Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[CH3:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=1[OH:24].C([O-])([O-])=O.[K+].[K+]>CC#N>[CH2:2]([O:24][C:18]1[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:17]=1[CH3:16])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCCCCCCCCCCBr
Reactant: Cc1cccc(C)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCCCCCCCCCCCCCOc1c(C)cccc1C
Yield: 99.3 %

Procedure:
The product was generated via general protocol A using 1-bromotetradecane (44.7 mL, 0.147 mol), 2,6-dimethylphenol (20.0 g, 0.162 mol), K2CO3 (81.3 g, 0.588 mol) and CH3CN (150 mL). Yielded 46.5 g (99.3%) of a yellow/orange liquid. 1H NMR (CDCl3, 400 MHz) δ: 7.01 (d, 4J=7.3 Hz, 2H, Ar—H), 6.91 (t, 3J=6.8 Hz, 3H, Ar—H), 3.76 (t, 3J=6.7 Hz, 2H, OCH2), 2.28 (s, 6H, Ar—CH3), 1.81 (p, 3J=7.1 Hz, 2H, OCH2CH2), 1.50 (p, 3J=7.4 Hz, 2H, OCH2CH2CH2), 1.36-1.27 (m, 22H), 0.89 (t, 3J=6.9 Hz, 3H, CH2CH3). 13C NMR (CDCl3, 100 MHz) δ: 156.08, 130.95, 128.71, 123.54, 77.32, 77.00, 76.68, 72.28, 31.93, 30.44, 29.70, 29.68, 29.66, 29.63, 29.57, 29.37, 26.16, 22.69, 16.26, 14.12.
Reaction SMILES: FC(F)(CCCC)C(=O)CC[C@H:6]1[C@H:13](OC2CCCCO2)[CH2:12][C@H:11]2[C@@H:7]1[CH2:8][C:9](=[O:21])[O:10]2.[BH4-].[Na+]>CO>[CH:11]12[CH2:12][CH2:13][CH2:6][CH:7]1[CH2:8][C:9](=[O:21])[O:10]2
Reactant: CCCCC(F)(F)C(=O)CC[C@@H]1[C@H]2CC(=O)O[C@H]2C[C@H]1OC1CCCCO1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: O=C1CC2CCCC2O1

Procedure:
The compound (51) (12.6 g) was reduced with sodium borohydride (1.25 g) in methanol (400 ml) at 0° C. to give the titled compound (52). Yield: 12.1 g (95.5%).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([S:12][C:13]1[N:17]3[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]3=[N:15][N:14]=1)=[CH:7][CH:6]=2.[CH2:23]([N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1)[CH3:24].C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O>[CH2:23]([N:25]1[CH:29]=[C:28]([C:2]2[CH:3]=[N:4][C:5]3[C:10]([CH:11]=2)=[CH:9][C:8]([S:12][C:13]2[N:17]4[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]4=[N:15][N:14]=2)=[CH:7][CH:6]=3)[CH:27]=[N:26]1)[CH3:24]
Reactant: Cc1ccc2nnc(Sc3ccc4ncc(Br)cc4c3)n2n1
Reactant: CCn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: ClCCl
Solvent: O
Product: CCn1cc(-c2cnc3ccc(Sc4nnc5ccc(C)nn45)cc3c2)cn1
Yield: 7 %

Procedure:
To a microwave vessel was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline (200 mg, 0.54 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (149 mg, 0.67 mmol), K2CO3 (186 mg, 1.34 mmol), 1,4-dioxane (7 mL) and water (3.5 mL). The solution was degassed by bubbling nitrogen for 10 min and then Pd(dppf)2Cl2 dichloromethane (20 mg, 0.0269 mmol) was added. The microwave vessel was capped and reacted in a microwave reactor at 120° C. for 20 min. The microwave vessel was cooled and then the mixture was extracted into dichloromethane and washed with water. The volatiles were removed in vacuo and the residue absorbed onto silica gel and purified by flash chromatography (SiO2, dichloromethane:CH3OH 100:0-80:20) to obtain 3-(1-ethyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline as a brown oil (7% yield).
Reaction SMILES: Cl[S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH:13][C:14]([C:16]2[CH:21]=[N:20][C:19]([CH3:22])=[CH:18][N:17]=2)=[O:15])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[NH3:23]>>[NH2:23][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH:13][C:14]([C:16]2[CH:21]=[N:20][C:19]([CH3:22])=[CH:18][N:17]=2)=[O:15])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: Cc1cnc(C(=O)NCCc2ccc(S(=O)(=O)Cl)cc2)cn1
Reactant: N
Product: Cc1cnc(C(=O)NCCc2ccc(S(N)(=O)=O)cc2)cn1

