Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:9]=2)[C:4](=[O:19])[CH2:3]1.[C:21]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[C:27]([F:29])[CH:28]=1)#[N:22]>>[CH3:20][C:2]1([CH3:1])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:25]3[CH:24]=[C:23]([CH:28]=[C:27]([F:29])[CH:26]=3)[C:21]#[N:22])[CH:9]=2)[C:4](=[O:19])[CH2:3]1
Reactant: CC1(C)CC(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc21
Reactant: N#Cc1cc(F)cc(B(O)O)c1
Product: CC1(C)CC(=O)c2ccc(-c3cc(F)cc(C#N)c3)cc21

Procedure:
The title compound was prepared from trifluoro-methanesulfonic acid 3,3-dimethyl-1-oxo-indan-5-yl ester and 3-cyano-5-fluorophenyl boronic acid according to the procedure described in example 21. MS (ES) m/z 280.1; HRMS: calcd for C18H14FNO+H+, 280.11322; found (ESI, [M+H]+), 280.1129.
Reaction SMILES: [CH3:1][N:2]([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[CH3:12][N:13]([CH3:31])[C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:22]2[CH:27]=[CH:26][C:25]([N:28]([CH3:30])[CH3:29])=[CH:24][CH:23]=2)[CH3:21])=[CH:16][CH:15]=1>C(O)C>[CH3:1][N:2]([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([C:7]([C:17]2[CH:16]=[CH:15][C:14]([N:13]([CH3:31])[CH3:12])=[CH:19][CH:18]=2)=[CH:21][CH:20]([CH:21]=[C:20]([C:17]2[CH:16]=[CH:15][C:14]([N:13]([CH3:12])[CH3:31])=[CH:19][CH:18]=2)[C:22]2[CH:23]=[CH:24][C:25]([N:28]([CH3:29])[CH3:30])=[CH:26][CH:27]=2)[C:22]2[CH:27]=[CH:26][C:25]([N:28]([CH3:29])[CH3:30])=[CH:24][CH:23]=2)=[CH:5][CH:4]=1
Reactant: CC(c1ccc(N(C)C)cc1)c1ccc(N(C)C)cc1
Reactant: CN(C)c1ccc(C=O)cc1
Solvent: CCO
Product: CN(C)c1ccc(C(=CC(C=C(c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)cc1
Temperature: 25 °C
Yield: 37.5 %

Procedure:
Proceeding in a manner similar to that described in Example 1 above, a mixture 1.5 g of 4-dimethylaminobenzaldehyde, 5.4 g of 1,1-bis(4-dimethylaminophenyl)ethane, 100.0 ml of ethyl alcohol and 2.0 ml of glacial aacetic acid was maintained at reflux approximately forty-two hours. After cooling to ambient temperature, the reaction mixture was poured into one liter of ice water, and the resulting solid was collected by filtration and recrystallized from isopropyl alcohol to obtain 2.5 g of bis{[1,1-bis(4-dimethylaminophenyl)ethenyl]}(4-dimethylaminophenyl)methane, a white solid which melted at 215°-220° C. Significant infrared maxima appeared at 1620 cm-1 (v.s.) and 1355 cm-1. The nuclear magnetic resonance spectrum was in accord with the assigned structure. An acetone solution of the product spotted onto clay, phenolic resin and organic acid coated papers slowly developed blue-colored images. Exposure of a paper coated with the product to bromine vapor developed a dark blue image. An acetone solution of the product, chloranil and a phenolic resin was coated onto a glass plate and dried. The transmission spectrum of the coating had a significant adsorption at 715 nonometers.
Reaction SMILES: [C:1]1(=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH:3]=[CH:2]1.[CH3:13][S-:14].[Na+].[Cl-].[Na+]>CO>[CH3:1][C:2]1[C:13](=[S:14])[C:6]2[C:5]([C:4](=[O:11])[CH:3]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: O=C1C=CC(=O)c2ccccc21
Reactant: C[S-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: CC1=CC(=O)c2ccccc2C1=S
Reaction time: 8 h
Yield: 14 %

