Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:4]=1[C:5]([OH:7])=O.[CH:15]1([CH2:18][NH2:19])[CH2:17][CH2:16]1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:15]1([CH2:18][NH:19][C:5](=[O:7])[C:4]2[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=[CH:11][C:3]=2[O:2][CH3:1])[CH2:17][CH2:16]1
Reactant: COc1ccc([N+](=O)[O-])cc1C(=O)O
Reactant: NCC1CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: CN(C)C=O
Product: COc1ccc([N+](=O)[O-])cc1C(=O)NCC1CC1
Reaction time: 24 h

Procedure:
A solution of 2-methoxy-5-nitrobenzoic acid (4.9 g) (Rec. Trav. Chim. Pays-Bas, 1936, 737) and cyclopropylmethylamine (1.75 g) in dimethylformamide was treated with N-hydroxybenzotriazole (0.2 g) and EDC.HCl (4.74 g). The mixture was stirred for 24 h. Saturated sodium hydrogen carbonate was added, the mixture stirred for 3 h and the precipitate collected as the title compound (6.95 g). m/z (API+): 251 (MH+).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]([CH:11]=O)=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.[NH2:14][OH:15].[OH-].[Na+]>CCO.O>[Cl:1][C:2]1[C:3]2[C:10]([CH:11]=[N:14][OH:15])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=Cc1c[nH]c2ncnc(Cl)c12
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: ON=Cc1c[nH]c2ncnc(Cl)c12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbaldehyde (E-3) (1.17 g, 6.47 mmol, 1.0 eq) and hydroxylamine hydrochloride (0.54 g, 7.77 mmol, 1.2 eq) in EtOH (25 mL), aqueous NaOH solution (0.31 g, 7.77 mmol, 1.2 eq) in H2O (4 mL) is added dropwise. The resulting mixture is stirred at RT for 30 min and then is diluted with a sufficient amount of EtOH to allow stirring for additional 30 min. The solid is collected by filtration, rinsed with H2O and dried in vacuo to afford the product, 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbaldehyde oxime (E-4) as a mixture of isomers.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[C:6]([O:13][C:14]2[C:19]([Cl:20])=[CH:18][C:17]([N+:21]([O-])=O)=[CH:16][N:15]=2)=[CH:5][CH:4]=1.[OH-].[Na+]>O1CCOCC1>[Cl:2][C:3]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[C:6]([O:13][C:14]2[C:19]([Cl:20])=[CH:18][C:17]([NH2:21])=[CH:16][N:15]=2)=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])c1cnc(Oc2ccc(Cl)c3c2CCCC3)c(Cl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: Nc1cnc(Oc2ccc(Cl)c3c2CCCC3)c(Cl)c1

Procedure:
To a solution of 2.64 g. (11.7 mmol.) of stannous chloride in 2.4 ml. of concentrated hydrochloric acid and 1.75 ml. of p-dioxane at 50° was added 1.2 g. (3.54 mmol.) of 2-(4-chloro-5,6,7,8-tetrahydro-1-naphthoxy)-3-chloro-5-nitropyridine. The resulting mixture was heated up to reflux for 0.5 hours, cooled, and poured into sodium hydroxide (pH 14) in cracked ice. This mixture was extracted twice with 150 ml. of methylene chloride. The combined organic layer was washed with water and brine. It was then dried (Na2SO4) and concentrated to give 1.0 g. (3.23 mmole) of light purple solid; mp. 129.8°-132.3°
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH:12]([F:14])[F:13].[CH3:15][CH:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[CH3:17].C([O-])([O-])=O.[K+].[K+].Cl>CS(C)=O.O>[F:13][CH:12]([F:14])[O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[N:21]1[CH2:22][CH2:23][N:18]([CH:16]([CH3:17])[CH3:15])[CH2:19][CH2:20]1
Reactant: O=[N+]([O-])c1ccc(Br)c(OC(F)F)c1
Reactant: CC(C)N1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)N1CCN(c2ccc([N+](=O)[O-])cc2OC(F)F)CC1
Temperature: 120 °C
Reaction time: 3 h

