Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]([CH3:10])([CH2:6][CH2:7][O:8][CH3:9])[CH2:3][C:4]#[CH:5].N1C=CN=C1.CN(C)C=O.[CH3:21][Si:22]([CH3:25])([CH3:24])Cl>CCCCCC>[CH3:10][C:2]([O:1][Si:22]([CH3:25])([CH3:24])[CH3:21])([CH2:6][CH2:7][O:8][CH3:9])[CH2:3][C:4]#[CH:5]
Reactant: C[Si](C)(C)Cl
Reactant: C#CCC(C)(O)CCOC
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: C#CCC(C)(CCOC)O[Si](C)(C)C

Procedure:
To a solution of 13 g. (0.091 moles) of 4-hydroxy-4-methyl-7-oxa-1-octyne and 16 g. (0.235 moles) of imidazole in 80 ml. of dry dimethylformamide is added dropwise, at 5° C. under nitrogen with stirring, 12.5 ml. (0.115 moles) of trimethylchlorosilane. After an additional 15 minutes at 5° C. the solution is stirred at ambient temperature for 18 hours then added to 450 ml. of hexane. The resulting solution is washed with ice-cold water, ice-cold saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness in vacuo. Distillation of the residual oil furnishes 16.8 g. (86%) of product; b.p. 87°-88° C. (7 mm.).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[S:12])[CH:6]2[CH3:13])#[N:2].[Cl:14]N1C(=O)CCC1=O>C(Cl)Cl>[Cl:14][C:6]1([CH3:13])[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([C:1]#[N:2])[CH:4]=2)[NH:8][C:7]1=[S:12]
Reactant: CC1C(=S)Nc2ccc(C#N)cc21
Reactant: O=C1CCC(=O)N1Cl
Solvent: ClCCl
Product: CC1(Cl)C(=S)Nc2ccc(C#N)cc21

Procedure:
A solution of 5-cyano-3-methylthiooxindole (950 mg, 4.66 mmol) and N-chlorosuccinimide (800 mg, 5.95 mmol) in 100 ml of methylene chloride was stirred at room temperature for 24 hours. The solvent was removed in vacuo, yielding 3-chloro-5-cyano-3-methylthiooxindole and the residue, which was dissolved in a minimum of tetrahydrofuran, was added to a vigorously stirred slurry of red mercuric oxide (1.00 g, 4.7 mmol) and boron trifluoride ethereate (670 mg, 4.7 mmol) in 100 ml of 50 percent aqueous tetrahydrofuran. After 2 hours, the reaction mixture was filtered through a pad of Celite. The pad was washed with three 100-ml portions of chloroform. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was chromatographed on silica gel. Elution with chloroform-ethanol (9:1 v/v) gave 5-cyanoisatin as an orange solid (525 mg, 65%), mp 270°-272° (dec); ir (KBr) 3100 (NH), 2220 (C≡N), 1730 (C=O) and 1710 cm-1 (C=O); nmr (DMSO-d6)τ-1.30 (1H, b s, NH), 2.00 (d of d, 1H, J4,6 =2 Hz, J6,7 =8.5 Hz, H6), 2.10 (d, 1H, J4,6 =2 Hz, H4), and 2.90 (d, 1H, J6,7 =8.5 Hz, H7); mass spectrum, m/e obs. 172.0238 (calc. 172.0272).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:6][CH:5]([CH2:7][CH2:8]O)[CH2:4][O:3]1.C(Br)(Br)(Br)[Br:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)Br>ClCCl>[Br:12][CH2:8][CH2:7][CH:5]1[CH2:4][O:3][C:2]([CH3:10])([CH3:1])[O:6]1
Reactant: CC1(C)OCC(CCO)O1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: BrC(Br)Br
Product: CC1(C)OCC(CCBr)O1
Temperature: 25 °C
Reaction time: 1.75 h