Procedure:
0.617 mM 1,4-naphtoquinone was dissolved in 30 ml of methanol in 100 ml one-neck round flask, and 1.54 mM sodium thiomethoxide was added thereto and stirred overnight. 50 ml of saturated sodium chloride solution was added to the reaction mixture, followed by extraction three times with 50 ml of chloroform, and an organic layer was dehydrated with an anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the obtained residue was re-crystallized with methanol to produce 2-methylthio-1,4-naphthoquinone that was yellow crystal.
Reaction SMILES: [C:1]([OH:10])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N+:4]([O-:8])[CH:3]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[CH3:26][CH:27]1[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][C:34]2[CH:35]=[C:36]([CH:42]=[CH:43][CH:44]=2)[O:37][CH2:38][CH2:39][CH2:40][NH2:41])[CH2:28]1>C(Cl)Cl>[CH3:26][CH:27]1[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][C:34]2[CH:35]=[C:36]([CH:42]=[CH:43][CH:44]=2)[O:37][CH2:38][CH2:39][CH2:40][NH:41][C:1]([C:2]2[CH:3]=[N+:4]([O-:8])[CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:28]1
Reactant: O=C(O)c1ccc[n+]([O-])c1
Reactant: CC1CCCN(Cc2cccc(OCCCN)c2)C1
Agent: CC(C)COC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1CCCN(Cc2cccc(OCCCNC(=O)c3ccc[n+]([O-])c3)c2)C1
Reaction time: 0.5 h

Procedure:
To a solution of 0.03 mol of nicotinic acid 1-oxide in 40 ml of methylene chloride containing 10 ml of triethylamine, is added, at the temperature of from 0° to 5° C. and within about 10 minutes, 0.03 mol of isobutyl chloroformate dissolved in 15 ml of methylene chloride, then the mixture is stirred 30 minutes at the same temperature. To the same mixture and at the same temperature there is added 0.03 mol of 3-[3-(3-methylpiperidinomethyl)phenoxy]propylamine dissolved in 15 ml of methylene chloride, then, after a 2 hours stirring at room temperature, the reaction mixture is washed with 10 ml of water. The organic phase is filtered, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is purified by chromatography on silica as described in Example 7 to yield the N-[3-[3-(3-methylpiperidinomethyl)phenoxy]propyl]-3-pyridinecarboxamide 1-oxide, identical to the product of Example 8.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:16][C:17]1[C:25]([OH:26])=[CH:24][CH:23]=[C:22]2[C:18]=1[CH:19]=[C:20]([CH3:27])[NH:21]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:26][C:25]1[C:17]([F:16])=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20]([CH3:27])=[CH:19]2)#[N:13]
Reactant: Cc1cc2c(F)c(O)ccc2[nH]1
Reactant: COc1cc2nccc(Cl)c2cc1C#N
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COc1cc2nccc(Oc3ccc4[nH]c(C)cc4c3F)c2cc1C#N
Temperature: 95 °C
Yield: 35.1 %

Procedure:
A suspension of 4-chloro-6-cyano-7-methoxyquinoline (200 mg, 0.91 mmol), (prepared as described for the starting material in Example 1), 4-fluoro-5-hydroxy-2-methylindole (181 mg, 1.1 mmol), (prepared as described for the starting material in Example 11), and cesium carbonate (444 mg, 1.36 mmol) in DMF (6 ml) was heated at 95° C. for 2.5 hours. After cooling, the mixture was filtered, the filtrate was evaporated under vacuum and the residue was purified by column chromatography eluting with methylene chloride, followed by methanol/ethyl acetate/methylene chloride (2/10/88 followed by 5/15/80) to give 6-cyano-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinoline (111 mg, 35%).
Reaction SMILES: Br[C:2]1C=C(N[C@@H]2CCCN(C(OC(C)(C)C)=O)C2)C(OC)=N[CH:7]=1.ClC[C:26]([N:28]1[CH2:33]CC[C@@H:30]([NH:34][C:35]2[C:40](=[O:41])[NH:39][CH:38]=[C:37]([C:42]3[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=3)[CH:36]=2)[CH2:29]1)=[O:27]>>[C:26]([N:28]1[CH2:33][CH:30]([NH:34][C:35]2[C:40](=[O:41])[NH:39][CH:38]=[C:37]([C:42]3[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=3)[CH:36]=2)[CH2:29]1)(=[O:27])[CH:2]=[CH2:7]
Reactant: COc1ncc(Br)cc1N[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Reactant: O=C(CCl)N1CCC[C@@H](Nc2cc(-c3ccncc3)c[nH]c2=O)C1
Product: C=CC(=O)N1CC(Nc2cc(-c3ccncc3)c[nH]c2=O)C1

