Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9]CC)=[O:8])=[CH:5][CH:4]=1)#[N:2].[CH3:14][NH:15][CH2:16][CH2:17]N.[Cl:19]CCl>Cl.O1CCOCC1.C(O)C>[ClH:19].[CH3:14][N:15]1[CH2:16][CH2:17][N:2]=[C:1]1[C:3]1[CH:4]=[CH:5][C:6]([C:7]([OH:9])=[O:8])=[CH:12][CH:13]=1
Reactant: CNCCN
Reactant: CCOC(=O)c1ccc(C#N)cc1
Reactant: ClCCl
Agent: Cl
Solvent: CCO
Solvent: C1COCCO1
Product: CN1CCN=C1c1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
1.8 g (10.3 mmol) of ethyl 4-cyanobenzoate was dissolved in a mixture of 20 ml of 4 N solution of hydrogen chloride in dioxane and 5 ml of ethanol, and the obtained solution was stirred at room temperature for 3 days. The solvent was evaporated, and the residue was washed with ethyl acetate. The obtained crude product was dissolved in 20 ml of ethanol. 1.52 g (20.6 mmol) of N-methylethylenediamine was added to the obtained solution, and they were heated under reflux for 6 hours. The solvent was evaporated, and the obtained crude product was treated with dichloromethane as the extraction solvent in an ordinary manner. The obtained crude product was dissolved in 10 ml of concentrated hydrochloric acid, and the obtained solution was stirred at 50° C. overnight. The solvent was evaporated to obtain the crude title compound.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[Br:10]Br>>[Br:10][C:5]1[CH:6]=[C:7]([F:9])[CH:8]=[C:2]([F:1])[C:3]=1[NH2:4]
Reactant: BrBr
Reactant: Nc1ccc(F)cc1F
Product: Nc1c(F)cc(F)cc1Br

Procedure:
reacting 2,4-difluoroaniline with Br2 so as to form 2-bromo-4,6-difluoroaniline.HBr;
Reaction SMILES: [NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@@H:3]([OH:32])[CH2:4][C@@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:40][C:41]([CH3:62])([CH3:61])[C@H:42]([N:46]1[CH2:50][C:49](=[O:51])[N:48]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[N:54]=2)[C:47]1=[O:60])[C:43](O)=[O:44].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:40][C:41]([CH3:62])([CH3:61])[C@H:42]([N:46]1[CH2:50][C:49](=[O:51])[N:48]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[N:54]=2)[C:47]1=[O:60])[C:43]([NH:1][C@@H:2]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C@@H:3]([OH:32])[CH2:4][C@@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1)=[O:44]
Reactant: Cc1cccc(CN2C(=O)CN([C@H](C(=O)O)C(C)(C)C)C2=O)n1
Reactant: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(-c2ccccn2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1)C(C)(C)C
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(-c2ccccn2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N1CC(=O)N(Cc2cccc(C)n2)C1=O)C(C)(C)C)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 63.1 %

Procedure:
A solution containing the product from Example 2C (0.020 g, 0.038 mmol) in THF (0.4 mL) was treated with the product from Example 46E (0.020 g, 0.046 mmol), DEPBT (0.017 g, 0.057 mmol), and N,N-diisopropylethylamine (0.035 mL, 0.201 mmol), stirred at 25° C. for 1 hour, and partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane to give the title compound (0.020 g, 64% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.85 (s, 9 H), 0.88 (s, 9 H), 1.54 (m, 2 H), 2.41 (s, 3 H), 2.65 (m, 4 H), 3.08 (d, J=18.02 Hz, 1 H), 3.51 (s, 3 H), 3.72 (m, 1 H), 3.89 (m, 2 H), 4.17 (m, 2 H), 4.39 (s, 1 H), 4.67 (m, 3 H), 6.66 (d, J=9.93 Hz, 1 H), 7.06 (m, 7 H), 7.23 (d, J=8.46 Hz, 2 H), 7.31 (m, 1 H), 7.66 (t, J=7.54 Hz, 1 H), 7.87 (m, 6 H), 8.64 (d, J=4.41 Hz, 1 H).
Reaction SMILES: [Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=3[Cl:21])[C:6]=2[CH:5]=[CH:4][N:3]=1.ClC1C=CC=C(C(OO)=[O:30])C=1>C(Cl)(Cl)Cl.ClCCl>[Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:20])[F:19])=[CH:13][C:12]=3[Cl:21])[C:6]=2[CH:5]=[CH:4][N+:3]=1[O-:30]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: FC(F)(F)c1ccc(-n2ccc3c(Cl)nccc32)c(Cl)c1
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: [O-][n+]1ccc2c(ccn2-c2ccc(C(F)(F)F)cc2Cl)c1Cl
Reaction time: 2 h
Yield: 29.8 %