Procedure:
treating 5-methylpyrazine-2-carboxylic acid of the formula VIII: ##STR10## with methanol under reflux to obtain 5-methylpyrazine-2-carboxylic acid methyl ester of the formula VIII A ##STR11## ii) reacting 5-methylpyrazine-2-carboxylic acid methyl ester of the formula VIII A with 2-phenylethylamine of the formula II: ##STR12## at 100° to 200° C. to obtain 5-methylpyrazine 2-(2-phenylethyl) carboxamide of the formula IX: ##STR13## iii) chlorosulfonating the 5-methylpyrazine-2(2-phenylethyl)carboxamide of the formula IX with chlorosulfonic acid at 0°-45° C. to obtain [N-[2-[4-Chlorosulfonyl) phenyl]ethyl]-5-methylpyrazine carboxamide] of the formula X: ##STR14## iv) and treating the (N-[2-[4-(chlorosulfonyl)phenyl]ethyl]-5-methyl pyrazine-carboxamide] of the formula X with ammonia to obtain N-[2-[4-(aminosulfonyl)phenyl]ethyl]-5-methylpyrazine carboxamide of the formula I.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[C:7](=[O:12])[NH:8][CH:9]=[CH:10][O:11][C:5]=2[CH:4]=1.[H-].[Na+].[Br:17][CH2:18][CH2:19][CH2:20][CH2:21]Br>CN(C)C=O>[Br:17][CH2:18][CH2:19][CH2:20][CH2:21][N:8]1[C:7](=[O:12])[C:6]2[CH:13]=[CH:14][C:3]([O:2][CH3:1])=[CH:4][C:5]=2[O:11][CH:10]=[CH:9]1
Reactant: COc1ccc2c(c1)OC=CNC2=O
Reactant: BrCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc2c(c1)OC=CN(CCCCBr)C2=O
Reaction time: 0.5 h

Procedure:
200 mg of 4,5-dihydro-8-methoxy-1,4-benzoxazepin-5-one was dissolved in 10 ml of dimethylformamide, then 50 mg (1.2 equivalents) of 60% sodium hydride was added under ice cooling. This was agitated for 30 minutes, then 790 mg (3 equivalents) of 1,4-dibromobutane was added and the resultant mixture was agitated at room temperature for 6 hours.
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]([Si:7]([CH3:48])([CH3:47])[O:8][C:9]([C:12]#[C:13][CH:14]([OH:46])[C@H:15]([C:17]1[C@:34]2([CH3:35])[C@H:20]([C:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[C:24]([CH2:25][C@@H:26]([O:36][Si:37]([CH3:45])([CH3:44])[C:38]([CH3:43])([CH3:42])[CH:39]([CH3:41])[CH3:40])[CH2:27][CH2:28]2)=[CH:23][CH:22]=3)[CH2:19][CH:18]=1)[CH3:16])([CH3:11])[CH3:10])([CH3:6])[CH3:5].[C:49]1([N:55]=[C:56]=[S:57])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C1COCC1.N1C=CN=C1>[CH3:3][C:4]([Si:7]([CH3:47])([CH3:48])[O:8][C:9]([C:12]#[C:13][CH:14]([O:46][C:56](=[S:57])[NH:55][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[C@H:15]([C:17]1[C@:34]2([CH3:35])[C@H:20]([C:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[C:24]([CH2:25][C@@H:26]([O:36][Si:37]([CH3:44])([CH3:45])[C:38]([CH3:43])([CH3:42])[CH:39]([CH3:40])[CH3:41])[CH2:27][CH2:28]2)=[CH:23][CH:22]=3)[CH2:19][CH:18]=1)[CH3:16])([CH3:10])[CH3:11])([CH3:6])[CH3:5]
Reactant: S=C=Nc1ccccc1
Reactant: CC(C)C(C)(C)[Si](C)(C)O[C@H]1CC[C@@]2(C)C(=CC=C3[C@@H]2CC[C@]2(C)C([C@H](C)C(O)C#CC(C)(C)O[Si](C)(C)C(C)(C)C)=CC[C@@H]32)C1
Agent: [H-]
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: C1CCOC1
Product: CC(C)C(C)(C)[Si](C)(C)O[C@H]1CC[C@@]2(C)C(=CC=C3[C@@H]2CC[C@]2(C)C([C@H](C)C(C#CC(C)(C)O[Si](C)(C)C(C)(C)C)OC(=S)Nc4ccccc4)=CC[C@@H]32)C1
Reaction time: 1 h
Yield: 111.3 %

