Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[C:8](Cl)=[N:7][C:5]([Cl:6])=[N:4][C:2]=1Cl.[OH:10][CH2:11][CH2:12][O:13][C:14](=[O:28])[NH:15][CH2:16][CH2:17][NH:18][CH2:19][CH2:20][NH:21][C:22](=[O:27])[O:23][CH2:24][CH2:25][OH:26]>CC(C)=O.O>[OH:10][CH2:11][CH2:12][O:13][C:14]([NH:15][CH2:16][CH2:17][N:18]([C:8]1[N:1]=[C:2]([N:18]([CH2:17][CH2:16][NH:15][C:14]([O:13][CH2:12][CH2:11][OH:10])=[O:28])[CH2:19][CH2:20][NH:21][C:22]([O:23][CH2:24][CH2:25][OH:26])=[O:27])[N:4]=[C:5]([Cl:6])[N:7]=1)[CH2:19][CH2:20][NH:21][C:22]([O:23][CH2:24][CH2:25][OH:26])=[O:27])=[O:28]
Reactant: O=C(NCCNCCNC(=O)OCCO)OCCO
Reactant: Clc1nc(Cl)nc(Cl)n1
Solvent: O
Solvent: CC(C)=O
Product: O=C(NCCN(CCNC(=O)OCCO)c1nc(Cl)nc(N(CCNC(=O)OCCO)CCNC(=O)OCCO)n1)OCCO
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To 50 g water in a 3-neck flask equipped with stirrer and a thermometer, were added 9.2 g (0.05 m) of cyanuric chloride, dissolved in 50 g acetone below 10° C. To the white slurry of cyanuric chloride, 27.9 g of bis(2-hydroxyethyl)(iminodiethylene)biscarbamate (HEC), NH(CH2CH2NHCO2CH2CH2OH)2 dissolved in 50 g of water was added over a period of 15 minutes. During the addition, the reaction temperature was maintained below 12° C. After complete addition of HEC, the slurry turned into a clear solution. To this was added 10% caustic to maintain the reaction pH at about 7 and the reaction mixture was allowed to warm up to 25° C. At 25° C., as the reaction progressed, a white crystalline solid slowly separated out. After 4 hrs. at 25°-35° C., the solids were separated by filtration, washed with water and recrystallized from ethanol. The product yield was 24 g and m.p. 174° C. The structure of the product was confirmed by nuclear magnetic resonance (nmr) and fast atomic bombardment (fab), mass spectrometry to be that of FORMULA I: ##STR20##
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:5]2[CH:14]=[CH:15][CH:16]=[CH:17][C:4]=2[O:3]1.S(=O)(=O)(O)O.[N+:24]([O-])([OH:26])=[O:25].[OH-].[Na+].C(=O)(O)[O-]>C(O)(=O)C>[N+:24]([C:15]1[CH:16]=[CH:17][C:4]2[O:3][C:2]([CH3:18])([CH3:1])[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=3)[C:5]=2[CH:14]=1)([O-:26])=[O:25]
Reactant: O=[N+]([O-])O
Reactant: CC1(C)N=C(c2ccccn2)c2ccccc2O1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC1(C)N=C(c2ccccn2)c2cc([N+](=O)[O-])ccc2O1
Reaction time: 0.17 h

Procedure:
2,2-Dimethyl-4-(2-pyridyl)-2H-1,3-benzoxazine (0.50 g) was dissolved in acetic acid (1 ml) and to the solution was added conc. sulfuric acid (3 ml) with ice-cooling. Conc. nitric acid (0.2 ml) was then added to the mixture, and the mixture was stirred for 10 minutes with ice-cooling. The reaction mixture was added slowly to a thoroughly cooled mixture of an aqueous 5N sodium hydroxide solution (50 ml) and saturated bicarbonate solution (20 ml) to quench the reaction. The mixture was extracted by addition of ethyl acetate. The mixture was successively washed with an aqueous sodium bicarbonate solution and saturated saline solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was crystallized from hexane to obtain 6-nitro-2,2-dimethyl-4-(2-pyridyl)-2H-1,3-benzoxazine (0.58 g) (Compound 11).
Reaction SMILES: [CH:1]([NH:4][C:5]1[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=3)=[O:18])[CH2:13][CH2:12]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[NH:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>C(Cl)Cl>[CH:1]([NH:4][C:5]1[C:6]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([C:19]3[CH:20]=[CH:21][C:22]([C:23]([N:42]4[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]4)=[O:24])=[CH:26][CH:27]=3)=[O:18])[CH2:15][CH2:16]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:2])[CH3:3]
Reactant: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)O)cc2)CC1
Reactant: C1CNCCN1
Agent: CC(C)(C)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)N3CCNCC3)cc2)CC1
Temperature: 5 °C
Reaction time: 2 h
Yield: 83.3 %