Procedure:
4-chloro-1-(2'-chloro-4'-trifluoromethylphenyl)-pyrrolo[3,2-c]pyridine (1.10 g, 33 mmol) and meta-chloroperbenzoic acid (approximately 80-85%, 1.15 g) were stirred together in chloroform (20 ml) at room temperature overnight. A further quantity of meta-chloroperbenzoic acid (1.15 g) was added, and stirring continued for 2 hours. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium carbonate solution. The organic portion was dried over magnesium sulfate, filtered, and the filtrate evaporated in vacuo. The residue was triturated with hexane to give 4-chloro-1-(2'-chloro-4'-trifluoromethylphenyl)-pyrrolo[3,2-c]-pyridine 5-oxide (0.69 g) as a tan solid, m.p. 119°-123° C. (with dec.)
Reaction SMILES: O[CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[C:15]1(=[O:25])[NH:19][C:18](=[O:20])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>O1CCCC1>[O:20]=[C:18]1[C:17]2[C:16](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15](=[O:25])[N:19]1[CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCCC(O)C1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCC(N2C(=O)c3ccccc3C2=O)C1
Yield: 28.4 %

Procedure:
tert-Butyl 3-hydroxypiperidine-1-carboxylate (4.38 g) (21.76 mmol), phthalimide (4.82 g, 32.76 mmol), and triphenylphosphine (8.62 g, 32.86 mmol) were added to tetrahydrofuran (60 ml), 40% diethyl azodicarboxylate-toluene solution (15 ml) was slowly added at room temperature with stirring, and the mixture was stirred at the same temperature overnight. The reaction mixture was concentrated under reduced pressure, diluted with diethyl ether, and the precipitated colorless solid was filtered off. The mother liquor was concentrated under reduced pressure and the obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane) to give the title compound (2.04 g, yield 28%) as a colorless solid.
Reaction SMILES: [NH2:1][C:2]([C:4]1[CH:29]=[CH:28][C:7]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)=[C:6]([CH2:30][CH2:31][CH3:32])[CH:5]=1)=[S:3].Cl[CH:34]1[C:38](=O)[CH2:37][O:36][C:35]1=[O:40].[CH3:41][CH2:42][OH:43]>>[CH2:26]([O:25][C:23](=[O:24])[CH2:22][C@H:18]1[C:19]2[C:15](=[CH:14][C:13]([O:12][CH2:11][CH2:10][CH2:9][O:8][C:7]3[CH:28]=[CH:29][C:4]([C:2]4[S:3][C:34]([C:35]([O:36][CH2:37][CH3:38])=[O:40])=[C:41]([CH2:42][OH:43])[N:1]=4)=[CH:5][C:6]=3[CH2:30][CH2:31][CH3:32])=[CH:21][CH:20]=2)[CH2:16][CH2:17]1)[CH3:27]
Reactant: CCO
Reactant: CCCc1cc(C(N)=S)ccc1OCCCOc1ccc2c(c1)CC[C@H]2CC(=O)OCC
Reactant: O=C1COC(=O)C1Cl
Product: CCCc1cc(-c2nc(CO)c(C(=O)OCC)s2)ccc1OCCCOc1ccc2c(c1)CC[C@H]2CC(=O)OCC
Temperature: 70 °C
Yield: 33 %