Procedure:
1-Bromo-2-difluoromethoxy-4-nitro-benzene (Step A, 2.0 g, 7.5 mmol, 1.0 eq.) and N-(2-propyl)piperazine (0.85 mL, 9.7 mmol, 1.3 eq.) were dissolved in 20 mL of DMSO. K2CO3 (1.5 g, 11.2 mmol, 1.5 eq.) and Bu4N+Br− (240 mg, 0.75 mmol, 0.1 eq.) were added and the mixture was heated to 120° C. The mixture was stirred for 3 h and cooled to RT, poured into H2O (200 mL) and 6 N HCl (20 mL). The aqueous solution was washed with EtOAc, and alkalinized with 6 N NaOH then extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered and concentrated. The crude material was further purified by column chromatography (0-100% EtOAc in hexanes) providing pure 1-(2-difluoromethoxy-4-nitro-phenyl)-4-isopropyl-piperazine.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[NH:6][N:7]=[C:8]1[C:17]2[CH2:16][CH2:15][CH2:14][C:13]=2[C:12]2[C:18]([O:44][CH3:45])=[C:19]([O:42][CH3:43])[C:20]([C:22]([NH:24][CH2:25][CH:26]([C:38]([O:40]C)=[O:39])[NH:27][C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])=[O:23])=[CH:21][C:11]=2[CH2:10][CH2:9]1>CO>[NH:3]1[CH2:4][CH2:5][N:1]=[C:2]1[NH:6][N:7]=[C:8]1[C:17]2[CH2:16][CH2:15][CH2:14][C:13]=2[C:12]2[C:18]([O:44][CH3:45])=[C:19]([O:42][CH3:43])[C:20]([C:22]([NH:24][CH2:25][CH:26]([C:38]([OH:40])=[O:39])[NH:27][C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])=[O:23])=[CH:21][C:11]=2[CH2:10][CH2:9]1
Reactant: COC(=O)C(CNC(=O)c1cc2c(c(OC)c1OC)C1=C(CCC1)C(=NNC1=NCCN1)CC2)NC(=O)OCc1ccccc1
Solvent: CO
Product: COc1c(C(=O)NCC(NC(=O)OCc2ccccc2)C(=O)O)cc2c(c1OC)C1=C(CCC1)C(=NNC1=NCCN1)CC2

Procedure:
262 mg of the ester obtained in Stage C, 3 ml of methanol and 0,45 ml of 2N soda are agitated at ambient temperature for 1 hour 30 minutes.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].[H-].[Na+].[NH2:14][C:15]1[CH:20]=[C:19](Cl)[N:18]=[CH:17][N:16]=1.[OH-].[Na+]>CS(C)=O.C(OCC)C.CCCCCC>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[O:11][C:19]1[N:18]=[CH:17][N:16]=[C:15]([NH2:14])[CH:20]=1
Reactant: Nc1cc(Cl)ncn1
Reactant: O=[N+]([O-])c1ccc(O)c(F)c1
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CCCCCC
Solvent: CS(C)=O
Product: Nc1cc(Oc2ccc([N+](=O)[O-])cc2F)ncn1
Temperature: 120 °C
Reaction time: 0.33 h
Yield: 16.1 %