Procedure:
To a solution of 2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-ethanol (292 mg, 2 mmol) in dichloromethane (20 mL) at 0° C. was added carbon tetrabromide (796 mg, 2.4 mmol) and polymer-supported triphenyl phosphine (1 g, 3 mmol). After stirring for 1.75 hours and slowly warming to room temperature, the reaction mixture was filtered through Celite and rinsed with additional dichloromethane. The filtrate was concentrated to give the product as a mixture of product and bromoform (2:1). MS (DCI) m/e 208 (M+NH4—H2O)+; 1H NMR (300 MHz, DMSO-d6) □ 4.15 (m, 1H), 4.02 (dd, J=8.1, 6.1 Hz, 1H), 3.47-3.62 (m, 3H), 1.94-2.09 (m, 2H), 1.32 (s, 3H), 1.26 (s, 3H).
Reaction SMILES: C(OC([NH:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[N:25]=[C:24]([NH:26][C:27]3[NH:28][N:29]=[C:30]([CH3:32])[CH:31]=3)[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)=[CH:11][CH:10]=1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[N:25]=[C:24]([NH:26][C:27]3[NH:28][N:29]=[C:30]([CH3:32])[CH:31]=3)[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)=[CH:11][CH:10]=1
Reactant: Cc1cc(Nc2nc(Nc3ccc(NC(=O)OC(C)(C)C)cc3)nc3ccccc23)[nH]n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(Nc2nc(Nc3ccc(N)cc3)nc3ccccc23)[nH]n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of [2-(4-tert-Butoxycarbonylamino-phenylamino)-quinazolin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amine (IIc-60, 100 mg, 0.232 mmol) in a mixture of DCM/TFA (5/1, 12 mL) was stirred for 2 hours at room temperature. The solvents were removed in vacuo and the residue triturated in aqueous K2CO3. The resulting solid was collected by filtration and washed with diethyl ether to afford IIc-66 (69 mg, 90%) as an off-white solid, mp 164-167° C.; 1H NMR (DMSO) δ2.24 (3H, s), 6.33 (1H, br s), 7.12 (2H, d), 7.48 (3H, m), 7.58 (1H, d), 7.86 (1H, t), 8.64 (1H, d), 10.86 (1H, br s), 11.46 (1H, s); IR (solid) 1681, 1512, 1496, 1433, 1415, 1187, 1129; MS 332.4 (M+H)+
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])=[C:4](F)[CH:3]=1.[C-:15]#[N:16].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])=[C:4]([C:15]#[N:16])[CH:3]=1
Reactant: CN(C)S(=O)(=O)c1ccc(Br)cc1F
Reactant: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C)S(=O)(=O)c1ccc(Br)cc1C#N
Yield: 7.1 %

Procedure:
4-Bromo-2-fluoro-N,N-dimethylbenzenesulfonamide (1.0 g, 3.5 mmol) and sodium cyanide (350 mg, 7.1 mmol) were dissolved in DMF (3 mL) and irradiated in the microwave at 150° C. for 20 minutes. DMF was removed in vacuo and the residue was redissolved in dichloromethane (5 mL). The organics were washed with 5 mL of each 1N aqueous HCl, saturated aqueous NaHCO3, and brine. Organics were dried over Na2SO4 and evaporated to dryness. Crude product was purified by chromatography on silica gel (eluting with 0-50% ethyl acetate in hexanes) to afford 4-bromo-2-cyano-N,N-dimethylbenzenesulfonamide (72 mg, 7%). ESI-MS m/z calc. 288.0, found 288.9 (M+1)+; retention time 1.44 minutes.
Reaction SMILES: [F:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([O:16][CH3:17])=[C:12]([CH:15]=2)[CH:13]=O)=[CH:4][CH:3]=1.[C:18]([O:22][C:23](=[O:33])[N:24]([CH:26]1[CH2:31][CH2:30][CH:29]([NH2:32])[CH2:28][CH2:27]1)[CH3:25])([CH3:21])([CH3:20])[CH3:19]>>[C:18]([O:22][C:23](=[O:33])[N:24]([CH:26]1[CH2:27][CH2:28][CH:29]([NH:32][CH2:13][C:12]2[CH:15]=[C:8]([C:5]3[CH:6]=[N:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH:9]=[CH:10][C:11]=2[O:16][CH3:17])[CH2:30][CH2:31]1)[CH3:25])([CH3:21])([CH3:19])[CH3:20]
Reactant: CN(C(=O)OC(C)(C)C)C1CCC(N)CC1
Reactant: COc1ccc(-c2ccc(F)nc2)cc1C=O
Product: COc1ccc(-c2ccc(F)nc2)cc1CNC1CCC(N(C)C(=O)OC(C)(C)C)CC1

