Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([O:16][CH2:17][CH3:18])(=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].[C:19](OCC)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[N:22][CH:21]=1>CCOCC>[CH2:17]([O:16][C:3]([CH:4]([C:19](=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[N:22][CH:21]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:15])[CH3:18]
Reactant: CCOC(=O)CCCCCCC(=O)OCC
Reactant: CCOC(=O)c1cccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Product: CCOC(=O)CCCCCC(C(=O)OCC)C(=O)c1cccnc1
Temperature: 0 °C

Procedure:
To a suspension of 16 g of 50% sodium hydride in 450 ml of ether is added dropwise 92.2 g of diethyl suberate and 27.3 ml (30.2 g) of ethyl nicotinate at room temperature, under nitrogen. The reaction mixture is heated at reflux temperature overnight, and, after cooling, 400 ml of ice water is added. The ether layer is separated (discarded) and the aqueous adjusted to pH 5 with 1N hydrochloric acid and extracted with ether (3×250 ml). The ether layer is dried and concentrated to give ethyl 7-ethoxycarbonyl-7-nicotinoylheptanoate as an oil. A solution of this ester in 300 ml of 1M sulfuric acid is heated for 12 hours at reflux temperature. The reaction solution is cooled by an ice bath and adjusted to pH=4.5-5.0 with saturated sodium bicarbonate solution. A white solid is collected and, after washing with water and air-drying, is recrystallized from ethanol to give 7-nicotinoylheptanoic acid, m.p. 113°-115°.
Reaction SMILES: [H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[CH3:9][N:10]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[C:16]2/[CH:19]=[CH:20]/[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:11]1.O>CS(C)=O>[CH3:9][N:10]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[C:16]2[C@@H:19]2[CH2:4][C@H:20]2[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:11]1
Reactant: CCOC(=O)/C=C/c1cccc2nn(C)cc12
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CCOC(=O)[C@@H]1C[C@H]1c1cccc2nn(C)cc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.6 %

Procedure:
Under nitrogen atmosphere, to a suspension of sodium hydride (0.650 g, 15.6 mmol) in dimethyl sulfoxide (5.0 mL) was added a solution of trimethylsulfoxonium iodide (3.34 g, 15.6 mmol) in dimethyl sulfoxide (35 mL) at 0° C., and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of ethyl (2E)-3-(2-methyl-2H-indazol-4-yl)acrylate (3.00 g, 13.0 mmol) in dimethyl sulfoxide (30 mL) at 0° C., and the mixture was stirred at room temperature for 12 hr. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1) to give the title compound (1.10 g, yield 35%).
Reaction SMILES: CC(C)([O-])C.[K+].[F:7][C:8]1[CH:9]=[C:10](/[CH:14]=[CH:15]/[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:11]=[CH:12][CH:13]=1.S([CH2:31][N+:32]#[C-:33])(C1C=CC(C)=CC=1)(=O)=O>O1CCCC1>[F:7][C:8]1[CH:9]=[C:10]([C:14]2[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:31][NH:32][CH:33]=2)[CH:11]=[CH:12][CH:13]=1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: CCOC(=O)/C=C/c1cccc(F)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)c1c[nH]cc1-c1cccc(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61.4 %

Procedure:
To a suspension of 38.3 g (341 mmol) of potassium tert-butoxide at 60% in oil in 500 ml of anhydrous tetrahydrofuran is added dropwise a mixture of 55.2 g (284 mmol) of ethyl(E)-3-(3-fluorophenyl)acrylate (CAS 166250-00-6) and 55.5 g (284 mmol) of tosylmethyl isocyanide (CAS 36635-61-7) dissolved in 500 ml of tetrahydrofuran, while maintaining the temperature of the reaction medium at about 25° C. The mixture is then stirred for 1 hour 30 minutes at room temperature. The mixture is then poured into saturated aqueous solution and the reaction product is extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure, to give a brown solid, which is chromatographed on a column of silica gel, eluting with dichloromethane, to give 40.7 g of ethyl 4-(3-fluorophenyl)-1H-pyrrole-3-carboxylate, in the form of a white powder after triturating in diisopropyl ether, filtering off and drying.
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH:12]=[C:13]([N+]([O-])=O)[CH3:14])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.Cl.C[OH:20]>O.[Fe]>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13](=[O:20])[CH3:14])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CO
Reactant: CC(=Cc1ccc(-n2ccnc2)cc1)[N+](=O)[O-]
Agent: [Fe]
Agent: Cl
Solvent: O
Product: CC(=O)Cc1ccc(-n2ccnc2)cc1

