Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[CH2:9][C@H:8]2[C@H:6]([CH2:7]2)[CH2:5][N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].Br[C:18]1[CH:23]=[N:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:25][C:24]([F:27])([F:26])[C:21]1[N:22]=[CH:23][C:18]([NH:1][CH2:2][C@@H:3]2[CH2:9][C@H:8]3[C@H:6]([CH2:7]3)[CH2:5][N:4]2[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[N:19][CH:20]=1
Reactant: CC(C)(C)OC(=O)N1C[C@H]2C[C@H]2C[C@H]1CN
Reactant: FC(F)(F)c1cnc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1C[C@H]2C[C@H]2C[C@H]1CNc1cnc(C(F)(F)F)cn1
Temperature: 50 °C

Procedure:
1,1-dimethylethyl (1S,4S,6S)-4-(aminomethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate D29 (400 mg) and 2-bromo-5-(trifluoromethyl)pyrazine (401 mg, 1.767 mmol) were dissolved in DMF (2 ml) then sodium carbonate (375 mg, 3.53 mmol) was added and the mixture was heated to 50° C. for 2 hours. DMF was concentrated under vacuum and the residue was taken up with DCM (3 ml) and washed with NaHCO3 saturated solution (4 ml). The organic phase was filtered through a phase separator tube, concentrated under vacuum and purified by silica gel chromatography (Biotage SP—column size 25 g SNAP using Cy:EtOAc=8:2 to 2:8 as eluent). It was recovered the title compound D30 (300 mg).
Reaction SMILES: Br[C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:17]2[CH:22]=[CH:21][C:20]([B:23]3[NH:28][C:27]4[CH:29]=[CH:30][CH:31]=[C:32]5[CH:33]=[CH:34][CH:35]=[C:25]([C:26]=45)[NH:24]3)=[CH:19][CH:18]=2)O1.O.O.O.O.O.O.O.O.O.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[NH:24]1[C:25]2=[CH:35][CH:34]=[CH:33][C:32]3=[CH:31][CH:30]=[CH:29][C:27](=[C:26]23)[NH:28][B:23]1[C:20]1[CH:19]=[CH:18][C:17]([C:2]2[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][CH:7]=2)=[CH:22][CH:21]=1
Reactant: CC1(C)OB(c2ccc(B3Nc4cccc5cccc(c45)N3)cc2)OC1(C)C
Reactant: Nc1ncccc1Br
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: O
Solvent: COCCOC
Product: Nc1ncccc1-c1ccc(B2Nc3cccc4cccc(c34)N2)cc1
Temperature: 70 °C
Reaction time: 8 h
Yield: 47.3 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (57.7 mg) was added to a suspension of 3-bromopyridin-2-amine (432 mg), 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine (1016 mg) and sodium carbonate decahydrate (1429 mg) in DME (10 mL) and water (2 ml) and the mixture was stirred at 80° C. under nitrogen for 3 hr and at 70° C. overnight. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). The filtrate was concentrated and the residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (397 mg) as a brown solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:32])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[CH2:12][C@@H:13]([OH:31])[C@@H:14]([NH:22][C:23](=[O:30])[C@H:24]([CH2:26][C:27](=[O:29])[NH2:28])[NH2:25])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:4])([CH3:3])[CH3:2].[C:33]1([CH3:43])[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][CH:34]=1.C(N(C(C)C)CC)(C)C>C(OCC)(=O)C.CCCCCC>[C:1]([O:5][C:6](=[O:32])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[CH2:12][C@@H:13]([OH:31])[C@@H:14]([NH:22][C:23](=[O:30])[C@H:24]([CH2:26][C:27](=[O:29])[NH2:28])[NH:25][S:39]([C:36]1[CH:37]=[CH:38][C:33]([CH3:43])=[CH:34][CH:35]=1)(=[O:41])=[O:40])[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCN1C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)CC(N)=O
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1ccc(S(=O)(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc2ccccc2)[C@H](O)CN2CCC[C@H]2C(=O)OC(C)(C)C)cc1
Yield: 56.7 %