Procedure:
2-Fluoro-4-nitrophenol (1.736 g) was dissolved in dimethyl sulfoxide (10 ml), and then sodium hydride (400 mg) was added thereto, followed by stirring for 20 min. Then, 4-amino-6-chloropyrimidine (648 mg) was added thereto, followed by stirring at 100° C. for 45 min. The reaction mixture was heated up to 120° C., followed by stirring for 1 hr and 25 min. Then, the reaction mixture was heated up to 140° C., followed by stirring overnight. The reaction mixture was cooled down to room temperature, and then a 1 N aqueous solution of sodium hydroxide (10 ml) was added thereto, followed by stirring and extracting with ethyl acetate. The organic layer was washed with a 1 N aqueous solution of sodium hydroxide, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2). The solvent was evaporated under a reduced pressure to give a residue, which was suspended in diethyl ether (7 ml)-hexane (3.5 ml). The solid was filtered off, and dried under aeration to provide the titled compound (201 mg, 16.0%) as pale brown powder.
Reaction SMILES: [C:1]([NH:8][C@@H:9]([C:13]([OH:15])=O)[C@@H:10]([CH3:12])[OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:19][CH2:18]1>O>[C:1]([NH:8][C@@H:9]([C:13]([N:26]1[CH2:25][CH2:24][N:23]([CH:20]2[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]2)[CH2:28][CH2:27]1)=[O:15])[C@@H:10]([CH3:12])[OH:11])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: C[C@@H](O)[C@@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: CN1CCC(N2CCNCC2)CC1
Solvent: O
Product: C[C@@H](O)[C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(C2CCN(C)CC2)CC1

Procedure:
Prepared from N-Boc-D-allo-threonine and 1-(1-methyl-piperidin-4-yl)piperazine using methods substantially equivalent to General Coupling Method 1. 1H NMR. ES-MS, m/z 385.5 (M+1)+. Analysis For C19H36N4O4.1.0 H2O: Calcd: C 56.69; H 9.52; N 13.92; Found: C 57.18; H 9.59; N 13.85.
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:59])([CH3:58])[O:6][C@@H:7]([C@@H:45]([CH3:57])[CH2:46][O:47]CC1C=CC(OC)=CC=1)[C@@H:8]([CH3:44])[CH2:9][N:10]([C:12](=[O:43])[C@H:13]([CH3:42])[C@@H:14]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C@H:15]([CH3:33])[C@@H:16]([O:23]CC1C=CC(OC)=CC=1)[C@@H:17]([CH3:22])/[CH:18]=[CH:19]\[CH:20]=[CH2:21])[CH3:11])([CH3:4])[CH3:3].C(Cl)Cl.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O>[CH3:1][C:2]([Si:5]([CH3:58])([CH3:59])[O:6][C@@H:7]([C@@H:45]([CH3:57])[CH2:46][OH:47])[C@@H:8]([CH3:44])[CH2:9][N:10]([C:12](=[O:43])[C@H:13]([CH3:42])[C@@H:14]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:36])[CH3:37])[C@H:15]([CH3:33])[C@@H:16]([OH:23])[C@@H:17]([CH3:22])/[CH:18]=[CH:19]\[CH:20]=[CH2:21])[CH3:11])([CH3:4])[CH3:3]
Reactant: C=C/C=C\[C@H](C)[C@H](OCc1ccc(OC)cc1)[C@@H](C)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)C(=O)N(C)C[C@H](C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)COCc1ccc(OC)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: O
Solvent: ClCCl
Product: C=C/C=C\[C@H](C)[C@H](O)[C@@H](C)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)C(=O)N(C)C[C@H](C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)CO
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 85.1 %