Procedure:
Ethyl ((1S)-5-{3-[4-aminocarbonothioyl)-2-propylphenoxy]propoxy}2,3-dihydro-1H-inden-1-yl)acetate (90 mg, 0.2 mmol) (Example 144) and 3-chloro-2,4(3H, 5H)-furandione (106 mg, 0.8 mmol) were dissolved in EtOH (anhydrous, 8 mL), and the mixture was heated at 70° C. for 18 h. The reaction was cooled to rt, and then concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc:hexane (v/v)=1:1) gave 38 mg (33%) of the btle compound as a clear oil. LC-MS: RT=4.38 min; (M+H)+ 582.3.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[C@H:7]([OH:8])[CH2:6][C@@H:5]([C:9]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[N:20]=3)[N:15]=[CH:14][C:13]=2[F:24])=[O:10])[CH2:4]1.[O:25]=[C:26]1[NH:31][C:30]2[N:32]=[C:33]([CH:36]=O)[CH:34]=[CH:35][C:29]=2[S:28][CH2:27]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[F:24][C:13]1[CH:14]=[N:15][C:16]2[C:21]([C:12]=1[NH:11][C:9]([C@H:5]1[CH2:4][C@H:3]([CH2:2][NH:1][CH2:36][C:33]3[CH:34]=[CH:35][C:29]4[S:28][CH2:27][C:26](=[O:25])[NH:31][C:30]=4[N:32]=3)[C@H:7]([OH:8])[CH2:6]1)=[O:10])=[N:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2
Reactant: O=Cc1ccc2c(n1)NC(=O)CS2
Reactant: COc1ccc2ncc(F)c(NC(=O)[C@H]3C[C@H](CN)[C@H](O)C3)c2n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: COc1ccc2ncc(F)c(NC(=O)[C@H]3C[C@H](CNCc4ccc5c(n4)NC(=O)CS5)[C@H](O)C3)c2n1
Reaction time: 24 h
Yield: 18.1 %

Procedure:
To a stirred solution of (±)-(1S,3R,4R)-3-(aminomethyl)-N-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-4-hydroxycyclopentanecarboxamide (0.43 g, 1.29 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (10 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (0.25 g, 1.29 mmole). After 24 h, at RT was added NaBH(OAc)3 (0.41 g, 1.93 mmole). After 4 h, the reaction solution was concentrated under vacuum to a solid. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (0.12 g, 18%) as light yellow solid: 1H NMR (400 MHz, d8-dioxane), δ8.75 (s, 1H), 8.27 (d, J=9.0 Hz, 1H), 7.64 (d, J=7.8 Hz, 1H), 7.15 (d, J=9.0 Hz, 1H), 7.02 (d, J=7.8 Hz, 1H), 4.35 (m, 1H), 4.10 (s, 3H), 3.78 (s, 2H), 3.49 (s, 2H), 3.36 (m, 1H), 2.81 (m, 1H), 2.73 (m, 1H), 2.20 (m, 3H), 2.04 (m, 1H), 1.87 (m, 1H). LC-MS (ES) m/e 513 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[CH2:4][C:5]1[S:9][C:8]([NH2:10])=[N:7][CH:6]=1.[C:12]1([C:18](Cl)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:11])[CH2:4][C:5]1[S:9][C:8]([NH:10][C:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:7][CH:6]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COC(=O)Cc1cnc(N)s1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)Cc1cnc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)s1
Yield: 91.9 %

Procedure:
Methyl-(2-amino-1,3-thiazole-5-yl)acetate (1 g, 5.8 mmol) in CH2Cl2 (15 ml) was reacted with triphenylmethyl chloride (1.73 g, 6.2 mmol) and triethylamine (0.89 ml, 6.4 mmol) at 0° C. for 1.5 hour. Water was added to the mixture which was extracted with ethyl acetate, dried, purified by silica gel chromatography to give title compound (2.21 g, 91%).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=[O:7].Br.Br[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=[O:7]
Reactant: O=Cc1ncc[nH]1
Reactant: BrCc1ccccn1
Agent: Br
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=Cc1nccn1Cc1ccccn1
Temperature: 80 °C
Yield: 37.4 %

Procedure:
To a solution of the 2-imidazolecarboxaldehyde (545 mg, 5.67 mmol) and 2-(bromomethyl)pyridine hydrobromide (1.58 g, 6.24 mmol) in DMF (20 mL) was added N,N-diisopropylethylamine (3.0 mL, 17.01 mmol). The reaction mixture was heated to 80° C. overnight. Then it was cooled and quenched with saturated NaHCO3 (20 mL). It was extracted with CH2Cl2 (c×20 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered, concentrated, and dried in vacuo to afford a dark brown oil. Purification by flash column chromatography on silica gel using 1% →2% CH3OH/CH2Cl2 afforded the product as a yellow solid (397 mg, 37%). 1H NMR (CDCl3) δ 5.71 (s, 2H), 7.18-7.24 (m, 2H), 7.32 (s, 1H), 7.36 (s, 1H), 7.65 (td, 1H, J=10.4, 1.5 Hz), 8.56 (d, 1H, J=4.5 Hz), 9.82 (s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)([NH2:11])[CH2:9][NH2:10])=[CH:4][CH:3]=1.CO[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#N)[CH:24]=1)=[NH:22]>CO>[C:21]([C:23]1[CH:24]=[C:25]([C:29]2[NH:10][CH2:9][C:8]([C:12]3[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=3)([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:11]=2)[CH:26]=[CH:27][CH:28]=1)#[N:22]
Reactant: NCC(N)(c1ccc(F)cc1)c1ccc(F)cc1
Reactant: COC(=N)c1cccc(C#N)c1
Solvent: CO
Product: N#Cc1cccc(C2=NC(c3ccc(F)cc3)(c3ccc(F)cc3)CN2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 51.1 %