Procedure:
4-[1-[3-(Isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]benzoic acid (1.5 g) was dissolved in methylene chloride (50 ml) and then, triethylamine (0.7 ml) was added and cooled. Pivaloyl chloride (0.58 ml) was added slowly to the solution at 0~5° C. and the mixture was stirred at 5° C. for 2 hours. With the addition of piperazine (0.9 g), the solution was stirred at 5~10° C. for 3 hours. The reaction mixture was washed with water and aqueous sodium bicarbonate and the solvent was concentrated under reduced pressure. The concentrated residue was crystallized by treatment with ether and further recrystallized using isopropanol and ether. The recrystallized product was filtered and dried to give 1.48 g (yield: 83%) of the desired compound as white crystal.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([NH2:11])[CH:5]=1.Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl.CCN(CC)CC>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]=[C:14]=[O:16])[CH:5]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COC(=O)c1ccc(C)c(N)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(C)c(N=C=O)c1

Procedure:
In analogy to the procedure described in example 9.1, 3-amino-4-methyl-benzoic acid methyl ester ([18595-18-1]) was reacted with triphosgene in the presence of Et3N in CH2Cl2 under reflux conditions for 16 h to give the title compound as brown solid which was used in the next step without further purification. MS: m/e=191 [M+].
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:22])([CH3:21])[C:16](OCC)=[O:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C>CCOCC>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:22])([CH3:21])[CH2:16][OH:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCOC(=O)C(C)(C)CCCCCCO[Si](C)(C)C(C)(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CCOCC
Product: CC(C)(CO)CCCCCCO[Si](C)(C)C(C)(C)C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Ethyl 8-(tert-butyldimethylsilyloxy)-2,2-dimethyloctanoate (example 279, step a) (20 g) in dry ether under nitrogen (300 mL) was cooled to 0° C. in an ice bath then diisobutylaluminium hydride (1M in toluene, 133 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 1 hour then quenched with saturated aqueous potassium sodium tartrate (Rochelle's salt, 400 mL) and stirred overnight. The mixture was extracted with ethyl acetate (3×300 mL) then the combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. Purification was by silica gel chromatography eluting with 0-20% ethyl acetate in cyclohexane to afford the subtitled compound as a colourless liquid. Yield 10.11 g.
Reaction SMILES: Cl.[OH:2][CH:3]1[O:11][C@H:10]([CH2:12][OH:13])[C@@H:8]([OH:9])[C@H:6]([OH:7])[C@H:4]1[NH2:5].C(=O)(O)[O-].[Na+].Cl.C([BH3-])#N.[Na+]>>[NH2:5][C@H:4]([C@H:6]([C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[OH:9])[OH:7])[CH:3]=[O:2]
Reactant: N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
Agent: Cl
Agent: O=C([O-])O
Agent: [BH3-]C#N
Product: N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
Reactions of carboxymethyl cellulose sodium salt (0.5-1.0% w/v) were carried out with glucosamine-hydrochloride (1.5-3.0% w/v) in the presence of equimolar amounts of base, such as a sodium bicarbonate solution (0.55-1.1% w/v) to neutralize the hydrochloride, sodium cyanoborohydride as reducing reagent (0.27-0.50% w/v), at room temperature, producing 2-amino-2-deoxy-glucose derivatives of carboxymethyl cellulose with nitrogen incorporation values of 2.60-3.07%, as shown in Table 2, page 17.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[CH2:3][O:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][CH2:8][N:9](C([O-])=O)[CH2:10]2.[C:20]([OH:26])([C:22]([F:25])([F:24])[F:23])=[O:21]>C(Cl)Cl>[F:23][C:22]([F:25])([F:24])[C:20]([OH:26])=[O:21].[F:19][C:2]([F:1])([F:18])[CH2:3][O:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][CH2:8][NH:9][CH2:10]2
Reactant: O=C([O-])N1CCc2c(cccc2OCC(F)(F)F)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: FC(F)(F)COc1cccc2c1CCNC2
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
5-(2,2,2-Trifluoroethoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate (120 mg) was dissolved in DCM (6 mL) followed by addition of TFA (2 mL). The reaction mixture was stirred at RT for 20 min. The reaction solvent was removed under reduced pressure and the residue was dried on high vacuum overnight to yield 5-(2,2,2-trifluoroethoxy)-1,2,3,4-tetrahydroisoquinoline 2,2,2-trifluoroacetate (125 mg) as a colorless oil which was used without purification.
Reaction SMILES: [H-].[Na+].[NH:3]1[C:8](=[O:9])[CH2:7][S:6][C:5]2[N:10]=[CH:11][CH:12]=[CH:13][C:4]1=2.[CH3:14][N:15]([CH3:20])[CH2:16][CH2:17][CH2:18]Cl>C1(C)C=CC=CC=1>[CH3:14][N:15]([CH3:20])[CH2:16][CH2:17][CH2:18][N:3]1[C:8](=[O:9])[CH2:7][S:6][C:5]2[N:10]=[CH:11][CH:12]=[CH:13][C:4]1=2
Reactant: CN(C)CCCCl
Reactant: O=C1CSc2ncccc2N1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CN(C)CCCN1C(=O)CSc2ncccc21
Reaction time: 8 h