Procedure:
Following Example 1, but using tert-butyl 3-aminoazetidine-1-carboxylate (Example 1 Step 3) and reaction with acroyl chloride (Example 1 Step 6) provided the desired compound after purification: 1H NMR (300 MHz, DMSO-d6) 11.86 (br s, 1H), 8.52 (d, J=6.3 Hz, 2H), 7.62 (dd, J=4.2, 1.5 Hz, 2H), 7.25-7.35 (m, 1H), 6.61 (d, J=2.1 Hz, 1H), 6.20-6.40 (m, 2H), 6.10 (dd, J=17.1, 2.4 Hz, 1H), 5.67 (dd, J=10.2, 2.1 Hz, 1H), 4.61 (apparent t, J=7.8 Hz, 1H), 4.25-4.45 (m, 2H), 4.05-4.15 (m, 1H), 3.80-3.95 (m, 1H); MS (ES) m/z 297 (M+H).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][C:23](OC)=[O:24])=[N:20][CH:21]=3)=[CH:12][CH:11]=2)[CH2:3][CH2:2]1.C1(OC)C=CC=CC=1.[CH2:35]([NH2:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CCCCCCC>[O:1]1[CH2:2][CH2:3][N:4]([CH2:7][CH2:8][O:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][C:23]([NH:42][CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[O:24])=[N:20][CH:21]=3)=[CH:14][CH:15]=2)[CH2:5][CH2:6]1
Reactant: COC(=O)Cc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1
Reactant: NCc1ccccc1
Solvent: CCCCCCC
Solvent: COc1ccccc1
Product: O=C(Cc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1)NCc1ccccc1
Temperature: 142 °C
Reaction time: 0.03 h

Procedure:
To a 22-L reactor was charged compound 7 (650 g, 1.82 mol), anisole (3.25 L, 5 vol, anhydrous) and benzylamine (600 mL, 0.92 vol, 3 equiv). The batch (approximately 18° C.) was heated to 142±5° C. over 1 hour 44 minutes, with dissolution occurring at 30° C. The batch was maintained at 142±5° C. for 69 hours 30 minutes at which point HPLC analysis indicated that compound 7 was 0.9% by conversion (specification ≦1.7% by conversion). The batch was cooled to 45-50° C. over 5 hours 12 minutes (to aid cooling the nitrogen flow was increased once the batch was approximately 72° C.). At that temperature range, the batch was poorly stirring and on mixing, the batch temperature increased to 52° C. It was >50° C. for ≦15 minutes. The batch was aged for 2 hours 2 minutes once initially <50° C., then n-heptane (9.75 L, 15 vol, 99%) was added to the batch over 1 hour 56 minutes, maintaining the batch temperature at 45-50° C. The heating was then discontinued and the batch cooled to 25° C. over 10 hours 32 minutes and then to approximately 20° C. over 20 minutes. The total time the batch was maintained ≦25° C. was 4 hours 50 minutes (2 hours 47 minutes at approximately 20° C.). The batch was filtered under suction via a 24-inch polypropylene filter funnel (fitted with a PTFE cloth) and the reactor rinsed with anisole/n-heptane (1.3 L, 4:1) and the rinse transferred to the cake. The cake was then washed successively with two portions of n-heptane (1.3 L, 0.65 L). The total filtration time was 39 minutes. The batch (net wet weight 1004 g of KX2•391) was transferred to three glass trays and placed into a vacuum oven set at 50° C. and dried to constant weight over 96 hours 26 minutes.
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH3:20])=[CH:4][C:5]2[N:9]=[C:8]3[S:10][CH:11]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=4)[CH2:12][N:7]3[C:6]=2[CH:19]=1.ClC1C=C(C=CC=1)C(OO)=[O:26]>>[CH3:1][C:2]1[C:3]([CH3:20])=[CH:4][C:5]2[N:9]=[C:8]3[S:10](=[O:26])[CH:11]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=4)[CH2:12][N:7]3[C:6]=2[CH:19]=1
Reactant: Cc1cc2nc3n(c2cc1C)CC(c1ccccn1)S3
Reactant: O=C(OO)c1cccc(Cl)c1
Product: Cc1cc2nc3n(c2cc1C)CC(c1ccccn1)S3=O