Procedure:
Following the synthetic protocol described in Method C′; {4-[5-(6-Fluoro-pyridin-3-yl)-2-methoxy-benzylamino]-cyclohexyl}-methyl-carbamic acid tert-butyl ester is prepared starting from 5-(6-Fluoro-pyridin-3-yl)-2-methoxy-benzaldehyde and (4-Amino-cyclohexyl)-methyl-carbamic acid tert-butyl ester. The desired product is isolated in 84%.
Reaction SMILES: [CH:1]1[C:6]([C@@H:7]2[O:16]C3C=C(O)C=[C:11](O)[C:10]=3[CH2:9][C@@H:8]2[OH:19])=[CH:5][C:4]([OH:20])=[C:3]([OH:21])[CH:2]=1.[C:22]([OH:33])(=[O:32])C1C=C(O)C(O)=C(O)C=1.[OH:34]O>CC(C)=O>[CH:11]1[C:1]2[C:6](=[C:5]([OH:34])[C:4]([OH:20])=[C:3]([OH:21])[CH:2]=2)[C:7](=[O:16])[C:8]([OH:19])=[C:9]([C:22]([OH:33])=[O:32])[CH:10]=1
Reactant: O=C(O)c1cc(O)c(O)c(O)c1
Reactant: OO
Reactant: Oc1cc(O)c2c(c1)O[C@@H](c1ccc(O)c(O)c1)[C@@H](O)C2
Solvent: CC(C)=O
Product: O=C(O)c1ccc2cc(O)c(O)c(O)c2c(=O)c1O

Procedure:
Epicatechin (EC) (0.5 g) and gallic acid (1 g) were dissolved in a mixture of acetone-pH 5.0 phosphate citrate buffer (1: 10, v/v, 50 mL), which contained 2 mg horseradish peroxidase. While being stirred, 2.0 mL of 3.13% H2O2 was added four times during 45 minutes. The reaction mixture was extracted by ethyl acetate (50 mL×3). After concentration, the residue was subjected to Sephadex LH 20 column eluted with acetone-water solvent system (45%). 70 mg epitheaflavic acid and 25 mg purpurogallin carboxylic acid were obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].I[CH2:25][CH2:26][F:27]>O1CCCC1>[F:27][CH2:26][CH2:25][N:21]1[CH2:20][CH2:19][N:18]([CH:15]2[CH2:14][CH2:13][N:12]([C:5]3[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:17][CH2:16]2)[CH2:23][CH2:22]1
Reactant: COc1cc(N2CCC(N3CCNCC3)CC2)ccc1[N+](=O)[O-]
Reactant: FCCI
Solvent: C1CCOC1
Product: COc1cc(N2CCC(N3CCN(CCF)CC3)CC2)ccc1[N+](=O)[O-]
Temperature: 85 °C
Reaction time: 8 h
Yield: 77.5 %

