Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH:8][C:9]2[CH:28]=[CH:27][CH:26]=[CH:25][C:10]=2[C:11]([NH:13][O:14][CH2:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)=[O:12])=[CH:3][CH:2]=1.Cl.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.O>CN(C=O)C>[N:30]1([C:20]([C:19]2[CH:18]=[CH:17][C:16]([CH2:15][O:14][NH:13][C:11](=[O:12])[C:10]3[CH:25]=[CH:26][CH:27]=[CH:28][C:9]=3[NH:8][CH2:7][C:4]3[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=3)=[CH:24][CH:23]=2)=[O:21])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1
Reactant: C1COCCN1
Reactant: O=C(O)c1ccc(CONC(=O)c2ccccc2NCc2ccncc2)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NOCc1ccc(C(=O)N2CCOCC2)cc1)c1ccccc1NCc1ccncc1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a stirred mixture of 4-{2-[(pyridin-4-ylmethyl)-amino]-benzoylaminooxymethyl}-benzoic acid (see example 404, 220 mg) in DMF (3 ml) was added N,N′-carbonyldiimidazole (99 mg). The mixture was stirred at room temperature for 45 minutes and morpholine hydrochloride (79 mg) was added. The reaction mixture was stirred at room temperature for 18 hours and poured into water. The product was extracted several times with EtOAc and the combined organic layers were washed with water and brine, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc as eluent) and gave the title compound. 13C-NMR (DMSO-d6) δ 168.7, 167.2, 149.5, 149.0, 148.3, 137.4, 135.3, 132.5, 128.8, 128.1, 127.0, 122.0, 114.8, 113.3, 111.5, 76.4, 66.0, 44.7
Reaction SMILES: C(#N)C.[CH:4]([NH2:7])([CH3:6])[CH3:5].Cl[C:9]1[S:10][C:11]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[C:12]([C:14]([F:17])([F:16])[F:15])[N:13]=1>C(OCC)C>[CH3:5][CH:4]([NH:7][C:9]1[S:10][C:11]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[C:12]([C:14]([F:16])([F:15])[F:17])[N:13]=1)[CH3:6]
Reactant: O=C(OCc1ccccc1)c1sc(Cl)nc1C(F)(F)F
Reactant: CC(C)N
Solvent: CCOCC
Solvent: CC#N
Product: CC(C)Nc1nc(C(F)(F)F)c(C(=O)OCc2ccccc2)s1
Temperature: 25 °C
Yield: 62 %

Procedure:
A reaction vessel was charged with 25 ml of acetonitrile, 2.94 g (49.8 mmol) of iso-propylamine, and 8 g (24.9 mmol) of benzyl 2-chloro-4-trifluoromethyl-5-thiazolecarboxylate (prepared as described in U.S. Pat. No. 4,199,506). The reaction mixture was heated at reflux for 16 hours. The mixture was then cooled to ambient temperature, diluted with ethyl ether, washed with large amounts of water, dried over magnesium sulfate, and concentrated under reduced pressure to yield 5.32 g of a gold oil. This oil was subjected - to Kugelrohr distillation (145°-155° C. @ 0.5 mm Hg) to yield 4.97 of a gold oil which was then triturated in hexane to yield 3.99 g of a yellow solid product (m.p.=49°-53° C.) identified in Table I.
Reaction SMILES: [Cu][C:2]#[N:3].Br[C:5]1[CH:10]=[C:9]([CH:11]([CH3:13])[CH3:12])[CH:8]=[CH:7][C:6]=1[NH2:14]>CN1CCCC1=O.C(OCC)(=O)C>[NH2:14][C:6]1[CH:7]=[CH:8][C:9]([CH:11]([CH3:13])[CH3:12])=[CH:10][C:5]=1[C:2]#[N:3]
Reactant: CC(C)c1ccc(N)c(Br)c1
Reactant: N#C[Cu]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: CC(C)c1ccc(N)c(C#N)c1
Yield: 88.5 %

