Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[F:18])[N:11]=[C:10]2[O:23][CH2:24][CH2:25][CH3:26])=[C:4]([F:27])[CH:3]=1.[CH2:28](Br)[C:29]#[CH:30].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[Cl:1][C:2]1[C:7]([O:8][CH2:30][C:29]#[CH:28])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:21])([F:22])[C:17]([F:20])([F:18])[F:19])[N:11]=[C:10]2[O:23][CH2:24][CH2:25][CH3:26])=[C:4]([F:27])[CH:3]=1
Reactant: CCCOc1nc(C(F)(F)C(F)(F)F)cc(=O)n1-c1cc(O)c(Cl)cc1F
Reactant: C#CCBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Product: C#CCOc1cc(-n2c(OCCC)nc(C(F)(F)C(F)(F)F)cc2=O)c(F)cc1Cl

Procedure:
using 1-(4-chloro-2-fluoro-5-hydroxyphenyl)-4-pentafluoroethyl-2-(n-propoxy)-6(1H)-pyrimidinone and propargyl bromide with sodium carbonate in acetone there is obtained 1-[4-chloro-2-fluoro-5-(2-propynyloxy)-phenyl]-4-pentafluoroethyl-2-(n-propoxy)-6(1H)-pyrimidinone, 1H-NMR (CDCl3, 400 MHz): 7.34 ppm (d,1H), 6.98 ppm (d,1H), 6.65 ppm (s,1H), 4.76 ppm (m,2H), 4.36 ppm (m,2H), 2.56 ppm (t,1H), 1.67 ppm (m,2H), 0.85 ppm (t,3H);
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1.[CH3:12][C:13]([OH:17])([C:15]#[CH:16])[CH3:14]>C(N(CC)CC)C.[Cu]I>[OH:11][CH2:10][CH2:9][CH2:8][C:4]1[CH:3]=[C:2]([C:16]#[C:15][C:13]([CH3:14])([OH:17])[CH3:12])[CH:7]=[CH:6][CH:5]=1
Reactant: OCCCc1cccc(Br)c1
Reactant: C#CC(C)(C)O
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: CC(C)(O)C#Cc1cccc(CCCO)c1
Temperature: 70 °C
Reaction time: 15 h

Procedure:
To a degassed solution of 3-(3-bromophenyl)propan-1-ol (47) (0.95 g, 4.5 mmol) and 2-methyl-3-butyn-2-ol (48) (1.6 mL, 16 mmol) in triethylamine (25 mL) was added PdCl2(PPh3)3 (0.095 g, 0.14 mmol) and CuI (0.027 g, 0.14 mmol). The resulting mixture was degassed and stirred under argon at 70° C. for 15 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and diluted with EtOAc (50 mL). Trace solids were removed by filtration then the filtrate was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure. Purification by flash chromatography (10 to 100% EtOAc-hexanes gradient) gave 4-(3-(3-hydroxypropyl)phenyl)-2-methylbut-3-yn-2-ol (49) as a light brown oil: Yield (0.78 g, 80%): 1H NMR (400 MHz, DMSO-d6) δ 7.18-7.29 (m, 4H), 5.46 (s, 1H), 4.48 (t, J=4.0 Hz, 1H), 3.38 (q, J=4.0 Hz, 2H), 2.59 (t, J=6.0 Hz, 2H), 2.46 (m, 2H), 1.46 (s, 6H).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[S:9][CH2:10][C@@H:11]2[C@@H:16]([C:17]([F:20])([F:19])[F:18])[O:15][CH2:14][C@:12]2([C:21]2[CH:26]=[C:25]([NH2:27])[CH:24]=[C:23]([F:28])[C:22]=2[F:29])[N:13]=1)(C)(C)C.[CH3:31][C:32]1[N:33]=[CH:34][C:35]([C:38](O)=[O:39])=[N:36][CH:37]=1>>[NH2:7][C:8]1[S:9][CH2:10][C@@H:11]2[C@@H:16]([C:17]([F:18])([F:20])[F:19])[O:15][CH2:14][C@:12]2([C:21]2[CH:26]=[C:25]([NH:27][C:38]([C:35]3[CH:34]=[N:33][C:32]([CH3:31])=[CH:37][N:36]=3)=[O:39])[CH:24]=[C:23]([F:28])[C:22]=2[F:29])[N:13]=1
Reactant: Cc1cnc(C(=O)O)cn1
Reactant: CC(C)(C)OC(=O)NC1=N[C@@]2(c3cc(N)cc(F)c3F)CO[C@H](C(F)(F)F)[C@H]2CS1
Product: Cc1cnc(C(=O)Nc2cc(F)c(F)c([C@]34CO[C@H](C(F)(F)F)[C@H]3CSC(N)=N4)c2)cn1