Procedure:
To a solution consisting of 1,2,4-trideoxy-3-O-[(1,1-dimethylethyl)dimethylsilyl]-1-[[(2R,3S,4R,5S,6S,7Z)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-5-[(4-methoxyphenyl)methoxy]-2,4,6-trimethyl-1-oxo-7,9-decadienyl]methylamino]-5-O-[(4-methoxyphenyl)methyl]-2,4-dimethyl-L-arabinitol (1.9 g, 2.2 mmol), CH2Cl2 (40 mL), and H2O (1 mL) at room temperature, is added 2,3-dichloro-5,6-Dicyano-1,4-benzoquinone (DDQ), (2.53 g, 11.1 mmol). After stirring at room temperature for 10 min, the reaction mixture is purified by column chromatography on silica gel with hexane/EtOAc (90/10) to give the desired product (1.15 g, 82.6%) as a white solid.
Reaction SMILES: C([N:8]1[C:12]([CH:13]2[C:21]3[C:16](=[C:17]([CH3:25])[C:18]([CH3:24])=[C:19]([O:22][CH3:23])[CH:20]=3)[C:15](=[O:26])[CH2:14]2)=[CH:11][N:10]=[CH:9]1)C1C=CC=CC=1>C(O)C.[Pd]>[NH:10]1[CH:11]=[C:12]([CH:13]2[C:21]3[C:16](=[C:17]([CH3:25])[C:18]([CH3:24])=[C:19]([O:22][CH3:23])[CH:20]=3)[C:15](=[O:26])[CH2:14]2)[N:8]=[CH:9]1
Reactant: COc1cc2c(c(C)c1C)C(=O)CC2c1cncn1Cc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: COc1cc2c(c(C)c1C)C(=O)CC2c1c[nH]cn1

Procedure:
3-(3-Benzyl-3H-imidazol-4-yl)-5-methoxy-6,7-dimethylindan-1-one (1.1 g) is dissolved in ethanol (90 ml). The reaction solution is hydrogenated at 50-55° C. with 10% palladium on carbon as catalyst for 7 hours. The mixture is filtered to remove the catalyst, and the filtrate is evaporated under reduced pressure. The product is converted to its hydrochloride salt in ethyl acetate using dry hydrochloric acid. The yield is 0.6 g, m.p. 258-261° C.
Reaction SMILES: [C:1]([N:11]([CH3:22])[C@H:12]([C:19]([OH:21])=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[NH2:23][C@H:24]([C:37]([NH2:39])=[O:38])[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([C:33]([CH3:36])([CH3:35])[CH3:34])[CH:27]=1.C1C=CC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C>CN(C=O)C.C(OCC)(=O)C>[C:1]([N:11]([CH3:22])[C@H:12]([C:19]([NH:23][C@H:24]([C:37]([NH2:39])=[O:38])[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([C:33]([CH3:36])([CH3:34])[CH3:35])[CH:27]=1)=[O:21])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: CN(C(=O)OCc1ccccc1)[C@H](C(=O)O)c1ccccc1
Reactant: CC(C)(C)c1cc(C[C@H](N)C(N)=O)ccc1O
Agent: CC(C)N=C=NC(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN(C(=O)OCc1ccccc1)[C@H](C(=O)N[C@@H](Cc1ccc(O)c(C(C)(C)C)c1)C(N)=O)c1ccccc1
Reaction time: 4 h