Procedure:
A mixture of 1-[4-(1H-imidazol-1-yl)phenyl]-2-nitropropene prepared above, iron powder (94.7 grams), and hydrated iron (III) chloride (1.2 grams) in 50 ml of methanol and 170 ml of water is heated to reflux and treated dropwise with 85 ml of 12N hydrochloric acid over four hours. After heating under reflux for one additional hour, the reaction mixture is cooled, and filtered. The filtrate is made basic with 40% ammonium hydroxide solution and the entire mixture is extracted thoroughly with ethyl acetate. The ethyl acetate is treated with charcoal, dried (magnesium sulfate) and concentrated on the rotary evaporator to give a dark yellow oil. This material is chromatographed on a Waters Prep 500A, using silica gel and eluting with 2% methanol in chloroform. The main fraction contains 1-[-4-(1H-imidazol-1-yl)-phenyl]-2-propanone.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][O:7][C:8]2=[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]2=[O:20])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:30](Cl)(=[O:32])[CH3:31]>C1COCC1>[O:20]=[C:12]1[C:11](=[C:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([NH:1][C:30](=[O:32])[CH3:31])[CH:10]=3)[CH2:6][O:7]2)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13]1
Reactant: Nc1ccc2c(c1)C(=C1C(=O)Nc3ccccc31)OC2
Reactant: CC(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(=O)Nc1ccc2c(c1)C(=C1C(=O)Nc3ccccc31)OC2
Reaction time: 1 h
Yield: 81.9 %

Procedure:
To a solution of 3-(6-Amino-3H-isobenzofuran-1-ylidene)-1,3-dihydro-indol-2-one (50.0 mg, 0.189 mmol) and N,N-diisopropylethylamine (98.8 μL, 0.567 mmol) in 2.0 mL THF was added acetyl chloride (13.4 μL, 0.189 mmol). After stirring a troom temperature for 1 h, the slurry was partitioned between NaHCO3 solution and EtOAc (warmed to dissolve solid). The organic phase was washed with H2O, 4% aqueout HCl solution, H2O, saturated NaHCO3, brine and dried with Na2SO4. After concentrating in vacuo the residue was triturated with EtOAc to give the title compound (47.4 mg, 82%) as a yellow solid.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:11]=[CH:10][CH:9]=[N:8]1.C([Li])CCC.B(F)(F)F.CCOCC.[CH:26]12[O:31][CH:27]1[CH2:28][CH2:29][CH2:30]2.C(=O)([O-])O.[Na+]>C1COCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]([C@H:26]2[CH2:30][CH2:29][CH2:28][C@@H:27]2[OH:31])=[CH:10][CH:9]=[N:8]1
Reactant: c1cnn(C2CCCCO2)c1
Reactant: C1CC2OC2C1
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: O[C@H]1CCC[C@@H]1c1ccnn1C1CCCCO1
Reaction time: 0.5 h
Yield: 32.6 %

Procedure:
To a solution of 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (3.04 g, 20.0 mmol) in THF (30 mL), n-butyl lithium (1.63 M solution in hexane; 12.7 mL, 20.7 mmol) was added dropwise at −78° C. for 7 minutes. The reaction solution was stirred for 30 minutes, and boron trifluoride-ethyl ether (3.14 mL, 25.0 mmol) was then added thereto. The reaction solution was further stirred for 10 minutes. Then, cyclopentene oxide (2.08 mL, 24.0 mmol) was added thereto, and the reaction solution was stirred at −78° C. for 3 hours. To the reaction solution, a saturated aqueous solution of sodium hydrogencarbonate (15 mL) was added, followed by extraction four times with ethyl acetate (20 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography (hexane/ethyl acetate=1:4) to yield the title compound (1.54 g, 33%) in the form of a diastereomeric mixture as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[C:34]([Cl:35])=[CH:33][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]3C(=O)C4C(=CC=CC=4)C3=O)[CH2:12][CH2:11]2)=[O:7])=[C:4]([O:36][CH3:37])[CH:3]=1.O.NN>>[NH2:1][C:2]1[C:34]([Cl:35])=[CH:33][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH2:22])[CH2:14][CH2:15]2)=[O:7])=[C:4]([O:36][CH3:37])[CH:3]=1
Reactant: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCCCN2C(=O)c3ccccc3C2=O)CC1
Agent: NN
Solvent: O
Product: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCCCN)CC1
Yield: 112.7 %

