Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@H:2]([CH2:6][OH:7])[CH:3]([CH3:5])[CH3:4].[CH:8](=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1(C)C(C)=CC=CC=1>[C:9]1([C:8]2[O:7][CH2:6][CH:2]([CH:3]([CH3:5])[CH3:4])[N:1]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)[C@H](N)CO
Reactant: O=Cc1ccccc1
Solvent: Cc1ccccc1C
Product: CC(C)C1COC(c2ccccc2)=N1
Temperature: 150 °C
Reaction time: 67 h

Procedure:
L-Valinol (206 mg, 2 mmol), benzaldehyde (0.205 ml, 2 mmol), 250 mg of an oxidation catalyst and 4 ml of xylene as solvent were charged into a 100 ml three-neck flask, and were stirred at 150° C. for 67 hours under an oxygen atmosphere. The reaction mixture was filtered through a cotton plug, and then the oxidation catalyst was washed with ethyl acetate. After the filtrate was condensed with a rotary evaporator, the product was separated by silica gel column chromatography. A resulting colorless liquid was weighed and the yield thereof was defined as a reaction yield.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[S:9]([O:12][C:13]1[CH:22]=[CH:21][C:16]2[N:17]=[C:18]([NH2:20])[S:19][C:15]=2[CH:14]=1)(=[O:11])=[O:10].Cl[C:24]([O:26][CH3:27])=[O:25].O>N1C=CC=CC=1>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[S:9]([O:12][C:13]1[CH:22]=[CH:21][C:16]2[N:17]=[C:18]([NH:20][C:24]([O:26][CH3:27])=[O:25])[S:19][C:15]=2[CH:14]=1)(=[O:11])=[O:10]
Reactant: Nc1nc2ccc(OS(=O)(=O)c3c(Cl)cccc3Cl)cc2s1
Reactant: COC(=O)Cl
Solvent: O
Solvent: c1ccncc1
Product: COC(=O)Nc1nc2ccc(OS(=O)(=O)c3c(Cl)cccc3Cl)cc2s1
Temperature: 20 °C
Reaction time: 8 h

Procedure:
To a solution of 1 g of 2-amino-1,3-benzothiazol-6-yl 2,6-dichlorobenzenesulfonate in 25 cm3 of pyridine is added 0.308 cm3 of methyl chloroformate. The solution is stirred at a temperature in the region of 20° C. overnight. After addition of 0.62 cm3 of methyl chloroformate, the mixture is stirred for 72 hours at a temperature in the region of 20° C. 50 cm3 of water are added, and the precipitate formed is filtered off by suction and then washed with three times 10 cm3 of water and dried under reduced pressure. 785 mg of 2-[(methoxycarbonyl)amino]-1,3-benzothiazol-6-yl 2,6-dichlorobenzenesulfonate are obtained in the form of a beige-coloured powder, the characteristics of which are as follows:
Reaction SMILES: [CH2:1]([N:8]1[CH2:23][CH2:22][C:11]2([CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:24].O1CCOCC1>CO>[ClH:24].[ClH:24].[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]2([CH2:14][NH:13][CH2:12]2)[CH2:22][CH2:23]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CC2(CCN(Cc3ccccc3)CC2)C1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: c1ccc(CN2CCC3(CC2)CNC3)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl 7-benzyl-2,7-diazaspiro[3.5]nonane-2-carboxylate (CAS 929301-99-5 WO2007030061) in methanol was added 4 N HCl/dioxane. The mixture was stirred at room temperature for 2 hours. The reaction mixture was then concentrated to obtain the title compound. MS (DCI+) m/z 217 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:4]([CH3:20])[N:3]=1.[C:21]1([S:27]([OH:29])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[Na].O>CN(C=O)C>[CH3:13][O:12][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([S:27]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:29])=[O:28])=[N:3][C:4]([CH3:20])=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=S(O)c1ccccc1
Reactant: COc1ccc2c(Cl)nc(C)c(-c3ccccc3)c2c1
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc2c(S(=O)(=O)c3ccccc3)nc(C)c(-c3ccccc3)c2c1