Procedure:
To a solution of 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine (intermediate 8120, 18.03 g, 56.10 mmol and 2.23 g, 6.96 mmol from separate batches) in tetrahydrofuran was added 1-Iodo-2-fluoroethane (7.38 mL, 90.79 mmol). The reaction was stirred at 85° C. overnight. The solution was transferred to a sealed tube. Upon addition of 1-Iodo-2-fluoroethane (7.38 mL, 90.79 mmol), the reaction was stirred at 85° C. for an additional 5 hours. The solvent was removed in vacuo and the residue was taken up in water and extracted with dichloromethane (×3), dried with magnesium sulfate, filtered and concentrated. Purification by flash chromatography provided 1-(2-fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine (15.94 g, 43.50 mmol, 69%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (qd, J=11.9, 3.7 Hz, 2 H) 1.79 (d, J=10.8 Hz, 2 H) 2.32-2.42 (m, J=7.0, 3.7 Hz, 9 H) 2.52 (dt, JHF=28.6 Hz, J=4.9 Hz 2 H) 2.86-2.95 (m, 2H) 3.85 (s, 3 H) 3.99 (d, J=13.4 Hz, 2 H) 4.46 (dt, JHF=47.8 Hz J=4.9 Hz 2 H), 6.45 (d, J=2.4 Hz, 1 H) 6.54 (dd, J=9.5, 2.6 Hz, 1 H) 7.82 (d, J=9.3 Hz, 1 H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[OH:27])([CH3:20])[CH3:19])[C:12]2=[O:28])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:37][CH2:38][N:39]([CH3:50])[C:40](=[O:49])[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(#N)C>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]([CH3:20])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH2:37][CH2:38][N:39]([CH3:50])[C:40]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:49])[CH3:19])[C:12]2=[O:28])[CH:5]=1
Reactant: CN(CCCl)C(=O)OCc1ccccc1
Reactant: COC(=O)c1ccc(C)c(-n2ccnc(NC(C)(C)c3ccccc3O)c2=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccc(C)c(-n2ccnc(NC(C)(C)c3ccccc3OCCN(C)C(=O)OCc3ccccc3)c2=O)c1
Temperature: 85 °C
Reaction time: 48 h
Yield: 53.1 %

Procedure:
To 3-[3-[[1-(2-Hydroxyphenyl)-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl ester (Example 220b, 2.495 g) in acetonitrile (150 mL) was added potassium carbonate (1.753 g) followed by benzyl 2-chloroethyl(methyl)carbamate (J. Med. Chem., 1992, 35 (17), 3246, 1.660 g) and the reaction heated at 85° C. for 72 h under nitrogen. Further benzyl 2-chloroethyl(methyl)carbamate (0.58 g) and potassium carbonate (0.35 g) were added and the reaction stirred for 2 days. The reaction mixture was cooled, evaporated to dryness and the residue partitioned between water and dichloromethane and the organic layer separated. The aqueous was further extracted with dichloromethane (2×) and the combined organics dried (Na2 SO4) and evaporated. Purification (SiO2 chromatography eluting with 40-100% ethyl acetate) gave the subtitle product (1.97 g).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:9].[S:10](Cl)(Cl)=O.O>N1C=CC=CC=1>[CH3:9][C:3]1[C:2]2=[N:1][S:10][N:8]=[C:7]2[CH:6]=[CH:5][CH:4]=1
Reactant: Cc1cccc(N)c1N
Reactant: O=S(Cl)Cl
Solvent: c1ccncc1
Solvent: O
Product: Cc1cccc2nsnc12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 90.7 %

Procedure:
To a solution of 2,3-diaminotoluene (5.0 g, 40.9 mmol) in pyridine (40 mL) at 0° C. was added thionyl chloride (7.0 mL, 98.2 mmol) dropwise. The reaction mixture was stirred at 0° C. for 30 mins, then water (200 n-L) was added. The solution was extracted with dicholomethane (2×250 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give compound 839A (5.57 g) as a dark brown liquid.
Reaction SMILES: [Br:1][C:2]1[C:3]2[C:4]3[C:15]([CH3:16])=[N:14][N:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:12](=[O:23])[C:5]=3[N:6]([CH3:11])[C:7]=2[CH:8]=[CH:9][CH:10]=1.[Br:24]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>>[Br:1][C:2]1[C:3]2[C:4]3[C:15]([CH2:16][Br:24])=[N:14][N:13]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:12](=[O:23])[C:5]=3[N:6]([CH3:11])[C:7]=2[CH:8]=[CH:9][CH:10]=1
Reactant: Cc1nn(-c2ccccc2)c(=O)c2c1c1c(Br)cccc1n2C
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Product: Cn1c2cccc(Br)c2c2c(CBr)nn(-c3ccccc3)c(=O)c21
Reaction time: 15 h
Yield: 48 %