Procedure:
Synthesized from tert-butyl[(4aS,5S,7aS)-7a-(5-amino-2,3-difluorophenyl)-5-trifluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]carbamate and 5-methylpyrazine-2-carboxylic acid according to the general procedure. 1H NMR (400 MHz, CDCl3+MeOD) δ ppm 2.68 (s, 3 H), 2.84 (dd, J=13.6, 3.8 Hz, 1 H), 3.15 (dd, J=13.9, 3.0 Hz, 1 H), 3.30-3.42 (m, 1 H), 3.88 (d, J=10.4 Hz, 1 H), 4.61 (d, J=8.6 Hz, 1 H), 4.68 (quin, J=7.2 Hz, 1 H), 7.13-7.25 (m, 1 H), 8.05 (ddd, J=11.6, 6.8, 2.8 Hz, 1H), 8.46 (s, 1 H), 9.30 (d, J=1.3 Hz, 1 H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[CH2:8][CH2:7][CH2:6]2.[C:14]1([NH:20][C:21]2[N:30]=[CH:29][CH:28]=[CH:27][C:22]=2[C:23](OC)=[O:24])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:9]3[N:20]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:21]4[C:22]([C:23](=[O:24])[C:8]=3[CH2:7][CH2:6][C:5]=2[CH:4]=1)=[CH:27][CH:28]=[CH:29][N:30]=4
Reactant: COc1ccc2c(c1)CCCC2=O
Reactant: COC(=O)c1cccnc1Nc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COc1ccc2c(c1)CCc1c-2n(-c2ccccc2)c2ncccc2c1=O
Reaction time: 8 h

Procedure:
For example, with 3,4-dihydro-6-methoxy-1-naphthalenone as the ketone and methyl 2-phenylaminonicotinate as the arylaminonicotinate, the 1,3-diketone,3,4-dihydro-6-methoxy-2-[[2-(phenylamino)-3-pyridinyl]-carbonyl]-1(2H)-napthalenone, results from the process of Example 8. To cyclize, reflux 9 g of the diketone in 400 ml of toluene containing a catalytic amount of p-toluenesulfonic acid. Collect the evolved water in a Dean-Stark trap. Remove the heat after 21/2 hours and allow the mixture to stand overnight. Distill the toluene under vacuum on a steam bath and crystallize the residue from acetonitrile, to provide the product 5,6-dihydro-3-methoxy-12-phenylnaphtho[1,2-b][1,8]naphthyridin-7(12H)-one, m.p. 234°-237.5° C., after crystallization from CH3CN.
Reaction SMILES: N[C:2]1[C:24](Cl)=[CH:23][C:5]([C:6]([NH:8]CC2CCN(CCCCCCN)CC2)=[O:7])=[C:4](OC)[CH:3]=1.C1(N=C=O)C=CC=CC=1>CN(C)C=O.C(Cl)Cl>[C:6]([NH2:8])(=[O:7])[C:5]1[CH:23]=[CH:24][CH:2]=[CH:3][CH:4]=1
Reactant: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCCCN)CC1
Solvent: ClCCl
Solvent: O=C=Nc1ccccc1
Solvent: CN(C)C=O
Product: NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
4-Amino-N-(1-(6-aminohexyl)piperidin-4-ylmethyl)-5-chloro-2-methoxybenzamide (1.00 g) was dissolved in dimethylformamide (15 ml). A solution of phenyl isocyanate (0.30 ml) in methylene chloride was dropwise added under ice-cooling. The mixture was stirred at room temperature for 12 hr. and the reaction mixture was concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography to give 0.30 g of 4-amino-5-chloro-2-methoxy-N-(1-(6-phenylureido)hexyl)piperidin-4-ylmethyl)benzamide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])[NH:10][N:9]=1.[CH3:23]I>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([CH3:23])[N:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:20])[F:21])[N:12]=1
Reactant: FC(F)(F)c1ccccc1-c1nc(-c2ccccc2Cl)n[nH]1
Reactant: CI
Product: Cn1nc(-c2ccccc2C(F)(F)F)nc1-c1ccccc1Cl

