Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7](I)=[CH:6][N:5]=[C:4]2[CH:9]=[CH:10][S:11][C:3]=12.[CH3:12][C@@H:13]([OH:16])[C:14]#[CH:15].C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[C:7]([C:15]#[C:14][C@H:13]([OH:16])[CH3:12])=[CH:6][N:5]=[C:4]2[CH:9]=[CH:10][S:11][C:3]=12
Reactant: Clc1c(I)cnc2ccsc12
Reactant: C#C[C@@H](C)O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: C[C@@H](O)C#Cc1cnc2ccsc2c1Cl

Procedure:
A mixture of 7-chloro-6-iodothieno[3,2-b]pyridine (0.46 g, 1.6 mmol), bis(triphenylphosphine)palladium(II) chloride (0.11 g, 0.16 mmol) and copper(I) iodide (30 mg, 0.16 mmol) was purged with N2. (2R)-but-3-yn-2-ol (0.13 g, 1.9 mmol) and triethylamine (4.5 mL, 33 mmol) was added via syringe. The reaction mixture was heated at reflux for 2 h. The mixture was concentrated under reduced pressure, and the resultant residue was purified on silica gel (eluting with 0-85% EtOAc/hexanes) to give the desired product. LCMS calculated for C11H9ClNOS (M+H)+: m/z=238.0. Found: 238.0.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH:18]=[O:19])=[C:11]([CH:15]([CH3:17])[CH3:16])[NH:12]2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].[H-].[Na+].Cl[CH2:23][C:24]1[O:25][CH:26]=[CH:27][N:28]=1>CN(C=O)C.CCOC(C)=O>[CH:18]([C:10]1[C:9]2[C:13](=[CH:14][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=2)[N:12]([CH2:23][C:24]2[O:25][CH:26]=[CH:27][N:28]=2)[C:11]=1[CH:15]([CH3:16])[CH3:17])=[O:19]
Reactant: CCOC(=O)c1ccc2c(C=O)c(C(C)C)[nH]c2c1
Reactant: ClCc1ncco1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc2c(C=O)c(C(C)C)n(Cc3ncco3)c2c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of ethyl3-formyl-2-isopropyl-1H-indole-6-carboxylate (Compound 34, 1.22 g, 4.72 mmol) in DMF (10 ml) was added NaH (170 mg, 7.08 mmol) and 2-(chloromethyl)oxazole (1.10 g, 9.44 mmol). The reaction was stirred at 25° C. for 12 h, diluted with EtOAc, washed with H2O, brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→50% EtOAc-hexanes) to yield the title compound as a yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:47]=[CH:46][CH:45]=[CH:44][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]2[O:30][CH2:31][CH2:32]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:13][CH:12]=1.[F:48][C:49]1[C:50]([OH:61])=[C:51]([CH2:55][CH2:56][NH:57][C:58](=[O:60])[CH3:59])[CH:52]=[CH:53][CH:54]=1>>[C:58]([NH:57][CH2:56][CH2:55][C:51]1[CH:52]=[CH:53][CH:54]=[C:49]([F:48])[C:50]=1[O:61][CH2:32][CH2:31][O:30][CH:18]1[CH:17]([C:14]2[CH:13]=[CH:12][C:11]([O:10][CH2:9][CH2:8][CH2:7][O:6][CH2:5][C:4]3[CH:44]=[CH:45][CH:46]=[CH:47][C:3]=3[O:2][CH3:1])=[CH:16][CH:15]=2)[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19]1)(=[O:60])[CH3:59]
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOS(=O)(=O)c2ccc(C)cc2)cc1
Reactant: CC(=O)NCCc1cccc(F)c1O
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2c(F)cccc2CCNC(C)=O)cc1

