Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1C=CC=C(C(OO)=O)C=1.[CH:12]([N:15]1[C:19](SC)=[N:18][N:17]=[C:16]1[C:22]1[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[C:25]([O:31][CH2:32][O:33][CH3:34])=[CH:24][C:23]=1[O:35][CH2:36][O:37][CH3:38])([CH3:14])[CH3:13].[S:39]([O-:43])([O-])(=[O:41])=S.[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH:12]([N:15]1[C:19]([S:39]([CH3:2])(=[O:43])=[O:41])=[N:18][N:17]=[C:16]1[C:22]1[CH:27]=[C:26]([CH:28]([CH3:29])[CH3:30])[C:25]([O:31][CH2:32][O:33][CH3:34])=[CH:24][C:23]=1[O:35][CH2:36][O:37][CH3:38])([CH3:13])[CH3:14]
Reactant: O=S([O-])([O-])=S
Reactant: COCOc1cc(OCOC)c(C(C)C)cc1-c1nnc(SC)n1C(C)C
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COCOc1cc(OCOC)c(C(C)C)cc1-c1nnc(S(C)(=O)=O)n1C(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
While stirring in ice cold conditions, 3-chloroperbenzoic acid (4.20 g, 24.4 mmol) was added to a methylene chloride (10 mL) solution of 4-isopropyl-3-(5-isopropyl-2,4-bis-methoxymethoxyphenyl)-5-methylsulfanyl-4H-[1,2,4]triazole (F63-04, 1.93 g, 4.87 mmol). After stirring at room temperature for 2 hours, the mixture was bring back to ice cold conditions again, and saturated aqueous sodium thiosulfate and then saturated aqueous sodium hydrogencarbonate were added. After stirring for a while, the reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated sodium chloride solution. After drying the extract over anhydrous sodium, sodium sulfate was removed by filtration and the solvent was distilled off under reduced pressure to obtain a pale yellow foam. After purification by silica gel column chromatography (hexane, ethyl acetate), 4-isopropyl-3-(5-isopropyl-2,4-bis-methoxymethoxyphenyl)-5-methylsulfonyl-4H-[1,2,4]triazole (F63-05, colorless foam, 1.65 g, 79%) was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]#[N+:13][O-])=[N:9]2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:17]>C(Cl)(Cl)Cl>[Cl:17][C:6]1[C:5]2[C:10](=[CH:11][C:2]([CH3:1])=[CH:3][CH:4]=2)[N:9]=[C:8]([C:12]#[N:13])[CH:7]=1
Reactant: Cc1ccc2ccc(C#[N+][O-])nc2c1
Reactant: O=P(Cl)(Cl)Cl
Solvent: ClC(Cl)Cl
Product: Cc1ccc2c(Cl)cc(C#N)nc2c1
Temperature: 70 °C

Procedure:
7-Methylquinoline-2-carbonitrile N-oxide (1-4, 5.3 g, 28.8 mmol, 1.0 equiv.) was dissolved in CHCl3 (80 ml, 0.36 M), and POCl3 was added (16.09 ml, 173 mmol, 6.0 equiv.). The mixture was heated to 70° C. overnight, quenched onto crushed ice and extracted three times with dichloromethane. The combined organic layers were washed with water followed by saturated aqueous sodium bicarbonate, dried over MgSO4, filtered and the solvent was removed to yield crude yellow solid. Recrystallization from heptane/EtOAc gave 95 g of 4-chloro-7-methylquinoline-2-carbonitrile (1-5). LRMS m/z (M+H)+203.2 found, 203.6 required.
Reaction SMILES: Br[CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]=[CH:3]1.[CH2:8]([OH:11])[CH2:9][OH:10].C([O-])([O-])=O.[Cs+].[Cs+].CC(=O)OCC>CN(C=O)C.O>[CH:2]1([O:10][CH2:9][CH2:8][OH:11])[CH2:7][CH2:6][CH2:5][CH:4]=[CH:3]1
Reactant: OCCO
Reactant: BrC1C=CCCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: OCCOC1C=CCCC1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To a solution of 3-bromocyclohex-1-ene (0.5 g) in anhydrous DMF (5 mL) were added ethylene glycol (3 eq) and Cs2CO3 (5 g). The mixture was heated to 80° C. and stirred overnight, after which TLC (PE:EA=20:1) showed the reaction was complete. Then the mixture was poured into water and extracted with EA, washed with water and brine, and concentrated to an oil, which was purified by column chromatography to obtain intermediate BU (0.3 g).
Reaction SMILES: [Br:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([S:11](=[O:14])(=[O:13])[NH2:12])[C:8]([CH3:15])=[C:7]([CH3:16])[CH:6]=1)=[O:4].[CH3:17][NH:18][C:19]([NH:21][CH3:22])=[S:20]>>[BrH:1].[CH3:16][C:7]1[CH:6]=[C:5]([C:3]2([OH:4])[CH2:2][S:20][C:19](=[N:18][CH3:17])[N:21]2[CH3:22])[CH:10]=[C:9]([S:11](=[O:14])(=[O:13])[NH2:12])[C:8]=1[CH3:15]
Reactant: CNC(=S)NC
Reactant: Cc1cc(C(=O)CBr)cc(S(N)(=O)=O)c1C
Product: Br
Product: CN=C1SCC(O)(c2cc(C)c(C)c(S(N)(=O)=O)c2)N1C