Procedure:
A 50% oil dispersion of NaH (7.8 g; 0.16 mole) is added to a stirred suspension of 26 g (0.16 mole) of 1H-pyrido[2,3-b][1,4]thiazin-2(3H)-one in 525 ml of toluene and the mixture gradually warmed, effervescence occurs at about 90°. After heating to reflux for 45 minutes, the mixture is cooled to 30°, treated with 120 ml (0.22 mole) of a 1.8 N toluene solution of 3-dimethylaminopropyl chloride and refluxed for 4 hours. After standing overnight, the mixture is worked up as described in Example 1, part A, to give 23 g of crude base. This is combined with 10 g of base from an earlier experiment and distilled; yield, 27.3 g; bp. 166°-169°/0.2 mm.
Reaction SMILES: Cl[CH:2]([CH2:6][CH2:7][Cl:8])[C:3](=[O:5])C.[SH:9][CH2:10][CH2:11]O.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Cl:8][CH2:7][CH2:6][C:2]1[S:9][CH2:10][CH2:11][O:5][CH:3]=1
Reactant: OCCS
Reactant: CC(=O)C(Cl)CCCl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: ClCCC1=COCCS1
Yield: 60 %

Procedure:
A mixture of the 3,5-dichloro-2-pentanone (39 g., 0.24 mole) and 2-mercaptoethanol (20 g., 0.26 mole) in toluene (250 ml) was stirred, and triethylamine (27 g., 0.27 mole) added dropwise thereto. After stirring overnight at ambient temperature, the mixture was washed with dilute hydrochloric acid and subsequently refluxed with p-toluenesulfonic acid (0.5 g.) with azeotropic removal of water for 4 hours. Upon cooling, the reaction mixture was washed with aqueous sodium bicarbonate, dried (magnesium sulfate), and the toluene removed to leave the product 3-(2-chloroethyl)-5,6-dihydro-1,4-oxathiin (bp. 62°-70°/0.025 mm) in 60% yield and 98% purity (G.C.). N.M.R. spectrum (Deuterchloroform) gave lambda values: 1.85 (3H,S) 2.3-2.65 (2H,t); 2.9-3.5 (2H,t); 3.95-3.7 (2H,t); 4.1-4.25 (2H,t).
Reaction SMILES: [C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][NH:19][CH2:18]1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2].[CH3:22][O:23][CH:24]([O:32][CH3:33])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH:30]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH:24]([O:23][CH3:22])[O:32][CH3:33])[CH2:18]1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]
Reactant: COC(CCCCCC=O)OC
Reactant: NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: COC(CCCCCCN1CC[C@@H](C(C(N)=O)(c2ccccc2)c2ccccc2)C1)OC
Temperature: 0 °C
Reaction time: 1 h
Yield: 71.7 %