Procedure:
To a solution of 1-chloro-6-methoxy-3-methyl-4-phenylisoquinoline (0.24 g) in 20 mL DMF was added benzenesulfinic acid, sodium salt dihydrate (0.60 g). The reaction was heated at 120 C overnight, then poured into water and extracted with EtOAc (3×). The combined organic solutions were washed with water (1×) and brine (1×), dried (Na2SO4) and concentrated. To a solution of the residue in 20 mL DMF was added benzenesulfinic acid, sodium salt dihydrate (0.74 g). The reaction was heated at 160 C overnight, then poured into water and extracted with EtOAc (3×). The combined organic solutions were washed with water (1×) and brine (1×), dried (Na2SO4) and concentrated. The residue was recrystallized from ethyl ether/hexanes, then further purified by flash chromatography (5% to 30% EtOAc/hexanes). A second recrystallization from ethyl ether/hexanes gave the titled compound.
Reaction SMILES: C[CH:2]([CH:6]1[C:10]2=[C:11]([S:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:12]3[C:13](Br)=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]2[CH2:8][CH2:7]1)[C:3]([O-:5])=[O:4].C([Sn](CCCC)(CCCC)[C:33]1[CH:37]=[CH:36][S:35][CH:34]=1)CCC>>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([S:20][C:11]2[C:12]3[C:13]([C:33]4[CH:37]=[CH:36][S:35][CH:34]=4)=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]3[CH2:8][CH2:7][CH:6]([CH2:2][C:3]([OH:5])=[O:4])[C:10]=23)=[CH:22][CH:23]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccsc1
Reactant: CC(C(=O)[O-])C1CCn2c1c(Sc1ccc(Cl)cc1)c1c(Br)cc(F)cc12
Product: O=C(O)CC1CCn2c1c(Sc1ccc(Cl)cc1)c1c(-c3ccsc3)cc(F)cc12

Procedure:
Starting from (+)-methyl{8-bromo-9-[(4-chlorophenyl)thio]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl}acetate and tributyl(thien-3-yl)stannane, the title compound was synthesized following the procedures described in Example 42 and Step 10 of Example 7.
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[C:9](/[CH:13]=[N:14]/[C:15]3[CH:16]=[CH:17][C:18]([C:21]#[N:22])=[N:19][CH:20]=3)[CH:10]=[CH:11][CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:23]=[C:24]([CH3:26])[CH3:25].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C(#N)C.C(OCC)(=O)C>[CH3:23][C:24]1([CH3:26])[C:20]2[N:19]=[C:18]([C:21]#[N:22])[CH:17]=[CH:16][C:15]=2[NH:14][CH:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[CH:8]=2)[CH2:25]1
Reactant: C=C(C)C
Reactant: N#Cc1ccc(/N=C/c2cccc(N3CCOCC3)c2)cn1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC1(C)CC(c2cccc(N3CCOCC3)c2)Nc2ccc(C#N)nc21
Temperature: 90 °C
Reaction time: 18 h
Yield: 12.1 %

Procedure:
To a stirred solution of 5-{[1-(3-morpholin-4-yl-phenyl)-meth-(E)-ylidene]amino}-pyridine-2-carbonitrile (22.9 g, 78.4 mmol) in acetonitrile (150 mL) were added isobutene (21.0 mL, 313.5 mmol) and ytterbium(III) trifluoromethanesulfonate (Yb(OTf)3) (5.8 g, 9.5 mmol). The resulting mixture was stirred at 90° C. for 18 h in sealed tube. The mixture was diluted with ethyl acetate (300 mL) and washed with water (100 mL×2) and brine (100 mL×2) and then dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 10-50% ethyl acetate in petroleum ether) to afford 8,8-dimethyl-6-(3-morpholin-4-yl-phenyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carbonitrile (3.3 g, 12.1%) as a light yellow solid: MS (ESI) M+1=349.1.
Reaction SMILES: [F:1][C:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[N:15]=[C:14]([NH2:16])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)([F:4])[CH3:3].[F:17][C:18]1[CH:19]=[C:20]([C:25]2[O:29][C:28]([CH3:30])=[N:27][C:26]=2[C:31](O)=[O:32])[CH:21]=[C:22]([F:24])[CH:23]=1>>[F:4][C:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[N:15]=[C:14]([NH:16][C:31]([C:26]3[N:27]=[C:28]([CH3:30])[O:29][C:25]=3[C:20]3[CH:21]=[C:22]([F:24])[CH:23]=[C:18]([F:17])[CH:19]=3)=[O:32])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)([F:1])[CH3:3]
Reactant: CC(F)(F)c1ccc(Cn2ncc(N)n2)o1
Reactant: Cc1nc(C(=O)O)c(-c2cc(F)cc(F)c2)o1
Product: Cc1nc(C(=O)Nc2cnn(Cc3ccc(C(C)(F)F)o3)n2)c(-c2cc(F)cc(F)c2)o1