Procedure:
In a manner analogous to that described in Example 21, from 223 mg of N-[3(S)-[[L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester, 95 mg of toluene-4-sulphonyl chloride and 65 mg of diisopropylethylamine there were obtained 170 mg of N-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(p-toluenesulphonyl)-L-asparaginyl]amino]butyl]-L-proline tert.butyl ester as a white solid (from ethyl acetate/n-hexane): MS: m/e 603 [M+H]+.
Reaction SMILES: [S:1](=[O:5])(=[O:4])([OH:3])[OH:2].[S:6]([O-:10])([OH:9])(=[O:8])=[O:7].[Na+].[OH-].[Cr+3:13].[OH-].[OH-]>>[S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[Cr+3:13].[S:6]([O-:10])([O-:9])(=[O:8])=[O:7].[S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[Cr+3:13]
Reactant: O=S(=O)([O-])O
Reactant: O=S(=O)(O)O
Agent: [Cr+3]
Agent: [Na+]
Agent: [OH-]
Product: O=S(=O)([O-])[O-]

Procedure:
A process, as claimed in claim 4, wherein sulfuric acid or sodium hydrogen sulfate is added to the chromium hydroxide obtained, to form chromium sulfate.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH2:13].O=O>CO.[Pd](Cl)Cl.[Ti]>[CH3:1][C:2](=[O:13])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: C=CCCCCCCCCCC
Reactant: O
Agent: Cl[Pd]Cl
Agent: [Ti]
Agent: O=O
Solvent: CO
Product: CCCCCCCCCCC(C)=O
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
2-dodecanone is prepared from 1-dodecene according to the process of the present invention as follows: A catalyst solution is prepared by dissolving .04 moles of palladium chloride in a mixture of 137 grams of methanol, 252 grams of polypropylene glycol having an average molecular weight of 430, and 15 grams of water. The catalyst solution is then charged to a 2 liter titanium autoclave where the catalyst solution is heated to a temperature of 60°C; while being stirred at 1,000 r.p.m. with the reactor being pressurized to 100 p.s.i.g. with oxygen. Using a piston pump, 600 grams of 1-dodecene is introduced to the autoclave over a period of 21/2 hours. During this period of addition, the reaction temperature is maintained at 60°C by cooling, with the reaction pressure of 100 p.s.i.g. being maintained by repressuration with oxygen. Stirring is continued for about 1/2 hour after the addition of 1-dodecene is completed.
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([N+:17]([O-])=O)=[C:10]([S:13]([OH:16])(=[O:15])=[O:14])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].CN(C=O)C>CO.[Pd]>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([NH2:17])=[C:10]([S:13]([OH:16])(=[O:15])=[O:14])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCc2cc([N+](=O)[O-])c(S(=O)(=O)O)cc21
Agent: [Pd]
Solvent: CO
Solvent: CN(C)C=O
Product: CC(=O)N1CCc2cc(N)c(S(=O)(=O)O)cc21
Yield: 79.4 %

Procedure:
A suspension of 1-acetyl-5-nitroindoline-6-sulfonic acid (Compound 2-3 in Scheme II) (9.0 g) in 250 mL of methanol was hydrogenated in the presence of 0.5 g of 10% Pd/C for 3 h. DMF (˜250 mL) was added to dissolve the precipitated product. The catalyst was removed by filtration through Celite® and the filtrate was concentrated to give a solid. The solid was suspended in methanol (50 mL), filtered and washed with small amount of methanol and ether. Drying under vacuum afforded 6.4 g of the desired amine as an off-white solid.
Reaction SMILES: [C:1]([O:5][C:6]([C@H:8]1[CH2:11][C@@H:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:9]1CC1C=CC=CC=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[H][H]>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([C@H:8]1[CH2:11][C@@H:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[NH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)[C@H]1C[C@@H](C(=O)OC(C)(C)C)N1Cc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)[C@@H]1C[C@H](C(=O)OC(C)(C)C)N1
Yield: 65.5 %