Procedure:
To a solution of 1,1-bis(4-fluorophenyl)-1,2-ethane-diamine (500 mg) in methanol (10 mL) was added 3-cyanobenzeneimidic acid methyl ester (792 mg), and the mixture was stirred at room temperature for 18 hrs. After concentrating the reaction mixture, the residue was dissolved in ethyl acetate (3 mL), washed with saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride aqueous solution in this order, and dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the organic solvent was evaporated in vacuo. The obtained residue was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=3:1→2:1) to give the objective compound (370 mg).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[O:6]1[CH:11]=[CH:10][CH2:9][CH2:8][CH2:7]1.C(O)(C(F)(F)F)=O>[H-].[Na+]>[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: C1=COCCC1
Reactant: c1cn[nH]c1
Agent: [H-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: c1cnn(C2CCCCO2)c1
Yield: 49.2 %

Procedure:
A mixture of 1H-pyrazole (6.00 g, 88.1 mmol), 3,4-dihydro-2H-pyran (9.00 g, 107 mmol), and TFA (cat. 2.00 mL) was heated to reflux for 5 hr. At the end of reaction, NaH (100 mg, 4.17 mmol) was added to quench the reaction. The resulting mixture was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and evaporated. The residue was purified by silica gel chromatography eluting with EtOAc/petroleum ether (1:100) to afford 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (6.6 g, 49% yield) as pale yellow sold. LCMS (ESI) m/z: 153.1 [M+H+].
Reaction SMILES: [Cl:1][C:2]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH2:7][C:8]([C:31]([F:34])([F:33])[F:32])([O:26][Si](C)(C)C)[C:9]=1[N:10]2S(C1C=CC(C)=CC=1)(=O)=O.[OH-].[K+].CCO>C1COCC1.O>[Cl:1][C:2]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH2:7][C:8]([C:31]([F:32])([F:33])[F:34])([OH:26])[C:9]=1[NH:10]2
Reactant: Cc1ccc(S(=O)(=O)n2c3c(c4c(Cl)c(F)ccc42)CCCC3(O[Si](C)(C)C)C(F)(F)F)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: OC1(C(F)(F)F)CCCc2c1[nH]c1ccc(F)c(Cl)c21
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 54.2 %

Procedure:
To a solution of 5-chloro-6-fluoro-9-tosyl-1-(trifluoromethyl)-1-(trimethylsilyloxy)-2,3,4,9-tetrahydro-1H-carbazole (0.08 g, 0.15 mmol) in THF (5 mL), cooled to 0° C., KOH (0.042 g, 0.7 mmol) in H2O (1 mL) was added and the resulting mixture was stirred for 30 min. EtOH (4 mL) was added to the reaction mixture and heated to 60° C. for 3 h, diluted with water (10 mL) and extracted with EtOAc (4×15 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude compound which was purified by column chromatography [EtOAc-hexane (3:17) as eluant] to give the title compound (0.025 g, 55%). 1H NMR (500 MHz, DMSO-d6, δ in ppm) 11.22 (s, 1H), 7.34 (dd, J=9.0, 4.5 Hz, 1H), 7.14 (t, J=9.0 Hz, 1H), 6.70 (s, 1H), 3.09 (t, J=11.0 Hz, 1H), 2.94-2.89 (m, 1H), 2.10 (t, 6.5 Hz, 1H), 2.00-1.92 (m, 3H).
Reaction SMILES: [CH2:1]([SiH:9]([Cl:11])[Cl:10])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]=1>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH:12]1([Si:9]([CH2:1][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)([Cl:11])[Cl:10])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: Cl[SiH](Cl)CCc1ccccc1
Reactant: C1=CCCCC1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: Cl[Si](Cl)(CCc1ccccc1)C1CCCCC1
Reaction time: 17.5 h
Yield: 60.7 %