Procedure:
To a solution of 3.28 g (11.0 mmol) of Z-N-Me-Phg-OH, 2.16 g (9.17 mmol) of Tyr(3-tBu)-NH2 and 1.40 g (9.17 mmol) of HOBT in 60 ml of DMF, 1.42 ml (9.17 mmol) of DIC was added dropwise under cooling with ice and the mixture was stirred for 4 hours under cooling with ice. The reaction mixture was diluted with ethyl acetate and washed with saturated brine. The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluting solvent consisting of methylene chloride, methanol and aqueous ammonia at a ratio of 100:5:1) to give Z-N-Me-Phg-Tyr(3-tBu)-NH2 in the amount of 4.03 g (85%).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:20][C:21]([Br:24])(Br)Br.[CH:25]([C:27]1[C:28]2[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[C:29]=2[S:30][CH:31]=1)=O.CCCCC>ClCCl.[Zn]>[Br:20][C:21]([Br:24])=[CH:25][C:27]1[C:28]2[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[C:29]=2[S:30][CH:31]=1
Reactant: BrC(Br)(Br)Br
Reactant: Cc1cccc2c(C=O)csc12
Agent: [Zn]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCCCC
Product: Cc1cccc2c(C=C(Br)Br)csc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.04 g of Zn dust and 4.17 g of triphenylphosphine are taken up in dichloromethane and 5.27 of tetrabromomethane dissolved in dichloromethane added dropwise under inert gas and with cooling. Following stirring for 24 hours at room temperature 1.4 g of 3-formyl-7-methylbenzo[b]thiophene dissolved in dichloromethane are added dropwise with ice-cooling and stirring continued overnight at room temperature. Pentane is added and the precipitated Ph3PO filtered off. Evaporation of the filtrate under vacuum yields a residue which is chromatographed over silica gel to yield the title compound, M.p.=75°-78°.
Reaction SMILES: [Cl:1][C:2]([Cl:6])=[CH:3][CH2:4]Cl.[OH:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[CH:14]=[C:13]([CH:18]([CH3:22])[C:19]([OH:21])=[O:20])[CH:12]=[CH:11]2>>[CH3:22][CH:18]([C:13]1[CH:12]=[CH:11][C:10]2[C:15](=[CH:16][CH:17]=[C:8]([O:7][CH2:4][CH:3]=[C:2]([Cl:6])[Cl:1])[CH:9]=2)[CH:14]=1)[C:19]([OH:21])=[O:20]
Reactant: CC(C(=O)O)c1ccc2cc(O)ccc2c1
Reactant: ClCC=C(Cl)Cl
Product: CC(C(=O)O)c1ccc2cc(OCC=C(Cl)Cl)ccc2c1

Procedure:
The title compound is prepared according to the method of Example 7 using 3,3-dichloroallyl chloride and racemic 6-hydroxy-α-methyl-2-naphthalene acetic acid. White crystals are obtained having a melting point of 107°-109° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]1[C:11](=[O:22])[NH:12][N:13]=[C:14]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH:15]=1.C1C(=O)N([I:30])C(=O)C1>CC(C)=O>[I:30][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]=1[C:10]1[C:11](=[O:22])[NH:12][N:13]=[C:14]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH:15]=1
Reactant: O=c1[nH]nc(-c2ccncc2)cc1-c1cc2ccccc2[nH]1
Reactant: O=C1CCC(=O)N1I
Solvent: CC(C)=O
Product: O=c1[nH]nc(-c2ccncc2)cc1-c1[nH]c2ccccc2c1I
Temperature: 25 °C
Reaction time: 3 h

Procedure:
577 mg 4-(1H-Indol-2-yl)-6-pyridin-4-yl-2H-pyridazin-3-one is suspended in 30 mL acetone and 550 mg NIS is added. The reaction mixture is stirred for 3 hours at room temperature, the precipitated product isolated by filtration and washed with acetone. The material product is used without further purification
Reaction SMILES: [C:1]([CH2:14][CH2:15][Si:16]([Cl:19])(Cl)[Cl:17])([C:4]([C:7]([C:10]([F:13])([F:12])[F:11])([F:9])[F:8])([F:6])[F:5])([F:3])[F:2].[SiH](Cl)(C)C.[C:24]([CH2:37][CH2:38][SiH](Cl)Cl)([C:27]([C:30]([C:33]([F:36])([F:35])[F:34])([F:32])[F:31])([F:29])[F:28])([F:26])[F:25].[Si](C)(C)(Cl)Cl>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Si:16]([CH2:38][CH2:37][C:24]([C:27]([C:30]([C:33]([F:34])([F:35])[F:36])([F:32])[F:31])([F:29])[F:28])([F:26])[F:25])([CH2:15][CH2:14][C:1]([C:4]([C:7]([C:10]([F:11])([F:13])[F:12])([F:9])[F:8])([F:5])[F:6])([F:2])[F:3])([Cl:17])[Cl:19]
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)CC[Si](Cl)(Cl)Cl
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)CC[SiH](Cl)Cl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: C[SiH](C)Cl
Agent: C[Si](C)(Cl)Cl
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)CC[Si](Cl)(Cl)CCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 80 °C