Procedure:
307 mg (884 μmol) of cis-N-benzylazetidine-2,4-dicarboxylic acid di-tert.butyl ester in 25 ml of methanol is hydrogenated in a Parr shaker over 100 mg of 20% Pd(OH)2 /C (containing 31% water) under 4 atm of hydrogen for 7.5 h. The catalyst is filtered off through a double paper filter and thoroughly washed with methanol. Evaporation and filtration over SiO2 (EtOAc/hexanes 1:1) affords 149 mg (66%) of cis-azetidine-2,4-dicarboxylic acid di-tert.butyl ester as a yellowish oil which solidifies spontaneously. mp. 47°-48.5° C. 1H NMR (CDCl3): δ4.04 (dd, 2H, J=5.5, 9), 3.2 (br., 1H), 2.97 (dt, 1H, J=12 (d), 9 (t)), 2.38 (dt, 1H, J=12 (d), 5.5 (t)), 1.48 (s, 18H). IR (neat): 3328, 2979, 2934, 1731, 1480, 1458, 1394, 1369, 1280, 1257, 1156, 1103, 1048, 1031, 892, 846, 734 cm-1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[OH:18].CS(O[CH2:24][CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)(=O)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:15])=[O:16])=[CH:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[O:18][CH2:24][CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1
Reactant: CC(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1
Reactant: CS(=O)(=O)c1ccc(-c2ccc(O)c(F)c2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)OC(=O)N1CCC(COc2ccc(-c3ccc(S(C)(=O)=O)cn3)cc2F)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 64.5 %

Procedure:
A mixture of 2-fluoro-4-[5-(methylsulfonyl)-2-pyridinyl]phenol (0.114 g, 0.43 mmol), 1-methylethyl 4-{[(methylsulfonyl)oxy]methyl}-1-piperidinecarboxylate (0.18 g, 0.55 mmol) and K2CO3 (0.12 g, 0.85 mmol) in DMF (5 mL) was stirred at ambient temperature for 30 min, then heated at 70° C. overnight. Cooled to ambient temperature, the mixture was poured into water (30 mL), and the precipitate was collected, washed with water and air dried. The solid was further triturated with hot MeOH to give 0.125 g (65%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 9.14 (d, 1H, J=1.7 Hz), 8.23 (dd, 1H, Ja=8.4 Hz, Jb=2.0 Hz), 7.90-7.75 (m, 3H), 7.05 (t, 1H, J=8.4 Hz), 4.92 (septet, 1H, J=6.2 Hz), 4.30-4.10 (m, 2H), 3.94 (d, 2H, J=6.6 Hz), 3.13 (s, 3H), 2.85-2.70 (m, 2H), 2.15-2.00 (m, 1H), 1.95-1.80 (m, 2H), 1.40-1.25 (m, 2H), 1.24 (d, 6H, J=6.3 Hz); LRMS (ESI), m/z 451 (M+H).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]([OH:19])[CH:7]=[CH:8][C:9]=1[CH2:10][CH2:11][CH2:12][CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[N:15]1.Cl[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[N:23]=1.O>CN(C)C=O>[CH3:3][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[CH2:10][CH2:11][CH2:12][CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[N:15]1)[O:19][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:30][CH:29]=2)[N:23]=1
Reactant: Cc1cc(O)ccc1CCCCn1ccnn1
Reactant: FC(F)(F)c1ccc(-c2cccc(CCl)n2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(OCc2cccc(-c3ccc(C(F)(F)F)cc3)n2)ccc1CCCCn1ccnn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 84 %

Procedure:
16 mg (0.39 mmol) of 95% sodium hydride were added at 0° C. to a solution of 86 mg (0.37 mmol) 3-methyl-4-(4-[1,2,3]triazol-1-yl-butyl)-phenol in 4.0 ml N,N-dimethylformamide and stirred for 30 min. at 0° C. 100 mg (0.37 mmol) 2-chloromethyl-6-(4-trifluoromethyl-phenyl)-pyridine were given to the reaction mixture and stirring continued at r.t overnight. After addition of 8 ml water the mixture was stirred for 1 h, the formed precipitate isolated by filtration, washed with water, methanol/water 1:1, and a small amount of ether. The residue was dried at 40° C. to give 145 mg (84%) of the title compound as white powder.
Reaction SMILES: [CH2:1]=[C:2]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]([O:5]CC)=[O:4].[OH-].[K+]>CO>[CH2:1]=[C:2]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]([OH:5])=[O:4]
Reactant: C=C(Cc1ccccc1)C(=O)OCC
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: C=C(Cc1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 4 h
Yield: 71 %