Procedure:
Analogously to Method G, 0.45 g of tert-butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-[2-(toluene-4-sulphonyloxy)ethoxy]piperidine-1-carboxylate (Example 14b) and 0.26 g of N-[2-(3-fluoro-2-hydroxyphenyl)ethyl]acetamide are reacted. The title compound is obtained as a yellow oil. Rf=0.42 (EtOAc); Rt=5.65.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][SH:10])=[CH:5][CH:4]=1.[H-].[Na+].[CH3:13][N:14]([CH3:26])[CH:15]=[N:16][S:17]([C:20]1[S:21][C:22](Br)=[CH:23][CH:24]=1)(=[O:19])=[O:18]>CN(C=O)C.O>[CH3:13][N:14]([CH3:26])[CH:15]=[N:16][S:17]([C:20]1[S:21][C:22]([S:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:23][CH:24]=1)(=[O:19])=[O:18]
Reactant: COc1ccc(CS)cc1
Reactant: CN(C)C=NS(=O)(=O)c1ccc(Br)s1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(CSc2ccc(S(=O)(=O)N=CN(C)C)s2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 4-methoxy-α-toluenethiol (7.7 g, 0.05 mol) in DMF (10 ml) was added dropwise to a stirred mixture of sodium hydride (2.50 g, 50% oil dispersion, 0.054 mol) in DMF (40 ml). When gas evolution was complete, N,N-dimethyl-N'-(5-bromothiophene-2-sulfonyl)formamidine (14.85 g; 0.05 mol) was added and the resulting mixture was stirred for 1 hour at 25° C. The reaction mixture was diluted with water and the solid that separated was collected, washed with water and dried to give 15.36 g., m.p. 92°-101° C. Recrystallization from 1-chlorobutane gave material with m.p. 110°-111.5° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.Cl[C:21]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:22]>ClCCl>[C:8]([C:4]1[CH:3]=[C:2]([NH:1][C:21](=[O:22])[O:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:7]=[CH:6][CH:5]=1)(=[O:10])[CH3:9]
Reactant: CC(=O)c1cccc(N)c1
Reactant: CCCCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCOC(=O)Nc1cccc(C(C)=O)c1
Yield: 89.5 %

Procedure:
A mixture of 27.03 g of m-aminoacetophenone, 25.85 g of diisopropylethylamine, 27.32 g of n-butyl chloroformate and 300 ml of dichloromethane was reacted as described in Example 1, giving 42.10 g of (3-acetylphenyl)carbamic acid, butyl ester, mp 59°-60° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:11]([NH2:16])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:5][CH:4]=1.O.N1C(=O)[C:24](=O)[C:22](=[O:23])NC1=O>C(O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:10]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:16]=[CH:24][C:22]2=[O:23])=[CH:7][CH:8]=1
Reactant: O=C1NC(=O)C(=O)C(=O)N1
Reactant: COc1ccc(Nc2ccccc2N)cc1
Solvent: O
Solvent: CCO
Product: COc1ccc(-n2c(=O)cnc3ccccc32)cc1
Reaction time: 0.5 h

Procedure:
To a solution of N-(4-methoxyphenyl)benzene-1,2-diamine (9.0 g) in ethanol (150 ml) was added a solution of alloxan monohydrate (6.7 g) in water (150 ml) and the mixture was stirred for 30 minutes. The precipitate was filtered off and recrystallised from glacial acetic acid giving the title compound mp 236°-238° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]([CH3:17])[CH3:16])=[CH:11][C:10]=2[O:18][CH3:19])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[C:42]([O:43][CH3:44])=[CH:41][C:25]2[CH2:26][CH2:27][N:28]([CH2:31][C:32]([N:34]3[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]3)=[O:33])[CH2:29][CH2:30][C:24]=2[CH:23]=1>>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]([CH3:17])[CH3:16])=[CH:11][C:10]=2[O:18][CH3:19])=[N:7][C:2]([NH:21][C:22]2[C:42]([O:43][CH3:44])=[CH:41][C:25]3[CH2:26][CH2:27][N:28]([CH2:31][C:32]([N:34]4[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]4)=[O:33])[CH2:29][CH2:30][C:24]=3[CH:23]=2)=[N:3][CH:4]=1
Reactant: COc1cc2c(cc1N)CCN(CC(=O)N1CCN(C)CC1)CC2
Reactant: COc1cc(N(C)C)ccc1Nc1nc(Cl)ncc1Cl
Product: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccc(N(C)C)cc3OC)n1)CCN(CC(=O)N1CCN(C)CC1)CC2
Yield: 43 %