Procedure:
Heat a mixture of copper (I) cyanide (2.5 g, 28.02 mmol), and 2-bromo4-isopropyl-phenylamine (5.0 g, 23.35 mmol) in 1-methyl-2-pyrrolidinone (20 ml) to 195° C. for four hours. Dilute the reaction mixture with 100 ml of ethyl acetate and wash the dark solution twice with 28% aqueous ammonium hydroxide, twice with saturated aqueous sodium chloride (brine) and twice with water. Collect the organic layer, dry over sodium sulfate and remove the solvent under reduced pressure. Purify the residue via flash chromatography eluting with a step gradient starting with hexanes and going to 80% hexanes with 20% ethyl acetate to obtain 3.31 g (20.66 mmol, 88% yield) of the title compound as an orange oil: Mass Spectrum (m/e): 161(M+1).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:20]([O:22][CH3:23])=[O:21])[C:5]2[CH2:6][CH2:7][N:8]([CH:13]([CH2:17][CH2:18][CH3:19])[CH2:14][CH2:15][CH3:16])[C:9](=[O:12])[C:10]=2[CH:11]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O>[C:9]([C:10]1[CH:11]=[CH:2][CH:3]=[CH:4][C:5]=1[C:2]1[CH:3]=[C:4]([C:20]([O:22][CH3:23])=[O:21])[C:5]2[CH2:6][CH2:7][N:8]([CH:13]([CH2:17][CH2:18][CH3:19])[CH2:14][CH2:15][CH3:16])[C:9](=[O:12])[C:10]=2[CH:11]=1)#[N:8]
Reactant: CCCC(CCC)N1CCc2c(C(=O)OC)cc(Br)cc2C1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CCCC(CCC)N1CCc2c(C(=O)OC)cc(-c3ccccc3C#N)cc2C1=O
Temperature: 150 °C

Procedure:
Added to a solution of 0.4 g of methyl 7-bromo-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate in 12.5 cm3 of dioxane and 2.5 cm3 of water, at a temperature close to 20° C., are 196 mg of sodium bicarbonate. The reaction medium is then degassed under an argon atmosphere, then 147.5 mg of 2-cyanophenylboronic acid and 96 mg of tetrakis(triphenylphosphine)palladium are added. The mixture is heated at 150° C. in a microwave oven for 4 minutes, cooled to a temperature close to 20° C. and filtered. The filtrate is taken up by 20 cm3 of dichloromethane and 20 cm3 of water. The organic phase is extracted, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa). The residual solution (around 3 cm3) is purified by flash chromatography over silica (column: 50 g; spherical silica of BP-SUP type, partical size: 20-40 μm; eluent: 80% heptane/20% ethyl acetate then 60% heptane/40% ethyl acetate then 50% heptane/50% ethyl acetate). After concentrating the fractions under reduced pressure, 178 mg of methyl 7-(2-cyanophenyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate are obtained in the form of a colorless oil.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([F:15])([F:14])[C:4]([F:13])([F:12])[C:5]([F:11])([F:10])[S:6]([O-:9])(=[O:8])=[O:7].C([O:22][C:23]1[CH:28]=[CH:27][C:26]([S+:29]([C:41]2[CH:46]=[CH:45][C:44]([O:47]CCCC)=[CH:43][CH:42]=2)[C:30]2[CH:35]=[CH:34][C:33]([O:36]CCCC)=[CH:32][CH:31]=2)=[CH:25][CH:24]=1)CCC.FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(O)(=O)=O>C(O)C.CN(C)C=O>[F:17][C:2]([F:1])([F:16])[C:3]([F:14])([F:15])[C:4]([F:12])([F:13])[C:5]([F:10])([F:11])[S:6]([O-:9])(=[O:8])=[O:7].[OH:22][C:23]1[CH:28]=[CH:27][C:26]([S+:29]([C:41]2[CH:46]=[CH:45][C:44]([OH:47])=[CH:43][CH:42]=2)[C:30]2[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=2)=[CH:25][CH:24]=1
Reactant: CCCCOc1ccc([S+](c2ccc(OCCCC)cc2)c2ccc(OCCCC)cc2)cc1
Agent: O=S(=O)(O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: O=S(=O)([O-])C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Solvent: CCO
Solvent: CN(C)C=O
Product: Oc1ccc([S+](c2ccc(O)cc2)c2ccc(O)cc2)cc1

