Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1([CH2:15][OH:16])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[C:17](N1C=CN=C1)(N1C=CN=C1)=[O:18]>ClCCl>[CH2:8]([N:5]1[CH2:6][CH2:7][C:2]2([CH2:15][O:16][C:17](=[O:18])[NH:1]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: NC1(CO)CCN(Cc2ccccc2)CC1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: O=C1NC2(CCN(Cc3ccccc3)CC2)CO1
Yield: 89.5 %

Procedure:
1.04 g (4.72 mmol) of 4-amino-1-benzyl-4-hydroxymethylpiperidine (for preparation see: Eur. J. Med. Chim. Ther. (1974) 9, 424-433) are suspended in 16 ml of dichloromethane and 842 mg (5.2 mmol) of carbonyldiimidazole are added. As the reaction progresses, a solution forms, which following complete reaction is diluted with dichloromethane and washed first with water, then with a 5 percent sodium bicarbonate solution and once again with water. The organic phase is dried over sodium sulfate and freed from the solvent on a rotary evaporator. 1.04 g of the title compound are obtained as a crude product, which is reacted further as it is.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:28])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[S:17][C:18]([CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[C:19]([CH3:21])[CH:20]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1.[CH3:29][N:30]([CH3:35])[S:31](Cl)(=[O:33])=[O:32]>>[CH3:29][N:30]([CH3:35])[S:31](=[O:33])(=[O:32])[NH:1][CH2:2][CH:3]([OH:28])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[S:17][C:18]([CH2:22][N:23]([CH2:24][CH3:25])[CH2:26][CH3:27])=[C:19]([CH3:21])[CH:20]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1
Reactant: CCN(CC)Cc1sc(-c2nc(-c3ccc(CC(O)CN)cc3)no2)cc1C
Reactant: CN(C)S(=O)(=O)Cl
Product: CCN(CC)Cc1sc(-c2nc(-c3ccc(CC(O)CNS(=O)(=O)N(C)C)cc3)no2)cc1C
Yield: 33.1 %

Procedure:
The title compound (21 mg) is prepared in analogy to Example 166 starting from rac-1-amino-3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-propan-2-ol (50 mg, 125 μmol) and dimethylsulfamoyl chloride (22 mg, 150 μmol); LC-MS: tR=0.76 min; [M+1]+=508.18; 1H NMR (CDCl3): δ1.11 (t, J=7.0 Hz, 6H), 2.25 (s, 3H), 2.64 (q, J=7.0 Hz, 4H), 2.83 (s, 6H), 2.85-2.94 (m, 2H), 3.03-3.10 (m, 1H), 3.24-3.30 (m, 1H), 3.73 (s, 2H), 4.04-4.11 (m, 1H), 7.37 (d, J=8.3 Hz, 2H), 7.66 (s, 1H), 8.10 (d, J=8.3 Hz, 2H).
Reaction SMILES: [C:1]([C:4]1[N:9]=[CH:8][CH:7]=[CH:6][N:5]=1)(=O)[CH3:2].Cl.[NH2:11][OH:12].C(N(CC)CC)C.O>C(O)C>[C:1](=[N:11][OH:12])([C:4]1[N:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:2]
Reactant: NO
Reactant: CC(=O)c1ncccn1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCO
Product: CC(=NO)c1ncccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 136.3 %

Procedure:
A mixture of 2-acetylpyrimidine (2.90 g), hydroxylamine hydrochloride (2.48 g) and triethylamine (5.3 ml) in ethanol (40 ml) was stirred at room temperature overnight. The reaction mixture was poured into water, and extracted with methylene chloride. The organic layer was washed with a saturated aqueous ammonium sulfate solution and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain 2-acetylpyrimidine oxime (4.44 g) as colorless powder.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15](C(OC(C)(C)C)=O)[C:16]1[N:24]=[C:23]2[C:19]([N:20]=[CH:21][N:22]2[O:25][CH2:26][C@@H:27]([O:37][CH2:38][P:39]([O:44][CH2:45][CH3:46])([O:41][CH2:42][CH3:43])=[O:40])[CH2:28][O:29]CC2C=CC=CC=2)=[C:18]([O:47][CH3:48])[N:17]=1)=O)(C)(C)C.ClCCl.CO>ClCCl.[Pd]>[NH2:15][C:16]1[N:24]=[C:23]2[C:19]([N:20]=[CH:21][N:22]2[O:25][CH2:26][C@@H:27]([O:37][CH2:38][P:39]([O:41][CH2:42][CH3:43])([O:44][CH2:45][CH3:46])=[O:40])[CH2:28][OH:29])=[C:18]([O:47][CH3:48])[N:17]=1
Reactant: CCOP(=O)(CO[C@@H](COCc1ccccc1)COn1cnc2c(OC)nc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc21)OCC
Agent: [Pd]
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Solvent: ClCCl
Product: CCOP(=O)(CO[C@@H](CO)COn1cnc2c(OC)nc(N)nc21)OCC
Temperature: 25 °C
Reaction time: 2 h
Yield: 69.7 %