Procedure:
A solution of 10.1 g (27.1 mmol) of 9-bromo-1,5-dimethyl-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indol-4-one, of 6 g (34 mmol) of N-bromosuccinimide and of 0.46 g (2.8 mmol) of 2,2′-azobis(2-methylpropionitrile) is heated at reflux for 5 h. 3 g (17 mmol) of N-bromosuccinimide and 0.23 g (1.4 mmol) of 2,2′-azobis(2-methylpropionitrile) are again added. The mixture is heated at reflux for 2 h, left at room temperature for 15 h and again heated at reflux for 5 h. The mixture is concentrated under reduced pressure and the residue is taken up in water and extracted with ethyl acetate. The organic phase is dried, the solvent is evaporated under reduced pressure and the residue is purified by chromatography on a column of silica gel. 5.9 g (13 mmol) of product are isolated.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH:4]1[O:9][C:8]2[CH:10]=[CH:11][C:12]([OH:14])=[CH:13][C:7]=2[O:6][CH2:5]1.Cl[CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][C:26](=[O:30])[O:27]2)=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C.[I-].[Na+]>CN(C=O)C>[OH:14][C:12]1[CH:11]=[CH:10][C:8]2[O:9][CH:4]([CH2:3][N:2]([CH3:1])[CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]4[CH:24]=[CH:25][C:26](=[O:30])[O:27][C:28]=4[CH:29]=3)[CH2:5][O:6][C:7]=2[CH:13]=1
Reactant: CNCC1COc2cc(O)ccc2O1
Reactant: O=c1ccc2ccc(OCCCCl)cc2o1
Agent: [I-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(CCCOc1ccc2ccc(=O)oc2c1)CC1COc2cc(O)ccc2O1
Temperature: 96 °C
Yield: 24.9 %

Procedure:
N-Methyl-2,3-dihydro-6-hydroxy-1,4-benzodioxin-2-methanamine (3.68 g, 17.3 mmole), 7-(3-chloropropoxy)coumarin (4.15 g, 17.4 mmole), diisopropylethylamine (4.4 ml, 25.3 mmole) and sodium iodide (2.59 g, 17.3 mmole) were combined in 75 ml of DMF and heated at 96° C. for 26 hours under a nitrogen atmosphere. The solvent was then removed in vacuum and the residue was column chromatographed on silica gel using first 1% methanol/dichloromethane, then 2% methanol/dichloromethane as eluant. The product-containing fractions were combined and concentrated in vacuum and the residue crystallized from isopropanol with addition of 4N HCl/isopropanol and diethyl ether to give 1.71 g of white solid, monohydrochloride, quarter hydrate, m.p. 186°-193° C.
Reaction SMILES: [H-].[Na+].CO[C:5](=[O:15])[CH2:6][CH2:7][C:8]1[CH:9]=[N:10][C:11]([CH3:14])=[N:12][CH:13]=1.[CH:16](OC)=O.[NH2:20][C:21]([NH2:23])=[S:22]>COCCOC.C(OCC)C>[CH3:14][C:11]1[N:12]=[CH:13][C:8]([CH2:7][C:6]2[C:5](=[O:15])[NH:20][C:21](=[S:22])[NH:23][CH:16]=2)=[CH:9][N:10]=1
Reactant: COC(=O)CCc1cnc(C)nc1
Reactant: COC=O
Reactant: NC(N)=S
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: COCCOC
Product: Cc1ncc(Cc2c[nH]c(=S)[nH]c2=O)cn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 35.9 %