Procedure:
To a three-necked 500 mL flask equipped with a mechanical stirrer, a nitrogen inlet, cooling bath, and a thermometer was added (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (25 g, 0.089 mol) and dichloromethane (200 mL). This mixture was cooled to about 0° C. and 7,7-dimethoxyheptanal (18.6 g, 0.107 mol) was added slowly. During the addition, the reaction temperature was maintained at 5° C. or less. The resulting mixture was stirred at 0 to 5° C. for 1 hour and then sodium triacetoxyborohydride (24.6 g, 0.116 mol) was then added over a 30 minute period. During this addition, the reaction temperature was also maintained at 5° C. or less. The resulting mixture was then stirred at 0 to 5° C. for 6 hours. The reaction was then quenched by adding 5% aqueous potassium carbonate solution (200 mL) while keeping the reaction temperature less than about 20° C. and the resulting mixture was stirred for 1 hour at room temperature. The organic layer was separated and washed with brine (100 mL) and then dried with sodium sulfate (20 g). The organic layer was then concentrated under vacuum to a volume of about 100 mL and this mixture was purified by silica gel chromatography eluting with a gradient of 1 to 10% v/v methanol in dichloromethane. The fractions containing the desired product were combined and concentration under vacuum to afford 28 g of the title intermediate as an oil (72% yield).
Reaction SMILES: ClC1C=CC=C(C)C=1N.ClC1C(C#N)=C(NC2C(C)=CC=CC=2Cl)N=CN=1.[Cl:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:30]=1[N:36]1[C:46]2[C:47]3[C:39](=[C:40]([C:48](O)=[O:49])[S:41][C:42]=3[N:43]=[CH:44][N:45]=2)[NH:38][C:37]1=[O:51].[N:52]1([CH2:58][C:59]2[CH:64]=[CH:63][C:62]([NH2:65])=[CH:61][CH:60]=2)[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1>>[N:52]1([CH2:58][C:59]2[CH:64]=[CH:63][C:62]([NH:65][C:48]([C:40]3[S:41][C:42]4[N:43]=[CH:44][N:45]=[C:46]5[C:47]=4[C:39]=3[NH:38][C:37](=[O:51])[N:36]5[C:30]3[C:31]([CH3:35])=[CH:32][CH:33]=[CH:34][C:29]=3[Cl:28])=[O:49])=[CH:61][CH:60]=2)[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1
Reactant: Cc1cccc(Cl)c1N1C(=O)Nc2c(C(=O)O)sc3ncnc1c23
Reactant: Nc1ccc(CN2CCOCC2)cc1
Agent: Cc1cccc(Cl)c1N
Agent: Cc1cccc(Cl)c1Nc1ncnc(Cl)c1C#N
Product: Cc1cccc(Cl)c1N1C(=O)Nc2c(C(=O)Nc3ccc(CN4CCOCC4)cc3)sc3ncnc1c23

Procedure:
Using the procedure of Example 1, 2-chloro-6-methyl-phenylamine Compound 48a was used in place of 3-chloro-4-fluoro-phenylamine Compound 1e to prepare 4-chloro-6-(2-chloro-6-methyl-phenylamino)-pyrimidine-5-carbonitrile Compound 48b. Using the procedure of Example 3, Compound 48b was used in place of 4-chloro-6-(2-chloro-4-fluoro-phenylamino)-pyrimidine-5-carbonitrile Compound 3b to prepare 5-(2-chloro-6-methyl-phenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,6,8-tetraaza-acenaphthylene-2-carboxylic acid Compound 4&. MS 361, 363 (MH+). Using the procedure of Example 1, Compound 48c was used in place of Compound 1 and 4-morpholin-4-ylmethyl-phenylamine Compound 3e was used in place of 4-piperidin-1-ylmethyl-phenylamine Compound 1k to prepare Compound 146. MS 535, 537 (MH+).
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[C:8]([O:12][C:13]([N:15]1[CH2:34][CH2:33][C:18]2([N:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([OH:31])=[O:30])[CH:24]=3)[NH:20][C:19]2=[O:32])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]>CO>[C:8]([O:12][C:13]([N:15]1[CH2:16][CH2:17][C:18]2([N:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([O:31][CH3:1])=[O:30])[CH:24]=3)[NH:20][C:19]2=[O:32])[CH2:33][CH2:34]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)N=C(c1cccc(C(=O)O)c1)NC2=O
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Product: COC(=O)c1cccc(C2=NC3(CCN(C(=O)OC(C)(C)C)CC3)C(=O)N2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 43.7 %