Procedure:
A solution of 62.2 g (0.08 mol) of tris-(4-butoxyphenyl) sulfonium nonafluorobutane sulfonate and 2.40 g (0.008 mol) of nonafluorobutane sulfonic acid in 200 ml of ethanol was refluxed for 8 hours with stirring. After evaporation of the solvent, the crude product of tris-(4-hydroxyphenyl) sulfonium nonafluorobutane sulfonate (yield about 100%) was dissolved in 160 g of N,N-dimethylformamide and reacted with 55.4 g (0.40 mol) of anhydrous potassium carbonate and 60.3 g (0.40 mol) of t-butyl chloroacetate at 80° C. for 3 hours. The cooled reaction mixture was poured into 700 ml of water and extracted with dichloromethane. The organic phase was washed with water and dried. The solvent was removed. The oily residue was purified by column chromatography on silica gel using a dichloromethane and methanol as the eluent. The white product was collected to yield 34.4 g (yield 45%) of analytically pure tris-(4-t-butoxycarbonylmethoxyphenyl) sulfonium nonafluorobutane sulfonate. The 1H-NMR spectrum gave the following signals (CDCl3): δ=1.45 (s, 27H), 4.76 (s, 6H), 7.15-7.18 (d, 6H). 7.74-7.87 (d, 6H).
Reaction SMILES: [Cu][C:2]#[N:3].Br[C:5]1[CH:6]=[CH:7][C:8]2[CH:12]=[CH:11][S:10][C:9]=2[CH:13]=1.C(N)CN>CCOCC>[S:10]1[CH:11]=[CH:12][C:8]2[CH:7]=[CH:6][C:5]([C:2]#[N:3])=[CH:13][C:9]1=2
Reactant: Brc1ccc2ccsc2c1
Reactant: N#C[Cu]
Solvent: NCCN
Solvent: CCOCC
Product: N#Cc1ccc2ccsc2c1
Temperature: 0 °C
Yield: 77.5 %

Procedure:
Heat copper(I) cyanide (0.84 g, 9.4 mmol) and 6-bromobenzo[b]thiophene (prepared as described in WO 01/23381) (1.0 g, 4.7 mmol) at 160° C. for 13 h. Cool the mixture to 0° C., add 33% aqueous ethylenediamine (20 mL) and dilute with ether. Wash the organic mixture with brine, dry over Na2SO4 and evaporate. Purify by chromatography on silica gel eluting with EtOAc/hexane (0:1 to 1:3) to give the desired intermediate (0.58 g, 78%). GC-MS m/z: 159 (M+).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([OH:9])=[C:4]([CH2:10][CH3:11])[CH:3]=1.Br[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:25])([F:26])[F:27])=[CH:19][CH:18]=2)=[C:4]([CH2:10][CH3:11])[CH:3]=1
Reactant: FC(F)(F)Oc1ccc(OCCCBr)cc1
Reactant: CCc1cc(Br)cc(C)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCc1cc(Br)cc(C)c1OCCCOc1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Yield: 89.9 %

Procedure:
To a mixture of 10 g of 4-bromo-2-ethyl-6-methylphenol, 14.0 g of 1-(3-bromopropyloxy)-4-trifluoromethoxybenzene and 100 ml of N,N-dimethylformamide was added 7 g of potassium carbonate, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice water, and extracted twice with 200 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 18.1 g of 4-bromo-2-ethyl-6-methyl-1-[3-(4-trifluoromethoxyphenoxy)propyloxy]benzene 90% yield).
Reaction SMILES: [O:1]([CH3:10])[CH:2]1[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[CH2:3]1.[C:11]1([C:17](Cl)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CO>N1C=CC=CC=1>[C:17]([O:9][CH2:8][C@H:6]1[O:7][CH:2]([O:1][CH3:10])[CH2:3][C@@H:4]1[OH:5])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COC1C[C@H](O)[C@@H](CO)O1
Solvent: CO
Solvent: c1ccncc1
Product: COC1C[C@H](O)[C@@H](COC(c2ccccc2)(c2ccccc2)c2ccccc2)O1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of 11.2 g (0.07 mole) of methyl 2-deoxyribofuranoside (90% pure) in 60 ml of dry pyridine under a dry nitrogen atmosphere were added 19.0 g (0.07 mole) of triphenylmethyl chloride. The mixture was stirred at ambient temperature for three days. Methanol (35 ml) was then added. The solvents were then evaporated under reduced pressure. The residue was taken up in 200 ml of ethyl acetate, washed with 75 ml of 5% sodium bicarbonate followed by a 75 ml wash with DI (deionized) water. The organic layer was dried (Na2SO4), filtered and the solvent removed under vacuum affording a sticky, viscous oil. This crude methyl 2-deoxy-5-O-tritylriboruanoside compound was used without further purification in subsequent synthetic procedures.
Reaction SMILES: [Br:1]([OH:4])(=[O:3])=[O:2].[NH2:5][CH2:6][CH2:7][C@H:8](O)[CH2:9]O.C(O)(=O)C.[Br:16](O)(=O)=O>C(O)C>[Br:1]([O:4][C@@H:8]([CH2:7][CH2:6][NH2:5])[CH2:9][Br:16])(=[O:3])=[O:2]
Reactant: [O-][Br+2]([O-])O
Reactant: NCC[C@H](O)CO
Solvent: CC(=O)O
Solvent: CCO
Product: NCC[C@@H](CBr)O[Br+2]([O-])[O-]
Temperature: 40 °C
Reaction time: 2 h