Procedure:
4-Amino-5-chloro-N-(1-(6-(2,3-dihydro-1,3-dioxo-1 H-isoindol-2-yl)hexyl)piperidin-4-ylmethyl)-2-methoxybenzamide (15.9 g) as starting compound and hydrazine monohydrate (2.2 ml) were reacted and treated in the same manner as in Example 117 to give 13.5 g of 4-amino-N-(1-(6-aminohexyl)piperidin-4-ylmethyl)-5-chloro-2-methoxybenzamide.
Reaction SMILES: [C:1]([C:3]1[S:7][C:6]([C:8]([OH:10])=O)=[CH:5][CH:4]=1)#[CH:2].[NH2:11][C@H:12]([CH2:30][O:31][CH3:32])[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][C:23]2=[O:28])=[C:18]([CH3:29])[CH:17]=1)=[O:14].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[C:1]([C:3]1[S:7][C:6]([C:8]([NH:11][C@@H:12]([C:13](=[O:14])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C:23]3=[O:28])=[C:18]([CH3:29])[CH:17]=2)[CH2:30][O:31][CH3:32])=[O:10])=[CH:5][CH:4]=1)#[CH:2]
Reactant: COC[C@@H](N)C(=O)Nc1ccc(N2CCOCC2=O)c(C)c1
Reactant: C#Cc1ccc(C(=O)O)s1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: C#Cc1ccc(C(=O)N[C@H](COC)C(=O)Nc2ccc(N3CCOCC3=O)c(C)c2)s1

Procedure:
Prepared analogously to Example 1a from 5-ethynylthiophene-2-carboxylic acid and 2-(R)-amino-3-methoxy-N-[3-methyl-4-(3-oxomorpholin-4-yl)phenyl]propionamide with TBTU and NMM in DMF.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([O:15][CH2:16][CH3:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.Br[CH2:19][CH:20]=[C:21]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[O:26][CH2:25][O:24][C:23]2[CH:33]=[CH:34][CH:35]=[CH:36][C:22]1=2.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1C=CC=CC=1>[CH:29]1[C:28]2[C:21](=[CH:20][CH2:19][O:1][C:2]3[CH:3]=[CH:4][C:5]([CH2:8][CH:9]([O:15][CH2:16][CH3:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=3)[C:22]3[CH:36]=[CH:35][CH:34]=[CH:33][C:23]=3[O:24][CH2:25][O:26][C:27]=2[CH:32]=[CH:31][CH:30]=1
Reactant: CCOC(=O)C(Cc1ccc(O)cc1)OCC
Reactant: BrCC=C1c2ccccc2OCOc2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CCOC(=O)C(Cc1ccc(OCC=C2c3ccccc3OCOc3ccccc32)cc1)OCC
Temperature: 60 °C

Procedure:
A mixture of ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (0.96 g, 4.0 mmol), 12-(2-bromoethylidene)-12H-dibenzo[d,g]-1,3-dioxocine (1.07 g, 3.3 mmol) and potassium carbonate (0.45 g, 4.5 mmol) in dimethylformamide (15 ml) was heated to 60° C. for 8.5 h. The reaction mixture was diluted with benzene (50 ml), washed with water (2×20 ml), dried (MgSO4) and evaporated. The residue (1.95 g) was purified by column chromatography on silica gel (benzene and benzenelethyl acetate (9:1) eluents). The benzene fractions were discarded, whilst the benzene/ethyl acetate fractions were evaporated to give the title compound as an oil: 0.97 g (62%).
Reaction SMILES: [CH3:1][CH:2]([CH2:5][O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([CH3:13])[CH3:12])[CH:3]=[O:4].[OH:14][CH2:15]/C=C(/C)\CCC=C(C)C>>[CH3:13][CH:11]([CH3:12])[CH2:10][CH2:9][CH2:8][CH2:7][O:6][CH2:5][CH2:2][CH2:3][CH:15]=[O:14].[CH3:1][CH:2]([CH2:5][O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([CH3:13])[CH3:12])[CH:3]=[O:4]
Reactant: CC(C)=CCC/C(C)=C\CO
Agent: CC(C)CCCCOCC(C)C=O
Product: CC(C)CCCCOCCCC=O