Procedure:
Sodium hydride (60% dispersion, 6.55 g, 164 mmol) was suspended in 200 mL of THF followed by the addition of 446 mg (6.55 mmol) imidazole at 5° C. To this gray suspension, a solution of crude 93 g (131 mmol) (3β)-25-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-[[dimethyl(1,1,2-trimethylpropyl)silyl]oxy]cholesta-5,7,16-trien-23-yn-22-ol in 700 mL of THF was added dropwise at 8°-10° C. over 30 min. The resulting dark brown suspension was stirred at the same temperature for 1 h. Then, a solution of 17.3 mL (144 mmol) phenyl isothiocyanate in 200 mL of THF was added, and the mixture was stirred at 10° C. for 1 h. The reaction was quenched by the dropwise addition of 500 mL of 10% aqueous NaHCO3 followed by 70 g of celite. After stirring for 10 minutes, the solid was filtered and washed with 500 ml of ethyl acetate. The aqueous layer was extracted twice with 500 ml each of ethyl acetate. The combined organic layers were washed successively with 10% aqueous NaHCO3 and brine, dried over MgSO4, and concentrated to dryness. Some polar, colored impurities were removed by dissolving 132 g of the residue in 200 mL of 3% ethyl acetate in hexane and filtering it through a plug of 120 g of silica gel. The plug was washed with 1 L of 3% ethyl acetate in hexane. The eluate was collected and concentrated to dryness to give 117 g (overweight) of crude phenylcarbamothioic acid O-[(3β)-25-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-[[dimethyl(1,1,2-trimethylpropyl)silyl]oxy]cholesta-5,7,16-trien-23-yn-22-yl] ester as an orange oil. This crude material was used for the next step.
Reaction SMILES: Br[C:2]1[C:22]([O:23][CH3:24])=[CH:21][C:5]2[N:6]([CH3:20])[C:7](=[O:19])[CH2:8][N:9]=[C:10]([C:11]3[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=3)[C:14]#[N:15])[C:4]=2[CH:3]=1.C1(B(O)O)C=CC=CC=1.[O:34]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1B(O)O)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>>[CH3:24][O:23][C:22]1[C:2]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[O:34][C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)=[CH:3][C:4]2[C:10]([C:11]3[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=3)[C:14]#[N:15])=[N:9][CH2:8][C:7](=[O:19])[N:6]([CH3:20])[C:5]=2[CH:21]=1
Reactant: OB(O)c1ccccc1Oc1ccccc1
Reactant: COc1cc2c(cc1Br)C(c1cccc(C#N)c1)=NCC(=O)N2C
Agent: OB(O)c1ccccc1
Product: COc1cc2c(cc1-c1ccccc1Oc1ccccc1)C(c1cccc(C#N)c1)=NCC(=O)N2C
Yield: 72 %

Procedure:
Prepared from 3-(7-bromo-8-methoxy-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-benzonitrile Intermediate 9 using the same method described for Example 1 and instead of using benzene boronic acid, we used 2-phenoxy-phenyl boronic acid The title compound (120 mg) was obtained as a pale green solid, (yield=72%).
Reaction SMILES: [H-].[Na+].[NH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1.Cl[C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][N:15]=1.O>CN(C=O)C>[F:21][C:20]([F:23])([F:22])[C:17]1[CH:18]=[CH:19][C:14]([O:12][C:9]2[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][NH2:3])=[CH:7][CH:8]=2)=[N:15][CH:16]=1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Reactant: NCCc1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: NCCc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
Temperature: 50 °C
Reaction time: 0.25 h
Yield: 71 %

