Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([O:9][CH3:10])[C:2](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O:3][CH3:4].S(Cl)([Cl:14])(=O)=O>>[CH3:4][O:3][C:2]1[CH:5]=[C:6]([Cl:14])[CH:7]=[CH:8][C:1]=1[O:9][CH3:10]
Reactant: COc1ccccc1OC
Reactant: O=S(=O)(Cl)Cl
Product: COc1ccc(Cl)cc1OC
Reaction time: 1 h

Procedure:
Into a triple-necked flask of a liter, provided with a magnetic stirring system, with a thermometer, with a calcium chloride trap and with a dropping funnel, were introduced in the cold at about 0° C. and successively 138 g (1 mole) of veratrol then drop by drop 135 g (1 mole) of sulfuryl chloride. When the addition was terminated, the reaction medium was brought to room temperature, then after standing one hour was distilled under reduced pressure.
Reaction SMILES: [F:1][C:2]1[C:50]([F:51])=[CH:49][CH:48]=[CH:47][C:3]=1[CH2:4][S:5][C:6]1[N:11]=[C:10]([NH:12][S:13]([N:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)(=[O:15])=[O:14])[CH:9]=[C:8]([O:23][C@H:24]([CH3:46])[CH2:25][O:26]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[C:50]([F:51])=[CH:49][CH:48]=[CH:47][C:3]=1[CH2:4][S:5][C:6]1[N:11]=[C:10]([NH:12][S:13]([N:16]2[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)(=[O:14])=[O:15])[CH:9]=[C:8]([O:23][C@H:24]([CH3:46])[CH2:25][OH:26])[N:7]=1
Reactant: C[C@H](COC(c1ccccc1)(c1ccccc1)c1ccccc1)Oc1cc(NS(=O)(=O)N2CCN(C)CC2)nc(SCc2cccc(F)c2F)n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@H](CO)Oc1cc(NS(=O)(=O)N2CCN(C)CC2)nc(SCc2cccc(F)c2F)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-1-methyl-2-(trityloxy)ethoxy]pyrimidin-4-yl}-4-methylpiperazine-1-sulfonamide (the product from step (100 mg) in DCM (3 ml) was added TFA (3 ml) dropwise. The reaction was then allowed to stir at room temperature for the following 3 h until complete. The reaction was then reduced in vacuo and the resulting residue was purified by preparative HPLC to yield the title compound as a white solid. Yield: 45 mg
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C@H:8]([CH3:11])[CH2:9][OH:10].C(N(CC)C(C)C)(C)C.[S:21](Cl)(Cl)=[O:22]>ClCCl>[CH3:11][CH:8]1[CH2:9][O:10][S@@:21](=[O:22])[N:7]1[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1
Reactant: O=S(Cl)Cl
Reactant: C[C@H](CO)Nc1ccccn1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC1CO[S@@](=O)N1c1ccccn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 59.8 %

Procedure:
A solution of (R)-N-(2-pyridyl)-2-aminopropanol (20.0 g, 0.13 moles) and N,N-diisopropylethylamine (33.6 g, 0.13 moles) in dichloromethane (500 ml) was cooled to 5° C. Then thionyl chloride (15.5 g, 0.13 moles) in dichloromethane (100 ml) was added slowly whilst the temperature was kept below 10° C. The mixture was stirred for 0.5 h. and ice cold water (500 ml) was added. The organic phase was separated and washed with water (5×500 ml). The aqueous phase was back-extracted with dichloromethane (2×500 ml), the organic phases were combined, dried (MgSO4) and evaporated in vacuo to give a brown oil. This was purified on a silica column, eluting with diethyl ether to give (R)4-methyl-3-(2-pyridyl)-[1,2,3]oxathiazolidine 2-oxide (15.4 g) as a clear oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]#[N:25])=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:5][CH:4]=1.C([Sn](=O)CCCC)CCC.C[Si]([N:46]=[N+:47]=[N-:48])(C)C.C(O)CO>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:17]3[C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]4[NH:48][N:47]=[N:46][N:25]=4)=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[CH:7][CH:8]=1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: COc1ccc(-c2c(-c3ccccc3)oc3ncnc(OCCCCCC#N)c23)cc1
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Solvent: OCCO
Product: COc1ccc(-c2c(-c3ccccc3)oc3ncnc(OCCCCCc4nnn[nH]4)c23)cc1
Reaction time: 1 h