Procedure:
Trifluoroacetic acid (2 ml) was added to an ice cooled solution of (S)-2-[bis-(t-butoxycarbonyl)amino]-9-[3-benzyloxy-2-(diethoxyphosphorylmethoxy]propoxy]-6-methoxypurine (1.65 g, 2.3 mmol) in dry dichloromethane (30 ml) an the resulting solution left for 2 hours. After warming to ambient temperature, 10% Pd-C (800 mg) was added and the mixture hydrogenated at ambient temperature and pressure for 2 hours. The reaction mixture was filtered, the catalyst washed with dichloromethane (20 ml), the filtrate washed with saturated aqueous sodium bicarbonate solution, brine, dried (MgSO4) and evaporated to leave a colourless viscous oil. Chromatography of the oil on silica gel using dichloromethane/methanol 95:5 as the initial eluant, then changing the eluant to dichloromethane/methanol 90:10 gave (S)-2-amino-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]-6-methoxypurine as a colourless oil (0.65 g, 67%). IR: νmax (film) 3360, 3230, 2990, 2940, 2910, 1620, 1585, 1500, 1485, 1455, 1390, 1335, 1265, 1240, 1165, 1120, 1060, 1025, 975, 825, 785 cm-1. 1H NMR: δH [(CD3)2SO] 1.23 (6H, t, J=7 Hz, (OCH2CH3)2), 3.45-3.60 (2H, m, collapses to d on D2O exchange, CH2OH), 3.70-3.85 (1H, m, CH), 3.96 (3H, s, OCH3), 3.9-4.15 (6H, m, (OCH2CH3, OCH2P), 4.31 (1H, dd, J=11.3 Hz, J=6.9 Hz, NOCHB), 4.45 (1H, dd, J =11.3 Hz, J=3 Hz, NOCHA), 4.84 (1H, t, J=5.5 Hz, D2O exchangeable OH), 6.59 (2H, br.s, D2O exchangeable NH2), 8.14 (3H, s, H-8). m/z: (FAB, thioglycerol matrix) 406 (MH+).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-])=O)[CH3:2]>CCOC(C)=O.CO>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)[CH:7]=[CH:8][C:9]=1[NH2:10])[CH3:2]
Reactant: CCOc1cc(-c2ccncc2)ccc1[N+](=O)[O-]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCOc1cc(-c2ccncc2)ccc1N
Reaction time: 6 h
Yield: 83.4 %