Procedure:
In an analogous manner to Example 1534, the product was prepared from N(1)-(2,5-Dichloro-pyrimidin-4-yl)-2-methoxy-N(4),N(4)-dimethyl-benzene-1,4-diamine and 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(4-methyl-piperazin-1-yl)-ethanone. Product isolated as a grey foam (50 mg, 43%). mp: 145° C. (glass @ 83), MS (ESI+): 609.5 (M+H), 1H-NMR (CDCl3, 400 MHz) δ 8.13 (s, 1H), 8.10 (s, 1H), 8.01 (s, 1H), 7.40 (s, 1H), 7.28 (s, 1H), 6.64 (s, 1H), 6.37 (s, 1H), 6.34 (s, 1H), 3.92 (s, 3H), 3.87 (s, 3H), 3.74 (m, 2H), 3.67 (m, 2H), 3.28 (s, 2H), 2.99 (s, 6H), 2.87 (m, 2H), 2.81 (m, 2H), 2.66 (m, 4H), 2.46 (m, 2H), 2.41 (m, 2H), 2.34 (s, 3H).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+]>S(=O)(=O)(O)O>[F:12][C:8]1[C:9]([N+:1]([O-:4])=[O:2])=[CH:10][CH:11]=[C:6]([F:5])[C:7]=1[C:13]1[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=1
Reactant: Fc1cccc(F)c1-c1ccncc1
Reactant: O=[N+]([O-])O
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: O=[N+]([O-])c1ccc(F)c(-c2ccncc2)c1F
Reaction time: 0.75 h
Yield: 88 %

Procedure:
A mixture of cold (0° C.) concentrated nitric acid (20.4 ml) and concentrated sulfuric acid (20.4 ml) was added in portions to a stirred solution of 10 g 4-(2,6-difluorophenyl)-pyridine in 56 ml concentrated sulfuric acid at 0° C. After 45 minutes at 0° C., the mixture was poured onto ice and the resulting solution was neutralized with solid sodium bicarbonate. The neutralized solution was then extracted twice with ethyl acetate and the organic extracts were dried and evaporated to give the product as a white solid of m p. 110°-112° C. (10.9 g, 88% yield). NMR (CDC13, 60 MHz): 8.8 (m, 2H), 8.2 (m, 1H), 7.0-7.6 (m, 3H).
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:18]=[C:19]([O:23][CH3:24])[C:20]=1[O:21][CH3:22])[NH2:17]>C(OCC)(=O)C>[CH3:24][O:23][C:19]1[CH:18]=[C:16]([NH:17][C:2]2[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=2[N+:8]([O-:10])=[O:9])[CH:15]=[C:14]([O:13][CH3:12])[C:20]=1[O:21][CH3:22]
Reactant: COc1cc(N)cc(OC)c1OC
Reactant: O=[N+]([O-])c1ccc(O)cc1F
Solvent: CCOC(C)=O
Product: COc1cc(Nc2cc(O)ccc2[N+](=O)[O-])cc(OC)c1OC
Temperature: 100 °C
Reaction time: 10 h