Procedure:
Stir 1.00 g (2.1 mmol) 6-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}hexanenitrile, 0.79 g (3.2 mmol) di-n-butyltin oxide and 3.68 g (32 mmol) trimethylsilylazide in 44 ml toluene overnight at 80° C. Then add 1 ml ethylene glycol, stir for 1 h under reflux and then concentrate by evaporation. Take up the residue in ethyl acetate, wash with dilute hydrochloric acid and with sodium chloride solution, dry, and concentrate by evaporation. Purify the raw product by RP-HPLC (column: Gromsil 250 mm×40 mm, 10 μm; acetonitrile/water gradient: 0-3 min 5% acetonitrile, 3-50 min 5%→98% acetonitrile, 50-55 min 98% acetonitrile). Crystallize the combined product fractions from diethyl ether. 372 mg (38% of theor.) of the title compound is obtained as beige crystals.
Reaction SMILES: [Cl:1][C:2]1[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][C:3]=1[CH2:4][N:5]=[N+:6]=[N-:7].[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14]>C(O)C>[NH2:14][C:13]1[N:5]([CH2:4][C:3]2[CH:8]=[CH:9][CH:10]=[C:11]([Cl:12])[C:2]=2[Cl:1])[N:6]=[N:7][C:15]=1[C:16]([NH2:18])=[O:17]
Reactant: [N-]=[N+]=NCc1cccc(Cl)c1Cl
Reactant: N#CCC(N)=O
Solvent: CCO
Product: NC(=O)c1nnn(Cc2cccc(Cl)c2Cl)c1N

Procedure:
In a manner analogous to that described in Example 2, by reacting 2,3-dichlorobenzyl azide with cyanoacetamide there is obtained 5-amino-1-(2,3-dichlorobenzyl)-1H-1,2,3-triazole-4-carboxamide having a melting point of 224°-226° (from ethanol). The starting material can be produced from 2,3-dichlorobenzyl alcohol as starting material by halogenation, for example with phosphorus tribromide, and reaction with sodium azide.
Reaction SMILES: [CH3:1][NH:2][CH:3]1[C:12]2[N:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:6][CH2:5][CH2:4]1.[CH2:13](Br)[C:14]#[CH:15].[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O>[CH3:1][N:2]([CH2:15][C:14]#[CH:13])[CH:3]1[C:12]2[N:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:6][CH2:5][CH2:4]1
Reactant: C#CCBr
Reactant: CNC1CCCc2cccnc21
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: C#CCN(C)C1CCCc2cccnc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of N-methyl-5,6,7,8-tetrahydroquinolin-8-amine, 5, (0.50 g, 3.08 mmol) in THF (15 mL) was added propargyl bromide (0.28 mL, 3.08 mmol), sodium iodide (0.05 g, 0.31 mmol) and sodium carbonate (0.98 g, 9.24 mmol). The reaction mixture was stirred at room temperature for 3 h. The mixture was diluted with water, extracted with ethyl acetate. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The crude solid was used without further purification: 1H NMR (d6-DMSO) δ 8.30 (d, J=4.4 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 7.13 (dd, J=8.0, 5.2 Hz, 1H), 3.74 (dd, J=4.8, 4.8 Hz, 1H), 3.47 (ddd, J=16.8, 2.4, 2.4 Hz, 2H), 3.06 (s, 1H), 2.80-2.60 (m, 2H), 2.12 (s, 3H), 2.12-1.87 (m, 2H), 1.74-1.68 (m, 1H), 1.62-1.55 (m, 1H); ESI+ MS: m/z (rel intensity) 201.1 (100, [M+H]+).
Reaction SMILES: Cl.[C:2](=[NH:9])(OC)[CH2:3][CH2:4][CH2:5][CH3:6].CN(C)C=O.[NH2:15][CH2:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=1>C(N(CC)CC)C>[NH:9]=[C:2]([NH:15][CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]([OH:23])=[O:22])=[CH:24][CH:25]=1)[CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCC(=N)OC
Reactant: NCc1ccc(C(=O)O)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCCCC(=N)NCc1ccc(C(=O)O)cc1
Temperature: 65 °C
Reaction time: 1 h
Yield: 92.8 %

