Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[NH:9][C:5]2[N:6]=[CH:7][S:8][C:4]=2[CH:3]=1.[Br:10]N1C(=O)CCC1=O>C(O)(=O)C>[Br:10][C:3]1[C:4]2[S:8][CH:7]=[N:6][C:5]=2[NH:9][C:2]=1[CH3:1]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc2scnc2[nH]1
Solvent: CC(=O)O
Product: Cc1[nH]c2ncsc2c1Br
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.7 %

Procedure:
To a solution of 5-methyl-4H-pyrrolo[2,3-d]thiazole (2.5 g, 18.09 mmol) in acetic acid (50 mL) was added 1-bromopyrrolidine-2,5-dione (3 g, 18.10 mmol) slowly below 0° C., and then warm to the ambient temperature and allowed to stir for 2 hours at room temperature. The reaction mixture was concentrated, and acetic acid was removed under reduced pressure. The pH was adjusted to around 7 by progressively adding saturated sodium bicarbonate below 0° C., extracted with acetic ester (50 mL×3). The combined organic phase was dried by anhydrous sodium sulphate, and then filtered. The filtrate was concentrated and purified by column chromatograph on silica gel eluted with (petrol ether/acetic ester 25:1→15:1→10:1) to give the title compound (2.5 g, 64%) as an yellow solid. LCMS (M+H+) m/z: calc'd. 215.94. found 219.2.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:9](=[O:11])[NH:8][C:7](=[O:12])[NH:6][C:5]=2[N:4]=[CH:3]1.[H-].[Na+].[CH2:15](Br)[C:16]1[O:20][CH:19]=[CH:18][CH:17]=1>CS(C)=O>[O:20]1[CH:19]=[CH:18][CH:17]=[C:16]1[CH2:15][N:6]1[C:5]2[N:4]=[CH:3][N:2]([CH3:1])[C:10]=2[C:9](=[O:11])[NH:8][C:7]1=[O:12]
Reactant: BrCc1ccco1
Reactant: Cn1cnc2[nH]c(=O)[nH]c(=O)c21
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: Cn1cnc2c1c(=O)[nH]c(=O)n2Cc1ccco1
Reaction time: 0.5 h
Yield: 14.3 %

Procedure:
To a stirring suspension of 7-methylxanthine (2.54 g, 15.3 mmol) in dimethylsulfoxide (80 ml) was added sodium hydride (0.37 mg, 15.3 mmol) in one portion. After stirring for 30 minutes, freshly prepared furfuryl bromide (2.5 g, 15.3 mmol) was added next. After stirring at room temperature for 18 hours, the reaction was quenched by addition of water (150 ml). Saturated aqueous sodium chloride solution (30 ml) was added and the mixture was extracted with chloroform (4×50 ml). The combined extracts were washed with saturated aqueous sodium bicarbonate solution (3×50 ml), with saturated aqueous sodium chloride solution (2×50 ml) and dried over a mixture of sodium sulfate and activated charcoal. After filtration through a pad of celite, the solvent was evaporated under reduced pressure. The residue was treated with ethyl acetate. The solid was filtered, rinsed with cold ethyl acetate (2×25 ml) and vacuum dried to give 3-(2-furylmethyl)-7-methylxanthine (0.54 g, 1496 yield) as a beige solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[S:14]([O-:17])([O-])=[O:15].[Na+].[Na+].S(Cl)([Cl:22])=O.C(OCC)(=O)C>C(O)C.O>[Cl:22][S:14]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])(=[O:17])=[O:15]
Reactant: O=S(Cl)Cl
Reactant: O=S([O-])[O-]
Reactant: CCOC(=O)CCCCCCCBr
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCOC(=O)CCCCCCCS(=O)(=O)Cl
Temperature: 25 °C
Yield: 85 %

