Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2Br)[CH:9]=[CH:10][CH:11]=1)=[O:5])[CH3:2].[CH2:19]([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:12]2[C:13]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[O:26][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:9]=[CH:10][CH:11]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cccc(-c2ccccc2Br)c1
Reactant: OB(O)c1ccccc1OCc1ccccc1
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: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1cccc(-c2ccccc2-c2ccccc2OCc2ccccc2)c1
Temperature: 90 °C
Yield: 41 %

Procedure:
2′-Bromobiphenyl-3-carboxylic acid ethyl ester (153 mg, 0.5 mmol) and 2-benzyloxyphenylboronic acid (125 mg (0.55 mmol) were dissolved in 1:1 toluene:ethanol (5 ml) under nitrogen. Potassium carbonate (552 mg, 4 mmol) and tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) were added and the mixture heated at 90° C. for 3 h. After cooling, the solvent was evaporated. The residue was partitioned between diethyl ether and water and the organic phase washed with water, dried (MgSO4) and the solvent removed in vacuo. The residue was flash chromatographed (silica gel, 2-10% EtOAc-isohexane) to give the title compound as a clear oil (84 mg, 41%). LC/MS Rt=4.09 [(M−OEt)H+]=363.1.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[Al+3].[Cl-].[Cl-].[Cl-].[CH2:11]([NH:18][C:19](=O)[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([F:33])[C:28]=2[O:30][CH2:31][CH3:32])[N:23]([CH3:34])[CH:22]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[CH2:11]([NH:18][CH2:19][CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([F:33])[C:28]=2[O:30][CH2:31][CH3:32])[N:23]([CH3:34])[CH:22]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CCOc1c(F)ccc2c1c(CC(=O)NCc1ccccc1)cn2C
Agent: [Al+3]
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Product: CCOc1c(F)ccc2c1c(CCNCc1ccccc1)cn2C
Yield: 61.3 %

Procedure:
To a solution of LiAlH4 (5 mg, 0.12 mmol) and AlCl3 (16 mg, 0.12 mmol) in THF (5 mL) was added a solution of 30-14 (14 mg, 0.04 mmol) in THF (5 mL) dropwise, the mixture was stirred at room temperature overnight before Na2SO4.10H2O was added. The mixture was filtered and the filtrate was evaporated to give a crude product which was purified by preparative HPLC (acid condition, water/CH3CN, 25-30% CH3CN in 7.5 min, RT=6.5 min) to afford 30-15 (8 mg, 61%) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.30-7.28 (m, 5H), 7.00-6.95 (m, 1H), 6.87-6.84 (m, 2H), 4.24 (q, J=7.2 Hz, 2H), 4.01-3.98 (br.s, 2H), 3.67 (s, 3H), 3.27-3.22 (br.s, 2H), 3.15-3.11 (br.s, 2H), 1.34 (t, J=6.8 Hz, 3H). LRMS: calc 326.2 and found: 327.0 [M+1].
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[CH3:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2].[C:20]([O:24][C:25]([NH:27][CH:28]1[CH2:32][CH2:31][NH:30][CH2:29]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C1CCN2C(=NCCC2)CC1>C(#N)C>[C:20]([O:24][C:25]([NH:27][CH:28]1[CH2:32][CH2:31][N:30]([C:10]2[C:11]([CH3:13])=[C:12]3[C:7]([C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4][N:3]3[CH2:1][CH3:2])=[CH:8][C:9]=2[F:15])[CH2:29]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(C)c21
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCC(NC(=O)OC(C)(C)C)C3)c(C)c21
Yield: 52.8 %