Procedure:
Odour (2-methyl-3-[(5-methylhexyl)oxy]propanal): Aldehydic, Citrus, Lemon, Nerol Like
Reaction SMILES: [CH2:1]([O:8][C:9]([C@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:19])[CH:17]=[CH2:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:20]1([CH2:23][NH2:24])[CH2:22][CH2:21]1>C(#N)C>[CH2:1]([O:8][C:9]([C@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:19])[CH2:17][CH2:18][N:24]([CH2:18][CH2:17][C:16]([N:12]1[CH2:13][CH2:14][CH2:15][C@@H:11]1[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])=[O:19])[CH2:23][CH:20]1[CH2:22][CH2:21]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NCC1CC1
Reactant: C=CC(=O)N1CCC[C@@H]1C(=O)OCc1ccccc1
Solvent: CC#N
Product: O=C(OCc1ccccc1)[C@H]1CCCN1C(=O)CCN(CCC(=O)N1CCC[C@@H]1C(=O)OCc1ccccc1)CC1CC1
Reaction time: 16 h
Yield: 43.9 %

Procedure:
A solution of 444 mg (1.71 mmol) (R)-1-acryloyl-pyrrolidine-2-carboxylic acid benzyl ester and 74 ml (0.85 mmol) cyclopropylmethylamine in 5 ml acetonitrile was stirred for 1 h at room temperature, then for 16 h at 80° C. Concentration in vacuo and flash chromatography (gradient: 0-100% MeOH in EtOAc) afforded 220 mg (44%) of the title compound as a yellow oil. MS m/e (%): 590 (M+H+, 100).
Reaction SMILES: O.[OH-].[Li+].[O:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH2:13][N:14]3[CH2:18][C@@H:17]([N:19]([C:29](=[O:35])[CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=4)[CH2:16][C@H:15]3[C:36]([O:38]C)=[O:37])=[CH:12][C:7]=2[O:6][CH2:5]1.CO>O>[O:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH2:13][N:14]3[CH2:18][C@@H:17]([N:19]([C:29](=[O:35])[CH2:30][C:31]([CH3:34])([CH3:32])[CH3:33])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=4)[CH2:16][C@H:15]3[C:36]([OH:38])=[O:37])=[CH:12][C:7]=2[O:6][CH2:5]1
Reactant: COC(=O)[C@@H]1C[C@H](N(Cc2cccc(OC)c2)C(=O)CC(C)(C)C)CN1Cc1ccc2c(c1)OCO2
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1cccc(CN(C(=O)CC(C)(C)C)[C@H]2C[C@@H](C(=O)O)N(Cc3ccc4c(c3)OCO4)C2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.2 %

Procedure:
Lithium hydroxide monohydrate (17 mg, 0.405 mmol) was added to a solution of methyl (2S,4S)-1-(1,3-benzodioxol-5-ylmethyl)-4-[(3,3-dimethylbutanoyl)(3-methoxybenzyl)amino]tetrahydro-1H-2-pyrrolecarboxylate (20) (100 mg, 0.20 mmol) in 66% v/v methanol in water (1.0 mL). The mixture was stirred overnight at room temperature, then the solvent was removed under reduced pressure and the residue partitioned between dichloromethane (1.0 mL) and water (1.0 ml). The aqueous phase was acidified with 1.0 M aqueous citric acid solution and the two layers were vigorously stirred for 10 min at room temperature. The layers were separated and the aqueous layer was back-extracted with dichloromethane. The combined dichloromethane extracts were dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using dichloromethane/ethyl acetate (1:1, v/v) and then dichloromethane/methanol (9:1, v/v) as eluents to give the title acid (21) (88 mg, 91%) as an off-white solid:
Reaction SMILES: [CH3:1][C:2]([CH3:28])([CH3:27])[C:3]([C:5]1[C:6]([CH3:26])=[C:7]([C:17]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:18])[N:8]2[C:13]=1[CH:12]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:10]=[CH:9]2)=[O:4].[C:29]([O:33][CH3:34])(=[O:32])[CH:30]=[CH2:31].C1CCN2C(=NCCC2)CC1.O>CN(C=O)C>[CH3:28][C:2]([CH3:1])([CH3:27])[C:3]([C:5]1[C:6]([CH3:26])=[C:7]([C:17]([N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:31][CH2:30][C:29]([O:33][CH3:34])=[O:32])=[O:18])[N:8]2[C:13]=1[CH:12]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:10]=[CH:9]2)=[O:4]
Reactant: C=CC(=O)OC
Reactant: Cc1c(C(=O)C(C)(C)C)c2cc(C(C)C)ccn2c1C(=O)Nc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)CCN(C(=O)c1c(C)c(C(=O)C(C)(C)C)c2cc(C(C)C)ccn12)c1ccccc1
Temperature: 50 °C
Yield: 68.3 %