Procedure:
3 moles C4F9CH=CH2 and 4.8 g isopropanolic chloroplatinic acid solution (concentration=10%) were placed in a flask and heated under reflux while stirring. 2.5 moles trichlorosilane was dripped in from an addition funnel over a period of 3 hours, and the reaction was then heated under reflux for another 5 hours. At this point, analysis by gas chromatography confirmed the disappearance of the C4F9CH=CH2, and C4F9CH2CH2SiCl3 was isolated by distillation at ambient pressure. The boiling point of this trichlorosilane was 162° C. 2 moles of this C4F9CH2CH2SiCl3, 3.5 moles Me2SiHCl, and 2.6 g tetra(n-butyl)ammonium chloride were placed in a flask and heated under reflux for 3 days while stirring. A mixture of chlorosilanes was then obtained by distillation in vacuo. Analysis by gas chromatography confirmed the main components of this reaction product to be C4F9CH2CH2SiCl3, C4F9CH2CH2SiHCl2, Me2SiHCl, and Me2SiCl2. The C4F9CH2CH2SiCl3 and C4F9CH2CH2SiHCl2 fraction was separated by distillation in vacuo, and the C4F9CH2CH2SiCl3 and C4F9CH2CH 2 SiHCl2 mixture was introduced into a flask along with 5 g isopropanolic chloroplatinic acid solution (concentration=10%). This was heated to 80° C., and C4F9CH=CH2 was added while stirring. This addition was discontinued when the peak for C4F9CH2CH2SiHCl2 disappeared in gas chromatographic analysis. Precision distillation in vacuo then afforded (C4F9CH2CH2)2SiCl2 (bp=128° C./20 mmHg).
Reaction SMILES: [CH3:1][S:2]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:22])OC2C=CC=CC=2)=[CH:9][CH:8]=1)(=[O:4])=[O:3].[C:23]1([CH3:41])[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=[C:31]([C:37]([F:40])([F:39])[F:38])[N:30]=2)[CH:24]=1>CN(C)C1C=CN=CC=1>[C:23]1([CH3:41])[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[C:34]([CH2:35][NH:36][C:14](=[O:22])[NH:13][C:10]3[CH:9]=[CH:8][C:7]([CH2:6][NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:12][CH:11]=3)=[CH:33][CH:32]=[C:31]([C:37]([F:39])([F:38])[F:40])[N:30]=2)[CH:24]=1
Reactant: Cc1cccc(-c2nc(C(F)(F)F)ccc2CN)c1
Reactant: CS(=O)(=O)NCc1ccc(NC(=O)Oc2ccccc2)cc1
Agent: CN(C)c1ccncc1
Product: Cc1cccc(-c2nc(C(F)(F)F)ccc2CNC(=O)Nc2ccc(CNS(C)(=O)=O)cc2)c1
Temperature: 50 °C

Procedure:
To a solution of phenyl 4-(methylsulfonamidomethyl)phenylcarbamate (59 mg, 0.18 mmol) acetonitrile (3 mL) was added 4-dimethylaminopyridine (23 mg, 0.18 mmol) and (2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methanamine (49 mg, 0.18 mmol) at room temperature. The reaction mixture was heated to 50° C. for 16 h. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic part was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to N-(4-(3-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)ureido)benzyl)methanesulfonamide (example 2) (57 mg, 63%).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH:10]([CH2:14][N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)[CH2:11][CH:12]=C)[CH:6]=[CH:7][C:8]=1[Cl:9].I([O-])(=O)(=O)=[O:21].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.[Os](=O)(=O)(=O)=O.C1(C)C=CC=CC=1>[Cl:2][C:3]1[CH:4]=[C:5]([CH:10]([CH2:14][N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)[CH2:11][CH:12]=[O:21])[CH:6]=[CH:7][C:8]=1[Cl:9]
Reactant: C=CCC(Cn1ccnc1)c1ccc(Cl)c(Cl)c1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: O=[Os](=O)(=O)=O
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CC#N
Solvent: Cc1ccccc1
Solvent: O
Product: O=CCC(Cn1ccnc1)c1ccc(Cl)c(Cl)c1
Reaction time: 0.5 h
Yield: 71 %