Procedure:
A 22 L, three-necked round bottom flask equipped with an air-powered mechanical stirrer was placed under a nitrogen atmosphere. The vessel was charged with methyl valerimidate hydrochloride (2.5 kg, 16 mol) and dimethylformamide (9.2 L). A thermometer was attached and the suspension cooled to 0°-15° C. with a cooling bath. Triethylamine (2.3 L) was added to the reaction at such a rate so that the internal temperature did not exceed 25° C. The cooling was stopped and the reaction was allowed to stir 1 hour. The reaction mixture was vacuum filtered using a Buchner funnel and a carboy (20 L). The filter cake was washed with additional dimethylformamide (1.0 L) and force-air dried for 15 min. The combined filtrates were saved. Another clean 22 L, three-necked round bottom flask equipped as above was placed under nitrogen. The vessel was charged with the combined filtrates from above followed by triethylamine (1.6 L) and 4-(aminomethyl)benzoic acid (1.7 kg, 11.5 mol). The thermometer was attached and the suspension was heated to an internal temperature of 65° C. with a heating mantle and a temperature controller. The heating was continued for 20 hours. The reaction was cooled to ambient temperature and filtered to yield 2.5 kg of product; 92% uncorrected yield.
Reaction SMILES: [C:1]([NH:10][NH2:11])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH3:12][CH:13]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH:15]=O>C(O)C>[CH3:12][CH:13]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14]/[CH:15]=[N:11]/[NH:10][C:1](=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CC(CC=O)CC(C)(C)C
Reactant: CCCCCCCC(=O)NN
Solvent: CCO
Product: CCCCCCCC(=O)N/N=C/CC(C)CC(C)(C)C
Temperature: 25 °C
Yield: 87.4 %

Procedure:
A mixture of 12a (3.00 g, 19.0 mmol) and 3,5,5-trimethylhexanal (4.05 g, 28.4 mmol) in ethanol (48 ml) was heated under reflux for 2 h. After cooling to room temperature, the product was concentrated and washed with ethanol. Drying under high vacuum (0.33 mbar) gave a total of 4.69 g (88%) of a colorless oil consisting of two isomers with respect to the amide bond conformation (E:Z ca. 56:44).
Reaction SMILES: O[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([P:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1.P(Cl)(Cl)[Cl:28]>C(Cl)(Cl)Cl>[Cl:28][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([P:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Oc1nccc(-c2cccc(P(c3ccccc3)c3ccccc3)c2)n1
Reactant: ClP(Cl)Cl
Solvent: ClC(Cl)Cl
Product: Clc1nccc(-c2cccc(P(c3ccccc3)c3ccccc3)c2)n1
Yield: 90 %

Procedure:
5 mmol of 20 are dissolved in 50 ml of CHCl3 and mixed with 10 mmol of PCl3. It is refluxed for 30 min, the volatiles are removed in a vacuum and the colorless solid is washed with water. Recrystallization from chloroform gives 21 in a yield above 90%. ESI MS, m/z (%): 375.8154 (100) [M+H]+. 31P{1H} NMR (101.2 MHz, 25° C., DMSO-d6): δ −7.40.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:55][CH2:54][CH2:53]1>CN(C=O)C>[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([N:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:55][CH2:54][CH2:53]1)=[O:9]
Reactant: O=C(O)c1ccccc1Oc1cc(Cl)ccc1Cl
Reactant: c1ccc2c(c1)CCCN2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(c1ccccc1Oc1cc(Cl)ccc1Cl)N1CCCc2ccccc21
Temperature: 50 °C
Reaction time: 1 h
Yield: 18.3 %