Procedure:
starting from 3-(o-chlorophenyl)-5-(o-trifluoromethyl-phenyl)-1H-1,2,4-triazole and methyl iodide there is obtained a mixture of isomeric N-methyltriazoles and therefrom there are obtained pure 5-(o-chlorophenyl)-1-methyl-3-(o-trifluoromethyl-phenyl)-1H-1,2,4-triazole as a resinous product, 1H-NMR(CDCl3): 3.86 (s, CH3); and pure 3-(o-chlorophenyl)-1-methyl-5-(o-trifluoromethyl-phenyl)-1H-1,2,4-triazole, m.p. 90°-92° C., 1H-NMR(CDCl3): 3.78 (s, CH3);
Reaction SMILES: [N:1]([C:4]1([C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([OH:45])([P:37]([O:42][O:43][CH3:44])([O:39][O:40][CH3:41])=[O:38])[P:29]([O:34][O:35][CH3:36])([O:31][O:32][CH3:33])=[O:30])=[O:22])[C:19](=[O:20])[N:6]2[C:7]([C:16]([OH:18])=[O:17])=[C:8]([CH2:11][O:12][C:13](=[O:15])[NH2:14])[CH2:9][S:10][C@H:5]12)=[N+]=[N-].[H][H]>[Pt]=O>[NH2:1][C:4]1([C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([OH:45])([P:37]([O:42][O:43][CH3:44])([O:39][O:40][CH3:41])=[O:38])[P:29]([O:34][O:35][CH3:36])([O:31][O:32][CH3:33])=[O:30])=[O:22])[C:19](=[O:20])[N:6]2[C:7]([C:16]([OH:18])=[O:17])=[C:8]([CH2:11][O:12][C:13](=[O:15])[NH2:14])[CH2:9][S:10][C@H:5]12
Reactant: [H][H]
Reactant: COOP(=O)(OOC)C(O)(CCCCNC(=O)C1(N=[N+]=[N-])C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@@H]21)P(=O)(OOC)OOC
Agent: O=[Pt]
Product: COOP(=O)(OOC)C(O)(CCCCNC(=O)C1(N)C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@@H]21)P(=O)(OOC)OOC