Procedure:
To a stirred solution of 1-(2,2-dimethylpropanoyl)-2-methyl-N-phenyl-7-(propan-2-yl)indolizine-3-carboxamide (70 mg, 0.19 mmol) in DMF (2.0 mL) is added Triton B (8 μl, 0.02 mmol) followed by methyl acrylate (18 μl, 0.20 mmol). The reaction is stirred for 3 days at 23° C. after which time DBU (0.20 mL, 1.31 mmol) and additional methyl acrylate (0.10 mL, 1.11 mmol) are introduced. The reaction is heated at 50° C. for 18 h and then cooled to 23° C., poured into water, extracted with EtOAc, dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to 30% EtOAc in hexanes) gives methyl N-{[1-(2,2-dimethylpropanoyl)-2-methyl-7-(propan-2-yl)indolizin-3-yl]carbonyl}-N-phenyl-beta-alaninate (60 mg, 70%).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[Br:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=1.[Cl-].[Ce+3].[Cl-].[Cl-].[CH2:25]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.CCCCCC>[CH2:25]([N:32]1[CH2:37][CH2:36][C:35]([CH2:20][C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([Br:13])[N:15]=2)([OH:38])[CH2:34][CH2:33]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: Cc1cccc(Br)n1
Agent: [Ce+3]
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OC1(Cc2cccc(Br)n2)CCN(Cc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1.11 ml of diisopropylamine in 20 ml of tetrahydrofuran was added 0.73 ml of a hexane solution containing 2.66 M n-butyl lithium at −78° C. The reaction mixture was warmed to 0° C., and then cooled to −78° C. 1.2 ml of 2-bromo-6-methylpyridine was slowly added to the reaction mixture below −70° C., followed by stirring the reaction mixture at −78° C. for 30 minutes. 1.95 g of cerium(III) chloride was added to the reaction mixture at −78° C., followed by stirring the reaction mixture at −78° C. for 1 hour. 0.98 ml of 1-benzyl-4-piperidone was slowly added to the reaction mixture below −70° C., followed by stirring the reaction mixture at −78° C. for 1 h. To the reaction mixture was added saturated aqueous ammonium chloride solution, followed by adding ethyl acetate. An insoluble matter was filtered off using Celite. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, and filtered.
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=2)[N:4]=[C:3]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([S:22](=[O:31])(=[O:30])[NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]=1>CO.O1CCCC1.[Pd]>[CH3:15][O:14][C:12]([C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[NH:4][CH:3]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([S:22](=[O:31])(=[O:30])[NH:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:17]=1)[C:2]([CH3:32])([CH3:1])[CH2:11]2)=[O:13]
Reactant: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(S(=O)(=O)Nc3ccccc3)c1)=N2
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(S(=O)(=O)Nc3ccccc3)c1)N2
Yield: 75.9 %

Procedure:
A mixture of methyl 3,3-dimethyl-2-(3-(N-phenylsulfamoyl)phenyl)-3,4-dihydroquinoline-6-carboxylate (170 mg, 0.38 mmol) and 10% Pd/C (150 mg) in methanol (4 mL) and tetrahydrofuran (5 mL) was hydrogenated by a H2 balloon at 30° C. After filtration, the filtrated was concentrated and purified on preparative thin layer chromatography to afford 130 mg of 3,3-Dimethyl-2-(3-phenylsulfamoyl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester.
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]([NH:11][C:12](=[O:14])[CH3:13])[CH:8]=[CH:9][CH:10]=1)C=C.[CH2:15](OC1C=C(C=CC=1)CCl)[CH:16]=[CH2:17].OC1C=C(NC(=O)C)C=CC=1>O(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC>[CH2:17]([C:10]1[CH:9]=[CH:8][C:7]([NH:11][C:12](=[O:14])[CH3:13])=[CH:6][C:5]=1[OH:4])[CH:16]=[CH2:15]
Reactant: C=CCOc1cccc(NC(C)=O)c1
Reactant: C=CCOc1cccc(CCl)c1
Agent: CC(=O)Nc1cccc(O)c1
Solvent: CCCCCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: C=CCc1ccc(NC(C)=O)cc1O