Procedure:
To a solution of 2-(2,5-dichloro-phenoxy)-benzoic acid (50.0 mg, 0.177 mmol, 1.0 equiv) in anhydrous DMF (1 mL) was added N-ethyldiisopropylamine (114.4 mg, 151 μL, 0.89 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (80.8 mg, 0.21 mmol, 1.2 equiv; [CAS RN 148893-10-1]). After stirring of the reaction mixture at 50° C. for 1 h, 1,2,3,4-tetrahydro-quinoline (28.3 mg, 27 μL, 0.21 mmol, 1.2 equiv; [CAS RN 635-46-1]) was added and stirring at 50° C. continued over night. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 12.9 mg (18%) of the title compound. MS (ISP): 398.2 [M+H]+.
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2([CH2:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)OCC[O:20]2)=[CH:15][CH:14]=1.C(N(CC)CC)C>C(O)(C)C>[N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[N:11][C:2]=1[N:30]1[CH2:29][CH2:28][N:27]([CH2:26][CH2:25][CH2:24][C:19]([C:16]2[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=2)=[O:20])[CH2:32][CH2:31]1
Reactant: Clc1ncc2ccccc2n1
Reactant: Fc1ccc(C2(CCCN3CCNCC3)OCCO2)cc1
Solvent: CCN(CC)CC
Solvent: CC(C)O
Product: O=C(CCCN1CCN(c2ncc3ccccc3n2)CC1)c1ccc(F)cc1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
2.25 g 2-Chloroquinazoline, 4.2 g 1-(3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]-propyl)piperazine and 2 ml triethylamine in 8 ml isopropanol are stirred and heated 21/2 hours at 80° C. The solvent is then evaporated in vacuo and the residue is taken up in hexane. The hexane solution is treated with charcoal, filtered and concentrated whereby the ketal of the title compound crystallizes out. The resulting precipitate is dissolved in 40 ml aqueous 1N hydrochloric acid. After 1 hour the acidic solution is made alkaline with aqueous ammonia. The resulting precipitate is filtered off and recrystallized from ethyl acetate to give the title compound, m.p. 129°-131° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.Br[CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1)=O.C(=O)(O)[O-].[Na+]>CCO>[CH3:7][C:5]1[N:6]2[CH:9]=[C:10]([C:12]3[CH:13]=[CH:14][C:15]([N+:18]([O-:20])=[O:19])=[CH:16][CH:17]=3)[N:1]=[C:2]2[S:3][CH:4]=1
Reactant: O=C(CBr)c1ccc([N+](=O)[O-])cc1
Reactant: Cc1csc(N)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Cc1csc2nc(-c3ccc([N+](=O)[O-])cc3)cn12
Temperature: 25 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
A mixture of 2-amino-4-methylthiazole (0.24 g, 2.11 mmol) and 2-bromo-4′-nitroaceto phenone (0.5 g, 2.05 mmol) in EtOH (20 ml) was heated under reflux for 16 h. The reaction mixture was allowed to cool and sodium bicarbonate (200 mg, 2.38 mmol) was added and heating was continued for 1 h. On cooling to room temperature, the solvent was removed under reduced pressure and DCM (75 ml) was added to the residue. The insoluble material was collected by filtration and purified by flash chromatography (50:1 DCM/MeOH) to give the title compound (0.266 g, 50%) as a yellow solid.
Reaction SMILES: [C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.N1C=CN=C1.[C:23]([Si:27](Cl)([CH3:29])[CH3:28])([CH3:26])([CH3:25])[CH3:24]>CN(C=O)C>[Si:27]([O:7][CH2:6][C@H:5]1[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2][C@@H:3]1[OH:4])([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:29])[CH3:28]
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 70.1 %

Procedure:
To a solution of 2.42 g (10 mmol) thymidine in 15 ml DMF was added 1.7 g (25 mmol) imidazole and 1.6 g (10.6 mmol) tert-butyldimethyl silyl chloride. The solution was stirred at room temperature for 3 hours. DMF was then removed in vacuo and the residue was dissolved in 150 ml of ethyl acetate. The solution was washed with water and the organic layer was dried over MgSO4. After removing the solvent, the solid was recrystallized with ethyl acetate/pentane to obtain 2.5 g pure 5'--O--(tert-butyldimethylsilyl) thymidine 1 (70% yield).: m.p. 193-194° C.; 1H NMR (500 MHz, CDCl3) δ9.0 (s, 1H, NH), 7.50 (s, 1H, H-6), 6.36 (dd, J=5.8, 8.1 Hz, 1H, H-1'), 4.44 (m, 1, H-3'), 4.03 (m, 1H, H-4'), 3.85 (m, 2H, H-5'), 2.66 (d, J=3.8 Hz, 1H, OH), 2.35 (m, 1H, H-2'), 2.07 (m, 1H, H-2'), 1.89 (s, 3H, C=CMe), 0.89 (s, 9H, CMe3), 0.09 (s, 6H, SiMe2); 13C NMR (125 MHz, CDCl3) δ163.8 (C-4), 150.4 (C-2), 135.4 (C-6), 110.9 (C-5), 87.2 (C-4'), 85.0 (C-1'), 72.6 (C-3'), 63.6 (C-5'), 41.1 (C-2'), 25.9 (SiCMe3), 18.3 (SiCMe3), 12.5 (C=CMe), -5.4 (SiMe2), -5.5 (SiMe2).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[N+:12]([C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1)([O-:14])=[O:13].N1C=CC=CC=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([N+:12]([O-:14])=[O:13])[CH:20]=3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Reactant: Clc1ncnc2[nH]cc(I)c12
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=[N+]([O-])c1cccc(-n2cc(I)c3c(Cl)ncnc32)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.6 %