Procedure:
A mixture of 1-ethyl-6,7-difluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylic acid (420 mg), 3-t-butoxycarbonylaminopyrrolidine (350 mg), DBU (260 mg) and anhydrous acetonitrile (10 ml) was refluxed for 35 hours. After the reacting mixture was concentrated under reduced pressure, the resulting residue was dissolved in chloroform (40 ml), washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution successively, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography eluting chloroform-methanol-concentrated aqueous ammonia (20:6:1) and recrystallized from methanol to give 7-(3-t-butoxycarbonylamino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylic acid (360 mg) as white prisms, mp 184.5°-187.5° C. (decompd.).
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:15][CH2:16][CH3:17])[CH2:5][NH:6][C:7]([C:9]1[S:10][C:11](Cl)=[CH:12][CH:13]=1)=[O:8])[CH3:2].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>[Pd](Cl)Cl.CCO>[CH2:1]([O:3][CH:4]([O:15][CH2:16][CH3:17])[CH2:5][NH:6][C:7]([C:9]1[S:10][C:11]([C:22]2[CH:23]=[CH:24][C:19]([Cl:18])=[CH:20][CH:21]=2)=[CH:12][CH:13]=1)=[O:8])[CH3:2]
Reactant: CCOC(CNC(=O)c1ccc(Cl)s1)OCC
Reactant: OB(O)c1ccc(Cl)cc1
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCOC(CNC(=O)c1ccc(-c2ccc(Cl)cc2)s1)OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 103.6 %

Procedure:
Add 5-chloro-thiophene-2-carboxylic acid (2,2-diethoxyethyl) amide (50.15 g, 0.18 mol), 4-chlorophenylboronic acid (29.84 g, 0.18 mol), potassium carbonate (50 g, 0.36 mol), [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)(3-chloropyridyl)]palladium (II) dichloride (4.40 g, 0.006 mol), and EtOH (1000 mL) to a 2 L three-necked round bottom flask equipped with a overhead stirrer, reflux condenser, nitrogen inlet/outlet, addition funnel, and thermocouple. Heat the resulting slurry for 35 min, then add activated carbon (5.8 g) and heat for an additional 30 min. Filter the resulting slurry through glass microfibre filter and rinse solids with EtOH (500 mL). Remove solvent from the filtrate under reduced pressure until 15-20% solvent remains. To this filtrate, add water (1300 mL) and stir the resulting slurry at room temperature for 1 h, then at 0-5° C. for 0.5 h. Filter the slurry, rinse the solids with water (1000 mL), and dry to afford 66 g of crude 5-(4-chlorophenyl)-thiophene-2-carboxylic acid (2,2-diethyoxyethyl) amide. Reflux the crude 5-(4-chlorophenyl)-thiophene-2-carboxylic acid (2,2-diethyoxyethyl) amide in heptane (1625 mL) for 1 h, then filter through a glass microfibre filter. Transfer the filtrate to a round bottom flask and remove solvent until 725 mL of solvent remained. Stir the mixture under chilled conditions for 40 minutes. Filter the resulting slurry, rinse with heptane (100 mL), and dry to afford 41 g (64%) as a white solid. 1H NMR (500 MHz, CDCl3): δ 1.25 (t, J=7.0 Hz, 6H), 3.57-3.62 (m, 4H), 3.73-3.79 (m, 2H), 4.62 (t, J=5.5 Hz, 1H), 6.20 (bs, 1H), 7.24 (d, J=4.5 Hz, 1H), 7.38 (d, J=9.0 Hz, 2H), 7.45 (d, J=4.5 Hz, 1H), 7.54 (d, J=9.0 Hz, 2H).
Reaction SMILES: [CH2:1]([C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1)[CH3:2].[CH2:10](N(CC)CC)C.ClC(OCC)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>ClCCl.C(OCC)(=O)C.C(OCC)C>[CH3:10][NH:7][C:6]1[CH:8]=[CH:9][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=1
Reactant: CCc1ccc(N)cc1
Reactant: CCN(CC)CC
Agent: CCOC(=O)Cl
Agent: [Al+3]
Agent: [H-]
Solvent: ClCCl
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: CCc1ccc(NC)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 66.6 %