Procedure:
Following general procedure Z2, starting from 2-[5-(1,1-difluoro-ethyl)-furan-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-(3,5-difluoro-phenyl)-2-methyl-oxazole-4-carboxylic acid.
Reaction SMILES: [CH2:1]([NH:9][C:10]([C:12]1[C:13]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH2:24][NH2:25])=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:11])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:26]([C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1)(=[O:28])[CH3:27].C(NC(C1C(C2C=CC=CC=2C(S(C2C=CC(C(=O)C)=CC=2)(=O)=O)N)=CC=CC=1)=O)CC1C=CC=CC=1>>[CH2:1]([NH:9][C:10]([C:12]1[C:13]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH2:24][NH:25][S:35]([C:32]2[CH:31]=[CH:30][C:29]([C:26](=[O:28])[CH3:27])=[CH:34][CH:33]=2)(=[O:37])=[O:36])=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:11])[CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: CC(=O)c1ccc(S(=O)(=O)Cl)cc1
Reactant: NCc1ccccc1-c1ccccc1C(=O)NCCc1ccccc1
Agent: CC(=O)c1ccc(S(=O)(=O)C(N)c2ccccc2-c2ccccc2C(=O)NCCc2ccccc2)cc1
Product: CC(=O)c1ccc(S(=O)(=O)NCc2ccccc2-c2ccccc2C(=O)NCCc2ccccc2)cc1

Procedure:
From 0.61 mmol of 2′-aminomethylbiphenyl-2carboxylic acid phenethylamide (precursor 5a) and 4-acetylphenylsulfonyl chloride, according to the general working procedure 258 mg of 2′-(4-acetylphenylsulfonyl-aminomethyl)biphenyl-2-carboxylic acid phenethylamide were obtained;
Reaction SMILES: [N+:1]([C:4]1[C:5](NN)=[N:6][CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)([O-:3])=[O:2].C(O)=O.C=O>CO.C([O-])(=O)C.[Ag+]>[N+:10]([C:8]1[CH:7]=[N:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:9]=1)([O-:12])=[O:11]
Reactant: NNc1ncc([N+](=O)[O-])cc1[N+](=O)[O-]
Agent: [Ag+]
Agent: C=O
Agent: CC(=O)[O-]
Solvent: CO
Solvent: O=CO
Product: O=[N+]([O-])c1cncc([N+](=O)[O-])c1
Yield: 21.4 %

Procedure:
Silver acetate (2.0 g) was added to a solution of the crude 3,5-dinitro-pyridinyl-hydrazine (2.2 g) in a mixture of methanol:H2O (1:1,6 ml), and the mixture was stirred at reflux overnight. Solvent was evaporated, then water and conc. NH4OH were added. The mixture was extracted with ethyl ether, the combined extracts were dried over MgSO4, concentrated and purified by column chromatography (5:1 hexane: ethyl acetate) to give the title compound (400 mg) in 21.8% yield. MS (DCI/NH3) m/e: 124 (M-46+1). 1H NMR (CDCl3, 300MHz) δ: 9.77 (m, 2H), 9.27 (m, 1H).
Reaction SMILES: Br[CH:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH:3]=O.[NH2:11][C:12]([NH2:14])=[S:13]>C(O)C>[C:5]1([C:2]2[S:13][C:12]([NH2:14])=[N:11][CH:3]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: NC(N)=S
Reactant: O=CC(Br)c1ccccc1
Solvent: CCO
Product: Nc1ncc(-c2ccccc2)s1
Temperature: 25 °C
Yield: 56.8 %