Procedure:
3.1 g of 2-bromo-3',4'-dimethyl-5'-sulfamoyl-acetophenon were reacted according to the method described in Example 6 with 1.1 g of 1,3-dimethyl-thiourea and the 4-(3,4-dimethyl-5-sulfamoylphenyl)-3-methyl-2-methylimino-1,3-thiazolidine-4-ol-hydrobromide was filtered off. M.p. 252°-255° C (decomposition).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH:8]2[CH2:9][CH:3]1[CH2:4][CH2:5][C:6]2=[CH2:7].[CH2:11]=[O:12]>>[OH:12][CH2:11][CH2:7][C:6]1[C@@H:8]2[CH2:9][C@@H:3]([CH2:4][CH:5]=1)[C:2]2([CH3:10])[CH3:1]
Reactant: C=C1CCC2CC1C2(C)C
Reactant: C=O
Product: CC1(C)[C@@H]2CC=C(CCO)[C@@H]1C2

Procedure:
A mixture of β-pinene (32 ml) and paraformaldehyde (4 g) in sealed tube was reacted for 18 hrs at 180° C. The reaction solution was distilled to give the title compound (15.5 g) having the following physical data:
Reaction SMILES: O.NN.[CH:4]1([O:10][N:11]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.C(Cl)[Cl:23]>CO>[ClH:23].[CH:4]1([O:10][NH2:11])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1
Reactant: ClCCl
Reactant: O=C1c2ccccc2C(=O)N1OC1CCCCC1
Agent: NN
Solvent: O
Solvent: CO
Product: Cl
Product: NOC1CCCCC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 45.7 %

Procedure:
Hydrazine monohydrate (2.24 mL, 42.20 mmol) was added to a solution of 2-cyclohexyloxy-isoindole-1,3-dione (4.88 g, 21.10 mmol) in a mixture of methanol (12 mL) and methylene chloride (120 mL), and the mixture was stirred at 25° C. for 4 h. The resulting precipitate was filtered off in vacuo, and the filtrate was washed with 5.0 N aqueous ammonium hydroxide (60 mL). The aqueous layer was extracted with methylene chloride (2×25 mL). The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was dissolved in a 4.0 M solution of hydrochloric acid in dioxane (12 mL) and diluted with diethyl ether (70 mL). The resulting precipitate was collected by filtration in vacuo to afford O-cyclohexyl-hydroxylamine hydrochloride (1.71 g, 45.7%) as a white solid, which was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:25]=[CH:24][C:12]([CH2:13][O:14][C:15]3[C:20]([CH2:21][C:22]#N)=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:11][CH:10]=2)=[CH:5][N:4]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[N:3]=1.C(O)C.[OH-:35].[Na+].Cl.[OH2:38]>>[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:25]=[CH:24][C:12]([CH2:13][O:14][C:15]3[C:20]([CH2:21][C:22]([OH:38])=[O:35])=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:11][CH:10]=2)=[CH:5][N:4]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[N:3]=1
Reactant: [OH-]
Reactant: Cc1nn(-c2ccccn2)cc1COc1ccc(COc2ncccc2CC#N)cc1
Reactant: O
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: Cc1nn(-c2ccccn2)cc1COc1ccc(COc2ncccc2CC(=O)O)cc1
Yield: 74 %