Procedure:
3.7 g of 3-fluoro-4-nitrophenol and 4.76 g of 3,4,5-trimethoxyaniline were mixed and stirred for 10 hours at 100° C. After cooling, it was taken up in ethyl acetate and water and extracted three times with ethyl acetate. The combined organic phases were extracted three times with 1N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried on sodium sulfate and concentrated by evaporation to a very large extent in a vacuum. The product was digested with diisopropyl ether.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH:11]2[CH3:16])[CH3:9])=[CH:4][CH:3]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27](=O)[CH2:26][CH:25]1[CH3:31])=[O:23])([CH3:20])([CH3:19])[CH3:18]>>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([N:13]2[CH2:14][CH2:15][N:10]([C@H:8]([C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=3)[CH3:9])[C@H:11]([CH3:16])[CH2:12]2)[CH2:26][CH:25]1[CH3:31])=[O:23])([CH3:20])([CH3:18])[CH3:19]
Reactant: CC1CNCCN1C(C)c1ccc(Br)cc1
Reactant: CC1CC(=O)CCN1C(=O)OC(C)(C)C
Product: CC1CC(N2CCN([C@@H](C)c3ccc(Br)cc3)[C@H](C)C2)CCN1C(=O)OC(C)(C)C

Procedure:
1-[1-(4-Bromo-phenyl)-ethyl]-2-methyl-piperazine (0.104 g) from preparation A step 4 was treated with 0.075 g 1-tert-butoxycarbonyl-2-methyl-4-oxo-piperidine from the previous step as described in preparation A step 5 to afford 1-tert-butoxycarbonyl-2-methyl-4-{4-[1 (S)-(4-Bromophenyl)-ethyl]-3(R)-methylpiperazin-1-yl}-piperidine.
Reaction SMILES: [CH2:1]([Si:3]([CH2:17][CH3:18])([CH2:15][CH3:16])[N:4]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:5][CH:6]=[CH2:7])[CH3:2].[CH3:19][SiH:20]([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23]>[Pt].C([Si](C)(C)O[Si](C=C)(C)C)=C.C1(C)C=CC=CC=1>[CH2:17]([Si:3]([CH2:15][CH3:16])([CH2:1][CH3:2])[N:4]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:5][CH2:6][CH2:7][Si:20]([CH3:19])([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23])[CH3:18]
Reactant: CCO[SiH](C)OCC
Reactant: C=CCN(Cc1ccccc1)[Si](CC)(CC)CC
Agent: [Pt]
Agent: C=C[Si](C)(C)O[Si](C)(C)C=C
Solvent: Cc1ccccc1
Product: CCO[Si](C)(CCCN(Cc1ccccc1)[Si](CC)(CC)CC)OCC
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A flask equipped with a stirrer, reflux condenser, dropping funnel and thermometer was charged with 26.2 g (0.1 mol) of N-triethylsilyl-N-benzyl-N-allylamine and 0.07 g of a toluene solution of platinum/1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (Pt concentration 3 wt %) and heated at 50° C. Once the internal temperature became steady, 13.4 g (0.1 mol) of methyldiethoxysilane was added dropwise over 1 hour. Stirring was continued at the temperature for a further 1 hour. The reaction solution was distilled, collecting 31.0 g of a fraction having a boiling point of 151-152° C./0.1 kPa.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:33][O:34][CH3:35])[C:8]([NH:10][CH:11]2[C:31](=[O:32])[N:13]3[C:14]([C:18]([O:20]CC4C=CC([N+]([O-])=O)=CC=4)=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[OH-].[K+].Cl>C(O)C.O>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:33][O:34][CH3:35])[C:8]([NH:10][CH:11]2[C:31](=[O:32])[N:13]3[C:14]([C:18]([OH:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=CCS[C@H]12)c1csc(N)n1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12)c1csc(N)n1
Temperature: 5 °C
Reaction time: 0.25 h
Yield: 39.9 %