Procedure:
A mixture of bromo-phenyl-acetaldehyde (1 g, 5 mmol), thiourea (0.64 g, 10 mmol) and ethanol (3.5 mL) was heated to reflux overnight. The mixture was then cooled to rt and the resulting yellow precipitate filtered. The precipitate was then washed with aqueous NaHCO3 solution (10 mL) and dried. Recrystallization from 30% methanol gave 5-phenylthiazol-2-amine (500 mg, 2.84 mmol, 56.5%) as a yellow solid. Anal. Calcd. for C9H8N2S m/z 176.2, found: 177.2 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.41 (m, 3H), 7.33 (m, 2H), 7.18 (m, 1H), 7.13 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:11]=3[N:10]=[C:9]2[C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:34]=[CH:33][NH:32][N:31]=3)=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.[C:35]([O-])([O-])=O.[K+].[K+].CI.O>CC#N>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:34]=[CH:33][N:32]([CH3:35])[N:31]=3)=[CH:26][CH:25]=2)=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: O=c1c2cnn(-c3ccccc3)c2nc(-c2ccc(-c3cc[nH]n3)cc2)n1-c1ccc(Cl)cc1
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CC#N
Product: Cn1ccc(-c2ccc(-c3nc4c(cnn4-c4ccccc4)c(=O)n3-c3ccc(Cl)cc3)cc2)n1
Temperature: 60 °C
Yield: 99.2 %

Procedure:
To a solution of 5-(4-chloro-phenyl)-1-phenyl-6-[4-(1H-pyrazol-3-yl)-phenyl]-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (4 mg, 0.008 mmol) in MeCN (0.5 mL) is added K2CO3 (5 mg) followed by MeI (0.05 mL). The mixture is heated to 60° C. for 16 h and then cooled down to room temperature. The reaction mixture is then treated with water (3 mL) and extracted with EtOAc. The combined extracts is concentrated and purified by preparative thin layer chromatography (silica gel, 30% EtOA/hexane) to provide the title compound 5-(4-chloro-phenyl)-6-[4-(1-methyl-1H-pyrazol-3-yl)-phenyl]-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one as white solid (3.8 mg, 92%). 1H NMR (CDCl3) δ (ppm) 8.33(s, 1H), 8.17(d, 2H), 7.70(d, 2H), 7.51(t, 2H), 7.38 (m, 4H), 7.11(d, 2H), 6.54(d, 1H), 3.97(s, 3H). HPLC-MS calculated C27H19ClN6O (M+1+): 479.1. Found: 479.1.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[F:12])[C:5]([O:7][CH3:8])=[O:6].Br[C:14]1[CH:15]=[N:16][CH:17]=[N:18][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[NH:1][C:14]1[CH:15]=[N:16][CH:17]=[N:18][CH:19]=1
Reactant: Brc1cncnc1
Reactant: COC(=O)c1ccc(F)c(N)c1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: COC(=O)c1ccc(F)c(Nc2cncnc2)c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 89.2 %