Procedure:
To a solution of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (5.58 g, 20 mmol) in DCM (200 mL) were added 3-nitrophenylboronic acid (5 g, 30 mmol), pyridine (9.49 g, 120 mmol), anhydrous Cu(OAc)2 (3.64 g, 20 mmol) and 4A MS (20 g). The resulting suspension was stirred at room temperature overnight under O2 atmosphere and then quenched with water and filtered through a pad of celite. The filtrate was concentrated under vacuum. The crude product was purified by flash chromatography (silica gel, 0-30% ethyl acetate in petroleum ether) to provide 4-chloro-5-iodo-7-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine (68) (5.9 g, 74%) as a yellow solid. LC-MS (ESI): m/z (M+1) 401.
Reaction SMILES: [C:1](Cl)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([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.[C:21]([C:24]1[CH:25]=[C:26]2[C:31](=[O:32])[NH:30][C:28](=[O:29])[C:27]2=[CH:33][CH:34]=1)([OH:23])=[O:22].CCN(C(C)C)C(C)C>C(#N)C>[C:1]([N:30]1[C:31](=[O:32])[C:26]2=[CH:25][C:24]([C:21]([OH:23])=[O:22])=[CH:34][CH:33]=[C:27]2[C:28]1=[O:29])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([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
Reactant: O=C(O)c1ccc2c(c1)C(=O)NC2=O
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=C(O)c1ccc2c(c1)C(=O)N(C(c1ccccc1)(c1ccccc1)c1ccccc1)C2=O

Procedure:
To trityl chloride resin (5 g; 10.25 retool; 200-400 mesh: 1% divinylbenzene-crosslinked polystyrene) presoaked in 80 mL dry acetonitrile for 30 min., 5 g (26 mmol) 4-carboxyphthalimide (2) from Example 2 and 6 mL (34 mmol) DIPEA were added, and the suspension was refluxed for 72 h. Following filtration, the polymer was washed with 300 mL DMF and then 300 mL CH2Cl2. The loading was determined by weight difference, and confirmed to be 0.5 mmol/g resin by TFA-induced cleavage of 4-carboxyphthalimide from the resin.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=3)[N:10]([CH3:18])[C:9]=2[CH3:19])=[CH:4][CH:3]=1.[CH2:20]([O:24][C:25](=[O:30])[C:26](Br)([CH3:28])[CH3:27])[CH2:21][CH2:22][CH3:23]>>[CH2:20]([O:24][C:25](=[O:30])[C:26]([O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:18])[C:9]([CH3:19])=[C:8]2[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)([CH3:28])[CH3:27])[CH2:21][CH2:22][CH3:23]
Reactant: CCCCOC(=O)C(C)(C)Br
Reactant: Cc1c(-c2ccc(Cl)cc2)c2cc(O)ccc2n1C
Product: CCCCOC(=O)C(C)(C)Oc1ccc2c(c1)c(-c1ccc(Cl)cc1)c(C)n2C

Procedure:
The above compound was prepared from 3-(4-chlorophenyl)-1,2-dimethyl-1H-indole-5-ol and 2-bromo-2-methyl-propanoic acid butylester, using a procedure analogous to that of Example 102.
Reaction SMILES: [NH2-:1].[Li+].Cl[SiH:4]1[N:8]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:7]=[CH:6][N:5]1[C:13]([CH3:16])([CH3:15])[CH3:14].CCCCCC>COCCOC>[NH2:1][SiH:4]1[N:8]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:7]=[CH:6][N:5]1[C:13]([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)N1C=CN(C(C)(C)C)[SiH]1Cl
Reactant: [NH2-]
Agent: [Li+]
Solvent: CCCCCC
Solvent: COCCOC
Product: CC(C)(C)N1C=CN(C(C)(C)C)[SiH]1N
Temperature: 25 °C
Reaction time: 2 h
Yield: 92 %