Procedure:
p-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (syn-isomer: 7.8 g.) was suspended in a mixture of ethanol (60 ml.) and water (60 ml.) 1 N Aqueous solution of potassium hydroxide (45 ml.) was added dropwise to the stirred suspension under ice-cooling over 10 minutes and stirred at 5° C. for 15 minutes. The resultant solution was adjusted to pH 7.0 with conc. hydrochloric acid, washed with ethyl acetate and the concentrated under reduced pressure to half of its initial volume. The concentrated solution was adjusted to pH 5.0 and subjected to column chromatography on macroporous, non-ionic adsorption resin "Diaion HP-20" (Trade mark; manufactured by Mitsubishi Chemical Industries Ltd.; 80 ml.), and eluted with 5% aqueous solution of isopropyl alcohol. The fractions containing the object compound were collected and adjusted to pH 3.2 with 10% hydrochloric acid. The precipitating crystals were collected by filtration, and dried to give 7-[2 -(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn-isomer: 2.3 g.)
Reaction SMILES: N(OC(C)(C)C)=O.N[C:9]1[S:10][C:11]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:12]=2[N:13]=1.[ClH:22]>C(#N)C.[Cu]>[Cl:22][C:9]1[S:10][C:11]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:12]=2[N:13]=1
Reactant: Cl
Reactant: Nc1nc2ccc(C(F)(F)F)cc2s1
Agent: [Cu]
Agent: CC(C)(C)ON=O
Solvent: CC#N
Product: FC(F)(F)c1ccc2nc(Cl)sc2c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 92 %

Procedure:
In a three-necked flask fitted with a condenser, a suspension of copper II chloride (370 mg, 2.75 mmol) in acetonitrile (5 mL) was treated with tert-butyl nitrite (0.41 mL, 3.44 mmol) and stirred at rt for 10 minutes. A solution of 2-amino-6-trifluoromethylbenzthiazole (500 mg, 2.29 mmol) in acetonitrile (1 mL) was then added dropwise. The mixture was heated at 65° C. for 30 minutes, then cooled and diluted with an excess of 1 N aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate. The organic phase was separated, dried (MgSO4), and concentrated under reduced pressure. An orange semi-solid (501 mg, 92%) was obtained and used without further purification. 1H NMR (300 MHz, CDCl3) δ 8.10-8.05 (m, 2H), 7.74 (d, 1H); LC-MS m/z 238.2 (MH+), ret. time 3.76 min TLC Rf=0.50 (9:1 hexanes/ethyl acetate).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:11]1([CH2:14][NH2:15])[CH2:13][CH2:12]1.O>O1CCCC1>[CH:11]1([CH2:14][NH:15][C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:13][CH2:12]1
Reactant: NCC1CC1
Reactant: O=[N+]([O-])c1cccnc1Cl
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1cccnc1NCC1CC1
Reaction time: 1 h
Yield: 95.7 %

Procedure:
3 g (18.9 mM) of 2-chloro-3-nitropyridine and 5 g (70.3 mM) of cyclopropylmethylamine in 12 ml of tetrahydrofurane were refluxed under stirring for 1 h. Water was added and the aqueous layer was extracted with ethylacetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was removed under vacuum to give 3.5 g of N-(cyclopropylmethyl)-3-nitropyridin-2-amine as a yellow oil. Yield: 95.7%.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1.Br[C:18]1[CH:19]=[CH:20][C:21](N)=[N:22][CH:23]=1.N1C=CC=C([Sn](CCCC)(CCCC)CCCC)C=1>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:16]=[C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([C:20]2[CH:21]=[N:22][CH:23]=[CH:18][CH:19]=2)=[CH:7][N:6]=1)[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]
Reactant: COC(=O)CCC(=O)Nc1ccc(Br)cn1
Reactant: Nc1ccc(Br)cn1
Agent: [Pd]
Agent: CCCC[Sn](CCCC)(CCCC)c1cccnc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: COC(=O)CCC(=O)Nc1ccc(-c2cccnc2)cn1
Temperature: 150 °C
Yield: 26 %