Procedure:
4-fluoro-3-nitrobenzoic acid (2.5 g, 14 mmol, 1.0 eq) was dissolved in MeOH (68 mL) and heated to reflux. 2.0M oxalyl chloride in CH2Cl2 (14 mL) was added to the refluxing solution slowly and stirred for 2 h at reflux. The reaction was concentrated in vacuo, crystallized at 0° C., and filtered to give 1.7 g (63%) of crude methyl 4-fluoro-3-nitrobenzoate as a white solid. The product was confirmed by LCMS (>98% @ 220 nm and 254 nm) and carried forward without purification. Methyl 4-fluoro-3-nitrobenzoate (1.7 g, 8.4 mmol, 1.0 eq) and 5% palladium on carbon (89 mg, 0.84 mmol, 0.10 eq) were dissolved in EtOH (40 mL) and stirred under H2 atmosphere (1 atm) for 24 h. The mixture was filtered through celite and concentrated in vacuo affording 1.4 g (97%) of crude methyl 3-amino-4-fluorobenzoate as a brown solid. The product was confirmed by LCMS (>98% @ 220 nm and 254 nm) and carried forward without purification. Methyl 3-amino-4-fluorobenzoate (1.4 g, 8.2 mmol, 1.2 eq), 5-bromopyrimidine (1.1 g, 6.8 mmol, 1.0 eq), cesium carbonate (3.1 g, 9.6 mmol, 1.4 eq), Bis(dibenzylideneacetone)palladium (0.50 g, 0.55 mmol, 0.080 eq), and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (0.47 g, 0.82 mmol, 0.12 eq) were dissolved in Dioxane (17 mL) and stirred under argon at 100° C. overnight. The mixture cooled to rt and was filtered through celite and washed with 5% MeOH in CH2Cl2. The filtrate was collected, concentrated in vacuo, and purified by flash chromatography on silica gel afforded 1.5 g (90%) of the title compound as an orange solid: 1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 1H), 8.63 (s, 1H), 8.50 (s, 2H), 7.84 (dd, J=8.1, 2.1 Hz, 1H), 7.63 (ddd, J=8.5, 4.7, 2.1 Hz, 1H), 7.42 (dd, J=11.2, 8.6 Hz, 1H), 3.83 (s, 3H); ES-MS [M+1]+:248.1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](Cl)[C:3]=1[CH3:9].[CH3:10][S-:11].[Na+].IC.O>CN(C)P(N(C)C)(N(C)C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:11][CH3:10])[C:3]=1[CH3:9]
Reactant: Cc1c(Cl)cccc1Cl
Reactant: C[S-]
Agent: [Na+]
Solvent: O
Solvent: CI
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CSc1cccc(Cl)c1C
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
200 g (1.24 mol) of 2,6-dichlorotoluene were dissolved in 600 ml of hexamethylphosphoramide and treated with 130.41 g (1.86 mol) of sodium thiomethoxide. The mixture was then heated at 100° C. for 3 h. It was allowed to cool, 88.2 g (0.5 mol) of iodomethane were added and it was stirred at room temperature for 0.5 h. The mixture was then added to 3.5 l of water and extracted with ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and completely concentrated on a rotary evaporator.
Reaction SMILES: N#N.[C:3]1([PH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N-:16]([S:24]([C:27]([F:30])([F:29])[F:28])(=[O:26])=[O:25])[S:17]([C:20]([F:23])([F:22])[F:21])(=[O:19])=[O:18]>CO>[F:30][C:27]([F:28])([F:29])[S:24]([N-:16][S:17]([C:20]([F:21])([F:22])[F:23])(=[O:18])=[O:19])(=[O:25])=[O:26].[C:10]1([PH2+:9][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: c1ccc(Pc2ccccc2)cc1
Agent: N#N
Agent: O=S(=O)([N-]S(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: CO
Product: c1ccc([PH2+]c2ccccc2)cc1
Temperature: 10 °C

Procedure:
In a reactor wherein air was replaced by N2, 400.0 g (2.2 mol) of diphenyl phosphine and 400 mL of methanol were added and cooled to 10° C. by a ice-bath. 604.3 g (2.2 mol) of trifluoromethanesulfonimide was then added dropwise under strong stirring. After one hour of reaction, the reaction temperature was increased to about 60° C., and the unreacted materials as well as the solvents were removed by distillation under vacuum to obtain diphenyl phosphonium bis(trifluoromethanesulfonyl)amide.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][OH:6])[CH3:2].N1C=CC=CC=1.[S:13](Cl)([CH3:16])(=[O:15])=[O:14]>O1CCCC1>[CH3:16][S:13]([O:6][CH2:5][CH2:4][O:3][CH2:1][CH3:2])(=[O:15])=[O:14]
Reactant: CCOCCO
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCOCCOS(C)(=O)=O