Procedure:
4-Ethylaniline (2.4 g, 20 mmol) was dissolved in dichloromethane (150 ml), and triethylamine (8.4 ml, 60 mmol) and ethyl chloroformate (5.8 ml, 60 mmol) were added to the solution to stir the mixture for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was dissolved in diethyl ether (20 ml). The solution was added dropwise to a suspension (20 ml) of lithium aluminum hydride (2.4 g, 63.2 mmol) in diethyl ether under cooling with ice water in a nitrogen atmosphere. The mixture was stirred for 1 hours as it was, and for 2 hours at room temperature. The solvent was distilled off under reduced pressure, and tetrahydrofuran (20 ml) was added to the residue. The resultant mixture was heated under reflux for 1 hour and 40 minutes. Ice and then water were gradually added to the reaction mixture. After potassium sulfate was additionally added, the mixture was extracted with ethyl acetate. The extract was additionally extracted with 1N hydrochloric acid. After the resultant extract was basified with a 4N aqueous solution of sodium hydroxide, it was extracted 3 times in total with ethyl acetate (twice) and diethyl ether (once), and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography on silica gel (hexane:ethyl acetate=20:1) to obtain 1.8 g of the title compound (oil).
Reaction SMILES: [C:1]([C:4]1[CH:27]=[CH:26][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:17]4[CH2:22][CH2:21][N:20](C(=O)C)[CH2:19][CH2:18]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+]>C(COC)OC>[C:1]([C:4]1[CH:27]=[CH:26][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCN(C(C)=O)CC2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: COCCOC
Product: CC(=O)c1ccc2c(c1)ncn2-c1cccc(N2CCNCC2)c1
Temperature: 80 °C
Yield: 65.3 %

Procedure:
To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v/v/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-Isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v/v/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][CH2:7][Si:8]([CH3:13])(OC)[O:9]C.[SiH4].[OH-].[K+:16]>O>[NH2:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][CH2:7][SiH:8]([CH3:13])[O-:9].[K+:16]
Reactant: CO[Si](C)(CCCNCCN)OC
Agent: [K+]
Agent: [OH-]
Agent: [SiH4]
Solvent: O
Product: C[SiH]([O-])CCCNCCN
Yield: 40 %

Procedure:
About 103 g of N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane (commercially available under the name "Silan GF 95" from Wacker-Chemie GmbH, Munich) are metered into a solution containing 63.7 g of potassium hydroxide (88 percent in water) in 200 g of water, with vigorous stirring. First methanol and then about 70 g of water are distilled off from the mixture, by heating. The mixture is then made up to a total weight of 317 g by addition of water. A 40 percent potassium N-(2-aminoethyl)-3-aminopropylmethylsilanolate solution is obtained.
Reaction SMILES: CC1C=CC(S(O[CH2:12][C@H:13]([C@H:15]2[O:24][C@@H:18]3[O:19][C:20]([CH3:23])([CH3:22])[O:21][C@@H:17]3[CH2:16]2)[OH:14])(=O)=O)=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[NH4+].[Cl-]>C1COCC1>[CH3:22][C:20]1([CH3:23])[O:19][C@H:18]2[O:24][C@H:15]([C@H:13]3[CH2:12][O:14]3)[CH2:16][C@H:17]2[O:21]1
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H](O)[C@@H]2C[C@H]3OC(C)(C)O[C@H]3O2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC1(C)O[C@H]2O[C@H]([C@H]3CO3)C[C@H]2O1
Temperature: -70 °C
Reaction time: 1 h
Yield: 77.7 %