Procedure:
The 7-azido-7-{[5-hydroxy-5,5-bis(dimethoxyphosphono)-1-pentylamino]-carbonyl}-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid, obtained as described in Example 30, is hydrogenated at atmospheric pressure with hydrogen in the presence of platinum oxide as catalyst and gives 7-amino-7-{[5-hydroxy-5,5-bis(dimethoxyphosphono)-1-pentylamino]-carbonyl}-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid. Reaction of the latter with 2-thienylacetyl chloride and pyridine yields 7-(2-thienyl-acetamido)-7-{[5-hydroxy-5,5-bis(dimethoxyphosphono)-1-pentylamino]-carbonyl}-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid.
Reaction SMILES: [CH:1]1([C:4]2[NH:5][C:6]3[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=3[N:8]=2)[CH2:3][CH2:2]1.Cl[C:14]1[N:15]=[C:16]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[C:17]2[N:23]=[C:22]([CH2:24][N:25]3[CH2:30][CH2:29][CH:28]([C:31]([OH:34])([CH3:33])[CH3:32])[CH2:27][CH2:26]3)[CH:21]=[CH:20][C:18]=2[N:19]=1>>[CH:1]1([C:4]2[N:5]([C:14]3[N:15]=[C:16]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:17]4[N:23]=[C:22]([CH2:24][N:25]5[CH2:30][CH2:29][CH:28]([C:31]([OH:34])([CH3:33])[CH3:32])[CH2:27][CH2:26]5)[CH:21]=[CH:20][C:18]=4[N:19]=3)[C:6]3[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=3[N:8]=2)[CH2:3][CH2:2]1
Reactant: CC(C)(O)C1CCN(Cc2ccc3nc(Cl)nc(N4CCOCC4)c3n2)CC1
Reactant: c1ccc2[nH]c(C3CC3)nc2c1
Product: CC(C)(O)C1CCN(Cc2ccc3nc(-n4c(C5CC5)nc5ccccc54)nc(N4CCOCC4)c3n2)CC1

Procedure:
Following General Procedure C, 2-cyclopropyl-benzimidazole and 2-(1-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol from Example 8 were reacted to give 102. LCMS (MH+)=528.3. 1H-NMR (DMSO-d6): δ 8.19 (d, 1H), 8.03 (m, 1H), 7.89 (d, 1H), 7.44 (m, 1H), 7.23 (m, 2H), 4.56 (s, 4H), 4.01 (s, 1H), 3.83 (m, 4H), 3.74 (2, 2H), 2.94 (m, 3H), 1.99 (m, 2H), 1.67 (m, 2H), 1.29 (m, 2H), 1.16 (m, 3H), 1.08 (m, 2H), 1.04 (s, 6H)
Reaction SMILES: C([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11](/[CH:14]=[CH:15]\[C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24]C(C)(C)C)=[O:23])=[CH:18][CH:17]=2)=[CH:10][CH:9]=1)=[O:7])(C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:11]1(/[CH:14]=[CH:15]\[C:16]2[CH:17]=[CH:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][CH:21]=2)[CH:10]=[CH:9][C:8]([C:6]([OH:7])=[O:5])=[CH:13][CH:12]=1
Reactant: CC(C)(C)OC(=O)c1ccc(/C=C\c2ccc(C(=O)OC(C)(C)C)cc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: O=C(O)c1ccc(/C=C\c2ccc(C(=O)O)cc2)cc1
Yield: 98.6 %

Procedure:
331 g of Z-4,4'-Stilbene-dicarboxylic acid di-tert.-butyl ester in 1700 ml of absolute toluene are boiled under reflux for 3 hours together with 10.3 g of p-toluene sulphonic acid. The reaction mixture is then concentrated by evaporation and boiled under reflux for 4 hours with 104.2 g of NaOH, 1300 ml of H2O and 1300 ml of ethanol. The reaction mixture is filtered hot after the addition of active charcoal, diluted with about 3 l of H2O and extracted twice, in each case with 1 l of CH2Cl2. Concentrated HCl is then added to the aqueous phase. 230 g of Z-4,4'-stilbene dicarboxylic acid are obtained after suction filtration and drying.
Reaction SMILES: [OH:1][B:2]1[C:6]2[CH:7]=[C:8]([OH:12])[CH:9]=[C:10]([CH3:11])[C:5]=2[CH:4]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[O:3]1.Cl[C:20]1[S:21][C:22]([C:25]#[N:26])=[CH:23][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:25]([C:22]1[S:21][C:20]([O:12][C:8]2[CH:9]=[C:10]([CH3:11])[C:5]3[CH:4]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[O:3][B:2]([OH:1])[C:6]=3[CH:7]=2)=[N:24][CH:23]=1)#[N:26]
Reactant: CCOC(=O)CC1OB(O)c2cc(O)cc(C)c21
Reactant: N#Cc1cnc(Cl)s1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC1OB(O)c2cc(Oc3ncc(C#N)s3)cc(C)c21
Temperature: 70 °C
Yield: 80 %