Procedure:
Then into a 100 ml pressure-proof stainless steel reactor; 6.21 g (30.3 millimol) of the above-mentioned phenethyldichlorosilane, 4.47 g (54.4 millimol) of cylcohexene and 0.1 ml of a chloroplatinic acid solution in isopropanol (0.03 mol % relative to phenethyldichlorosilane) were charged and sealed. Reaction was carried out in an oil bath at 100° C. with stirring for 17.5 hours. After completion of reaction, the reacted solution was subjected to vacuum distillation to obtain 5.30 g (18.4 millimol) of cyclohexylphenethyldichlorosilane. This cyclohexylphenethyldichlorosilane had a boiling point of 112.8°~115.4° C./2.0 mmHg. The infrared spectrum of this compound is shown in FIG. 4. There is no characteristic absorption of Si-H at 2100 cm-1. The NMR spectrum is shown in FIG. 9. There are signals of δ value at 1.0~2.0 ppm (Si--CH2 and C--CH2 --); 2.4~3.0 ppm (--CH2 --C6H5) and 7.15 ppm (--C6H 5). The integral ratio thereof was 14:2:5. In the mass spectrum analysis, parent ion was M+ 286.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][N:9]2[C:15]=1I)=[O:4].[Li+].[CH3:20]CC[CH2-].CI>O1CCCC1>[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][N:9]2[C:15]=1[CH3:20])=[O:4]
Reactant: O=C(Nc1nc2ccc(F)cn2c1I)C(F)(F)F
Reactant: [CH2-]CCC
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CI
Product: Cc1c(NC(=O)C(F)(F)F)nc2ccc(F)cn12
Temperature: -78 °C

Procedure:
2,2,2-trifluoro-N-(6-fluoro-3-iodoimidazo[1,2-a]pyridin-2-yl)acetamide (500 g, 0.00134 mol) was dissolved in tetrahydrofuran (16 mL) and was cooled at −78° C. N-Butyllithium (2 molarin cyclohexane, 1.6 mL) was added and the reaction was warmed to −20 for 15 minutes then chilled to 78° C. Methyl iodide (110 uL, 0.0017 mol) was added and the reaction was allowed to warm to room temperature. The reaction was poured into ice water and extracted with ethyl acetate (3×50 mL). The combined organics were dried (magnesium sulfate) and solvent removed. Residue chromatographed on silica (50% ethyl acetate/hexanes) to give 2,2,2-trifluoro-N-(6-fluoro-3-methylimidazo[1,2-a]pyridin-2-yl)acetamide 5 Rf 0.47, 50% ethyl acetate/hexanes; MS m/z 262 (M+H).
Reaction SMILES: [CH2:1]([CH:4]1[N:7]([C:8]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])=P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C:6](=[O:38])[CH:5]1[CH3:39])[CH:2]=C.FC(F)(F)C(O)=O>C(OCC)(=O)C>[CH3:39][CH:5]1[C:6](=[O:38])[N:7]2[CH:4]1[CH2:1][CH:2]=[C:8]2[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]
Reactant: C=CCC1C(C)C(=O)N1C(C(=O)OCc1ccccc1)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: CC1C(=O)N2C(C(=O)OCc3ccccc3)=CCC12
Reaction time: 0.17 h
Yield: 57.2 %