Procedure:
The ethyl α-methylenebenzenepropanoate of Step 7 (4.6 g, 24.3 mmol) was dissolved in methanol (12 mL) and then reacted with 2N potassium hydroxide (24 mL) solution. The mixture was stirred at room temperature for 4 hours and concentrated by evaporation. The residue was diluted with water and washed with ether. The aqueous layer was acidified to pH 2 with 1N HCl, and then extracted with ethyl acetate. The extracts were dried (Na2SO4) and evaporated to give the title compound as colorless oil (2.8 g, 66% yield). 1H NMR: 300 MHz spectrum consistent with proposed structure.
Reaction SMILES: [N:1]([C:4]1[CH:5]=[C:6]([S:10]([N:13]=[C:14]=[O:15])(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)=[C:2]=[O:3].[NH2:16][C:17]1[N:22]=[C:21]([O:23][CH3:24])[CH:20]=[C:19]([CH3:25])[N:18]=1.[CH3:26][CH:27]([OH:29])[CH3:28]>C(Cl)Cl>[CH3:24][O:23][C:21]1[CH:20]=[C:19]([CH3:25])[N:18]=[C:17]([NH:16][C:14]([NH:13][S:10]([C:6]2[CH:5]=[C:4]([NH:1][C:2](=[O:3])[O:29][CH:27]([CH3:28])[CH3:26])[CH:9]=[CH:8][CH:7]=2)(=[O:11])=[O:12])=[O:15])[N:22]=1
Reactant: COc1cc(C)nc(N)n1
Reactant: O=C=Nc1cccc(S(=O)(=O)N=C=O)c1
Reactant: CC(C)O
Solvent: ClCCl
Product: COc1cc(C)nc(NC(=O)NS(=O)(=O)c2cccc(NC(=O)OC(C)C)c2)n1

Procedure:
To an anhydrous solution of 2.3 g of m-isocyanatobenzenesulfonyl isocyanate in 50 ml of methylene chloride was added in small portions 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine. Efficient stirring was maintained during the addition and for three additional hours. The intermediate thus obtained, 3-isocyanto-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]benzenesulfonamide, was reacted further by adding one gram of 2 -propanol and stirring the resultant mixture for an additional sixteen hours. Filtration of the reaction mixture and evaporation of the filtrate yielded the desired product melting at 173°-180°.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:24][C:25]1[CH:33]=[C:32]([C:34]#[C:35][CH2:36][CH2:37][O:38][CH3:39])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH2:40].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:24][C:25]1[CH:33]=[C:32]([C:34]#[C:35][CH2:36][CH2:37][O:38][CH3:39])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH:40][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
Reactant: COCCC#Cc1cc(Cl)c(N)c2c1OCO2
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
Yield: 33.3 %

Procedure:
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-amine (165 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml). The crude product was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent. There was thus obtained the title compound (109 mg, 33%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 1.96 (quintet, 2H), 2.40 (m, 4H), 2.47 (t, 2H), 2.72 (t, 2H), 3.35 (s, 3), 3.55 (t, 2H), 3.60 (m, 4H), 3.94 (s, 3H), 4.20 (t, 2H), 6.14 (s, 2H), 7.07 (s, 1H), 7.19 (s, 1H), 7.83 (s, 1H), 8.32 (s, 1H), 9.48 (s, 1H); Mass Spectrum: M+H+ 555/557.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:14][C:15]([C:17]2[N:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[O:16])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[Cl:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][C:25]=1[CH3:33]>>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[C:4]([NH:14][C:15]([C:17]3[N:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[O:16])[CH:5]=[N:6][C:7]=2[O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:26][C:25]=1[CH3:33]
Reactant: Cc1cc(B(O)O)ccc1Cl
Reactant: O=C(Nc1cnc(OCC(F)(F)F)c(Br)c1)c1cccnn1
Product: Cc1cc(-c2cc(NC(=O)c3cccnn3)cnc2OCC(F)(F)F)ccc1Cl