Procedure:
To 30g of 2-ethoxyethanol in 300ml of tetrahydrofuran 27.4ml of pyridine were added and 26.4ml of mesyl chloride added dropwise at room temperature over 15 minutes. The mixture was refluxed overnight, the solid that formed filtered off and the solvent evaporated off from the residue. The residue was distilled under 20m Hg to give 2-ethoxyethyl methanesulphonate.
Reaction SMILES: Br[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6](=[O:13])[C:5]2[CH:14]=[CH:15][CH:16]=[CH:17][C:4]=2[CH:3]=1.[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.CC(C)([O-])C.[K+]>C(O)(C)(C)C>[N:18]1([C:2]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[C:6](=[O:13])[C:5]3[CH:14]=[CH:15][CH:16]=[CH:17][C:4]=3[CH:3]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: C1CCNCC1
Reactant: O=c1c2ccccc2cc(Br)c2ccccc12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Product: O=c1c2ccccc2cc(N2CCCCC2)c2ccccc12

Procedure:
A mixture of 71.3 g of 10-bromo-5H-dibenzo[a,d]cyclohepten-5-one, 50 ml. of piperidine, 1 liter of t-butanol and finally 33.6 g of potassium t-butoxide was stirred under reflux 2 hours, then at room temperature overnight. The mixture was filtered, and concentrated to dryness. The residue was slurried with water and decanted. The residue was slurried with methanol and filtered to give 59.8 g of 10-(1-piperidyl)-5H-dibenzo[a,d]cyclohepten-5-one, m.p. 103°-105° C.
Reaction SMILES: [Br:1][CH:2]([F:14])[C:3]([F:13])([F:12])[O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.S(Cl)([Cl:18])(=O)=O>C1(SC2C=CC=CC=2)C=CC=CC=1.C(O)(=O)C>[Cl:18][C:7]1[CH:6]=[C:5]([O:4][C:3]([F:12])([F:13])[CH:2]([Br:1])[F:14])[CH:10]=[CH:9][C:8]=1[OH:11]
Reactant: Oc1ccc(OC(F)(F)C(F)Br)cc1
Reactant: O=S(=O)(Cl)Cl
Agent: c1ccc(Sc2ccccc2)cc1
Solvent: CC(=O)O
Product: Oc1ccc(OC(F)(F)C(F)Br)cc1Cl
Reaction time: 3 h

Procedure:
12.2 g of 4-(2-bromo-1,1,2-trifluoroethoxy)-phenol and 5 drops of diphenyl sulfide were dissolved in 30 ml of glacial acetic acid, and 6.1 g of sulfuryl chloride were added, a little at a time, at 25° C. After 3 hours at 25° C., the volatile components were removed, the residue was taken up with 300 ml of methylene chloride, and the solution was washed with 100 ml of 10% strength NaHCO3 solution and 100 ml of water, dried over Na2SO4 and distilled at 82° C./0.3 mbar. Yield: 12.6 g.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[CH:8][NH:9][C:5]=2[CH:4]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Cl.[NH2:19][OH:20]>CCO.CCOCC>[OH:20][NH:19][C:1]([C:3]1[CH:11]=[CH:10][C:6]2[NH:7][CH:8]=[N:9][C:5]=2[CH:4]=1)=[NH:2]
Reactant: NO
Reactant: N#Cc1ccc2nc[nH]c2c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CCOCC
Product: N=C(NO)c1ccc2[nH]cnc2c1
Temperature: 25 °C

Procedure:
A solution of 5-cyanobenzimidazole (1.43 g; 10 mmol; 1 eq.) in EtOH (30 ml) was treated with K2CO3 (2.76 g; 20 mmol; 2 eq.) and hydroxylaminehydrochloride (765 mg; 11 mmol; 1.1 eq.) and heated to reflux over night. After cooling to room temperature, the mixture was diluted with Et2O. The resulting solid was collected by filtration, washed with Et2O and water and used without further purification. Yield: 1.28 g (72.7%); MS m/z: 177.3 [M+H]+
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH3:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]([CH3:30])[CH3:29])[C:23]=1[N:31]=[C:32]=[O:33])([CH3:21])[CH3:20]>>[CH2:1]([N:8]([C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][CH2:17][CH3:18])=[CH:13][CH:14]=1)[C:32]([NH:31][C:23]1[C:22]([CH:19]([CH3:20])[CH3:21])=[CH:27][CH:26]=[CH:25][C:24]=1[CH:28]([CH3:30])[CH3:29])=[O:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCc1ccc(NCc2ccccc2)cc1
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Product: CCCCc1ccc(N(Cc2ccccc2)C(=O)Nc2c(C(C)C)cccc2C(C)C)cc1
Yield: 27.6 %