Procedure:
To a mixture of ethyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (3.75 g, 15 mmol, 1 eq.) and 2-chlorothiazole-5-carbonitrile (3.25 g, 22.5 mmol, 1.5 eq.) in 100 ml DMF was added cesium carbonate (14 g, 45 mmol, 3 eq.). The reaction was heated at 70° C. for two hours. It was then quenched by water, extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude was purified by column chromatography (4.3 g, yield 80%). MS (ESI) m/z=717 [2M+H]+.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3](=O)[CH2:4][CH2:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)(=O)C.CO>[CH3:28][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]([C:7]1[CH:8]=[CH:9][C:10]([N:13]2[CH2:14][CH2:15][N:16]([CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:17][CH2:18]2)=[CH:11][CH:12]=1)[OH:26]
Reactant: CN(C)C(=O)CCC(=O)c1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CN(C)CCCC(O)c1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Yield: 61 %

Procedure:
Prepared analogously to example A51 from N,N-dimethyl-γ-oxo-4-[4-(phenylmethyl)-1-piperazinyl]-benzenebutanoic acid amide by reduction with lithium aluminium hydride in a yield of 61% of theory. Colourless, amorphous substance of Rf=0.62 (eluant: ethyl acetate/methanol 1/1 v/v).
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([NH:9][C:10]([NH:12][C:4]2=[CH:3][CH:2]=1)=O)=[O:8].[Li]C(C)(C)C.C(=O)=O>C1COCC1.CCOC(C)=O>[CH:1]1[CH:2]=[CH:3][C:4]2[N:12]=[CH:10][NH:9][C:7](=[O:8])[C:5]=2[CH:6]=1
Reactant: O=c1[nH]c(=O)c2ccccc2[nH]1
Agent: O=C=O
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=c1[nH]cnc2ccccc12
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 136.8 %

Procedure:
The quinazoline 1 (1.5 g, 3.0 mmol) was dissolved in THF (150 mL). After cooling to −78° C., t-BuLi (1.7 M in heptane, 1.76 mL) was added dropwise. After stirring for 10 min at −78° C., CO2 (crushed) was added to the solution, then warmed up to RT and stirred for 30 min. Quenched the reaction with H2O (100 mL), diluted with EtOAc (100 mL), The organic layer was dried, concentrated, purified by flash chromatography (1%-10% MeOH/DCM) to obtain 2 (600 mg, 43% yield).
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[N:11]1([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12]1.[CH3:30]I.[Cl-].[NH4+]>C1COCC1>[CH3:30][C:13]1([C:16]([O:18][CH3:19])=[O:17])[CH2:14][CH2:15][N:11]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:12]1
Reactant: CI
Reactant: COC(=O)C1CCN(C(=O)OCc2ccccc2)C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)C1(C)CCN(C(=O)OCc2ccccc2)C1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 74.9 %