Procedure:
To a mixture of 2-[2-[4-[[3-methyl-1-(2-pyridyl)-1H-pyrazol-4-yl]methoxy]benzyloxy]-3-pyridyl]acetonitrile (0.30 g) and ethanol (15 mL) was added a 2N aqueous sodium hydroxide solution (10 mL) and the mixture was heated under reflux for 24 hrs. 1N Hydrochloric acid (20 mL) and water were added to the reaction mixture. The precipitated crystals were collected by filtration and dried with air to give crystals (0.23 g, 74%) of 2-[2-[4-[[3-methyl-1-(2-pyridyl)-1H-pyrazol-4-yl]methoxy]benzyloxy]-3-pyridyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 150-151° C.
Reaction SMILES: C([C:4]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=1)=[CH:5][S:6]([N:9]([CH3:11])[CH3:10])(=[O:8])=[O:7])(=O)C.[CH:21]([O:24][C:25](=[O:30])/[CH:26]=[C:27](\[NH2:29])/[CH3:28])([CH3:23])[CH3:22].[CH:31](O)(C)[CH3:32]>>[CH:21]([O:24][C:25](=[O:30])[C:26]1[CH:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:5]([S:6](=[O:7])(=[O:8])[N:9]([CH3:10])[CH3:11])=[C:31]([CH3:32])[NH:29][C:27]=1[CH3:28])([CH3:23])[CH3:22]
Reactant: CC(=O)C(=CS(=O)(=O)N(C)C)c1cccc([N+](=O)[O-])c1
Reactant: C/C(N)=C/C(=O)OC(C)C
Reactant: CC(C)O
Product: CC1=C(C(=O)OC(C)C)C(c2cccc([N+](=O)[O-])c2)C(S(=O)(=O)N(C)C)=C(C)N1
Yield: 75.5 %

Procedure:
A solution of 3.0 g (0.001 mol) of α-acetyl-N,N-dimethyl-3-nitrostyrenesulfonamide and 1.43 g (0.01 mol) of 3-aminocrotonic acid isopropyl ester in 30 ml of isopropanol is heated to reflux for 2 hours, thereupon treated with 1.16 g (0.005 mol) of DL-camphor-10-sulfonic acid and then heated to reflux for an additional 15 minutes. After concentration under reduced pressure, the oily residue is partitioned between water and methylene chloride, the organic phase is washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and concentrated to dryness. The residual yellow oil is chromatographed on 350 g of silica gel with methylene chloride/ethyl acetate (9:1) as the elution agent. The homogeneous fractions yield an oil which crystallizes upon trituration with ether. After recrystallization from methylene chloride/ether, there are obtained 3.2 g (75.5%) of 5-(dimethylsulfamoyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-nicotinic acid isopropyl ester, m.p. 136°-138°, as a yellowish crystalline powder.
Reaction SMILES: [CH3:1][CH2:2][O-:3].[Na+].C(C(CC)(C([O-])=O)C([O-])=O)C.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]=[CH:25][C:26](=[O:28])[CH3:27]>C(O)C>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]1[CH2:1][C:2](=[O:3])[CH2:27][C:26](=[O:28])[CH2:25]1
Reactant: COc1ccccc1C=CC(C)=O
Reactant: CC[O-]
Agent: CCC(CC)(C(=O)[O-])C(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: COc1ccccc1C1CC(=O)CC(=O)C1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a stirred solution of NaOEt (21% in EtOH) (9.8 ml, 26.5 mmol) under nitrogen was added diethylmalonate (3.7 ml, 24.3 mmol). The reaction mixture was stirred at ambient temperature for 20 min. 4-(2-methoxy-phenyl)-but-3-en-2-one (3.89 g, 22.1 mmol), Stage 1, was dissolved in ethanol (20 ml) and added to the reaction mixture, which was stirred at reflux and monitored by LC-MS until 4-(2-methoxy-phenyl)-but-3-en-2-one was consumed. The reaction mixture was cooled to ambient temperature. An aqueous solution of sodium hydroxide (2M, 10 ml) was added to the reaction mixture, which was heated at 80° C. for 1.5 h. Excess ethanol was removed by evaporation and the aqueous phase was washed with toluene (20 ml). The aqueous phase was acidified with conc. HCl (5 ml) and the reaction mixture was refluxed for 1 h and left to cool to ambient temperature. The compound was extracted with ethyl acetate (2×30 ml), dried with MgSO4 and filtered. The solvent was removed under reduced pressure. The title compound was purified by column chromatography eluting with ethyl acetate/heptane (1/1) to give a beige solid.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:8][C:9]=1[N:10]([C:14](=[O:23])[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[Cl:22])[N:11]([CH3:13])[CH3:12])=[O:4].O[Li].O>C1COCC1.CO.O>[Cl:22][C:16]1[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:15]=1[C:14]([N:10]([C:9]1[CH:8]=[C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])[N:11]([CH3:13])[CH3:12])=[O:23]
Reactant: COC(=O)c1sc(-c2ccccc2)cc1N(C(=O)c1ccc(Cl)cc1Cl)N(C)C
Agent: [Li]O
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CN(C)N(C(=O)c1ccc(Cl)cc1Cl)c1cc(-c2ccccc2)sc1C(=O)O
Temperature: 60 °C
Reaction time: 2 h
Yield: 16.7 %