Procedure:
By the reaction and treatment in the same manner as in Example 2 using benzyl(4-butylphenyl)amine (1.0 g) and 2,6-diisopropylphenyl isocyanate (1.7 g) as starting materials, N-benzyl-N-(4-butylphenyl)-N′-(2,6-diisopropylphenyl)urea (0.51 g) was obtained.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[C:3]=1[O:9][CH3:10].[C:11]([C:15]1[CH:23]=[CH:22][C:18]([CH2:19][O:20][NH2:21])=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12]>>[C:11]([C:15]1[CH:16]=[CH:17][C:18]([CH2:19][O:20][NH:21][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[C:3]=2[O:9][CH3:10])=[CH:22][CH:23]=1)([CH3:14])([CH3:12])[CH3:13]
Reactant: CC(C)(C)c1ccc(CON)cc1
Reactant: COc1c(Cl)ccnc1C
Product: COc1c(NOCc2ccc(C(C)(C)C)cc2)ccnc1C
Yield: 80 %

Procedure:
Prepared analogously to Example 1 from 4-chloro-3-methoxy-2-methylpyridine and O-(4-tert-butylbenzyl)hydroxylamine. Yield: 80%; m.p.: 113° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][CH2:7][CH2:8][CH2:9][NH2:10].[NH2:11][CH2:12][CH2:13][CH2:14]CN>>[NH2:10][CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][CH2:14][CH2:13][CH2:12][NH2:11].[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][CH2:7][CH2:8][CH2:9][NH2:10]
Reactant: NCCCCN
Agent: NCCCCNCCCN
Product: NCCCNCCCCNCCCN

Procedure:
In vivo, the first step in the biosynthesis of spermidine and spermine is decarboxylation of ornithine (2,5-diaminopentanoic acid, H2 N(CH2)3CH(NH2)CO2H) by ornithine decarboxylase (ODC) to yield putrescine. Spermidine is then synthesized by transfer of an activated aminopropyl group from S-adenosyl S-methyl homocystaeamine to putrescine. Spermine is formed by addition of a further aminopropyl group to spermidine.
Reaction SMILES: C1N=C[N:3]([C:6]([N:8]2[CH:12]=[N:11][CH:10]=[CH:9]2)=[S:7])C=1.C1C2[C:17](=[CH:18][CH:19]=[CH:20]C=2)[CH:16]=[C:15](N)N=1.C([O-])(=O)C.[NH4+]>C(#N)C>[CH:10]1[C:9]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:12]([NH:8][C:6]([NH2:3])=[S:7])[N:11]=1
Reactant: S=C(n1ccnc1)n1ccnc1
Reactant: Nc1cc2ccccc2cn1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC#N
Product: NC(=S)Nc1cc2ccccc2cn1
Reaction time: 12 h

Procedure:
0.618 g (3.47 mmol) N,N′-thiocarbonyldiimidazole was dissolved in 20 mL acetonitrile, and 0.500 g (3.47 mmol) isoquinoline-3-amine in the form of a suspension in 15 mL acetonitrile was added dropwise in portions. The clear orange solution which formed was stirred for 12 hr, whereupon a reddish precipitate formed. The intermediate product was directly reacted, without workup, with 0.535 g (6.940 mmol) ammonium acetate for 25 min at 85° C. in a CEM microwave (100 watts). The solvent was removed under vacuum. The residue was stirred in water, and the resulting precipitate was suctioned off and washed with water. For further purification the solid was taken up in 5 mL acetonitrile and combined with 50 mL diisopropyl ether. The precipitate was filtered again and dried in a vacuum drying oven at 40° C., resulting in the isolation of 0.540 g (2.647 mmol, 76%) purified N-isoquinolin-3-yl-thiourea.