Procedure:
To a solution of [(2R)-2-[(3aR,5S,6aR)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-hydroxy-ethyl] 4-methylbenzenesulfonate (compound 6a, 100 g, 280 mmol) in anhydrous THF (1500 mL) cooled at −70° C. was added potassium bis(trimethylsilyl)amide (340 mL, 340 mmol, 1 M in THF) under N2 atmosphere. After being stirred at −70° C. for 1 hour, the reaction mixture was poured into saturated NH4Cl solution. The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 1:3 EtOAc in petroleum ether) to afford 40.5 g of (3aR,5S,6aR)-2,2-dimethyl-5-[(2R)-oxiran-2-yl]-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxole (compound 6b) as a slight yellow oil.
Reaction SMILES: [OH:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[Cl:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[N:20]=[C:21]=[O:22]>>[OH:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH:4][C:21]([NH:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[Cl:12])=[O:22]
Reactant: Nc1ccc([N+](=O)[O-])cc1O
Reactant: O=C=Nc1cccc(Cl)c1Cl
Product: O=C(Nc1ccc([N+](=O)[O-])cc1O)Nc1cccc(Cl)c1Cl
Yield: 73.1 %

Procedure:
The urea was prepared from 2-hydroxy 4-nitro aniline (308 mg, 2 mmol) and 2,3-dichloro phenyl isocyanate (2 mmol) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the title compound (0.5 g, 73%). EI-MS m/z 342 (M+H)+
Reaction SMILES: [C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:19]([NH:21][N:22]1[C:27](=[O:28])[NH:26][C:25](=O)N[C:23]1=[O:30])=[O:20])[CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(=O)CN[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)C.C(N(CC)CC)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:41]([N:26]1[CH2:25][C:23](=[O:30])[N:22]([NH:21][C:19](=[O:20])[C@@H:18]([C@@H:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:9][CH:10]=[CH:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:31][CH:32]([CH3:34])[CH3:33])[C:27]1=[O:28])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: CCOC(=O)CNCc1ccccc1
Reactant: CC(C)C[C@@H](C(=O)Nn1c(=O)[nH]c(=O)[nH]c1=O)[C@H](CCCc1ccccc1)C(=O)OC(C)(C)C
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(C)C[C@@H](C(=O)NN1C(=O)CN(Cc2ccccc2)C1=O)[C@H](CC=Cc1ccccc1)C(=O)OC(C)(C)C
Yield: 105.7 %

Procedure:
A solution of 0.772 g of (E)-2(S)-(tert-butoxycarbonyl)-1(R)-isobutyl-5-phenylpent-4-enyl-1,3,4-oxadiazol-2(3H)-one (prepared as described in Example 34, part (i)) in 10 ml of toluene was treated with 0.387 g of N-benzyl glycine ethyl ester and 0.278 ml of triethylamine and heated overnight at reflux temperature. The mixture was cooled then diluted with ethyl acetate and washed in sequence with 5% aqueous citric acid, 5% aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride and then dried over anhydrous magnesium sulphate. Evaporation gave 0.918 g of N-(3-Benzyl-2,5-dioxo-1-imidazolidinyl)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleramide in the form of a white foam.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](O)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH3:13].O=P(Cl)(Cl)[Cl:16]>C(#N)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:16])=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH3:13]
Reactant: Cc1cc2c(O)ccnc2cc1Br
Reactant: O=P(Cl)(Cl)Cl
Solvent: CC#N
Product: Cc1cc2c(Cl)ccnc2cc1Br
Temperature: 90 °C

Procedure:
To a flask charged with 7-bromo-6-methylquinolin-4-ol (0.675 g, 2.84 mmol) was added acetonitrile (14.18 ml) and POCl3 (0.277 ml, 2.98 mmol) and the resulting suspension was heated to 90° C. for 2.5 h affording a brown solution and near complete conversion to desired product. The material was added to cold sat. aq. NaHCO3 and extracted with EtOAc (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure and purified with an 40 g Silicycle HP column ramping EtOAc in heptane (0-50%, 10% DCM throughout) affording isomer separation, both obtained as off-white solids. The first eluting isomer corresponds to product based on the proton NMR, obtained as a light yellow solid, 7-bromo-4-chloro-6-methylquinoline (240 mg, 0.936 mmol, 33.0% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.68 (d, J=4.70 Hz, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.43 (d, J=4.69 Hz, 1H), 2.59 (s, 3H). m/z (ESI) 256.1/258.1 (M+H)+.
Reaction SMILES: O.[NH2:2][NH2:3].C(O)C.Cl.[NH2:8][N:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14](=O)[CH3:15]>O>[NH2:8][N:9]1[CH:13]=[CH:12][CH:11]=[C:10]1/[C:14](=[N:2]/[NH2:3])/[CH3:15]
Reactant: NN
Reactant: CC(=O)c1cccn1N
Agent: Cl
Solvent: O
Solvent: CCO
Product: C/C(=N\N)c1cccn1N
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 76.6 %