Procedure:
Methyl 4-[(5-bromo-2-pyridyl)amino]-4-oxo-butanoate (Commercially available or prepared as described in example II using as starting material the commercially available: 5-bromo-2-aminopyridine, 200 mg, 0.697 mmol) was dissolved in toluene in a microwave vial and 3-pyridyltributylstannane (0.836 mmol, 0.290 mL) and tetrakis(triphenylphosphine) palladium(0) (0.069 mmol) were added. Argon was bubbling through the mixture for ca. 5 min and the vial was heated under microwave irradiations for 10 min at 150° C. The solvent was evaporated and the residue was diluted with acetonitrile, washed with cyclohexane (2×) and evaporated. The product was purified by flash chromatography (RF-machine, AcOEt/cyclohexane: 0/100→100/0) to give methyl 4-oxo-4-[[5-(3-pyridyl)-2-pyridyl]amino]butanoate (compound A82) (0.051 g, 26% Yield). LC-MS (Method F) RT 0.50, 286 (M+H+). Compound A83, A84 and A85 from table A were prepared by the same method using the corresponding coupling reagent.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:11]([CH:15]([CH3:17])[CH3:16])[C:12](O)=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH3:10].CN(C)C=O.S(Cl)([Cl:25])=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:11]([CH:15]([CH3:17])[CH3:16])[C:12]([Cl:25])=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH3:10]
Reactant: CCOc1ccc(C(C(=O)O)C(C)C)cc1F
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCOc1ccc(C(C(=O)Cl)C(C)C)cc1F
Temperature: 40 °C
Reaction time: 2 h

Procedure:
Into a solution of 0.15 g (0.62 mM) of 2-(3-fluoro-4-ethoxyphenyl)isovaleric acid in 3.0 ml of anhydrous methylene chloride, a catalytic amount of dimethylformamide and 0.16 g (1.37 mM) of thionyl chloride were added, and the mixture was stirred for 2 hours in an oil bath at 40° C. Thereafter, an excess of thionyl chloride and methylene chloride were distilled off from the reaction mixture under a reduced pressure to obtain 2-(3-fluoro-4-ethoxyphenyl)isovaleric chloride as an oily substance.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]1[CH:26]=[CH:25][C:6]([O:7][C:8]2[CH:24]=[CH:23][C:11]([O:12][CH:13]([CH3:22])[C:14](=[O:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.[BH4-].[Na+]>C(O)C.C(Cl)Cl>[F:1][C:2]([F:27])([F:28])[C:3]1[CH:4]=[CH:5][C:6]([O:7][C:8]2[CH:24]=[CH:23][C:11]([O:12][CH:13]([CH3:22])[CH:14]([OH:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][CH:9]=2)=[CH:25][CH:26]=1
Reactant: CCOC(=O)CC(=O)C(C)Oc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)CC(O)C(C)Oc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1
Reaction time: 0.17 h

Procedure:
To a solution of ethyl 4-[4-(4-trifluoromethylphenoxy)phenoxy]-3-oxopentanoate (450 mg) in ethanol (5 ml) is added NaBH4 (150 mg) at 0°. The resulting mixture is then stirred at 0° for about 10 minutes. The mixture is diluted with CH2Cl2, washed with saturated NaCl solution, dried and evaporated to dryness to give ethyl 4-[4-(4-trifluoromethylphenoxy)phenoxy]-3-hydroxypentanoate, in quantitative yield, MS m/e 398 (M+).
Reaction SMILES: C(O[C:6](=[O:12])[O:7][CH2:8][CH2:9][CH2:10][CH3:11])CCC.[NH2:13][CH2:14][CH:15]([OH:18])[CH2:16][OH:17]>>[OH:18][CH:15]([CH2:16][OH:17])[CH2:14][NH:13][C:6](=[O:12])[O:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: NCC(O)CO
Reactant: CCCCOC(=O)OCCCC
Product: CCCCOC(=O)NCC(O)CO