Procedure:
3-[N-(2,4-Dichloro-benzoyl)-N′,N′-dimethyl-hydrazino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (0.050 g, 0.11 mmol) was taken in a mixture of THF:MeOH:H2O (3:2:1, 10 mL) and then added 1N aqueous solution of LiOH.H2O (0.67 mL, 0.67 mmol). The reaction mixture was stirred at 60° C. for 2 h. Solvents were removed and the residue was partitioned between water and ethyl acetate. The aqueous layer was acidified using 10% KHSO4 solution. The organic layer was separated, dried (Na2SO4) and concentrated. The residue was purified by preparative TLC using dicholomethane:methanol (9:1) to obtain 3-[N-(2,4-Dichloro-benzoyl)-N′,N′-dimethyl-hydrazino]-5-phenyl-thiophene-2-carboxylic acid (Compound 72) (0.008 g, 17%). 1H NMR (DMSO, 400 MHz): δ 7.81 (d, 2H), 7.69 (d, 2H), 7.54-7.40 (m, 5H), 2.42 (s, 6H).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=O)=[CH:4][C:3]=1[CH2:12][CH2:13][CH3:14].[Cl-].[Na+].[CH2:17]([Mg]Br)[CH3:18].[Cl-].[NH4+].O1CC[CH2:25][CH2:24]1>C(OCC)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])([CH2:17][CH3:18])[CH2:24][CH3:25])=[CH:4][C:3]=1[CH2:12][CH2:13][CH3:14]
Reactant: CCCc1cc(C(=O)OC)ccc1Br
Reactant: CC[Mg]Br
Reactant: C1CCOC1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: CCCc1cc(C(O)(CC)CC)ccc1Br
Yield: 96 %

Procedure:
In a 1-liter three-necked round-bottomed flask, equipped with a magnetic stirrer, a thermometer and a dropping funnel, introduce under nitrogen 47 g (0.18 mol) of methyl 4-bromo-3-propylbenzoate in solution in 250 ml of tetrahydrofuran. Cool the mixture to −5° C. with the aid of a bath of ice and sodium chloride. Add 134 cm3 of a 3M solution of ethylmagnesium bromide in diethyl ether, then allow the reaction temperature to increase without exceeding 5° C. After three hours of reaction, hydrolyze the reaction mixture with 170 cm3 of 2.5M ammonium chloride solution. Extend the organic phase with 200 cm3 of ethyl acetate. Separate the phases and extract the aqueous phase with 2×200 cm3 of methylene chloride. Combine the organic phases, dry them over sodium sulfate and evaporate the solvents. This gives 49.8 g of 3-(4-bromo-3-propylphenyl)pentan-3-ol in the form of colorless oil. (Yield=96%)
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][CH:31]4[CH2:34][N:33]([CH3:35])[CH2:32]4)[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:30][CH:31]4[CH2:32][N:33]([CH3:35])[CH2:34]4)[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN1CC(Cn2nc(-c3cnc4c(n3)c(C(=O)NC(C)(C)C)cn4COCC[Si](C)(C)C)c3cc(OC(F)F)ccc32)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN1CC(Cn2nc(-c3cnc4[nH]cc(C(=O)NC(C)(C)C)c4n3)c3cc(OC(F)F)ccc32)C1
Temperature: 25 °C
Reaction time: 15 h
Yield: 69.2 %