Procedure:
Sodium hydride/60 percent oil dispersion (0.72 mg, 18 mmol) was added in portions to a slurry of tyramine (2.1 g, 15 mmol) in anh. DMF (25 mL). After 15 minutes, 2-chloro-5-(trifluoromethyl)pyridine (2.9 g, 16 mmol) was added neat and the reaction heated to 50° C. for 3 hours. After cooling, the reaction was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The organic portions were combined and washed with brine (50 mL) and dried (Na2SO4). Filtration and removal of solvent left a brown residue that partially solidified. This was triturated in minimal ethyl acetate and collected by filtration, leaving product as a white solid, 3.0 g, 10.6 mmol, 71 percent yield.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[C:15]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:16]([CH:21]=O)=[CH:17][CH:18]=[CH:19][CH:20]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C1(C2C=CC=CC=2)C=CC=CC=1CN1CCN(C2C=CC=CC=2)CC1>>[C:15]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][N:12]1[CH2:11][CH2:10][N:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=2[CH3:1])[CH2:14][CH2:13]1
Reactant: O=Cc1ccccc1-c1ccccc1
Reactant: Cc1cccc(N2CCNCC2)c1C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: c1ccc(-c2ccccc2CN2CCN(c3ccccc3)CC2)cc1
Product: Cc1cccc(N2CCN(Cc3ccccc3-c3ccccc3)CC2)c1C

Procedure:
52.7 mg of the target compound (0.15 mmol, 18.3%) was obtained using 1-(2,3-dimethylphenyl)piperazine (312 mg, 1.64 mmol), biphenyl-2-carbaldehyde (150 mg, 0.82 mmol) and NaBH(OAc)3 (529 mg, 2.46 mmol) according to the synthesis method of Compound 1.
Reaction SMILES: [BH4-].[Na+].[CH:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:7]=2[CH2:6][CH2:5][N:4]=1.[ClH:16]>CO.C(O)(C)C>[ClH:16].[CH2:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:7]=2[CH2:6][CH2:5][NH:4]1
Reactant: C1=NCCc2c1oc1ccccc21
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: CO
Product: c1ccc2c3c(oc2c1)CNCC3
Temperature: 20 °C
Reaction time: 20 h

Procedure:
9.2 g (240 mmol) of sodium borohydride are added in small portions and in the space of 3 h to a suspension of 8.2 g (47.8 mmol) of 3,4-dihydrobenzofuro[2,3-c]pyridine in 350 ml of methanol. The mixture is stirred for 20 h at 20° C. and the solvent then evaporated off under reduced pressure. The residue is washed with water and the 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine extracted by means of ethyl acetate. The organic phase is separated off after settling has taken place, dried over sodium sulphale and evaporated under reduced pressure, and the residue is treated with one equivalent of 0.1N hydrochloric acid in isopropyl alcohol. The hydrochloride is isolated and recrystallized in a mixture of isopropyl alcohol and ethanol.
Reaction SMILES: [I:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[I:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([S:22]([CH3:21])(=[O:24])=[O:23])[CH2:12][CH2:13]2)=[N:6][CH:7]=1
Reactant: Ic1ccc(N2CCNCC2)nc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCN(c2ccc(I)cn2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.2 %

Procedure:
To a stirred solution of 1-(5-iodopyridin-2-yl)piperazine (CAS number 219635-89-9, 5.083 g, 17.6 mmol), and triethylamine (4.91 mL, 35.2 mmol) in CH2Cl2 (75 mL) at 0° C. was added methane sulfonyl chloride (2.04 mL, 26.4 mmol) dropwise and the resulting suspension stirred for 30 mins at room temperature. The reaction mixture was diluted with CH2Cl2 (200 mL) and washed twice with water (2×200 mL). The organic phase was washed with saturated brine solution (1×200 mL), dried (MgSO4), filtered and concentrated in vacuo to give a dark yellow solid. This was triturated with ether, filtered and dried to give 1-(5-iodopyridin-2-yl)-4-(methylsulfonyl)piperazine as a yellow solid (5.378 g, 83%).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[CH:5][CH:4]=1.[CH2:11]1[C:16](=[O:17])[S:15][CH2:14][C:12]1=[O:13].[OH-].[K+].Cl>O1CCOCC1.O>[OH:13][C:12]1[CH2:14][S:15][C:16](=[O:17])[C:11]=1[CH2:7][C:6]1[CH:9]=[CH:10][C:3]([S:2][CH3:1])=[CH:4][CH:5]=1
Reactant: CSc1ccc(CBr)cc1
Reactant: O=C1CSC(=O)C1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CSc1ccc(CC2=C(O)CSC2=O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 26.4 %