Procedure:
In a manner analogous to Example 10 2,3-Dihydro-6,7-dimethyl-2-(2-pyridyl)thiazolo- [3,2-a]benzimidazole (2.63 g) was reacted with m-chloroperoxybenzoic acid (1.45 g) to give the title compound as the 1/4 hydrate, mp 177°-8° C. decomp.
Reaction SMILES: [C:1]1([C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C@@H:9]2[CH2:13][CH2:12][CH2:11][NH:10]2)[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH3:20].C1COCC1>>[C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:8][BH:20][N:10]3[CH2:11][CH2:12][CH2:13][C@@H:9]23)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: B
Reactant: OC(c1ccccc1)(c1ccccc1)[C@@H]1CCCN1
Solvent: C1CCOC1
Product: B1OC(c2ccccc2)(c2ccccc2)[C@@H]2CCCN12
Yield: 25.4 %

Procedure:
(S)-(-)-α,α-diphenyl-2-pyrrolidinemethanol (378.5 mg, 1.5 mmol) was dissolved in 4.09 mL (4.5 mmol) of BH3.THF (1.1M), and the resulting solution was refluxed for 48 h under argon atmosphere (1 bar). The solvent was removed under vacuum, and the residue was sublimed (150°-160° C./0.1 Torr) to give 258 mg of a crude product. This product (94.1 mg) was resublimed (145°-160° C./0.05 Torr) to give 36.7 mg (0.139 mmol), 25.4% yield) of (S)-5,5-diphenyl-3,4-propano-1,3,2-oxazaborolidine as colorless crystals, mp 107°-124° C.,
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([OH:17])=O)[CH3:14])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:18][CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[NH:21][C:20]1=[O:35]>>[F:8][C:6]1[CH:5]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:18][CH:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[NH:21][C:20]2=[O:35])=[O:17])[CH3:14])=[O:11])[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: NC1C(=O)NC(c2ccccn2)c2ccccc21
Reactant: C[C@H](NC(=O)Cc1cc(F)cc(F)c1)C(=O)O
Product: C[C@H](NC(=O)Cc1cc(F)cc(F)c1)C(=O)NC1C(=O)NC(c2ccccn2)c2ccccc21

Procedure:
Following General Procedure D above using N-(3,5-difluorophenylacetyl)-L-alanine (Example B) and 4-amino-1-(pyrid-2-yl)-1,2,3,4-tetrahydroisoquinoline-3-one (Example 5-C), the title compound was prepared as a solid having a melting point of 100° C.
Reaction SMILES: [CH:1]([N:4]([C:8]1[CH:13]=[CH:12][C:11]2[O:14][CH2:15][O:16][C:10]=2[CH:9]=1)[C:5]([NH2:7])=[O:6])([CH3:3])[CH3:2].[N:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]=O)[CH:18]=1>>[CH:1]([N:4]1[C:8]2[C:13](=[CH:12][C:11]3[O:14][CH2:15][O:16][C:10]=3[CH:9]=2)[CH:23]([C:19]2[CH:18]=[N:17][CH:22]=[CH:21][CH:20]=2)[NH:7][C:5]1=[O:6])([CH3:3])[CH3:2]
Reactant: O=Cc1cccnc1
Reactant: CC(C)N(C(N)=O)c1ccc2c(c1)OCO2
Product: CC(C)N1C(=O)NC(c2cccnc2)c2cc3c(cc21)OCO3
Yield: 36 %