Procedure:
4-Amino-(S)-1,2-butandiol bromate 6 (0.537 mol, 100 g) and an acetic acid solution (185 g) with 33% bromic acid dissolved therein were added to a 500□ round-bottom flask and the mixture was agitated at 40° C. for 2 hours. After the preparation of an intermediate was confirmed by Thin Layer Chromatography (TLC), anhydrous ethanol (285 g) was added thereto. The reaction mixture was agitated under reflux for 3 hours to complete the reaction and then concentrated under reduced pressure to completely remove the solvent, thereby obtaining 115 g of crude 4-amino-1-bromo-(S)-2-butanol bromate 7.
Reaction SMILES: C1(C)C=CC=CC=1.Cl[C:9]1[N:14]=[N:13][C:12]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[O:18][C:11]=2[CH:10]=1.[C:23]1(/[CH:29]=[CH:30]/B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:23]1(/[CH:29]=[CH:30]/[C:9]2[N:14]=[N:13][C:12]3[O:15][C:16]4[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=4[O:18][C:11]=3[CH:10]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: OB(O)/C=C/c1ccccc1
Reactant: Clc1cc2c(nn1)Oc1ccccc1O2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: C(=C/c1cc2c(nn1)Oc1ccccc1O2)\c1ccccc1
Temperature: 120 °C
Reaction time: 14 h
Yield: 49.2 %

Procedure:
Toluene (10 ml) was added to 3-chloro[1,4]benzodioxino[2,3-c]pyridazine (600 mg), and (E)-2-phenylvinylboronic acid (480 mg), tetrakis(triphenylphosphine)palladium (315 mg) and 2M aqueous sodium carbonate solution (1.6 mL) were added at room temperature. The reaction mixture was stirred at 120° C. for 14 hr. Water was added and the mixture was extracted with chloroform. The organic layer was washed with saturated aqueous ammonium chloride solution and saturated brine, dried over anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure. The obtained residue was washed with a mixed solvent of hexane and ethyl acetate and filtered. The obtained solid was dried under reduced pressure to give 3-[(E)-2-phenylvinyl][1,4]benzodioxino[2,3-c]pyridazine (386 mg).
Reaction SMILES: [CH2:1]=[C:2]([C:4]1[CH:5]=[C:6]([C:10](=O)[CH3:11])[CH:7]=[N:8][CH:9]=1)[CH3:3].[NH2:13][OH:14].Cl>CCO.O.[OH-].[Na+]>[CH2:1]=[C:2]([C:4]1[CH:5]=[C:6]([C:10](=[N:13][OH:14])[CH3:11])[CH:7]=[N:8][CH:9]=1)[CH3:3]
Reactant: C=C(C)c1cncc(C(C)=O)c1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C=C(C)c1cncc(C(C)=NO)c1
Yield: 79.4 %

Procedure:
To a stirred solution of 1-(5-(prop-1-en-2-yl)pyridin-3-yl)ethanone (460 mg, 2.86 mmol) in 95% EtOH was added a solution of NH2OH.HCl (1.19 g, 17.14 mmol) in a mixture of water (5.8 mL) and 10% NaOH (5.8 mL) and refluxed for 2.5 h. All solvent was removed. The residue was dissolved in CHCl3, washed with water, dried with Na2SO4 and concentrated under reduced pressure to yield 400 mg of crude 1-(5-(prop-1-en-2-yl)pyridin-3-yl)ethanone oxime.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([C:15]([OH:17])=O)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2.[NH2:18][C:19]1[NH:23][N:22]=[N:21][N:20]=1>O1CCCC1.CN(C)C=O>[CH3:1][O:2][C:3]1[C:4]([C:15]([NH:18][C:19]2[NH:23][N:22]=[N:21][N:20]=2)=[O:17])=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2
Reactant: COc1ccc2nc(C(=O)O)c(OC)nc2c1
Reactant: Nc1nnn[nH]1
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COc1ccc2nc(C(=O)Nc3nnn[nH]3)c(OC)nc2c1