Procedure:
To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-((1-methylazetidin-3-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (33 mg, 53.8 μmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL). After stirring at room temperature for 15 h the mixture was concentrated in vacuo then 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane solution was added. After 1 h, the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-[5-difluoromethoxy-1-(1-methyl-azetidin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (18 mg, 69%). MS (M+H)+=484; 1H NMR (DMSO-d6) δ: 9.07 (s, 1H), 8.39 (s, 1H), 8.21 (d, J=2.3 Hz, 2H), 7.93 (d, J=9.0 Hz, 1H), 7.87 (s, 1H), 7.38-7.46 (m, 2H), 7.20 (s, 1H), 4.76 (d, J=7.3 Hz, 2H), 4.55 (s, 2H), 3.48 (t, J=8.0 Hz, 1H), 2.36 (s, 3H), 1.50 (s, 9H), 1.05 (t, J=7.3 Hz, 2H).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[C:7]([OH:10])[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[I:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[I:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15][O:10][C:7]1[CH:8]=[CH:9][C:4]2[CH:3]=[CH:2][O:1][C:5]=2[CH:6]=1
Reactant: BrCc1cccc(I)c1
Reactant: Oc1ccc2ccoc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Ic1cccc(COc2ccc3ccoc3c2)c1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of 1-benzofuran-6-ol (1.0 g, 7.5 mmol) and 3-iodobenzylbromide (2.7 g, 9.0 mmol) in DMF (10 mL) was added potassium carbonate (1.5 g, 11.0 mmol). The reaction mixture was stirred under nitrogen at room temperature for 3 days. The reaction was diluted with ethyl acetate, washed with water (2×) and brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified on a silica gel column, eluting with ethyl acetate (10-50%) in hexane. The final product was collected as a slightly yellow viscous oil.
Reaction SMILES: [CH3:1][N:2]([CH3:22])[C:3](=[O:21])[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[CH:6][C:5]=1[S:13]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])(=[O:15])=[O:14].[H-].[Na+].N#N.[H][H].[CH3:29]C1C=CC(S(C)(=O)=O)=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH3:22][N:2]([CH3:1])[C:3](=[O:21])[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[CH:6][C:5]=1[S:13]([N:16]([CH2:17][CH2:18][CH2:19][OH:20])[CH3:29])(=[O:15])=[O:14]
Reactant: [H][H]
Reactant: Cc1ccc(S(C)(=O)=O)cc1
Reactant: CN(C)C(=O)c1c([N+](=O)[O-])cccc1S(=O)(=O)NCCCO
Agent: N#N
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN(C)C(=O)c1c([N+](=O)[O-])cccc1S(=O)(=O)N(C)CCCO
Reaction time: 17 h
Yield: 116.4 %

Procedure:
N,N-Dimethyl-2-[N-(3-hydroxypropyl)aminosulfonyl]-6-nitrobenzamide (1.37 g, 4.13 mmol) in 12 ml of DMF, was added dropwise to a suspension of 198 mg (4.13 mmol) of 50% NaH in 3 ml of DMF in an atmosphere of N2. When evolution of hydrogen was complete, a solution of methyl p-toluene sulfonate (0.794 g, 4.14 mmol) in DMF, 2 ml, was added. The clear deep Yellow solution was stirred at 25° for 17 hours, then at 60° for 23 hours. The solution then was mixed with 175 ml of ethyl acetate and the precipitate that separated collected on a filter and washed with 50 ml of ethyl acetate. The combined filtrate and washings were extracted with 6×25 ml of saturated NaCl solution and the ethyl acetate evaporated to give 1.66 g of a clear yellow oil. Flash chromatography over E. Merck silica gel 60 (230-400 mesh) gave 0.49 g of a clear light yellow oil. This material was dissolved in 50 ml of CHCl3, the solution extracted with 4×5 ml of lN NaOH, then with 3 x 5 ml of saturated NaCl and dried over MgSO4.After evaporation of the CHCl3, the residue was dissolved in ethyl acetate and the solution filtered to remove a trace of MgSO4. Evaporation of the solvent gave 0.44 g of light yellow crystalline product, m.p., 91.5°-92.5°.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][C:14]([NH:16][C@H:17]([C:21]([OH:23])=O)[CH:18]([CH3:20])[CH3:19])=[O:15])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:49][C:50]1[S:54][C:53](=[S:55])[NH:52][N:51]=1>>[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][C:14]([NH:16][C@H:17]([C:21]([NH:49][C:50]3[S:54][C:53](=[S:55])[NH:52][N:51]=3)=[O:23])[CH:18]([CH3:20])[CH3:19])=[O:15])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)[C@H](NC(=O)Cc1ccc(-c2ccccc2)cc1)C(=O)O
Reactant: Nc1n[nH]c(=S)s1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Product: CC(C)[C@H](NC(=O)Cc1ccc(-c2ccccc2)cc1)C(=O)Nc1n[nH]c(=S)s1