Procedure:
In an argon atmosphere, 505 mg (purity: 95%, 20.9 mmol) of lithium amide was suspended in 20 mL of 1,2-dimethoxyethane and after adding 4.65 g (20.0 mmol) of Si(tBuNCHCHNtBu)(H)Cl, the mixture was stirred at room temperature for 2 hours. Subsequently, 20 mL of hexane was added to the reaction mixture, and the mixture was stirred at room temperature for 10 minutes. Insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 78° C./3.8×102 Pa) to obtain 2-amino-1,3-di-tert-butyl-1,3-diaza-2-silacyclopent-4-ene (Si(tBuNCHCHNtBu)(H)NH2) as a pale yellow liquid (yielded amount: 3.93 g, yield: 92%).
Reaction SMILES: [C:1]([C:9]1[O:10][C:11]2[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=2[C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([N+:27]([O-:29])=[O:28])[CH:21]=2)=[CH:16][CH:15]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[S:35]([C:38]1[CH:46]=[CH:45][C:41]([C:42]([OH:44])=[O:43])=[C:40]([OH:47])[CH:39]=1)(=[O:37])=[O:36]>>[C:1]([C:9]1[O:10][C:11]2[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=2[C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([O:26][S:35]([C:38]3[CH:46]=[CH:45][C:41]([C:42]([OH:44])=[O:43])=[C:40]([OH:47])[CH:39]=3)(=[O:37])=[O:36])=[C:22]([N+:27]([O-:29])=[O:28])[CH:21]=2)=[CH:16][CH:15]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1ccccc1)c1oc2ccccc2c1-c1ccc(-c2ccc(O)c([N+](=O)[O-])c2)cc1
Reactant: O=C(O)c1ccc(S(=O)(=O)Cl)cc1O
Product: O=C(O)c1ccc(S(=O)(=O)Oc2ccc(-c3ccc(-c4c(C(=O)c5ccccc5)oc5ccccc45)cc3)cc2[N+](=O)[O-])cc1O

Procedure:
The title compound was prepared from 4′-(2-benzoyl-benzofuran-3-yl)-3-nitro-biphenyl-4-ol and 4-chlorosulfonyl-2-hydroxy-benzoic acid, in substantially the same manner, as described in Example 1 step g, and was obtained as a yellow solid, mp 105-107° C.; MS m/e 683 (M−H)+;
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:17])=[CH:4][C:5]2[C:6]([CH3:16])([CH3:15])[CH2:7][CH:8]=[C:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1.I[CH2:19][CH2:20][CH3:21]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][C:3]=1[O:17][CH2:19][CH2:20][CH3:21])[C:6]([CH3:15])([CH3:16])[CH2:7][CH:8]=[C:9]2[CH:12]([CH3:13])[CH3:14]
Reactant: CCCI
Reactant: CC(C)C1=CCC(C)(C)c2cc(O)c(Br)cc21
Product: CCCOc1cc2c(cc1Br)C(C(C)C)=CCC2(C)C
Yield: 70 %

Procedure:
Following General Procedure O, 3-bromo-5-isopropyl-8,8-dimethyl-7,8-dihydronaphthalen-2-ol (Compound 97, 0.36 g, 1.2 mmol) was reacted with 1-iodopropane to afford 0.29 g (70%) of the title compound as a clear oil.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=[O:7])=[CH:2]1.S(=O)(=O)(O)O.[CH3:14]O>>[S:1]1[CH:5]=[CH:4][C:3]([C:6]([O:8][CH3:14])=[O:7])=[CH:2]1
Reactant: CO
Reactant: O=C(O)c1ccsc1
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccsc1

Procedure:
3-thiophenecarboxylic acid (2.0 g) was dissolved in MeOH (27 mL) and concentrated sulphuric acid (1.5 mL) was added. The reaction mixture was refluxed for 3 hours and 30 min., then concentrated under reduced pressure. A saturated NaHCO3 solution was added and the mixture was extracted with ethyl acetate. The organic phase was dried over Na2SO4 and concentrated in vacuo to give 1.98 g of the title compound as a colourless liquid which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[N:10][C:11](=O)[NH:12][N:13]=1.C(Cl)(Cl)[Cl:16].P(Cl)(Cl)(Cl)=O>CN(C)C=O>[Cl:16][C:11]1[N:12]=[N:13][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[CH:9][N:10]=1
Reactant: ClC(Cl)Cl
Reactant: O=c1ncc(-c2ccccc2Cl)n[nH]1
Solvent: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: Clc1ncc(-c2ccccc2Cl)nn1

Procedure:
A suspension of 53 g. of 6-(o-chlorophenyl)-1,2,4-triazin-3(2H)-one in 400 ml. of chloroform is cooled in an ice bath and 400 ml. of phosphorus oxychloride is added followed by 3 g. of N,N-dimethylformamide. The mixture is refluxed overnight and treated as described in Example 12, giving 3-chloro-6-(o-chlorophenyl)-1,2,4-triazine as white needles.