Procedure:
3,6-Dimethoxy-2-quinoxalinecarboxylic acid (Example 12c) (2 g) and N,N'-carbonyldiimidazole (1.4 g) in tetrahydrofuran (50 ml) were heated under reflux for 15 minutes. 5-Amino-1H-tetrazole (0.8 g) in dimethylformamide (5 ml) was added and the mixture was heated under reflux for a further 30 minutes. The solid that crystallised from the solution on cooling was collected and dried. It had m.p. 250°-251° (d) (59%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:16](Cl)(=[O:18])[CH3:17].[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(=S)=S.O>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[CH:12][C:13]([C:16](=[O:18])[CH3:17])=[CH:14][CH:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: CC(=O)Cl
Reactant: COc1ccc(-c2ccccc2)cc1F
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: S=C=S
Product: COc1ccc(-c2ccc(C(C)=O)cc2)cc1F
Reaction time: 10 h
Yield: 75.9 %

Procedure:
Three grams of said 3-fluoro-4-methoxybiphenyl was dissolved in 14 ml of carbon disulfide, and 1.17 g of acetyl chloride and 2.36 g of aluminum chloride were added, followed by stirring the mixture for 10 hours. Twenty milliliters of 10% hydrochloric acid and then 5 ml of water were added, and the precipitate was filtered and washed with water. The resulting crude crystals were recrystallized from ethanol to obtain 2.75 g of 3'-fluoro-4'-methoxy-4-acetylbiphenyl (yield 76%).
Reaction SMILES: [Cl:1][CH2:2][C:3]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)([OH:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:11].[Br:20]N1C(C)(C)C(=O)N(Br)C1=O>ClC(Cl)(Cl)Cl>[Br:20][CH:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:11])[C:3]([C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)([OH:12])[CH2:2][Cl:1]
Reactant: OC(CCl)(Cc1ccccc1Cl)c1ccc(F)cc1
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: OC(CCl)(c1ccc(F)cc1)C(Br)c1ccccc1Cl

Procedure:
4.0 g (13.4 mmol) of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol are photobrominated with 2.3 g (8.0 mmol) of 1,3-dibromo-5,5-dimethylhydantoin in 80 ml of tetrachloromethane at 35° C. while stirring vigorously and irradiating with mixed light from an Osram HWL 235 V/500 W lamp. The hydantoin is filtered off with suction, the filtrate is extracted with dilute sodium carbonate solution and water, and conventional working up provides 5.1 g of crude product as an oil which is employed for the next stage. The erythro:threo isomer ratio found from the signals for the --CHBr--groups in the 1H-NMR spectrum, which appear at 6.4 ppm for the erythro compounds and at 6.2 ppm for the threo compound (each measured in CDCl3), is 4:1. The erythro isomer is also characterized by a doublet of doublets at 4.1 ppm.
Reaction SMILES: Cl.Cl.[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH2:11])[CH3:4].[CH3:13][C:14]1[N:15]=[C:16]([S:19](Cl)(=[O:21])=[O:20])[S:17][CH:18]=1>>[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH:11][S:19]([C:16]1[S:17][CH:18]=[C:14]([CH3:13])[N:15]=1)(=[O:21])=[O:20])[CH3:4]
Reactant: CCOC(=O)CNCCN
Reactant: Cc1csc(S(=O)(=O)Cl)n1
Agent: Cl
Product: CCOC(=O)CNCCNS(=O)(=O)c1nc(C)cs1

Procedure:
The title compound was synthesized by the reaction of N-(2-aminoethyl)-glycine ethyl ester 2HCl with 4-methyl-thiazole-2-sulfonyl chloride as per the procedure of example 1. 1H NMR (500 MHz; DMSO-d6) δ 7.68 (s, 1H), 4.07 (q, 2H), 3.26 (s, 2H), 3.02 (t, 2H), 2.58 (t, 2H), 2.43 (s, 3H), 1.18 (t, 3H).
Reaction SMILES: COCCOC.Cl[C:8]1[S:12][N:11]=[C:10]([S:13][CH3:14])[N:9]=1.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O>[CH3:14][S:13][C:10]1[N:9]=[C:8]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[CH:17]=2)[S:12][N:11]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: CSc1nsc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CSc1nsc(-c2cccc(Cl)c2)n1
Yield: 57.3 %