Procedure:
4-[3-(Ethyloxy)-4-nitrophenyl]pyridine (3.57 g, 14.62 mmol) was place in a 250 mL high pressure vessel and dissolved in 60 mL of 1 to 1 EtOAc/MeOH. 5 wt % Platinum(sulfided)/carbon (2.85 g, 0.73 mmol) was added followed quickly by a rubber septum. The flask was evacuated and filled with N2 six times to remove any oxygen. The vessel was then pressurized with H2 (60 psi). The solution stirred for 6 hours. The vessel was evacuated and filled with N2 six times to remove any H2. The solution was filtered through celite and evaporated to give the title compound of step C (2.62 g, 12.2 mmol, 83%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44-8.48 (m, 2H), 7.57 (dd, J=4.58, 1.46 Hz, 2H), 7.16-7.21 (m, 2H), 6.70 (d, J=7.87 Hz, 1H), 5.09 (bs, 2H), 4.09 (q, J=6.96 Hz, 2H), 1.34 (t, J=6.96 Hz, 3H).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[C:5]([N:11]2[C:15]([CH3:16])=[CH:14][CH:13]=[C:12]2[CH3:17])=[CH:4][C:3]=1[C:18]([F:21])([F:20])[F:19].[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>C1COCC1>[CH3:17][C:12]1[N:11]([C:5]2[C:6]([C:8]([OH:10])=[O:9])=[N:7][C:2]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[C:3]([C:18]([F:21])([F:20])[F:19])[CH:4]=2)[C:15]([CH3:16])=[CH:14][CH:13]=1
Reactant: Cc1ccc(C)n1-c1cc(C(F)(F)F)c(Br)nc1C(=O)O
Reactant: C1CCNC1
Solvent: C1CCOC1
Product: Cc1ccc(C)n1-c1cc(C(F)(F)F)c(N2CCCC2)nc1C(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirring solution of 6-bromo-3-(2,5-dimethyl-1H-pyrrol-1-yl)-5-(trifluoromethyl)picolinic acid (300 mg, 0.826 mmol) in THF (1 ml), pyrrolidine (0.136 ml, 1.652 mmol) was added. The orange solution was stirred at RT overnight. The reaction mixture was partitioned between 0.5M HCl (30 ml) and EtOAc (30 ml) and shaken. The organic portion was separated and washed with brine (30 ml), dried over MgSO4, filtered and concentrated in vacuo to give a red oil. The crude product was purified on silica eluting with 0-40% EtOAc in iso-hexane to afford the title product;
Reaction SMILES: [CH2:1]1[C@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1.FF.B(F)(F)F.CCOCC>C(#N)C>[CH2:9]1[CH:10]2[CH:5]([CH2:4][CH2:3][CH2:2][CH2:1]2)[CH2:6][CH2:7][CH2:8]1
Reactant: C1CC[C@H]2CCCC[C@@H]2C1
Agent: FB(F)F
Agent: FF
Solvent: CCOCC
Solvent: CC#N
Product: C1CCC2CCCCC2C1
Temperature: 82 °C
Yield: 50 %

Procedure:
Using a similar procedure to that described above (Method 2), trans-decalin (3.0 g, 22 mmol), elemental fluorine (44 mmol), boron trifluoride etherate (3.1 g, 22 mmol), and anhydrous acetonitrile (120 cm3) gave, after heating (82° C.) and the work-up as detailed above, a crude product mixture which was distilled to give decalin (1.5 g, 11 mmol); bp 50° C./8 mmHg. The brown solid which remained gave, after recrystallisation, N-(trans-9-decalyl)acetamide (1.0 g, 45%, 49% conv.) as a white solid; spectral and physical data as described in Example 3.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[C:12](N)[C:11]([N+:15]([O-:17])=[O:16])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.N1C=CC=CC=1.N([O-])=[O:25].[Na+]>F>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[C:12]([OH:25])[C:11]([N+:15]([O-:17])=[O:16])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1
Reactant: CN1CCN(c2ccc([N+](=O)[O-])c(N)n2)CC1
Reactant: O=N[O-]
Agent: F
Agent: [Na+]
Solvent: c1ccncc1
Product: CN1CCN(c2ccc([N+](=O)[O-])c(O)n2)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-amine (1.2 g, 5.0 mmol) in hydrogen fluoride.pyridine (15 mL) is cooled to 0° C. in an ice-water bath. Sodium nitrite (0.36 g, 5.2 mmol) is added in a single portion, and the mixture is stirred for 30 minutes at 0° C. The bath is removed and the mixture is heated for 15 minutes in an oil bath on a 70° C. hot plate. After cooling to room temperature, the reaction mixture is poured onto ice (50 g), neutralized with saturated aqueous sodium hydrogen carbonate solution, and basified with 10 N sodium hydroxide solution. The mixture is extracted 3× with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Eighty-percent of the crude residue is purified by reverse-phase HPLC to give 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-ol.trifluoroacetic acid salt (0.18 g, 7.8%).
Reaction SMILES: [CH3:1][S:2]([OH:5])(=[O:4])=[O:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:25]([O:32][CH2:33][C@H:34]1[N:38]([S:39]([C:42]2[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=2)(=[O:41])=[O:40])[CH2:37][C@H:36](O)[CH2:35]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N(C([O-])=O)=NC([O-])=O>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:25]([O:32][CH2:33][C@H:34]1[N:38]([S:39]([C:42]2[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=2)(=[O:41])=[O:40])[CH2:37][C@@H:36]([O:3][S:2]([CH3:1])(=[O:5])=[O:4])[CH2:35]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=S(=O)(c1ccc2ccccc2c1)N1C[C@H](O)C[C@H]1COCc1ccccc1
Reactant: CS(=O)(=O)O
Agent: O=C([O-])N=NC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)O[C@H]1C[C@@H](COCc2ccccc2)N(S(=O)(=O)c2ccc3ccccc3c2)C1
Reaction time: 0.08 h
Yield: 80.9 %