Procedure:
((4-Phenyl)phenylacetyl)-valine (0.98 grams), 1-hydroxybenzotriazole (0.6 grams), dicyclohexylcarbodiimide (0.64 grams) and 5-amino-1,3,4-thiadiazole-2-thione (1.2 grams) were reacted according to the procedure described in Example 1. The resulting product was recrystallized from ethanol/pentane to give a white solid. M.P. 232°-236° C. NMR spectrum (d6 -DMSO) 14.1 (s, 1H), 12.6 (s, 1H), 8.42 (d, 1H, NH), 7.8-7.2 (m, 9H, aromatics), 4.35 (m, 1H), 3.75-3.4 (m, 2H), 2.05 (m, 1H), 0.9 (d, 6H).
Reaction SMILES: C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][N:11]([CH2:24][CH2:25][S:26]([CH3:28])=[O:27])[C:10]1=[O:29].Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].Cl.Cl.[O:45]=[C:46]1[NH:54][C:49]2=[N:50][CH:51]=[CH:52][CH:53]=[C:48]2[N:47]1[CH:55]1[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1>O1CCCC1>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH2:12][N:11]([CH2:24][CH2:25][S:26]([CH3:28])=[O:27])[C:10](=[O:29])[C@H:9]([NH:8][C:31]([N:58]2[CH2:59][CH2:60][CH:55]([N:47]3[C:48]4[C:49](=[N:50][CH:51]=[CH:52][CH:53]=4)[NH:54][C:46]3=[O:45])[CH2:56][CH2:57]2)=[O:32])[CH2:15][CH2:14]1
Reactant: CS(=O)CCN1C[C@H](c2cccc(F)c2F)CC[C@@H](N)C1=O
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: O=c1[nH]c2ncccc2n1C1CCNCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CS(=O)CCN1C[C@H](c2cccc(F)c2F)CC[C@@H](NC(=O)N2CCC(n3c(=O)[nH]c4ncccc43)CC2)C1=O
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
Triethylamine (0.010 mL, 0.027 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-[2-(methylsulfinyl)ethyl]azepan-2-one (8.9 mg, 0.027 mmol) and 4-nitrophenyl chloroformate (5.4 mg, 0.027 mmol) in tetrahydrofuran (0.700 mL) at 0° C. After 45 min, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (7.9 mg, 0.027 mmol) and triethylamine (0.040 mL, 0.108 mmol) were added and the mixture allowed to warm to ambient temperature. After 16 h, the mixture was concentrated.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH3:9][Si:10]([CH3:26])(N(CC)CC)[CH2:11][CH2:12][Si:13]([CH3:20])([CH3:19])N(CC)CC>>[Br:1][C:2]1[CH:3]=[C:4]([N:5]2[Si:13]([CH3:20])([CH3:19])[CH2:12][CH2:11][Si:10]2([CH3:26])[CH3:9])[CH:6]=[CH:7][CH:8]=1
Reactant: CCN(CC)[Si](C)(C)CC[Si](C)(C)N(CC)CC
Reactant: Nc1cccc(Br)c1
Product: C[Si]1(C)CC[Si](C)(C)N1c1cccc(Br)c1

Procedure:
The alpha,omega-aniline terminated dimethyl siloxanes are prepared, starting with 3-bromoaniline, in which the amine functionality is protected, such as by reaction with 1,1,4,4-tetramethyl-1,4-bis(N,N-diethylamino)-1,4-disilabutane, to form 1-(3-bromophenyl)-2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane. The protected bromoaniline is then reacted with an alkyllithium or with magnesium to form the corresponding lithio or Grignard compound, respectively, which is then reacted with chlorodialkylsilane to form 1-(3-(dialkylsilyl)phenyl)-2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane. This reaction places the silane functionality in the meta position. Next, the protected dimethylsilane aniline is subjected to deprotection to form 3-aminophenyldialkyl silane, which is considered to be novel. This silane is then hydrolyzed to form the corresponding silanol, also considered to be novel. The silanol is then condensed to form bis(3-aminophenyl)-1,1,3,3-tetraalkyldisiloxane.