on silica gel (eluting with 10% hexanes in ethyl acetate) to provide the title compound (800 mg, 54%) as a colorless oil.
Reaction SMILES: C[O:2][C:3]([C:5]1[O:9][C:8]([C:10]2[C:11]3[Se:23][CH:22]=[CH:21][C:12]=3[N:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:14]=2)=[CH:7][CH:6]=1)=O.C(OCC)(=O)C.CCCCCC>O>[OH:2][CH2:3][C:5]1[O:9][C:8]([C:10]2[C:11]3[Se:23][CH:22]=[CH:21][C:12]=3[N:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:14]=2)=[CH:7][CH:6]=1
Reactant: COC(=O)c1ccc(-c2nn(-c3ccccc3)c3cc[se]c23)o1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: O
Product: OCc1ccc(-c2nn(-c3ccccc3)c3cc[se]c23)o1
Temperature: 25 °C
Yield: 72 %

Procedure:
7.5 g (0.068 mole) of granular anhydrous calcium chloride, 5.0 g (0.132 mole) of sodium brorhydride and 100 ml of anhydrous THF were reacted at room temperature for 4 h to form a white dispersion of calcium borohydride (Ca(BH4)2). To the dispersion compound 34 (3 g, 0.008 mole) was added and was reduced by heating under refluxing for 24 h. The progress of the reduction reaction was monitored by TLC with ethyl acetate (EA):n-hexane=3:2. When the reaction was completed, the reaction mixture was cooled to room temperature, and THF was evaporated under a reduced pressure. The remaining reaction mixture was poured into water to stop the reaction, and then was extracted with chloroform. The organic layer was recovered, dried over MgSO4 and filtered. The solvent of the filtrate was evaporated under a reduced pressure, and the residue was subjected to a column chromatography with EA:n-hexane=3:2, and then recrystallized from EA to afford compound 43 in viscous liquid (2.09 g). Yield: 72%.
Reaction SMILES: [C:1]1([C:7]#[C:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H].C(C1C=CC=CC=1)CC>COCCOC>[CH3:9][CH:8]=[CH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC#Cc1ccccc1
Reactant: [H][H]
Solvent: CCCc1ccccc1
Solvent: COCCOC
Product: CC=Cc1ccccc1
Yield: 79 %

Procedure:
In 1.0 ml of DME were heated 1.0 mmol of 1-phenyl-1-propyne and 0.01 mmol of tetraethylammonium μ-hydride-bis(pentacarbonylchromium(O)) at 100° C. and at a hydrogen pressure of 50 atm for 18 hours with stirring. GLC analysis of the reaction mixture revealed that propylbenzene and β-methylstyrene were produced in a yield of 79% and 19%, respectively.
Reaction SMILES: S(Cl)([Cl:3])=O.[CH:5]1[C:15]2[CH2:14][CH2:13][C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[CH:10](O)[C:9]=2[CH:8]=[CH:7][CH:6]=1>C1C=CC=CC=1>[Cl:3][CH:10]1[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:15]=2[CH2:14][CH2:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]1=2
Reactant: OC1c2ccccc2CCc2ccccc21
Reactant: O=S(Cl)Cl
Solvent: c1ccccc1
Product: ClC1c2ccccc2CCc2ccccc21

Procedure:
350 ml of thionyl chloride are added dropwise at a temperature of 30° to 40° to a solution of 201.5 g of crude 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol in 700 ml of dry benzene over a period of 40 minutes. Subsequently, the mixture is heated to boiling under reflux for an additional 1.5 hours and concentrated in vacuo. The residue is diluted 2 to 3 times with 300 ml of benzene each time and in each case again evaporated. There is obtained 5-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene as a beige crystalline mass of melting point 99°-101° which is used in the next step without further purification. By recrystallization from carbon tetrachloride there is obtained material of melting point 104°-105° C.
Reaction SMILES: [N:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C=O.[C:16](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CC(O)=O>[CH3:16][N:4]1[CH2:3][CH2:2][N:1]([C:7]2[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=2)[CH2:6][CH2:5]1
Reactant: Oc1ccc(N2CCNCC2)cc1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CN1CCN(c2ccc(O)cc2)CC1
Temperature: 25 °C
Yield: 106.4 %

Procedure:
4-(piperazin-1-yl)phenol 2 g (11.24 mmol) and formaldehyde 4.5 mL (37% in water, 56 mmol) were suspended in a mixture of THF/AcOH 5/1 and let under stirring at room temperature. After 30 minutes sodium triacetoxyborohydride 4.7 g (22.5 mmol) was added portion-wise. The reaction was let stir a few hours and evaporated down. The crude was purified on silica gel with AcOEt/EtOH/(NH3 7 N in MeOH) 8/2/0.2 to give 2.3 g of pink solid as a free base.
Reaction SMILES: [C:1]([N:9]1[C:17]2[CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:14][C:13](=O)[C:12]=2[CH:11]=[CH:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25]([NH:28][NH2:29])([NH2:27])=[NH:26].[ClH:30].Cl.O>C(O)C>[ClH:30].[C:1]([N:9]1[C:17]2[CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:14][C:13](=[N:29][NH:28][C:25]([NH2:27])=[NH:26])[C:12]=2[CH:11]=[CH:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N=C(N)NN
Reactant: O=C1CC(c2ccccc2)Cc2c1ccn2C(=O)c1ccccc1
Agent: Cl
Solvent: O
Solvent: CCO
Product: N=C(N)NN=C1CC(c2ccccc2)Cc2c1ccn2C(=O)c1ccccc1
Yield: 94.4 %

Procedure:
A mixture of 1-benzoyl-6-phenyl-4,5,6,7-tetrahydroindol-4-one (0.68 g), aminoguanidine hydrochloride (0.26 g), concentrated hydrochloric acid (0.11 ml), water (0.11 ml) and ethanol (50 ml) was refluxed for 30 minutes. Under reduced pressure, the solvent was evaporated, and the residue was washed with water to give crystals, which were recrystallized from ethanol to give 1-benzoyl-4-guanidinoimino-6-phenyl-4,5,6,7-tetrahydroindole hydrochloride (Compound 11) (0.83 g) as colorless crystals.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([CH2:15][CH2:16][CH3:17])[CH2:7]/[C:8]/2=[CH:11]\[C:12](O)=[O:13])=[CH:4][CH:3]=1.[Cl:18]CCl>>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([CH2:15][CH2:16][CH3:17])[CH2:7]/[C:8]/2=[CH:11]\[C:12]([Cl:18])=[O:13])=[CH:4][CH:3]=1
Reactant: CCCC1C/C(=C\C(=O)O)c2cc(F)ccc21
Reactant: ClCCl
Product: CCCC1C/C(=C\C(=O)Cl)c2cc(F)ccc21

Procedure:
This compound was prepared in an analogous manner to Example 18h with replacement of (E)-2-(6-fluoro-3-methyl-1-indanylidnene)acetic acid with (E)-2-(6-fluoro-3-propyl-1-indanylidene)acetic acid (15.01 g, 64.07 mmol). The product residue was dissolved in dichloromethane and used without purification in Example 27j.