Procedure:
To 25 ml of 1,2-dimethoxyethane were added about 2.0 g of 5-chloro-3-methylthio-1,2,4-thiadiazole, 2.25 g of 2-chlorophenylboronic acid, 694 mg of tetrakistriphenylphosphine palladium and 25 ml of a 2 M aqueous sodium carbonate solution, and the mixture was heated under reflux for 3 hours in a nitrogen atmosphere. Then, the reaction mixture was poured into water, and the mixture was extracted with t-butyl methyl ether. The organic layer was dried over anhydrous sodium sulfate, and the residue obtained by concentration was subjected to silica gel column chromatography to obtain 1.67 g of 3-methylthio-5-(3-chlorophenyl)-1,2,4-thiadiazole.
Reaction SMILES: [H-].[Na+].[C:3]1([CH2:9][O:10][C:11]([NH:13][C:14]2([C:17]([O:19][CH3:20])=[O:18])[CH2:16][CH2:15]2)=[O:12])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.I[CH3:22]>CN(C=O)C.O>[CH3:22][N:13]([C:11]([O:10][CH2:9][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)=[O:12])[C:14]1([C:17]([O:19][CH3:20])=[O:18])[CH2:16][CH2:15]1
Reactant: COC(=O)C1(NC(=O)OCc2ccccc2)CC1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)C1(N(C)C(=O)OCc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 247.7 %

Procedure:
Sodium hydride (995 mg, 41.466 mmol) was taken up in DMF (50 mL) and was cooled to 0° C. for 30 min. Then a mixture of methyl 1-({[(phenylmethyl)oxy]carbonyl}amino)cyclopropanecarboxylate (6.46 g, 25.916 mmol) in DMF (25 mL) was slowly added over 10 min. The resulting mixture was allowed to stir for 45 min, and then iodomethane (4.84 mL, 77.74 mmol) was added, and the reaction was allowed to warm to room temperature overnight. The mixture was then carefully diluted with water (10 mL), and the aqueous layer was extracted with Et2O (5×50 mL). The organic extracts were washed with water (5×50 mL), then dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via Combiflash, utilizing a 0%-50 EtOAc/Hex gradient to provide methyl 1-(methyl{[(phenylmethyl)oxy]carbonyl}amino)cyclopropanecarboxylate (16.9 g, >100%) LCMS: (M+H)+: 264.1.
Reaction SMILES: [F:1][B-:2]([F:5])([F:4])[F:3].[N:6]#[O+].[F:8][C:9]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:10]=1[NH2:11]>C(#N)C.C(OCC)C>[F:1][B-:2]([F:5])([F:4])[F:3].[F:8][C:9]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:10]=1[N+:11]#[N:6]
Reactant: Nc1cc(F)ccc1F
Reactant: N#[O+]
Agent: F[B-](F)(F)F
Solvent: CCOCC
Solvent: CC#N
Product: N#[N+]c1cc(F)ccc1F
Reaction time: 1 h

Procedure:
Nitrosonium tetrafluoroborate (905 mg, 7.75 mmol, 1.00 equiv) was added to a solution of 2,5-difluoroaniline (0.780 mL, 7.75 mmol, 1 equiv) in acetonitrile (50 mL) at 0° C. The resulting mixture was stirred for 1 hour, then diluted with ethyl ether (150 mL). The precipitate was filtered and air-dried to give 2,5-difluorobenzenediazonium tetrafluoroborate (1-1) as a tan solid. 1H NMR (300 MHz, CD3OD) δ 8.54 (m, 1H), 8.24 (m, 1H), 7.95 (m, 1H).
Reaction SMILES: S(=O)(=O)(O)O.[N+:6]1([O-:13])[C:7]([CH3:12])=[CH:8][CH:9]=[CH:10][CH:11]=1.[N+:14]([O-])([OH:16])=[O:15].[OH-].[Na+]>O>[N+:14]([C:9]1[CH:8]=[C:7]([CH3:12])[N+:6]([O-:13])=[CH:11][CH:10]=1)([O-:16])=[O:15]
Reactant: Cc1cccc[n+]1[O-]
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cc1cc([N+](=O)[O-])cc[n+]1[O-]
Temperature: 25 °C

Procedure:
98% sulfuric acid (17.5 ml) was added dropwise to 2-picoline-1-oxide (5.22 g) under stirring at cooling in an ice-bath. To the mixture was added dropwise nitric acid (fuming, 15 ml) under the same condition. After completion of the additieon, the mixture was heated at 80°-90° C. for 2 hours. The reaction mixture was allowed to cool to room temperature, poured into water (100 ml) and alkalined with aN aqueous sodium hydroxide. The resultant mixture was extracted with chloroform four times. The combined extracts were dried over sodium sulfate. Removal of the solvent gave 4-nitro-2-picoline-1-oxide (6.52 g).