Procedure:
At room temperature, ethyl 8-bromo-octanoate (753.5 mg, 3.00 mmol) was dissolved in ethanol (1.88 mL), and a solution of sodium sulfite (718.4 mg, 5.70 mmol) in water (2.64 mL) was added. The mixture was then stirred under reflux for 2 hours, and cooled to room temperature. The solvent was then distilled off under reduced pressure. To the residue was added ethanol, and the solvent was again distilled off under reduced pressure. The residue was dried in an oil bath at 60° C. under reduced pressure, and toluene (11.3 mL) and DMF (10 μL) were then added at room temperature. Thionyl chloride (2.16 mL, 30.0 mmol) was added dropwise. The mixture was then stirred under reflux for 6 hours and cooled to room temperature. The progress of the reaction was then stopped by adding water. Ethyl acetate was added, and the mixture was extracted. The organic layer was washed with water and a saturated brine, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off. The resulting residue was then purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.2) to obtain ethyl 8-chlorosulfonyl-octanoate (No. 6804260; 692.3 mg, 85% yield).
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3](N)=O.F[B-](F)(F)F.C([O+](CC)CC)C.[O:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([NH:25][C:26]2[C:31]([NH2:32])=[CH:30][N:29]=[C:28]3[CH:33]=[CH:34][S:35][C:27]=23)[CH2:20]1>O1CCCC1.C(O)C>[O:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([N:25]2[C:26]3=[C:27]4[S:35][CH:34]=[CH:33][C:28]4=[N:29][CH:30]=[C:31]3[N:32]=[C:3]2[C@H:2]([OH:1])[CH3:6])[CH2:20]1
Reactant: Nc1cnc2ccsc2c1N[C@H]1CCCOC1
Reactant: C[C@@H](O)C(N)=O
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCO
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CCCOC1
Reaction time: 0.25 h
Yield: 64.8 %

Procedure:
A mixture of (2R)-2-hydroxypropanamide (from Aldrich, 5.4 mg, 0.060 mmol) and triethyloxonium tetrafluoroborate (12 mg, 0.062 mmol) in tetrahydrofuran (0.1 mL) became a solution after stirred for 15 min. After another 45 min, this solution was added to a mixture of N7-[(3S)-tetrahydro-2H-pyran-3-yl]thieno[3,2-b]pyridine-6,7-diamine (7.5 mg, 0.030 mmol) in ethanol (0.24 mL) and the resultant mixture was heated at reflux for 2 h. The crude mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (5.9 mg, 65%). LCMS calculated for C15H18N3O2S (M+H)+: m/z=304.1. Found: 304.0.
Reaction SMILES: [C:1]([C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8](=[O:30])[C:9]4[CH:21]=[CH:20][C:19](OS(C(F)(F)F)(=O)=O)=[CH:18][C:10]=4[C:11]([CH3:17])([CH3:16])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1)#[N:2].[N:31]1([CH:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH2:35][CH2:34][CH2:33][CH2:32]1>>[CH3:16][C:11]1([CH3:17])[C:12]2[NH:13][C:14]3[C:6](=[CH:5][CH:4]=[C:3]([C:1]#[N:2])[CH:15]=3)[C:7]=2[C:8](=[O:30])[C:9]2[CH:21]=[CH:20][C:19]([N:39]3[CH2:40][CH2:41][CH:36]([N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)[CH2:37][CH2:38]3)=[CH:18][C:10]1=2
Reactant: C1CCN(C2CCNCC2)C1
Reactant: CC1(C)c2cc(OS(=O)(=O)C(F)(F)F)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
Product: CC1(C)c2cc(N3CCC(N4CCCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21

Procedure:
With the same condition as the method for synthesizing the Compound B2-1, the title compound was synthesized from the Compound B1 and 4-pyrrolidin-1-yl-piperidine.
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]([F:22])([F:21])[S:10]([O:13]S(C(F)(F)F)(=O)=O)(=[O:12])=[O:11].O[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[N:28]([CH3:34])[C:27]2([CH3:36])[CH3:35].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[F:8][C:9]([F:22])([F:21])[S:10]([O:13][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[N:28]([CH3:34])[C:27]2([CH3:36])[CH3:35])(=[O:12])=[O:11]
Reactant: CN1C(=O)c2ccc(O)cc2C1(C)C
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CN1C(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc2C1(C)C
Reaction time: 1 h

Procedure:
With cooling with ice, 0.192 mL of triethylamine and 0.174 mL of trifluoromethanesulfonic acid anhydride were added to 4.3 mL of a chloroform solution of 165 mg of 5-hydroxy-2,3,3-trimethylisoindolin-1-one obtained in Production Example 49-2, and stirred for 1 hour with cooling with ice. 2 mL of aqueous saturated sodium hydrogencarbonate solution was added to the reaction liquid, and extracted with chloroform. The organic layer was dried with anhydrous sodium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (chloroform) to obtain 257 mg of the entitled compound as a colorless solid.
Reaction SMILES: [CH:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([N:11]2[CH2:16][C:15]3([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[O:14][CH2:13][CH2:12]2)=[O:10])[N:8]=1)([CH3:3])[CH3:2].FC(F)(F)C([O-])=O.C(N(CC)CC)C.CS(O[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([CH3:52])([CH3:51])[CH2:48][CH:49]=[O:50])(=O)=O>C(#N)C>[CH:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([N:11]2[CH2:16][C:15]3([CH2:17][CH2:18][N:19]([CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([CH3:51])([CH3:52])[CH2:48][CH:49]=[O:50])[CH2:20][CH2:21]3)[O:14][CH2:13][CH2:12]2)=[O:10])[N:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)(CC=O)CCCCCCOS(C)(=O)=O
Reactant: CC(C)c1nc(C(=O)N2CCOC3(CCNCC3)C2)cs1
Agent: O=C([O-])C(F)(F)F
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)c1nc(C(=O)N2CCOC3(CCN(CCCCCCC(C)(C)CC=O)CC3)C2)cs1