Procedure:
A mixture of N-(3-allyloxyphenyl)acetamide (13.2 g) prepared by a similar method to that of Example 2, Footnote c (A), from N-(3-hydroxyphenyl)acetamide, in Ph2O (100 ml) was heated at 250° C. for 10 minutes, cooled and diluted with hexane (100 ml) to give crystals. The crystals were re-crystallised from ethyl acetate. The liquors were evaporated and dissolved in 0.2M aqueous NaOH, filtered though Celite, and acidified with 1M aqueous HCl solution to give N-(4-allyl-3- hydroxyphenyl)acetamide (3.6 g) mpt. 164°-165° C.
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][O:10][C:11]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:33]=1)[C:18](=[O:32])[C:19]([CH2:30][CH3:31])=[C:20](/[CH:22]=[CH:23]/[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[N:21]=2)=[O:12]>CN(C)C=O>[C:24]1(/[CH:23]=[CH:22]/[C:20]2[N:21]=[C:16]3[CH:15]=[CH:14][C:13]4([CH2:2][CH:33]4[N:17]3[C:18](=[O:32])[C:19]=2[CH2:30][CH3:31])[C:11]([O:10][CH3:9])=[O:12])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: C[S+](C)(C)=O
Reactant: CCc1c(/C=C/c2ccccc2)nc2ccc(C(=O)OC)cn2c1=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCc1c(/C=C/c2ccccc2)nc2n(c1=O)C1CC1(C(=O)OC)C=C2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Trimethyl-sulphoxonium iodide (0.7 g) was reacted with 50% sodium hydride (0.15 g) in dimethylformamide (30 ml) under stirring at room temperature for 1 hour, then a solution of 2-trans-(2-phenyl-ethenyl)-3-ethyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid methyl ester, m.p. 214°-216° C., (0.82 g) in dimethyl-formamide (20 ml) was added. The mixture was allowed to react under stirring at room temperature for 3 hours, then it was diluted with ice water and filtered. Crystallization from acetone gave 2-trans-(2-phenyl-ethenyl)-3-ethyl-6,7-methylen-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid, methyl ester, m.p. 194°-195° C. (0.58 g), which was reacted with 1% KOH in 95% ethanol solution (11 ml) at reflux temperature for 15 minutes. After cooling the reaction mixture was acidified with acetic acid, concentrated in vacuo and diluted with ice water: the precipitate was filtered and washed with water until neutral. Crystallization from acetone gave 0.34 g of 2-trans-(2-phenyl-ethenyl)-3-ethyl-6,7-methylen-4-oxo-4H-pyrido[1,2]pyrimidine-7-carboxylic acid, m.p. 215°-216° C., NMR (CF3COOD) δ: 1.22(m) and 2.93(m)(6,7-CH2 protons), 1.36(t) (CH2CH3), 2.93(m)(CH2 --CH3), 5.51(d.d)(C-6 proton), 7.01(d) (C-9 proton), 7.31(d)(Hβ vinyl proton), 7.63(b.s.)(phenyl protons), 7.76(d)(Hα vinyl proton), 8.26(d)(C-8 proton).
Reaction SMILES: [N+:1]([C:4]1[C:9]([CH3:10])=[CH:8][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][C:5]=1[CH3:16])([O-])=O>C(OCC)(=O)C.[C].[Pd]>[NH2:1][C:4]1[C:9]([CH3:10])=[CH:8][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][C:5]=1[CH3:16]
Reactant: CCOC(=O)c1cc(C)c([N+](=O)[O-])c(C)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc(C)c(N)c(C)c1
Reaction time: 3.5 h
Yield: 99 %

Procedure:
To a solution of ethyl 4-nitromesitylenate (7.7 g) in ethyl acetate (300 ml) was added 10% palladium-carbon (3 g) and the mixture was stirred for 3.5 hr under a hydrogen atmosphere. The catalyst was filtered off from the reaction mixture and the filtrate was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give the title compound (6.6 g) as pale-brown crystals.