Procedure:
Under a nitrogen atmosphere, hydrazine monohydrate (530 g) was added to ethanol (1.7 L) over 55 minutes. To the mixture was added 1-(1-amino-1H-pyrrol-2-yl)ethanone hydrochloride (170 g) over 20 minutes. The mixture was stirred for 10 minutes at room temperature and heated to refluxing temperature over 55 minutes, and refluxed for 15 minutes. After cooling the mixture under a water bath, water (1.7 L) was added to the mixture (30 to 31° C.). Ethanol was evaporated off, and the resulting mixture was extracted with chloroform (0.85×4 mL). The combined organic extract was washed with brine (1.3 L). The brine was extracted with chloroform (0.85 L). The combined organic extract was dried over anhydrous magnesium sulfate, and evaporated to give (1E)-1-(1-amino-1H-pyrrol-2-yl)ethanone hydrazone as a brown crystal (112 g).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH:6](O)[C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[OH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.S(=O)(=O)(O)O.C(OCC)(=O)C>O>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH:6]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)[C:21]2[CH:22]=[CH:23][C:18](=[O:17])[NH:19][CH:20]=2)=[CH:4][CH:3]=1
Reactant: Oc1ccccn1
Reactant: OC(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CCOC(C)=O
Product: O=c1ccc(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)c[nH]1
Temperature: 200 °C

Procedure:
Combine 50.6 g. (0.2 mole) of 4,4'-dichlorobenzhydrol with 57.1 g. (0.6 mole) of 2-hydroxy pyridine, with stirring heat to 200° C. and add dropwise 1.0 ml. of concentrated sulfuric acid. Increase the reaction temperature to 240°-250° C. and maintain at that temperature range while collecting water emanating from the reaction. Cool the reaction mixture, add a mixture of ethyl acetate and water with stirring and separate the liquid phases. Dry the organic phase, reduce the volume of ethyl acetate, cool to precipitate the crude product, yield 43 g. Crystallization from ethanol affords the product of this step, m.p. 211°-215° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:9][C:7](=O)[CH2:6][C:4](=[O:5])[CH2:3]1>[Pd]>[CH3:1][C:2]1([CH3:10])[CH2:9][CH2:7][CH2:6][C:4](=[O:5])[CH2:3]1
Reactant: CC1(C)CC(=O)CC(=O)C1
Agent: [Pd]
Product: CC1(C)CCCC(=O)C1
Yield: 52 %

Procedure:
On the other hand dimedone is a cheap and readily available starting material for a multi-step synthesis of green ketone. In U.S. Pat. No. 4,147,672 the reduction of dimedone in 52% yield in a two-step reaction sequence to the α,β-unsaturated mono-ketone via the monotosylhydrazone (G. A. Hiegel et al., J. Org. Chem. 38, 3637 (1973)) is described. The catalytic hydrogenation of the ketone in the presence of palladium on charcoal gave 3,3-dimethylcyclohexan-1-one (no yield given) and subsequent ethynylation with ethyne in basic medium gave 1-ethynyl-1-hydroxy-3,3-dimethylcyclohexane in about 50% yield. Reaction with CuCl and allyl chloride in basic medium gave 1-(1-hydroxy-3,3-dimethylcyclohexyl)-pent-4-en-1-yne after distillation in 50% yield. Treatment with boric acid yielded (70%) a 2:3 mixture of 1-(3,3-dimethyl-cyclohex-1-ene-1-yl)- and -6-en-1-yl)-pent-4-en-1-ine which was transformed into a 2:3 mixture of the corresponding -pent-4-en-1-ones by treatment with 80% formic acid at 90° C.
Reaction SMILES: [Br:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6][OH:7]>CC(C)=O.[O-2].[Mn+4].[O-2]>[Br:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[O:7]
Reactant: OCc1cccc(CBr)c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: CC(C)=O
Product: O=Cc1cccc(CBr)c1
Yield: 55 %