Procedure:
To a suspension of methanesulphonic acid (0.96 g) in toluene (30 ml) was added triethylamine (1.40 ml) and triphenylphosphine (2.72 g) at 0–5° C. The suspension was stirred for 5 minutes, and (3R,5S)-5-benzyloxymethyl-1-(naphthalene-2-sulfonyl)-pyrrolidin-3-ol (3.46 g) dissolved in toluene (20 ml) was added dropwise in 5 minutes, followed by diisipropyl azodicarboxylate (2.0 ml). The reaction mixture was stirred for 3 h at 85° C., poured onto ice/water and extracted with ethy acetate. The organic phase was washed with 10% KHSO4— and NaCl solutions, dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel using EtOAc/hexane 1:2 and 1:1 as eluents to obtain (3S,5S)-methanesulfonic acid 5-benzyloxymethyl-1-(naphthalene-2-sulfonyl)-pyrrolidin-3-yl ester (3.35 g) as a slightly yellow syrup, MS: 476 (MH+).
Reaction SMILES: C1(CCCC2C=C[N+]([O-:16])=CC=2)C=CC=CC=1.Cl[O-].[Na+].[Cl:20][C:21]1[CH:29]=[C:28]2[C:24]([CH:25]=[CH:26][CH2:27]2)=[CH:23][CH:22]=1>C(Cl)Cl>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]2[C@H:25]3[O:16][C@H:26]3[CH2:27][C:28]=2[CH:29]=1
Reactant: [O-][n+]1ccc(CCCc2ccccc2)cc1
Reactant: Clc1ccc2c(c1)CC=C2
Agent: [Na+]
Agent: [O-]Cl
Solvent: ClCCl
Product: Clc1ccc2c(c1)C[C@@H]1O[C@H]21
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a stirring solution of 4-phenylpropylpyridine-N-oxide (278 mg, 1.31 mmol) in methylene chloride (20 mL) was added (R,R)-Jacobsen catalyst (237.0 mg, 0.3732 mmol) and a solution of sodium hypochlorite (2.0 M in water; 16 mL, 32 mmol) at 0° C. The resulting brown suspension was stirred at 0° C. for 15 minutes then a solution of 6-chloro-1H-indene (1) (2.81 g, 18.6 mmol) in methylene chloride (20 mL) was added via syringe with simultaneous addition of additional sodium hypochlorite (2.0M in water; 16 mL, 32 mmol). The reaction was stirred at 0° C. for one hour then the ice bath was removed and the reaction was stirred at room temperature for 1 hr. An aliquot was taken and TLC on silica (hexanes) showed all starting material consumed. The reaction was poured into brine and extracted with methylene chloride. The combined extracts were washed with saline, then dried over sodium sulfate, filtered, and evaporated under reduced pressure to leave crude product which solidified when placed under hi-vacuum. Yield ˜3.7 g of a brown solid. 1H NMR (400 MHz, DMSO) δ 7.55 (d, J=7.6 Hz, 1H), 7.32 (s, 1H), 7.23 (d, J=7.3 Hz, 1H), 4.36 (s, 1H), 4.16 (s, 1H), 3.03 (dd, J=45.8, 18.2 Hz, 2H).
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[NH:10][NH:9][C:8]2=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.O.O.[C:17]([O-:20])(=O)[CH3:18].[C:21]([O-])(=[O:23])[CH3:22].[Pb+2].C(OC(=O)C)(=O)C>C(Cl)(Cl)Cl>[CH3:22][C:21]([N:10]1[C:11](=[O:12])[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8](=[O:13])[N:9]1[C:17]([CH3:18])=[O:20])=[O:23]
Reactant: CC(=O)[O-]
Reactant: O=c1[nH][nH]c(=O)n1-c1ccccc1
Agent: [Pb+2]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: CC(=O)n1c(=O)n(-c2ccccc2)c(=O)n1C(C)=O
Temperature: 25 °C
Yield: 35.1 %