Procedure:
This compound was synthesized from N-isopropyl-N-[3,4-(methylenedioxy)-phenyl]urea (238 mg) and 3-pyridinecarboxaldehyde (100 μL) by the procedure described in example 10 in 36% yield. mp: 172-174° C. 1H NMR (CDCl3): 8.58-8.56 (m, 3H), 7.63 (m, 1H), 7.29 (m, 2H), 6.70 (s, 1H), 6.34 (s, 1H), 5.94 (d, J=1.3, 1H), 5.92 (d, J=1.3, 1H), 5.33 (s, 1H), 5.29 (s, 1H), 4.41 (m, 1H), 1.53 (d, J=6.8, 3H), 1.50 (d, J=6.8, 3H).
Reaction SMILES: C([Li])CCC.CO[C:8]([C:10]1[CH:24]=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:22]=[CH:21][C:11]=1[O:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:9]>C1COCC1.C(NC(C)C)(C)C>[O:28]1[CH2:27][CH2:26][N:25]([C:23]2[CH:22]=[CH:21][C:11]3[O:12][CH2:13][CH2:14][CH:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:8](=[O:9])[C:10]=3[CH:24]=2)[CH2:30][CH2:29]1
Reactant: CCOC(=O)CCCOc1ccc(N2CCOCC2)cc1C(=O)OC
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C1CCOc2ccc(N3CCOCC3)cc2C1=O
Reaction time: 0.5 h
Yield: 55.8 %

Procedure:
In THF (15 ml) was dissolved diisopropylamine (1.018 ml), and to the mixture was added dropwise at 0° C. n-butyl lithium (4.2 ml). The mixture was stirred at the same temperature for 30 minutes. To the mixture was added dropwise a solution of ethyl 4-(2-methoxycarbonyl-4-morpholinophenoxy)butyrate (1829 mg, 5.18 mmol) in THF (5 ml) at −78° C., ice bath was removed, and the mixture was stirred for 7 hours. To the mixture was added at 0° C. 10% ammonium chloride solution (30 ml), and the mixture was extracted with ethyl acetate (30 ml×3). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified with column chromatography (silica gel 50 g, ethyl acetate/hexane=1/5), and the desired fraction was concentrated under reduced pressure to give ethyl 7-morpholino-5-oxo-2,3,4,5-tetrahydro-1-benzoxepine-4-carboxylate (924 mg, 2.89 mmol, 56%).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10]CC2C=CC=CC=2)=[CH:6][C:5]=1[CH2:18][C:19]#[N:20])([O-])=O.C1CCCCC=1>[Pd].C(O)C>[C:19]([CH2:18][C:5]1[CH:6]=[C:7]([OH:10])[CH:8]=[CH:9][C:4]=1[NH2:1])#[N:20]
Reactant: N#CCc1cc(OCc2ccccc2)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Solvent: C1=CCCCC1
Product: N#CCc1cc(O)ccc1N

Procedure:
A suspension of 5.4 g of 2-nitro 5-benzyloxyphenylacetonitrile, 5.4 ml of cyclohexene, 22 ml of ethanol and 3 g of 10% palladium on activated charcoal was refluxed for five hours. The suspension was then hot filtered and the filtrate evaporated. The residue was recrystallised from ethanol to produce dark beige crystals.
Reaction SMILES: [C:1]([O:4][C@@H:5]([CH2:8][CH2:9][C@H:10]([OH:13])[CH2:11][OH:12])[C:6]#[CH:7])(=[O:3])[CH3:2].N1C=CC=CC=1.[C:20]1([CH3:30])[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1>C(Cl)Cl>[C:1]([O:4][C@@H:5]([CH2:8][CH2:9][C@H:10]([OH:13])[CH2:11][O:12][S:26]([C:23]1[CH:24]=[CH:25][C:20]([CH3:30])=[CH:21][CH:22]=1)(=[O:28])=[O:27])[C:6]#[CH:7])(=[O:3])[CH3:2]
Reactant: C#C[C@H](CC[C@H](O)CO)OC(C)=O
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: C#C[C@H](CC[C@H](O)COS(=O)(=O)c1ccc(C)cc1)OC(C)=O
Temperature: 0 °C
Reaction time: 5 h
Yield: 10 %