Procedure:
3-Bromomethylbenzyl alcohol (1.015 g, 5 mmol) and activated manganese (IV) oxide (10 g) in acetone (30 ml) were stirred at 20° C. for 22 h. The reaction mixture was filtered and the filtrate evaporated in vacuo to yield 3-bromomethylbenzaldehyde as a pale yellow liquid (547 mg, 55%).
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([C:14]([O:16]C)=[O:15])=[CH:10][C:9]=2[S:18][CH3:19])=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].Cl>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([C:14]([OH:16])=[O:15])=[CH:10][C:9]=2[S:18][CH3:19])=[O:7])=[CH:20][CH:21]=1
Reactant: COC(=O)c1cc(SC)c(C(=O)c2ccc(Cl)cc2)n1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CSc1cc(C(=O)O)n(C)c1C(=O)c1ccc(Cl)cc1
Reaction time: 0.5 h

Procedure:
5-(p-Chlorobenzoyl)-2-methoxycarbonyl-4-methylthio-1-methylpyrrole (39 mg) is dissolved in 1 ml of warm ethanol and 0.5 ml of 2.5 N sodium hydroxide is added. After standing at room temperature for 30 minutes under nitrogen, 0.7 ml of 2.5 N hydrochloric acid is aded. The resulting precipitate is filtered, washed and dried in vacuo to yield the crude 5-(p-chlorobenzoyl)-2-hydroxycarbonyl-4-methylthio-1-methylpyrrole.
Reaction SMILES: C(C1C=C(C(C)C)C=C(C(C)C)C=1S(NN=[C:21]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])(=O)=O)(C)C.[CH2:33]1[CH2:43][C:41](=[O:42])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34]1>>[OH:42][C:41]1([C:21]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:22][CH2:23][N:24]([CH3:25])[CH3:26])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33][CH2:43]1
Reactant: CC(C)c1cc(C(C)C)c(S(=O)(=O)NN=C(CCN(C)C)c2ccccc2)c(C(C)C)c1
Reactant: O=C1CCCc2ccccc21
Product: CN(C)CC=C(c1ccccc1)C1(O)CCCc2ccccc21

Procedure:
By using a method similar to that described in Example 22 but starting from β-dimethylaminopropiophenone 2,4,6-triisopropylbenzenesulphonylhydrazone (20 g) and from α-tetralone (6.4 cc), 1-(1-hydroxy-1,2,3,4-tetrahydro-1-naphthyl)-3-dimethylamino-1-phenyl-1-propene (Z) (3.8 g) is obtained in the form of a white powder melting at 108° C. after recrystallisation from a mixture (65 cc) of petroleum ether and isopropanol (95/5 by volume).
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH2:12]>C(Cl)Cl>[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH:12][C:1](=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: COC(CN)OC
Solvent: ClCCl
Product: COC(CNC(C)=O)OC
Yield: 95.1 %

Procedure:
30.6 g (0.3 mol) of acetic anhydride are added to 31.5 g (0.3 mol) of aminoacetaldehyd dimethyl acetal in 50 ml of methylene chloride. When the exothermic reaction is complete, the methylene chloride is removed by distillation, the product is distilled, giving 42 g of colourless product (97% of theory), boiling point 110° C., 0.001 mbar. The product is a single compound according to GC.