Procedure:
A solution of 4allyl-3-methyl-1-(1-benzyloxycarbonyl-1-triphenylphosphoranylidenemethyl)azetidine-2-one (38) (0.29 g) in ethyl acetate (25 ml) was treated with trifluoroacetic acid (0.4 ml) and then cooled to -78°. Ozone was bubbled through the solution until it just became pale blue in colour. The excess ozone was blown off in a stream of argon and an ethyl acetate solution of triphenylphosphine (0.14 g) was then added. After a further 10 minutes the reaction flask was transferred to an ice bath and saturated aqueous sodium bicarbonate (45 ml) was added with vigorous stirring. This was continued for 30 minutes and the ethyl acetate solution was then separated, washed with brine and dried over sodium sulphate. The solution was concentrated and chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether mixtures grading from 3:7 to 6:4. This gave the trans-isomer of benzyl 6-methyl-7-oxo-1-azabicyclo[3,2,0]hept-2-ene- 2-carboxylate (39) (0.08 g, 55%); νmax (CHCl3) 3000, 1780, 1725 and 1615 cm-1 ; δppm ((CD3)2CO) 1.34 (3H, d, J 7 Hz, CH3), 2.85 (2H, dd, J 9 and 2 Hz, C4-H2), 3.24 (1H, dq, J 3 and 7 Hz, C6-H), 3.91 (1H, dt, J 3 and 9 Hz, C5-H), 5.20 (2H, s, benzyl CH2), 6.45 (1H, t, J 2 Hz, C3-H) and 7.2-7.5 (5H, m, phenyl); (M+ at m/e 257.1052 C15H15NO3 requires 257.1051).
Reaction SMILES: [F:1][C:2]([F:6])([F:5])[S:3]Cl.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[NH:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+]>CCOCC.O.CCOCC>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[NH:15][C:16]([S:3][C:2]([F:6])([F:5])[F:1])=[CH:17][CH:18]=2)=[CH:12][CH:13]=1
Reactant: FC(F)(F)SCl
Reactant: Clc1ccc(-c2ccc[nH]2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: FC(F)(F)Sc1ccc(-c2ccc(Cl)cc2)[nH]1
Reaction time: 0.5 h

Procedure:
Trifluoromethylsulfenyl chloride is bubbled into a solution of 2-(p-chlorophenyl)pyrrole (0.5 g, 0.00281 mol) and sodium carbonate (0.36 g, 0.00338 mol) in ether at -30° C. under nitrogen. The reaction mixture is stirred for 1/2 hour and diluted with a water/ether mixture. The organic phase is separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title product as a purple solid (0.78 g, mp 34°-39° C.) which is identified by 1HNMR and 13CNMR spectral analyses.
Reaction SMILES: [CH:1]([NH:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([OH:17])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2].Br[CH2:19][C:20]1[CH:21]=[C:22]([S:26]([CH2:34][CH3:35])(=[N:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:27])[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C(OCC)(=O)C>[CH2:32]([O:31][C:29]([N:28]=[S:26]([CH2:34][CH3:35])([C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([CH2:19][O:17][C:11]2[CH:10]=[C:9]3[C:14]([C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:6][CH:7]=[N:8]3)=[CH:13][C:12]=2[O:15][CH3:16])[CH:21]=1)=[O:27])=[O:30])[CH3:33]
Reactant: COc1cc2c(NC(C)C)ncnc2cc1O
Reactant: CCOC(=O)N=S(=O)(CC)c1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: CCOC(=O)N=S(=O)(CC)c1cccc(COc2cc3ncnc(NC(C)C)c3cc2OC)c1
Yield: 62 %

Procedure:
4-(Isopropylamino)-6-methoxyquinazolin-7-ol (50 mg, 0.21 mmol) and (RS)-S-[3-(bromomethyl)phenyl]-N-(ethoxycarbonyl)-S-ethylsulphoximide (108 mg, 0.32 mmol) are suspended in 5.0 mL of acetone. After addition of potassium carbonate (55 mg, 0.4 mmol), the reaction mixture is refluxed for 6 hours. The batch is diluted with ethyl acetate and the organic phase is washed with water and dried over sodium sulphate to leave, after removal of the solvent and also after chromatographic purification (silica gel, hexane/ethyl acetate: 0→100% ethyl acetate, followed by ethyl acetate/methanol: 9/1) the desired product in 62% yield (65 mg).
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][CH:5]=[O:6].[OH-].[Na+]>>[CH3:1][S:2][CH2:3][C:4]([CH:5]=[O:6])=[CH:5][CH2:4][CH2:3][S:2][CH3:1]
Reactant: CSCCC=O
Agent: [Na+]
Agent: [OH-]
Product: CSCCC=C(C=O)CSC
Temperature: 0 °C

Procedure:
Into a 1 liter reaction flask equipped with mechanical stirrer, 250 ml addition funnel, Y adapter, thermometer and Friedrich condenser is placed 208 grams of methional. The reaction mass is cooled to 0° C. and 100 ml of a 0.5 molar solution of sodium hydroxide is added dropwise with stirring. The resulting reaction mass is extracted with three 100 ml portions of methylene chloride and the extracts are combined, dried over anhydrous sodium sulfate and evaporated on a rotary evaporator. The resulting product was then subjected to vacuum distillation to give the product, boiling point 129° C. (1 mm Hg).