Procedure:
The title compound was synthesized in analogy to Example 39, using pyridazine-3-carboxylic acid[5-bromo-6-(2,2,2-trifluoro-ethoxy)-pyridin-3-yl]-amide (example 62 a) and B-(4-chloro-3-methylphenyl)-boronic acid (CAN 161950-10-3) as starting materials; LC-MS (UV peak area/ESI) 94.2%, 423.0828 (M+H)+.
Reaction SMILES: C([O-])=O.Cl[C:5]1C=CC(C=O)=C[CH:6]=1.[CH2:13]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH:24][S:25]([C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]([CH2:38][NH:39][CH:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)=[CH:30][CH:29]=2)(=[O:27])=[O:26])[CH2:20][CH2:19]1)=[O:17])[CH3:14].C(OC(N1CCC(NS(C2C3C(=CC=CC=3)C(CN)=CC=2)(=O)=O)CC1)=O)C>>[CH2:13]([O:15][C:16]([N:18]1[CH2:19][CH2:20][CH:21]([NH:24][S:25]([C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]([CH2:38][N:39]([CH:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)[CH2:5][CH3:6])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[CH2:22][CH2:23]1)=[O:17])[CH3:14]
Reactant: CCOC(=O)N1CCC(NS(=O)(=O)c2ccc(CNC3CCCCC3)c3ccccc23)CC1
Reactant: O=Cc1ccc(Cl)cc1
Agent: CCOC(=O)N1CCC(NS(=O)(=O)c2ccc(CN)c3ccccc23)CC1
Agent: O=C[O-]
Product: CCOC(=O)N1CCC(NS(=O)(=O)c2ccc(CN(CC)C3CCCCC3)c3ccccc23)CC1

Procedure:
The title compound was prepared as its formate salt following the general procedure in Scheme 13, substituting acetaldehyde for 4-chloro-benzaldehyde, and substituting 4-(4-cyclohexylaminomethyl-naphthalene-1-sulfonylamino)-piperidine-1-carboxylic acid ethyl ester (G-8) for 4-(4-aminomethyl-naphthalene-1-sulfonylamino)-piperidine-1-carboxylic acid ethyl ester. 1H NMR (300 MHz, MeOD) δ 8.79 (m, 1H), 8.36 (m, 2H), 8.27 (dd, 1H), 7.77 (m, 3H), 4.62 (s, 2H), 4.05 (q, 2H), 3.80 (d, 2H), 3.25 (m, 1H), 3.05 (m, 3H), 2.75 (m, 2H), 2.10 (d, 2H), 1.80 (d, 2H), 1.65 (m, 3H), 1.48 (m, 2H), 1.22 (m, 1H); LC/MS m/z 502 (M+H)+
Reaction SMILES: [CH3:1][C@@H:2]([CH2:11][CH2:12][CH:13]=[C:14]([CH3:16])[CH3:15])[CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.C(=O)(O)[O-:18].[Na+].C(OO)(=O)C.S([O-])([O-])=O.[Na+].[Na+]>ClCCl>[CH:5]1([CH2:4][CH2:3][C@@H:2]([CH3:1])[CH2:11][CH2:12][CH:13]2[O:18][C:14]2([CH3:15])[CH3:16])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: O=C([O-])O
Reactant: CC(C)=CCC[C@H](C)CCC1CCCCC1
Agent: CC(=O)OO
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: C[C@H](CCC1CCCCC1)CCC1OC1(C)C
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A flask was charged with 11.48 g (51.6 mmol) of crude (3R)-(3,7-dimethyl-oct-6-enyl)-cyclohexane, 100 mL of dichloromethane, and 9.33 g (111 mmol) of sodium bicarbonate. The mixture was cooled in a 0° C. bath. Slowly 11.6 mL (55.2 mmol) 32% peracetic acid was added. The mixture was stirred for 4 hours at 0° C. Then 10% aqueous sodium sulfite was added slowly until bubbling ceased. The layers were separated, and the organic layer was washed twice with 10% aqueous sodium sulfite and dried over magnesium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The remaining residue was 10.65 g (87%) of a clear oil: 1H NMR (400 MHz, CDCl3) ppm 0.86 (m, 5H) 1.00 (d, J=6.59 Hz, 2H) 1.14 (m, 7H) 1.25 (s, 3H) 1.29 (s, 3H) 1.35 (m, 2H) 1.50 (m, 3H) 1.65 (m, 5H) 2.68 (td, J=6.16, 1.83 Hz, 1H). MS (APCI) m+1/z=239.
Reaction SMILES: [C:1]([O:5][C:6](=[O:42])[NH:7][CH2:8][C:9]1[N:10]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:11](=[O:37])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[CH:16][C:15]([CH2:25][N:26]1C(=O)C3C(=CC=CC=3)C1=O)=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2].O.NN>C(O)C.O1CCCC1>[C:1]([O:5][C:6](=[O:42])[NH:7][CH2:8][C:9]1[N:10]([CH2:38][CH:39]([CH3:40])[CH3:41])[C:11](=[O:37])[C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[CH:16][C:15]([CH2:25][NH2:26])=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)Cn1c(CNC(=O)OC(C)(C)C)c(-c2ccccc2)c2cc(CN3C(=O)c4ccccc4C3=O)ccc2c1=O
Agent: NN
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: CC(C)Cn1c(CNC(=O)OC(C)(C)C)c(-c2ccccc2)c2cc(CN)ccc2c1=O
Temperature: 25 °C
Reaction time: 17 h
Yield: 125.5 %