Procedure:
To the suspension of NaH, 60% (1.3 eq, 130 mg) in 600 μl of dry 1,2-dimethoxyethane, under argon atmosphere was carefully added, via syringe, a solution of 3-(2-Methyl-pyrimidin-5-yl)-propionic acid methyl ester (450 mg, 2.5 mmol, 1 eq) and methyl formate (4 eq, 616 μl) in 3 ml of dry 1,2-dimethoxyethane. The resulting suspension was stirred overnight (16 hours) at room temperature. In the reaction mixture was then added 3 ml of dry diethyl ether. The resulting precipitate was collected; it was washed with 3 ml of diethyl ether and dried. It was dissolved in 4 ml of absolute ethanol, thiourea (1.5 eq, 285 mg) was added and the reaction mixture was stirred at reflux under argon atmosphere for 8 hours. Solvent was then evaporated, the rest was dissolved in 3 ml of water and pH value of the solution was adjusted to 4.5-5 using 3N HCl water solution. The resulting precipitate was collected, it was washed with water and dried to afford 5-(2-Methyl-pyrimidin-5-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (210 mg, yield=35.9%, purity=95%) in form of white powder. MS: [M+H]+=235.17 1H NMR (300 MHz; DMSO-d6) δ/ppm 2.54 (s, 3H), 3.50 (s, 2H), 7.48 (s, 1H), 8.55 (s, 2H), 12.38 (br.s., 2H)
Reaction SMILES: [CH2:1]([Li])CCC.CCCCCC.[CH3:12][C:13]([CH3:33])([CH3:32])[C:14]#[C:15]/[CH:16]=[CH:17]/[CH2:18][N:19]([CH2:22][C:23]1[CH:24]=[C:25]([C:29](=O)[CH3:30])[CH:26]=[CH:27][CH:28]=1)[CH2:20][CH3:21]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:12][C:13]([CH3:33])([CH3:32])[C:14]#[C:15]/[CH:16]=[CH:17]/[CH2:18][N:19]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([CH3:1])=[CH2:30])[CH:24]=1)[CH2:20][CH3:21]
Reactant: [Li]CCCC
Reactant: CCN(C/C=C/C#CC(C)(C)C)Cc1cccc(C(C)=O)c1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCCCCC
Product: C=C(C)c1cccc(CN(CC)C/C=C/C#CC(C)(C)C)c1
Yield: 73.6 %

Procedure:
The procedure described in Example 9 was repeated, except that methyl triphenylphosphonium bromide (2.35 g; 6.6 mmol), n-butyl lithium in n-hexane (1.56 M: 4.2 ml; 6.6 mmol), and Compound 43 (1.3 g; 4.4 mmol) were used, to thereby yield 950 mg of the target compound (yield: 73.6%).
Reaction SMILES: [CH:1]([NH:14][C:15]([C:17]1[C:18]([OH:28])=[N:19][C:20]([N:23]2[CH:27]=[CH:26][CH:25]=[N:24]2)=[N:21][CH:22]=1)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].[I:56]I>C(#N)C>[CH:1]([NH:14][C:15]([C:17]1[C:18]([OH:28])=[N:19][C:20]([N:23]2[CH:27]=[C:26]([I:56])[CH:25]=[N:24]2)=[N:21][CH:22]=1)=[O:16])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: II
Reactant: O=C(NC(c1ccccc1)c1ccccc1)c1cnc(-n2cccn2)nc1O
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: CC#N
Product: O=C(NC(c1ccccc1)c1ccccc1)c1cnc(-n2cc(I)cn2)nc1O
Temperature: 85 °C
Reaction time: 16 h
Yield: 84 %

Procedure:
The product of step B, compound 1-1-b, (3.2 g, 8.6 mmol) was dissolved in acetonitrile (100 mL), and treated with CAN (6.62 g, 12.1 mmol) and I2 (1.42 g, 5.6 mmol). The reaction mixture was stirred for 16 h at 85° C. The resulting mixture was concentrated, diluted with 50 mL of water, stirred for 20 min and filtered. The solid filtrate was dried under vacuum to provide the product, 1-1-c (3.6 g, 84%). 1H NMR (300 MHz, DMSO-d6) δ 6.22-6.24 (d, J=6.6, 1H), 7.22-7.39 (m, 11H), 7.55-7.74 (m, 1H), 8.07 (m, 1H), 8.47 (m, 1H), 8.71 (s, 1H), 10.49 (s, 1H). LC-MS 498[MH]+.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[CH:9]1([CH2:12][NH2:13])[CH2:11][CH2:10]1.C(=O)([O-])[O-].[K+].[K+].CC(N(C)C)=O>O>[Cl:8][C:4]1[N:3]=[C:2]([NH:13][CH2:12][CH:9]2[CH2:11][CH2:10]2)[CH:7]=[N:6][CH:5]=1
Reactant: NCC1CC1
Reactant: Clc1cncc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: Clc1cncc(NCC2CC2)n1
Temperature: 80 °C
Reaction time: 23 h