Procedure:
Lithium bis(trimethylsilyl)amide (16.4 mL, 16.4 mmol) was added to 1-benzyl 3-methyl pyrrolidine-1,3-dicarboxylate (3.45 g, 13.1 mmol) in THF (20 mL) at −78° C., and the reaction was stirred at −78° C. for 20 minutes. MeI (1.10 mL, 17.7 mmol) was added, and the reaction was warmed to room temperature. After 2 hours at room temperature, the mixture was poured onto saturated ammonium chloride (20 mL), extracted with ether, washed with brine and dried over sodium sulfate. After removal of the solvent, the residue was purified by chromatography (hexane:ethyl acetate, 4:1) to give 1-benzyl 3-methyl 3-methylpyrrolidine-1,3-dicarboxylate (2.72 g, 75% yield) as an oil.
Reaction SMILES: [CH2:1]([SH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]#[N:19])[N:13]=1.C(OCC)(=O)C>C1COCC1.[Cl-].[Na+].O>[CH2:1]([S:8][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]#[N:19])[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#Cc1cccc(Cl)n1
Reactant: SCc1ccccc1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: N#Cc1cccc(SCc2ccccc2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
Benzyl mercaptan (0.99 g, 7.94 mmol) and sodium hydride (60% in oil, 0.35 g, 8.66 mmol) were added to THF (30 ml), and the mixture was stirred at room temperature for 1 hr. A solution of 2-chloro-6-cyanopyridine (1.00 g, 7.22 mmol) in THF (10 ml) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 18 hrs. The reaction mixture was combined with ethyl acetate and brine. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give the titled compound (1.63 g, 100%) as a pale pink oil.
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][N:5]=[C:6]([C:11]1[CH:15]=[N:14][S:13][N:12]=1)[C:7]([O:9]C)=[O:8]>CO>[CH3:3][O:4][N:5]=[C:6]([C:11]1[CH:15]=[N:14][S:13][N:12]=1)[C:7]([OH:9])=[O:8]
Reactant: CON=C(C(=O)OC)c1cnsn1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CON=C(C(=O)O)c1cnsn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
An aqueous solution of 1 N sodium hydroxide (5.4 ml.) was added with stirring at ambient temperature to a solution of methyl 2-methoxyimino-2-(1,2,5-thiadiazol-3-yl)acetate (syn isomer) (0.9 g.) in methanol (10 ml.) and the mixture was stirred for 1 hour at ambient temperature. Methanol was distilled off and water was added to the residue, after which the mixture was washed with ether. The aqueous layer was adjusted to pH 1.5 with 10% hydrochloric acid, subjected to salting-out and extracted with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. Ether was distilled off. Benzene was added to the residue and removed to give crystals of 2-methoxyimino-2-(1,2,5-thiadiazol-3-yl)acetic acid (syn isomer) (0.67 g.), mp 99° to 100° C.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:7]([CH2:16][CH3:17])[C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3)=O.[C:18]1([CH:24](P([O-])(OCC)OCC)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C)([O-])C.[K+]>CN(C=O)C>[C:18]1([C:24]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:1][C:3]2[CH:4]=[CH:5][C:6]3[N:7]([CH2:16][CH3:17])[C:8]4[C:13]([C:14]=3[CH:15]=2)=[CH:12][CH:11]=[CH:10][CH:9]=4)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CCn1c2ccccc2c2cc(C=O)ccc21
Reactant: CCO[PH]([O-])(OCC)C(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCn1c2ccccc2c2cc(C=C(c3ccccc3)c3ccccc3)ccc21
Yield: 87.3 %

Procedure:
25.3 g (111.7 mmol) of 3-formyl-9-ethylcarbazole (2') (manufactured by Tokyo Kasei Kogyo Co.), 39.6 g (122.9 mmol) of diethyl diphenylmethylphosphite, 253 ml of DMF and 15.04 g (134.0 mmol) of potassium-t-butoxide were allowed to react and after treated in the same manner as with Example 1 (2) to obtain 36.44 g of 3-(2',2'-diphenylvinyl)-9-ethylcarbazole.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.C1C=C(Cl)C=C(C(OO)=[O:17])C=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N+:3]=1[O-:17]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1ccnc(Cl)c1
Solvent: ClCCl
Product: Cc1cc[n+]([O-])c(Cl)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 88.8 %