Procedure:
To a mixture of 5.3 g (30 mmol) of 4-phenyl-1,2,4-triazolidine-3,5-dione and 22.7 g (60 mmol) of lead diacetate trihydrate in 200 ml of chloroform was added dropwise over a 15 minute period 45.9 g (450 mmol) of acetic anhydride. The mixture was stirred at room temperature. After 25 hours the pale yellow solution was washed with three 100 ml portions of water and three 75 ml portions of 10% sodium carbonate. The carbonate washings were acidified with concentrated hydrochloric acid. No precipitate was produced. The chloroform solution was dried (Na2SO4) and evaporated under reduced pressure to give a solid-liquid residue. The residue was filtered and the filtered solid was washed with 25 ml of 95% ethanol to give 2.75 g (35.1%) of the 1,2,4-triazolidine-3,5-dione product as a white solid. An additional quantity of the product precipitated from the ethanol filtrate. This solid was filtered to give an additional 1.20 g (15.3%) of the 1,2,4-triazolidine-3,5-dione product (50.4% total yield). the solids were recrystallized from 95% ethanol to give pure 1,2-dimethylcarbonyl-4-phenyl-1,2,4-triazolidine-3,5-dione; m.p. 169°-170.5° C.; IR (Nujol) 1750, 1732 (shoulder), 1714 (shoulder) cm-1 (CO); 1H NMR (60 MHz, CDCl3) δ7.80(s, 5H), 2.55 (s, 6H); Found: C, 55.2; H, 4.45; N, 16.0; C12H11N3O4 requires C, 55.2; H, 4.2; N, 16.0.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[NH2:12][CH2:13][CH2:14][NH:15][C:16]1[C:25]([CH3:26])=[N:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=1.O>CN(C)C=O>[O:5]([CH2:1][CH:2]([OH:4])[CH2:3][NH:12][CH2:13][CH2:14][NH:15][C:16]1[C:25]([CH3:26])=[N:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: c1ccc(OCC2CO2)cc1
Reactant: Cc1nc2ccccc2nc1NCCN
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nc2ccccc2nc1NCCNCC(O)COc1ccccc1
Temperature: 40 °C

Procedure:
5.6 g. Phenyl glycidyl ether and 15 g. 2-(2-aminoethylamino)-3-methylquinoxaline are dissolved in a little dimethylformamide and warmed to 40° C. for 32 hours. The reaction mixture is then poured into water, extracted with methylene chloride, dried and purified chromatographically on silica gel in the manner described in Example 25. There are obtained 4.2 g. (33% of theory) of the desired product in the form of a viscous oil.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:6]([OH:8])=[O:7])[CH2:4][SH:5].[CH2:9]([OH:31])[C@H:10]1[O:15][C@H:14]([O:16][C@H:17]2[C@H:22]([OH:23])[C@@H:21]([OH:24])[C@H:20](O)[O:19][C@@H:18]2[CH2:26][OH:27])[C@H:13]([OH:28])[C@@H:12]([OH:29])[C@@H:11]1[OH:30].N1C=CC=CC=1.C(O)C>O>[OH:24][CH:21]([CH:20]1[NH:2][CH:3]([C:6]([OH:8])=[O:7])[CH2:4][S:5]1)[CH:22]([OH:23])[CH:17]([O:16][CH:14]1[O:15][C@H:10]([CH2:9][OH:31])[C@@H:11]([OH:30])[C@H:12]([OH:29])[C@H:13]1[OH:28])[CH:18]([OH:19])[CH2:26][OH:27]
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Reactant: N[C@@H](CS)C(=O)O
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Solvent: O
Product: O=C(O)C1CSC(C(O)C(O)C(OC2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C(O)CO)N1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
17.56 Grams (100 mmol) of cysteine hydrochloride and 34.20 g (100 mmol) of maltose were dissolved in 35 ml of pure water, 8.36 ml (100 mmol) of pyridine was then added thereto, and the resulting solution was stirred at room temperature for 72 hours. 300 Milliliters of ethanol was added to the stirred solution, and the solution was left to stand in a refrigerator, whereby a paste-like precipitate was formed. The solvent was removed by decantation, and the precipitate was dissolved in 100 ml of water. After the insoluble matters were removed by filtration, the remaining solution was condensed to about 30 ml. Ethanol was continuously added to the condensed solution until a precipitate was about to appear, and the solution was then left to stand in a refrigerator overnight. The produced crystals were collected by filtration. The crystals were then dissolved in water again, the insoluble matters were removed by filtration, the resulting solution was condensed, and ethanol was added to the solution to cause recrystallization. The produced crystals were collected by filtration and dried under reduced pressure to obtain 2.2 g of a white powder (molar yield based on cysteine: 4.9%).
Reaction SMILES: [CH2:1]([SH:4])[CH2:2][SH:3].C[O-].[Na+].Cl[CH2:9][CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[CH:12]1>C(O)C>[N:11]1([CH2:10][CH2:9][S:3][CH2:2][CH2:1][SH:4])[CH:15]=[CH:14][N:13]=[CH:12]1
Reactant: SCCS
Reactant: ClCCn1ccnc1
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: SCCSCCn1ccnc1