Procedure:
(Trimethylsilyl)diazomethane (2.0 M in hexane, 4.0 ml, 8.0 mmol) was added dropwise to a solution of 2-(3-carboxy-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-carboxylic acid tert-butyl ester (200 mg, 0.54 mmol) in methanol (10 ml). The mixture was stirred at room temperature for one hour, and (trimethylsilyl)diazomethane (1.0 ml, 2.0 mmol) was then further added, followed by stirring for one hour. The reaction mixture was concentrated under reduced pressure, and the resulting solid was then washed with a solution of hexane/ethyl acetate=5/1 to give 2-(3-methoxycarbonyl-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-carboxylic acid tert-butyl ester (91.5 mg, 44%).
Reaction SMILES: C1(S([CH2:10][C:11]2[N:12]=[C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[NH:14][N:15]=2)(=O)=O)C=CC=CC=1.[Cl:22][C:23]1[N:28]=[CH:27][C:26](/[CH:29]=[CH:30]\[C:31]#[N:32])=[CH:25][CH:24]=1>>[Cl:22][C:23]1[N:28]=[CH:27][C:26]([C:29]2[CH:30]=[C:31]([NH2:32])[N:15]3[N:14]=[C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=4)[N:12]=[C:11]3[CH:10]=2)=[CH:25][CH:24]=1
Reactant: O=S(=O)(Cc1n[nH]c(-c2ccccn2)n1)c1ccccc1
Reactant: N#C/C=C\c1ccc(Cl)nc1
Product: Nc1cc(-c2ccc(Cl)nc2)cc2nc(-c3ccccn3)nn12

Procedure:
The title compound, MS m/e (%):323 (M+H+,100), was prepared in accordance with the general method of example 1 from 2-(5-benzenesulfonylmethyl-2H-[1,2,4]triazol-3-yl)-pyridine and (E)/(Z)-3-(6-chloro-pyridin-3-yl)-acrylonitrile.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH2:14].[F:15][C:16]([F:29])([F:28])[C:17]1[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=1)/[CH:20]=[CH:21]/[C:22]([Cl:24])=O.N1C=CC=CC=1N1C2C=CC=CC=2N=C1/C=C/C1C=CC=CC=1.Cl>CO>[ClH:24].[F:15][C:16]([F:28])([F:29])[C:17]1[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=1)/[CH:20]=[CH:21]/[C:22]1[N:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:14]=1
Reactant: Nc1ccccc1Nc1ccccn1
Reactant: O=C(Cl)/C=C/c1cccc(C(F)(F)F)c1
Agent: C(=C/c1nc2ccccc2n1-c1ccccn1)\c1ccccc1
Agent: Cl
Solvent: CO
Product: FC(F)(F)c1cccc(/C=C/c2nc3ccccc3n2-c2ccccn2)c1