Procedure:
A mixture of tert-butyl{6-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-isobutyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-3-yl}methylcarbamate (0.85 g, 1.5 mmol), and hydrazine monohydrate (0.6 mL, 12 mmol) in ethanol (20 mL) and tetrahydrofuran (10 mL) was stirred at room temperature for 17 h. The reaction mixture was filtered, and the filtrate was concentrated. After the residue was dissolved in ethyl acetate (50 mL), the solution was filtrated to remove insoluble material. The filtrate was concentrated to give tert-butyl[6-(aminomethyl)-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-3-isoquinolinyl]methylcarbamate (0.82 g) as a crude pale yellow oil. To a solution of the crude oil (0.16 g) in tetrahydrofuran (2 mL) was added acetic anhydride (0.034 mL, 0.36 mmol), and then the mixture was stirred at room temperature for 4 h. The reaction mixture was washed with water (4 mL) and concentrated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1 (v/v)) to give tert-butyl{6-[(acetylamino)methyl]-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-3-isoquinolinyl}methylcarbamate (0.090 g, 63%) as a pale yellow solid.
Reaction SMILES: C1CC=CC=1.[CH:6]([CH:8]=[CH2:9])=[O:7].[C:10]12(C=O)[CH2:16]C(C[CH2:15]1)[CH:12]=[CH:11]2.[CH2:19]=[O:20]>>[CH:9]12[CH2:16][CH:10]([CH:11]=[CH:12]1)[CH2:15][C:8]2([CH2:19][OH:20])[CH2:6][OH:7]
Reactant: O=CC12C=CC(CC1)C2
Reactant: C=CC=O
Reactant: C=O
Agent: C1=CCC=C1
Product: OCC1(CO)CC2C=CC1C2

Procedure:
Briefly, the process of Bailey may be described as follows. Dicyclopentadiene is heated to between 240°-250° C. to form an 80-85% yield cyclopentadiene, which is allowed to react with acrolein to produce norbornene carboxaldehyde in a yield of 79% based on the cyclopentadiene (83% based on the acrolein). The resulting norbornene carboxaldehyde is allowed to react with formaldehyde and caustic to form 5-norbornene-2,2-dimethanol which is heated to between 420°-450° C. to form 1,1-dihydroxymethyl ethylene and cyclopentadiene in a yield of 10-40%. The 1,1-dihydroxymethyl ethylene, is allowed to react with dibutyl tin oxide to form a cyclic tin intermediate which is allowed to react with carbon disulfide (CS2) to form 3,9-dimethylene-1,5,7,11-tetraoxa-spiro[5,5]undecane (BMSOC).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([OH:18])[CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(=O)([O-])[O-].[K+].[K+].Br[CH:26]1[CH2:28][CH2:27]1.C[C:30]([CH2:32][CH3:33])=O>>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:26]3[CH2:28][CH2:27]3)=[C:13]([O:18][CH:30]3[CH2:32][CH2:33]3)[CH:12]=2)=[CH:9][CH:10]=1)(=[O:3])=[O:4]
Reactant: CCC(C)=O
Reactant: BrC1CC1
Reactant: CS(=O)(=O)c1ccc(-c2ccc(O)c(O)c2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CS(=O)(=O)c1ccc(-c2ccc(OC3CC3)c(OC3CC3)c2)cc1
Temperature: 40 °C
Yield: 87 %

Procedure:
4′-methanesulfonyl-biphenyl-3,4-diol (30 mg) and potassium carbonate (38 mg) were dissolved in methylethylketone. Afterward, bromocyclopropane (0.027 ml) was added and heated for 24 hours at 40° C. After filtering just potassium carbonate, the residue was separated through a silica gel attributed chromatography (an eluting agent: ethylacetate/n-hexane=1/1, v/v). As a result, the present compound (29 mg, productive yield 87%) was obtained.