Procedure:
A solution of(3S,6S)-3-acetoxy-6,7-dihydroxy-hept-1-yne 14 (4.3 g, 23.1 mmol) in CH2Cl2 (50 mL) containing pyridine (3.7 mL, 46.2 mmol) was cooled to 0° C. and treated with p-toluene sulfonyl chloride (4.4 g, 23.1 mmol) and stirred at room temperature for 5 h. The reaction mixture was diluted with CH2Cl2 (25 mL) and washed with aqueous CuSO4 solution (2×25 mL) followed by water (2×25 n mL). Organic layer was dried (Na2SO4), evaporated and purified by chromatography (Si-gel, 15% EtOAc-hexane); first eluted was (3S,6S)-3-acetoxy-6,7-di-p-toluene sulfonyloxy-hept-1-yne 15a (1.14 g) in 10% yield as a yellow syrup. 1HNMR (CDCl3, 200 MHz): δ1.48-1.8 (m, 4H, H-3,4), 2.0 (s, 3H, OAc), 2.31 (d, 1H, J 2.5 Hz, H-7) 2.4 (s, 3H, Ar—CH3), 3.94 (d, 2H, J 4.5 Hz, H-1), 4.5-4.64 (m, 1H, H-2), 5.06-5.18 (m, 1H, H-5), 7.20-7.3, 7.56-7.7 (m, 4H each, Ar—H).
Reaction SMILES: Br[C:2]1[C:3](C2C=CC=CC=2)=[N:4][NH:5][CH:6]=1.C1C=C[C:16](/[CH:19]=[CH:20]/[C:21](/[CH:23]=[CH:24]/[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=O)=[CH:17][CH:18]=1.C1C=C[C:34](/[CH:37]=[CH:38]/[C:39](/[CH:41]=[CH:42]/[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd:67].[Pd].C.Cl.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[CH2:2]([C:3]1[N:4]([C:48]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[C:42]2[CH:34]=[CH:37][CH:38]=[C:39]([OH:40])[CH:41]=2)[N:5]=[C:24]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:23]=1[C:21]1[CH:18]=[CH:17][CH:16]=[CH:19][CH:20]=1)[CH3:6].[Pd:67]
Reactant: Brc1c[nH]nc1-c1ccccc1
Reactant: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [Pd]
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCc1c(-c2ccccc2)c(-c2ccccc2)nn1-c1ccccc1-c1cccc(O)c1

Procedure:
The reaction of Example 1 (reaction scale: 10 mmol of bromophenyl pyrazole) was conducted with 0.15 mole % of Pd2(dba)3. After the reaction was judged to be essentially complete, THF (10 mL/g of bromophenyl pyrazole starting material) was added to dissolve the precipitates, and the solution was passed through a Darco zeta pad twice. The filtrate was neutralized with 1N aq. HCl to a pH of 7.0 to 7.5. After filtration, the crude solid, whose palladium level was 111 ppm, was dissolved in THF (9 mL/g of bromophenyl pyrazole starting material), and the mixture was stirred in the presence of PS-PPh3 resin (Argonaut Technologies, 1.61 mmol PPh3/g, 5 wt %) at ambient temperature for 21 h, then filtered twice through a Darco zeta pad. The filtrate was concentrated and the product was recrystallized from THF/acetone/water to afford 2′-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-[1,1′]-biphenyl-3-ol containing less than 2 ppm of palladium.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]([N+:12]([O-])=[O:13])[C:9]([NH:15][C:16]([C:18]([O:20]CC)=O)=[O:17])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2>C(O)C>[Br:1][C:2]1[C:3]2[CH:4]=[CH:5][CH:6]=[N:7][C:8]=2[C:9]2[NH:15][C:16](=[O:17])[C:18](=[O:20])[N:12]([OH:13])[C:10]=2[CH:11]=1
Reactant: CCOC(=O)C(=O)Nc1c([N+](=O)[O-])cc(Br)c2cccnc12
Solvent: CCO
Product: O=c1[nH]c2c3ncccc3c(Br)cc2n(O)c1=O
Yield: 69.6 %