Procedure:
2-Chloro-4-methylpyridine (1 g, 7.84 mmol) was dissolved in DCM (10 ml), cooled to 0° C., mCPBA (70%, 2.32 g, 9.41 mmol) was added and the mixture was stirred at 0° C. for several hours and allowed to reach room temperature overnight. The mixture was diluted with DCM and washed with saturated Na2S2O3 solution and saturated sodium bicarbonate solution. After drying (sodium sulfate) and concentration under reduced pressure, 1.0 g of a yellow oil was obtained (6.27 mmol, 80%) MS(ESI) m/z=144.0 [M+1]+.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([C:9]([OH:18])([C:14]([F:17])([F:16])[F:15])[C:10]([F:13])([F:12])[F:11])[CH:6]=[C:5]([CH3:19])[C:3]=1[NH2:4].[N+:20]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26](Cl)=[O:27])([O-:22])=[O:21].N1C=CC=CC=1.C(=O)([O-])O.[Na+]>O.C(OCC)(=O)C.O1CCCC1>[CH3:1][C:2]1[CH:8]=[C:7]([C:9]([OH:18])([C:10]([F:12])([F:13])[F:11])[C:14]([F:15])([F:16])[F:17])[CH:6]=[C:5]([CH3:19])[C:3]=1[NH:4][C:26](=[O:27])[C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([N+:20]([O-:22])=[O:21])[CH:24]=1
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: Cc1cc(C(O)(C(F)(F)F)C(F)(F)F)cc(C)c1N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1cc(C(O)(C(F)(F)F)C(F)(F)F)cc(C)c1NC(=O)c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Yield: 98.7 %

Procedure:
At room temperature, 5.0 g of 2,6-dimethyl-4-[1-hydroxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]aniline, 3.9 g of 3-nitrobenzoyl chloride and 2.1 g of pyridine were introduced to 50 ml of tetrahydrofuran in a reactor, and the mixture was stirred at room temperature. After the loss of the starting material was confirmed through TLC, a saturated sodium hydrogen carbonate solution was added to the reaction solution and the solution was stirred for a while. Subsequently, ethyl acetate and water were added to the reaction solution, and phase separation was carried out. The separated organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and dried, and thus obtained residue was grinded to give 7.5 g (yield 95%) of the title compound as a powder form.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[Na+].[C:17](NC1C=CC(O)=CC=1)(=[O:19])[CH3:18].CC(C)=O.C(Cl)(Cl)Cl>>[NH:1]([C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=[O:9])=[CH:13][CH:14]=1)[C:17]([CH3:18])=[O:19]
Reactant: CC(=O)Nc1ccc(O)cc1
Reactant: CC(C)(Oc1ccc(N)cc1)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CC(C)=O
Product: CC(=O)Nc1ccc(OC(C)(C)C(=O)O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60 %

Procedure:
FIG. 2A illustrates a reaction scheme for preparing 2-(4-aminophenoxy)-2-methyl propionic acid, a compound that is useful as a precursor in the preparation of Group I compounds. In accordance with the scheme of FIG. 2A, 8 grams (g) (0.2 mol) of pulverized sodium hydroxide is added to a suspension of 5.28 g (0.035 mol) of p-acetamidophenol in 23 ml (0.4 mol) of acetone. The reaction mixture is stirred at room temperature for 1/2 hour. Subsequently, 3.58 g (0.03 mol) of chloroform is added dropwise over the course of 30 minutes. The reaction mixture is stirred overnight at room temperature and acetone is removed under vacuum. The residue is dissolved in water (10 ml), followed by acidification with 37% hydrochloric acid (HCl) to produce a pale yellow precipitate of 2-(4-acetaminophenoxy)-2-methyl propionic acid (5 g, 60% yield), crystallized from methanol, mp 69°-71° C.
Reaction SMILES: [Mg:1].[S:2]([O-:6])([O-:5])(=[O:4])=[O:3].[Mg+2]>>[S:2]([O-:6])([O-:5])(=[O:4])=[O:3].[Mg+2:1].[OH2:3].[S:2]([O-:6])([O-:5])(=[O:4])=[O:3].[Mg+2:1]
Reactant: [Mg]
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Product: O

Procedure:
The reaction product obtained by the reaction of ammonium sulfate with the metal oxide or hydroxide in which the metal is magnesium is usually an aqueous solution or slurry of magnesium sulfate in a concentration of at least 15% by weight. If this aqueous solution or slurry is fed to the next step as such, the energy for dehydration is consumed greatly. This is not industrially desirable. Usually, anhydrous magnesium sulfate and magnesium sulfate monohydrate are obtained by dehydrating magnesium heptahydrate by heating it in an open system, hot air drying, etc. It is well known that the energy consumed for evaporating and removing the water of crystallization is very great.