Procedure:
(2-Isopropyl-thiazol-4-yl)-(1-oxa-4,9-diaza-spiro[5.5]undec-4-yl)-methanone (0.262 g) (prepared from the trifluoroacetate salt as in Example 102, step c) was dissolved in acetonitrile (4 mL) and triethylamine (0.22 mL) was added. This solution was then added to a solution of 7,7-dimethyl-9-oxononyl methanesulfonate (Example 279, step e) (0.291 g) in acetonitrile (4 mL) and the resultant mixture heated at 80° C. overnight. The solvents were removed under vacuum. Purification was by silica gel chromatography eluting with 0-10% Methanol in DCM to afford the subtitled compound as a colourless oil. Yield 0.361 g.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[Br:10]N1C(=O)CCC1=O>C(=S)=S>[Br:10][C:3]1[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][C:4]=1[OH:9]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc(C)cc(O)c1
Solvent: S=C=S
Product: Cc1cc(C)c(Br)c(O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 65.9 %

Procedure:
To a solution of 3,5-dimethylphenol (15.0 g, 123 mmol) in carbon disulfide (330 mL) was slowly added N-bromosuccinimide (21.9 g, 123 mmol) in several batches with ice-cooling, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the precipitated crystals were filtered and then were washed with ethyl acetate-hexane (10:1). The solution was concentrated, and the residue was purified by silica gel chromatography (ethyl-acetate:hexane=1:9) to obtain 16.3 g (yield 66%) of the title compound. Oily matter.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[O:6][C:5]2[CH:7]=[C:8]3[O:12][C:11]([CH3:14])([CH3:13])[O:10][C:9]3=[CH:15][C:4]=2[O:3]1.C([Li])CCC.[CH3:22][C:23]1([CH3:55])[O:27][C:26]2[C:28]([C:37]([C:39]3[C:49]4[O:50][C:51]([CH3:54])([CH3:53])[O:52][C:48]=4[CH:47]=[C:41]4[O:42][C:43]([CH3:46])([CH3:45])[O:44][C:40]=34)=[O:38])=[C:29]3[O:33][C:32]([CH3:35])([CH3:34])[O:31][C:30]3=[CH:36][C:25]=2[O:24]1>C1COCC1>[CH3:13][C:11]1([CH3:14])[O:10][C:9]2[C:15]([C:37]([C:28]3[C:26]4[O:27][C:23]([CH3:55])([CH3:22])[O:24][C:25]=4[CH:36]=[C:30]4[O:31][C:32]([CH3:35])([CH3:34])[O:33][C:29]=34)([C:39]3[C:49]4[O:50][C:51]([CH3:53])([CH3:54])[O:52][C:48]=4[CH:47]=[C:41]4[O:42][C:43]([CH3:45])([CH3:46])[O:44][C:40]=34)[OH:38])=[C:4]3[O:3][C:2]([CH3:16])([CH3:1])[O:6][C:5]3=[CH:7][C:8]=2[O:12]1
Reactant: CC1(C)Oc2cc3c(cc2O1)OC(C)(C)O3
Reactant: CC1(C)Oc2cc3c(c(C(=O)c4c5c(cc6c4OC(C)(C)O6)OC(C)(C)O5)c2O1)OC(C)(C)O3
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1(C)Oc2cc3c(c(C(O)(c4c5c(cc6c4OC(C)(C)O6)OC(C)(C)O5)c4c5c(cc6c4OC(C)(C)O6)OC(C)(C)O5)c2O1)OC(C)(C)O3
Reaction time: 0.5 h