Procedure:
To a suspension of 4-methylthiobenzyl bromide (5.6 g. 25.8 mmol), thiotetronic acid (3.0 g, 25.8 mmol) in dioxane (50 ml), was added aqueous potassium hydroxide (25.8 mL). The mixture was stirred at temperatures in the range of 65°-70° C. for 3 hours. Then, the mixture was cooled to room temperature, poured into H2O, acidified with HCl (2N) and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography on acid washed (5% H3PO4 in MeOH) silica gel (eluting solvent hexane/EtOAc 1/3) gave a white solid (1.72 g, 26.5%): m.p. 206°-208° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N:8](S(C)(=O)=O)[S:9]([CH3:12])(=[O:11])=[O:10])[C:5]([I:17])=[CH:4][N:3]=1.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5]([I:17])=[CH:4][N:3]=1
Reactant: CS(=O)(=O)N(c1cc(Cl)ncc1I)S(C)(=O)=O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CS(=O)(=O)Nc1cc(Cl)ncc1I
Temperature: 2.5 °C
Yield: 86.7 %

Procedure:
N-(2-chloro-5-iodopyridin-4-yl)-N-(methylsulfonyl)methanesulfonamide (13) (1.1 g) was stirred with THF (6.8 mL) and 10% sodium hydroxide (6.8 mL) at room temperature overnight. The THF was evaporated and the aqueous was brought to pH about 5 with 10% citric acid solution. Product was deposited—the mixture was cooled at 0-5° C. for 0.5 h and the product filtered off. It was washed with a little water and dried over sodium hydroxide in a vacuum desiccator to give the title compound (772 mg, 83%). 1H-NMR (500 MHz, DMSO-d6): 3.29 (s, 3H), 7.42 (s, 1H), 8.66 (s, 1H).
Reaction SMILES: [CH:1]([Mg]Br)=[CH2:2].[F:5][C:6]([F:16])([F:15])[C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=1)[CH:10]=[O:11]>C1COCC1>[F:5][C:6]([F:15])([F:16])[C:7]1[CH:8]=[C:9]([C:10]([OH:11])=[CH:1][CH3:2])[CH:12]=[CH:13][CH:14]=1
Reactant: O=Cc1cccc(C(F)(F)F)c1
Reactant: C=C[Mg]Br
Solvent: C1CCOC1
Product: CC=C(O)c1cccc(C(F)(F)F)c1
Temperature: -10 °C
Reaction time: 1 h
Yield: 87 %

Procedure:
Vinylmagnesium bromide (40 mL of a 1.0 M THF solution, 40 mmol) was added to a dry round bottom flask under nitrogen. The solution was cooled to −10° C. and charged with meta-trifluoromethylbenzaldehyde (5.0 g, 29 mmol). The reaction was stirred for 1 h, warmed to RT and quenched with sat. NH4Cl. The mixture was extracted with EtOAC three times, and the organic extracts were dried (MgSO4) and concentrated in vacuo. The crude material was purified via flash chromatography to give 1-(3-trifluoromethylphenyl)propen-1-ol as an oil (5.0 g, 87% yield). A portion of 1-(3-trifluoromethylphenyl)propen-1-ol (0.5 g, 2.5 mmol) was dissolved in acetone (20 mL). The resultant solution was cooled to 0° C., treated with Jones reagent (1.14 mL of a 2.6 M solution, 2.96 mmol), and stirred for 10 minutes before being quenched with the addition of isopropyl alcohol (1.5 mL). The mixture was stirred for 5 min at rt, diluted with Et2O, filtered through Celite, washed with 10% Na2SO3. The material was purified via filtration through a plug of silica gel (1:1 Et2O:hexanes as eluant) to provide the 1-(3-trifluoromethylphenyl)propenone as an oil (320 mg, 65% yield), which solidified upon standing in the freezer. 1H-NMR (300 MHz, CDCl3): δ 8.20 (s, 1H), 8.13 (d, 1H, J=7.7 Hz), 7.84 (d, 1H, J=9.0 Hz),7.64 (t, 1H, J=7.7 Hz), 7.16 (dd, 1H, J=17.2, 10.6 Hz), 6.49 (dd, 1H, J=17.2, 1.5 Hz), 6.03 (dd, 1H, J=10.6, 1.5 Hz).
Reaction SMILES: [C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:14]1([O:22][CH3:23])[C:15](=[CH:18][CH:19]=[CH:20][CH:21]=1)[O:16][CH3:17].[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(Cl)Cl>[CH3:17][O:16][C:15]1[CH:18]=[C:19]([CH:20]=[CH:21][C:14]=1[O:22][CH3:23])[C:9]([C:8]1[CH:12]=[CH:13][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=1)=[O:10]
Reactant: COc1ccccc1OC
Reactant: CC(C)(C)c1ccc(C(=O)Cl)cc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(C(=O)c2ccc(C(C)(C)C)cc2)cc1OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a 2 L three-neck flask was added 4-t-butylbenzoyl chloride (100 mL), veratrole (70 mL) and methylene chloride (800 mL). The flask was seated in ice bath. Anhydrous aluminum chloride (100 g) was added to the flask through a solid addition funnel slowly. The mixture was stirred at room temperature for 1 hour and then poured into ice water (1 L). Hydrochloric acid (12N, 150 mL) was added to the mixture. The bottom layer was isolated. The top layer was further extracted with methylene chloride twice (400+200 mL). The combined organic layers were washed with brine (200 mL) and filtered over magnesium sulfate. The final solution was condensed to an oily residue and the residue was dried in vacuum oven to provide 150 g waxy 3,4-dimethoxy-4′-t-butylbenzophenone.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6](=[O:23])[O:7][C:8]2[CH:14]=[C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:12]=[CH:11][C:9]=2[CH:10]=1)=[O:4].[OH-].[Na+].Cl.O>C(O)C>[CH2:16]([O:15][C:13]1[CH:12]=[CH:11][C:9]2[CH:10]=[C:5]([C:3]([OH:4])=[O:2])[C:6](=[O:23])[O:7][C:8]=2[CH:14]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)c1cc2ccc(OCc3ccccc3)cc2oc1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1cc2ccc(OCc3ccccc3)cc2oc1=O
Reaction time: 0.17 h
Yield: 94.9 %