Procedure:
0.5 g (1.4 mmol) 5-Bromo-8-ethoxalylamino-7-nitroquinoline in 30 ml ethanol was hydrogenated at atm. pressure by using 100 mg (5%) Pt/c as a catalyst. The reaction mixture was filtered and the filtrate was evaporated in vacuo. The residue was stirred with water and the precipitate was filtered off. The crude product was washed with ethanol to give 0.3 g (72%) of 6-Bromo-4-hydroxypyrido[2,3-f]quinoxaline-2,3(1H,4H)-dione. M.p. decomp. MS m/z: 307 (M 20%), 291 (70%), 156 (100%), 128 (70%).
Reaction SMILES: [CH3:1][N:2]([CH2:24][CH2:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([Sn](CCCC)(CCCC)CCCC)=[CH:6][CH:5]=1.Br[C:35]1[N:36]=[C:37]([N:45]2[CH2:50][CH2:49][N:48]([CH2:51][CH3:52])[CH2:47][CH2:46]2)[C:38]2[C:43]([CH:44]=1)=[CH:42][CH:41]=[CH:40][CH:39]=2>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C.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>[CH2:51]([N:48]1[CH2:47][CH2:46][N:45]([C:37]2[C:38]3[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH:44]=[C:35]([C:7]3[CH:6]=[CH:5][C:4]([C:3](=[O:23])[N:2]([CH2:24][CH2:25][O:26][CH2:27][C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH3:1])=[CH:9][CH:8]=3)[N:36]=2)[CH2:50][CH2:49]1)[CH3:52]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C(=O)N(C)CCOCc2ccccc2)cc1
Reactant: CCN1CCN(c2nc(Br)cc3ccccc23)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1C
Product: CCN1CCN(c2nc(-c3ccc(C(=O)N(C)CCOCc4ccccc4)cc3)cc3ccccc23)CC1
Yield: 46.7 %

Procedure:
N-Methyl-N-(2-benzyloxyethyl)-4-tributylstannylbenzamide (1.93 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.93 g) were heated under reflux overnight in the presence of tetrakistriphenylphosphinepalladium(0) (0.13 g) in xylene in nitrogen atmosphere. After cooling, the reaction solution was diluted with ethyl acetate and filtered. The filtrate was extracted with 2N hydrochloric acid. The aqueous layer was washed with ethyl acetate and adjusted to pH 10 by a 8N aqueous solution of sodium hydroxide, which was then extracted with ethyl acetate, washed with a 10% aqueous solution of sodium carbonate and brine, and then dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (chloroform/methanol system), to give 1-(4-ethylpiperazin-1-yl)-3-{4-[N-(2-benzyloxyethyl)-N-methylcarbamoyl]phenyl}isoquinoline (0.69 g) as a pale yellow viscous oil.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:15][CH3:16])=[C:4]([C:9]([CH:12](Br)Br)=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:17]1([S:23]([O-:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Na+].C(=O)([O-])O.[Na+]>CC(N(C)C)=O.O>[C:17]1([S:23]([CH2:12][C:9]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[C:3]([O:15][CH3:16])[C:2]([Br:1])=[CH:11][CH:10]=2)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=S([O-])c1ccccc1
Reactant: COC(=O)c1c(C(Br)Br)ccc(Br)c1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: COC(=O)c1c(CS(=O)(=O)c2ccccc2)ccc(Br)c1OC
Temperature: 90 °C
Yield: 75.8 %

Procedure:
A solution of methyl 3-bromo-6-dibromomethyl-2-methoxybenzoate (Intermediate 42A, 19 g) in DMA (300 mL) was added to a stirred solution of sodium benzenesulfinate 17.9 g) and sodium hydrogen carbonate (9.5 g) in water (70 mL) and the mixture was heated at 90° C. for 2 hours. After cooling, the mixture was poured into water and filtered through Celite and the pad was washed with ethyl acetate. The organic layer was separated, washed with water and brine, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and pentane with a gradient of 0-100% to give methyl 6-(benzenesulfonylmethyl)-3-bromo-2-methoxybenzoate (13.8 g).