Procedure:
4-(3,4-Dichlorophenyl)-5-(imidazol-1-yl)pent-1-ene hydrochloride (3.6 g) (see Preparation 24) was dissolved in a mixture of acetonitrile (50 ml) and water (20 ml) and osmium tetroxide (4 ml of a 0.05M solution in toluene) added. The mixture was stirred for 30 minutes, sodium periodate (5.3 g) added and stirring continued for 2 hours. A further portion of acetonitrile (20 ml) was added and stirring continued for 16 hours before removal of the organic solvent under reduced pressure to give an aqueous suspension. This was basified to pH>7 by the addition of solid sodium carbonate. The mixture was then extracted with dichloromethane, the organic phase dried over anhydrous sodium sulphate and the solvent removed under reduced pressure to give a dark oil which was chromatographed on silica gel eluting with a solvent gradient of 98:2 changing to 92.5:7.5, by volume, dichloromethane:methanol to give 3-(3,4-dichlorophenyl)-4-(imidazol-1-yl)butan-1-al (2.28 g) as a colourless, viscous oil.
Reaction SMILES: Cl.[CH3:2][NH:3][O:4][CH3:5].[CH2:6]([N:13]1[CH2:17][CH:16]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH:15]([C:26](O)=[O:27])[CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[CH3:5][O:4][N:3]([CH3:2])[C:26]([CH:15]1[CH:16]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:17][N:13]([CH2:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:14]1)=[O:27]
Reactant: O=C(O)C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Reactant: CNOC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CON(C)C(=O)C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Reaction time: 1 h
Yield: 98.8 %

Procedure:
To a solution of N,O-dimethylhydroxylamine hydrochloride (0.41 g, 4.2 mmol) and 1.23 g (3.5 mmol) of (3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carboxylic acid in DMF (20 mL) at RT was added Hunig base (1.79 ml, 10.5 mmol) and HATU (1.468 g, 3.9 mmol) and stirring was continued for one hour. The reaction mixture was diluted with ethyl acetate and washed with aq. ammonium chloride solution three times. The separated organic layer was washed with brine and dried on Na2SO4 and concentrated under vacuo yielding 1.36 g (99%) of the title compound as a light yellow oil. ES-MS m/e: 393.1 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[C:16]3[CH2:15][C@H:14]([CH3:17])[N:13](C(OC(C)(C)C)=O)[CH2:12][C:11]=3[N:10]=[N:9]2)=[N:6][CH:7]=1.[ClH:25].O1CCOCC1>C(Cl)Cl>[ClH:25].[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[C:16]3[CH2:15][C@H:14]([CH3:17])[NH:13][CH2:12][C:11]=3[N:10]=[N:9]2)=[N:6][CH:7]=1
Reactant: C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1C(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of (S)-tert-butyl 1-(5-fluoropyrimidin-2-yl)-6-methyl-6,7-dihydro-1H-[1,2,3]triazolo[4,5-c]pyridine-5(4H)-carboxylate (0.711 g, 2.13 mmol) in CH2Cl2 (10 mL) was added 4M HCl in dioxane (2.66 mL, 10.6 mmol). After stirring overnight at rt, the reaction was concentrated in vacuo to give the desired product as a light yellow solid (0.580 mg, 100%). MS (ESI) mass calcd. C10H11FN6, 234.23. m/z found, 235.1 [M+H]+. 1H NMR (400 MHz, DMSO) δ 9.97-9.69 (m, 1H), 9.15 (s, 2H), 4.58-4.35 (m, 2H), 3.80-3.47 (m, 2H), 3.21-3.03 (m, 1H), 1.46 (d, J=6.5 Hz, 3H).