Procedure:
In ethanol (30 ml) was dissolved 1-(2-chloroethyl)imidazole, to which were added 1,2-ethanedithiol (25 ml) and sodium methoxide (28% methanol solution) (16.6 ml), and the mixture was heated for 30 minutes under reflux. Insoluble substances were filtered off, and the filtrate was concentrated under reduced pressure. To the concentrate was added dichloromethane (300 ml). The organic layer was washed with water, then with a saturated aqueous sodium chloride solution, followed by drying (sodium sulfate). The solvent was distilled off, and the residue was subjected to a silica gel column chromatography (3.0×40 cm:ethyl acetate→ethyl acetate:methanol=10:1) to give 2-[2-(1 -imidazolyl)ethylthio]ethanethiol (3.0 g) as a pale yellow oily substance.
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([C:8]2[CH:28]=[CH:27][C:11]([CH2:12][N:13]3[C:17]4[N:18]=[C:19]([S:24][CH3:25])[N:20]=[C:21]([O:22]C)[C:16]=4[C:15]([CH3:26])=[CH:14]3)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.S(C1C(C)=CC(O)=C(C(C)(C)C)C=1)C1C(C)=CC(O)=C(C(C)(C)C)C=1.Cl.O>O1CCOCC1>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([C:8]2[CH:28]=[CH:27][C:11]([CH2:12][N:13]3[C:17]4[N:18]=[C:19]([S:24][CH3:25])[NH:20][C:21](=[O:22])[C:16]=4[C:15]([CH3:26])=[CH:14]3)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: COc1nc(SC)nc2c1c(C)cn2Cc1ccc(C(=O)c2ccc(Cl)cc2)cc1
Agent: Cc1cc(O)c(C(C)(C)C)cc1Sc1cc(C(C)(C)C)c(O)cc1C
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: CSc1nc2c(c(C)cn2Cc2ccc(C(=O)c3ccc(Cl)cc3)cc2)c(=O)[nH]1
Temperature: 105 °C
Reaction time: 36 h
Yield: 48 %

Procedure:
Under argon gas, 7-[4-(4-chlorobenzoyl)benzyl]-4-methoxy-5-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine (0.671 g) was dissolved in dioxane (8 ml) followed by addition of 4,4'-thiobis(6-t-butyl-m-cresol) (7.2 mg). Then, 0.5N-hydrochloric acid (1.12 ml) was added and the mixture was stirred at 105° C. for 36 hours. Thereafter, 0.5 N-hydrochloric acid (1.12 ml) was added again and the mixture was further stirred at the same temperature as above for 24 hours. To this reaction mixture was added water (30 ml) and the resulting precipitate was collected by filtration and dried. The dried precipitate was purified by flash column chromatography (chloroform) to provide the title compound (0.312 g). 1H-NMR (DMSO-d6) 8: 2.24(3H,s), 2.51(3H,d,J=l.OHz), 5.33(2H,s), 6.83(1H,d,J=l.OHz), 7.43(2H,d,J=8.2Hz), 7.60(2H,d,J=8.6Hz), 7.71(2H,d,J=8.2Hz), 7.73(2H,d,J=8.6Hz), 12.01(1H,s).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([SH:9])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.Cl[CH:22]([F:24])[F:23]>O>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([S:9][CH:22]([F:24])[F:23])[N:3]=1
Reactant: Nc1nc(N)nc(S)n1
Reactant: FC(F)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Nc1nc(N)nc(SC(F)F)n1

Procedure:
To a mixture of 2.8 g of 2,4-diamino-6-mercapto-1,3,5-triazine, 5.5 g of potassium carbonate, and 20 ml of N,N-dimethylformamide is added and chlorodifluoromethane gas is aspirated at a temperature of 55°~65° C. for 2 hours in a 100 ml three-necked flask. After cooling, the mixture is mixed with water and extracted with ethyl acetate. The extract is evaported, and the resulting residue is purified by silica-gel chromatography to produce 0.8 g of 2,4-diamino-6-difluoromethylthio-1,3,5-triazine.