Procedure:
The compound 1 (0.1 g, 0.32 mmol) is dissolved in ethanol (0.5 mL), and 10% of sodium hydroxide aqueous solution (0.5 mL) is added into. The resulting mixture is reacted for 1 hour with reflux. After cooling, the strong hydrochloric acid (0.3 mL) is added and followed by stirring for 10 minutes. 5 mL of water is added, and produced solid is obtained by filtration. The filter cake is washed with water, followed by drying to obtain 0.09 g of the captioned compound, yield: 90%. m.p. 196-197° C. 1H NMR (DMSO-d6): δ=5.25(s, 2 H), 7.08(dd, J=2.2 Hz, 8.8 Hz, 1H), 7.12(d, J=2.2 Hz, 1H), 7.30-7.50(m, 5H), 7.83(d, J=8.8 Hz, 1H), 8.73(s, 1H); Elements Analysis, C17H12O5 (296): Calculated C, 68.92; H, 4.05; Found C, 68.50; H, 4.12; IR(KBr) : 3054.7, 1747.2, 1677.8, 1600.7, 1556.3, 1421.3, 1378.9, 1257.4, 1209.2, 1120.2, 732.8 cm−1; EI-MS(m/z): 296(4, M+), 91(100).
Reaction SMILES: O1CCCC1.CN(OC)[C:8](=[O:17])[C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[NH2:16].[C:20]([O:24][C:25]([NH:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32](Br)[CH:31]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C([Li])CCC>C(OC(=O)C)C.O.CCCCCC>[NH2:16][C:10]1[CH:11]=[CH:12][C:13]([Cl:15])=[CH:14][C:9]=1[C:8]([C:33]1[CH:32]=[CH:31][C:30]([CH2:29][CH2:28][NH:27][C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])=[CH:35][CH:34]=1)=[O:17]
Reactant: CON(C)C(=O)c1cc(Cl)ccc1N
Reactant: CC(C)(C)OC(=O)NCCc1cccc(Br)c1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCCc1ccc(C(=O)c2cc(Cl)ccc2N)cc1
Yield: 53 %

Procedure:
A tetrahydrofuran (70 ml) solution of N-methyl-N-methyloxy-2-amino-5-chlorobenzamide (6.4 g) and N-tert-butoxycarbonyl-3-bromophenethylamine (6.0 g) was cooled to −78° C., to which was gradually added dropwise a hexane solution of n-butyl lithium (1.6 mol/L) (67 ml). To the mixture were then added water (300 ml) and acetic acid ethyl ester (300 ml). The organic layer was washed with water and dried over anhydrous MgSO4, and the solvent was distilled off. The residual oily compound was purified by means of a silica gel column chromatography, followed by recrystallization from hexane to afford 2-amino-4′-(2-tert-butoxycarbonylaminoethyl)-5-chlorobenzophenone (3.97 g) as a pale yellow crystalline product.