Procedure:
2,2,6,6-Tetramethylbenzo[1,2-d:4,5-d']bis(1,3)dioxole (8.80 g, 40.00 mmol, Example 5) was dissolved in THF (100 mL) and cooled to -20° C. n-Butyllithium (25.0 mL, 40.0 mmol, 1.6M) was added and the temperature was adjusted to ambient temperature over a period of 30 minutes and then recooled to -20° C. Bis(2,2,6,6-tetramethylbenzo-(1,2-d:4,5-d']bis(1,3)dioxole-4-yl)ketone (18.80 g, 39.83 mmol, Example 57) was added and the temperature was once more adjusted to room temperature and the mixture was stirred for 18 hours. The mixture was then poured on water/AcOH (100 mL, 2% AcOH) and extracted with diethyl ether (2×100 mL). The organic phase was washed with water (2×100 ml) and dried (Na2SO4). The solvent was evaporated and the product was washed with petroleum ether (20 mL, 40-60° C.). Yield 10.80 g (64.1%). Spectral data see example 44.
Reaction SMILES: C=C[C:3]1[CH:8]=[CH:7][CH:6]=CC=1.[C:9]([O:13]CCC(O)=O)(=[O:12])[CH:10]=[CH2:11]>C(OC(OC(=O)C=C)CCCCCCCCCCC)(=O)C=C.C(S)CCCCCCCCCCC>[C:9]([O:13][CH2:6][CH2:7][CH2:8][CH3:3])(=[O:12])[CH:10]=[CH2:11]
Reactant: C=Cc1ccccc1
Reactant: C=CC(=O)OCCC(=O)O
Agent: C=CC(=O)OC(CCCCCCCCCCC)OC(=O)C=C
Agent: CCCCCCCCCCCCS
Product: C=CC(=O)OCCCC
Yield: 686.3 %

Procedure:
A mixture of about 1581 grams styrene, about 58 grams beta carboxyethyl acrylate (β-CEA), about 7 grams dodecanediol diacrylate (A-DOD), about 7.25 grams dodecanethiol and about 354 grams butyl acrylate was produced by dispersing under high shear conditions in a separate mixing vessel to form a homogenous emulsion.
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:33]=[CH:32][C:21]([C:22]([O:24][CH:25]=[CH:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[H][H]>O1CCCC1>[CH2:1]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:23])=[CH:32][CH:33]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OC=CC(=O)OCC)cc1
Reactant: [H][H]
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OCCC(=O)OCC)cc1

Procedure:
A solution of 4 g. (8.7 m moles) 2-(ethoxycarbonyl)-vinyl 4-(hexadecylamino)benzoate and 400 mg. 10% Pd(C) in 100 ml. tetrahydrofuran is hydrogenated at 50 psi until hydrogen uptake stops. The catalyst is filtered, the solution is evaporated, and the residue is crystallized from acetonitrile to yield 2-(ethoxycarbonyl)ethyl 4-(hexadecylamino)benzoate.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([CH3:11])[C:3]=1[NH2:12].[CH:13]1([CH2:18][C:19](Cl)=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14]1.O>C(#N)C>[CH:13]1([CH2:18][C:19]([NH:12][C:3]2[C:2]([CH3:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][C:4]=2[CH3:11])=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: O=C(Cl)CC1CCCC1
Reactant: Cc1cc([N+](=O)[O-])cc(C)c1N
Solvent: CC#N
Solvent: O
Product: Cc1cc([N+](=O)[O-])cc(C)c1NC(=O)CC1CCCC1
Temperature: 150 °C
Yield: 89 %

Procedure:
2,6-Dimethyl-4-nitro-phenylamine (0.98 g) and cyclopentylacetyl chloride (0.99 mL) were dissolved in acetonitrile (10 mL) and heated to 150° C. for 5 minutes in a sealed microwave process vial. Water (10 mL) was added to the reaction mixture, and the product was collected by filtration and washed with water (20 mL) and heptane (20 mL) to furnish 1.45 g (89% yield) of the title compound as a yellow solid. 1H NMR (500 MHz, DMSO-d6): 1.24 (m, 2H), 1.54 (m, 2H), 1.63 (m, 2H), 1.79 (m, 2H), 2.25 (s, 6H), 2.27 (m, 1H), 2.36 (d, 2H), 7.98 (s, 2H), 9.56 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:12][S:13](Cl)(=[O:15])=[O:14]>N1C=CC=CC=1>[CH3:12][S:13]([NH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2)(=[O:15])=[O:14]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cccc2cccnc12
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1cccc2cccnc12
Yield: 92.2 %