Procedure:
A mixture of 2,6-dichloropyrazine (2.99 g), 1-cyclopropylmethanamine (2.14 g), potassium carbonate (4.14 g) and DMA (20 ml) was stirred at 80° C. for 23 hr. Water (15 mL) was added, and the mixture was extracted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. This was used without purification for the next reaction.
Reaction SMILES: [CH3:1][CH2:2][CH:3]([Cl:5])[Cl:4].C1C([Cl:12])=C(Cl)C=C(Cl)C=1OCCO.C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-][Cr](O[Cr]([O-])(=O)=O)(=O)=O>>[Cl:4][CH:3]([Cl:5])[CH:2]([Cl:12])[CH3:1].[Cl:4][C:3]([Cl:12])([Cl:5])[CH2:2][CH3:1]
Reactant: CCC(Cl)Cl
Reactant: OCCOc1cc(Cl)c(Cl)cc1Cl
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Product: CC(Cl)C(Cl)Cl
Product: CCC(Cl)(Cl)Cl

Procedure:
In the present process, dichloropropane is converted to a chlorinated alkene, e.g., TCPE, using a series of consecutive chlorination and dehydrochlorination steps. In one exemplary embodiment, PDC is fed to a liquid phase chlorination reactor, e.g., such as a batch or continuous stirred tank autoclave reactor with an internal cooling coil. A shell and multitube exchanger operating in plug flow, followed by vapor liquid disengagement tank or vessel can also be used. Suitable reaction conditions include, e.g., a temperature of from 30° C. to 150° C., a pressure of from 100 kPa to 2000 kPa. The reaction is carried out in the presence of one or more regioselective catalysts that provide a regioselectivity to, e.g., 1,1,2-trichloropropane of at least 5:1 over other trichloropropane isomers.
Reaction SMILES: [C:1]([CH:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:11]([CH3:16])([CH3:15])[CH2:10][CH2:9][C:8]([CH3:18])([CH3:17])[C:7]=2[CH:6]=1)[OH:4])#[CH:2].Br[C:20]1[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][CH:21]=1>>[OH:4][CH:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:11]([CH3:16])([CH3:15])[CH2:10][CH2:9][C:8]([CH3:18])([CH3:17])[C:7]=2[CH:6]=1)[C:1]#[C:2][C:20]1[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][CH:21]=1
Reactant: CS(=O)(=O)c1ccc(Br)cc1
Reactant: C#CC(O)c1ccc2c(c1)C(C)(C)CCC2(C)C
Product: CC1(C)CCC(C)(C)c2cc(C(O)C#Cc3ccc(S(C)(=O)=O)cc3)ccc21

Procedure:
Following the basic procedure of Example 32, by reacting 1.21 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 1.18 g (5 mmol) of 4-bromophenylsulfonylmethane, 610 mg (31%) of the expected sulfone compound, with a melting point of 112°-113° C., were obtained.
Reaction SMILES: [C:1]([S:5]([NH:7][CH:8]1[CH2:13][CH2:12][N:11](C(OCC)=O)[CH2:10][CH2:9]1)=[O:6])([CH3:4])([CH3:3])[CH3:2].[OH-].[Ba+2].[OH-]>CC(O)C.O.CO>[C:1]([S:5]([NH:7][CH:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1)=[O:6])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)N1CCC(NS(=O)C(C)(C)C)CC1
Agent: [Ba+2]
Agent: [OH-]
Solvent: CC(C)O
Solvent: CO
Solvent: O
Product: CC(C)(C)S(=O)NC1CCNCC1

Procedure:
In a mixture of 5 ml of 2-propanol and 5 ml of water, 378 mg of 4-t-butylsulfinylamino-1-ethoxycarbonyl piperidine was suspended and 1.77 g of barium hydroxide was added. The mixture was refluxed with stirring and heating for 4 hours. The mixture was diluted with methanol and the insoluble material was filtered off. The solvent was removed under reduced pressure to give 4-t-butylsulfinylaminopiperidine. Without purification, the obtained material was dissolved in 5 ml of THF, and 984 mg of N-phenoxycarbonyl-4-butyl aniline and 236 mg of diisopropyl ethylamine were added, followed by stirring at room temperature overnight. An aqueous solution of potassium hydrogen sulfate was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate anhydride. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography to give 291 mg of 4-t-butylsulfinylaminopiperidine-1-carboxylic acid(4-t-butylphenyl)amide.