Procedure:
An equimolar mixture of dibutylcarbonate and 3-amino-1,2-propanediol was allowed to react resulting in formation of butyl 2,3-dihydroxypropylcarbamate.
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([C:9]([Br:16])=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].CCO>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.C1(C)C=CC=CC=1>[Br:16][C:9]1[C:10]2[C:15]([C:2]([C:19]3[CH:18]=[CH:17][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=3)=[C:3]3[C:8]=1[CH:7]=[CH:6][CH:5]=[CH:4]3)=[CH:14][CH:13]=[CH:12][CH:11]=2
Reactant: OB(O)c1ccc2ccccc2c1
Reactant: Brc1c2ccccc2c(Br)c2ccccc12
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: CCO
Solvent: Cc1ccccc1
Product: Brc1c2ccccc2c(-c2ccc3ccccc3c2)c2ccccc12
Temperature: 90 °C
Yield: 60.8 %

Procedure:
A mixture of 15 g (44.6 mmol) of 9,10-dibromoanthracene, 7.7 g (44.6 mmol) of naphthalen-2-ylboronic acid, 0.52 g (0.446 mmol) of Tetrakis(triphenylphosphine)Palladium, 33 ml of 2M Na2CO3, 60 ml of EtOH and 150 ml toluene was degassed and placed under nitrogen, and then heated at 90° C. for 24 h. After the reaction finish, the mixture was allowed to cool to room temperature. The organic layer was extracted with ethyl acetate and water, dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica (hexane-dichloromethane) to give product 10.4 g (61%) as a yellow solid.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:15])[CH3:14])=[CH:9][CH:8]=1)=[O:6].[Br:16]([O-])(=O)=O.[Na+].[Br-].[Na+]>C(Cl)Cl.O.S(S([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+]>[Br:16][C:13]([C:10]1[CH:9]=[CH:8][C:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][Cl:1])=[CH:12][CH:11]=1)([CH3:15])[CH3:14]
Reactant: CC(C)c1ccc(C(=O)CCCCl)cc1
Reactant: [O-][Br+2]([O-])[O-]
Agent: O=S(=O)([O-])S(=O)(=O)[O-]
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CC(C)(Br)c1ccc(C(=O)CCCCl)cc1
Temperature: 10 °C
Yield: 281.5 %

Procedure:
Dissolve 4-chloro-1-(4-isopropyl-phenyl)-butan-1-one (74.7 g, 333 mmol) in methylene chloride (250 mL) and add sodium bromate (17.6 g, 117 mmol) in water (75 mL) in a three-necked Morton flask equipped with an overhead stirrer. Cool the solution to 10° C. and irradiate with two 150W incandescent flood lamps. Add, by dropwise addition, a solution of sodium bromide (24 g, 233 mmol) and stir for 2 hours. Illuminate for another 30 minutes, add sodium dithionate (2.0 g), separate the organic phase, dry (MgSO4) and evaporate the solvent in vacuo to give the title compound (100 g, 99%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH:6]=[CH:7][N+:8]([O-:10])=[O:9].[CH3:16][N:17]([CH3:21])[C:18](=[S:20])[S-:19].C[NH2+]C>C(=S)=S>[CH3:16][N:17]([CH3:21])[C:18](=[S:19])[S:20][CH:6]([CH2:7][N+:8]([O-:10])=[O:9])[C:5]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: COc1ccc(C=C[N+](=O)[O-])cc1OC
Reactant: CN(C)C(=S)[S-]
Agent: C[NH2+]C
Solvent: S=C=S
Product: COc1ccc(C(C[N+](=O)[O-])SC(=S)N(C)C)cc1OC

Procedure:
As in Example 17, reaction of 3,4-dimethoxy-β-nitrostyrene with dimethylammonium dimethyldithiocarbamate in the presence of carbon disulfide gave 3,4-dimethoxy-α-(nitromethyl)benzyl dimethyldithiocarbamate melting at 108° - 110° C. after recrystallization without heating from acetone-methanol solution.