Procedure:
Free base of the titled compound was prepared from N-(2-pyridyl)-o-phenylenediamine and (E)-3-trifluoromethylcinnamoyl chloride (Amino, Y.; Kawada, K.; Toi, K.; Kumashiro, I.; Fukushima, K. Chem. Pharm. Bull., 1988, 36, 4426) according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A). The free base was dissolved with a 10% methanol solution of hydrogen chloride (5 ml). Concentration and recrystallization from ethanol yielded the titled compound. MW: 401.82; mp:>230° C.; 1H-NMR (DMSO) δ: 8.83-8.77 (1H, m), 8.14-8.06 (1H, m), 7.81(1H, d, J=7.7 Hz), 7.67 (1H, dd, J=7.3,4.8 Hz), 7.56-7.22 (10H, m).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9]([OH:11])[CH3:10])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[N:3]=1.C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-][Cr](O[Cr]([O-])(=O)=O)(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9](=[O:11])[CH3:10])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[N:3]=1
Reactant: CC(O)c1c(Cl)nc(Cl)nc1Nc1ccccc1S(=O)(=O)C(C)C
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(=O)c1c(Cl)nc(Cl)nc1Nc1ccccc1S(=O)(=O)C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To the solution of 1-(2,4-dichloro-6-(2-(isopropylsulfonyl)phenylamino)pyrimidin-5-yl)ethanol (580 mg, 1.49 mmol) in DCM (30 mL) was added PDC (561 mg, 1.49 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered through a pad of silica gel, and the pad was washed by 1 L of DCM. The filtrate was concentrated in vacuo to afford 1-(2,4-dichloro-6-(2-(isopropylsulfonyl)phenylamino)pyrimidin-5-yl)ethanone as a pale yellow solid. MS (ES+): 388.0 (MH+).
Reaction SMILES: 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+].C(#N)C.C[O:32][C:33]1[C:41]([O:42][CH3:43])=[C:40]([O:44][CH3:45])[C:39]([O:46]C)=[C:38]2[C:34]=1[CH2:35][CH:36]([CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:37]2>O>[CH3:45][O:44][C:40]1[C:39](=[O:46])[C:38]2[CH2:37][CH:36]([CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:35][C:34]=2[C:33](=[O:32])[C:41]=1[O:42][CH3:43]
Reactant: CCOC(=O)CCCCCCCC1Cc2c(c(OC)c(OC)c(OC)c2OC)C1
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: O
Solvent: CC#N
Product: CCOC(=O)CCCCCCCC1CC2=C(C1)C(=O)C(OC)=C(OC)C2=O
Reaction time: 0.25 h
Yield: 16.2 %

Procedure:
A water (1.0 ml) solution of CAN (336 mg, 0.613 mmols) was dropwise added to an acetonitrile (2.0 ml) solution of ethyl 8-(4,5,6,7-tetramethoxyindan-2-yl)octanoate (100 mg, 0.245 mmols) with cooling with ice and stirring was continued for 15 minutes. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and then dried. The solvent was evaporated in vacuo, and the resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) followed by recrystallization from hexane to obtain the entitled compound (15 mg) as crystals.
Reaction SMILES: C[Si](C)(C)[C:3]1[S:4][CH:5]=[CH:6][N:7]=1.Cl[C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH2:14]([O:13][C:11]([C:3]1[S:4][CH:5]=[CH:6][N:7]=1)=[O:12])[CH3:15]
Reactant: C[Si](C)(C)c1nccs1
Reactant: CCOC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1nccs1
Yield: 85247 %

Procedure:
To a mixture of 2-trimethylsilylthiazole (135 g, 858 1 mmol) in toluene (1350 mL) add a solution of ethyl chloroformate (98.4 mL, 1.03 mol) in toluene (1350 mL) over 15 min. Stir the reaction at 22° C. for 2 h. Add the solution over aqueous sodium carbonate 25% (wt/wt) (5 L) and stir for 30 min. Separate the organic layer and re-extract the aqueous layer with methylene chloride (2×1 L). Combine the organic layers and evaporate the solvent to provide the title compound (134 g, 99%). ES/MS m/z 158 (M+1)+.
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[S:15][CH2:16][CH2:17][C:18]([OH:20])=O.Cl>C1C=CC=CC=1>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:10]=1[S:15][CH2:16][CH2:17][C:18]2=[O:20]
Reactant: COc1ccccc1SCCC(=O)O
Agent: Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: c1ccccc1
Product: COc1cccc2c1SCCC2=O
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 76 %

Procedure:
8.64 g of phosphorous pentachloride was added to a solution of 8.0 g of 2-(2-methoxyphenylthio)ethanecarboxylic acid in 24 ml of benzene under the atmosphere of argon while cooling to 0° C. After stirring the reaction mixture for 20 minutes at 100° C., 9.13 ml of stannous tetrachloride was dropwise added to the mixture while cooling to -10° C. Following completion of dropping, the reaction mixture was warmed to 0° C. and stirred for 30 minutes. Next, 24 g of ice followed by 14 ml of concentrated hydrochloric acid were added followed by refluxing for about 30 minutes. After cooling the reaction mixture to room temperature, the organic layer was separated and the aqueous layer was extracted three times with benzene. After combining the organic layers and washing twice with water, the combined organic layer was dried over magnesium sulfate, the solvent was distilled off and the resulting crystal was recrystallized from ethyl acetate-hexane to obtain 5.53 g of the target compound 8-methoxythiochroman-4-one (yield: 76%, m.p.: 110°-110.5° C.).