Procedure:
The reaction of 5.0 g (0.0347 mole) of 8-aminoquinoline with 3.97 g (0.0347 mole) of methylsulfonyl chloride was carried out in 10 ml of pyridine at room temperature. After 2 hours from the start of the reaction, the reaction mixture was washed with water, extracted with diethyl ether, purified by column chromatography and concentrated to give 10.32 g (0.032 mole, 92%) of 8-(methylsulfonamido)quinoline. Then, 5.0 g (0.016 mole) of the 8-(methylsulfonamido)quinoline, 3.07 g (0.023 mole) of zinc chloride and 6.98 g (0.069 mole) of triethylamine were suspended in 30 ml of ethanol and allowed to react at room temperature. After 3 hours, the separated yellow powder was filtered, washed with ethanol and purified by column chromatography to give 10.48 g (90.0%) of Compound M as yellow crystals. The maximum PL wavelength of this compound in chloroform was 505 nm.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=3)=[O:20])[C@@H:11]([CH3:29])[CH2:10]2)=[N:6][CH:7]=1.[C:30](Cl)(=[O:33])[CH2:31]C>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([C:19](=[O:20])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=3)[C@@H:11]([CH3:29])[CH2:10]2)[C:30](=[O:33])[CH3:31])=[N:6][CH:7]=1
Reactant: COc1cccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cn3)C[C@@H]2C)c1
Reactant: CCC(=O)Cl
Product: COc1cccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cn3)C[C@@H]2C)c1

Procedure:
To a flask was added Pd2(dba)3 (molar 0.05 equ.), and rac-BINAP (0.1 equ.) in degassed toluene and stirred for 1 h. To the above solution was added 2,5-dichloropyridinepyridine (1.1 equ.) and NaOtBu (1.1 equ.) and stirred for 30 min. The corresponding amine, (±)-cis-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(3-methoxy-phenyl)-methanone was dissolved in degassed toluene and added to the solution and heated to 60° C. for 40 h. The reaction was diluted with ether and filtered through celite and concentrated down. The compound was purified by Biotage with 20% EtOAc/80% Hexane to give 45% of the product. (±)-Cis-[4-(5-chloro-pyridin-2-ylamino)-2-methyl-3,4-dihydro-2H-quinolin-1-yl]-(3-methoxy-phenyl)-methanone was acetylated with propionyl chloride as previously described to give (±)-cis-N-(5-chloro-pyridin-2-yl)-N-[1-(3-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide.
Reaction SMILES: CI.[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[NH:9][CH:10]=[C:11]([CH:13]=[O:14])[N:12]=1.[C:15](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:15][N:12]1[C:11]([CH:13]=[O:14])=[CH:10][N:9]=[C:8]1[C:4]1[S:3][CH:7]=[CH:6][CH:5]=1
Reactant: O=Cc1c[nH]c(-c2cccs2)n1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: Cn1c(C=O)cnc1-c1cccs1
Temperature: 70 °C

Procedure:
Methyl iodide (477 mg, 3.36 mmol) dissolved in DMF (0.5 ml) was added dropwise to a stirred solution of 2-Thiophen-2-yl-1H-imidazole-4-carbaldehyde (0.57 g, 3.2 mmol) and Potassium carbonate (0.486 g, 3.52 mmol) in dry N,N-Dimethylformamide (6 mL) at rt. The solution was stirred at 70° C. 3 h. Most of the DMF was evaporated off and the residue was partioned between EtOAc (50 ml) and brine (25 ml). The phases were separated and the organic phase was dried (Na2SO4) and the solvent was evaporated off. The crude product was purified by silica gel chromatography (Eluent: 50%-100% EtOAc in n-heptane). Yield: 211 mg of the title compound as an oil. H-NMR (DMSO-d6): δ 9.71 (s, 1H), 7.80 (s, 1H) 7.54 (m, 2H), 7.17 (m, 1H), 4.14 (s, 3H). LC-MS: m/z=192.9 (MH+), tR=0.34 min, method C. (211 mg of a fast eluting isomer (3-Methyl-2-thiophen-2-yl-3H-imidazole-4-carbaldehyde) was also isolated and discarded).
Reaction SMILES: [C:1]([C:5](=[CH:10]OC)[C:6]([O:8][CH3:9])=[O:7])(=[O:4])[CH2:2][CH3:3].[CH3:13][O:14][C:15]1[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=1[NH2:17]>>[C:1]([C:5](=[CH:10][NH:17][C:16]1[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=1[O:14][CH3:13])[C:6]([O:8][CH3:9])=[O:7])(=[O:4])[CH2:2][CH3:3]
Reactant: CCC(=O)C(=COC)C(=O)OC
Reactant: COc1ccccc1N
Product: CCC(=O)C(=CNc1ccccc1OC)C(=O)OC

Procedure:
A mixture of methyl 2-propanoyl-3-methoxyacrylate (70 g) and 2-methoxyaniline (45 ml) was heated on a steam bath for 30 minutes, then diluted with petroleum ether and left to crystallise. Filtration and washing with ether gave methyl 2-propanoyl-3-(2-methoxyphenylamino)acrylate (78.2 g) as a mixture of E/Z isomers.
Reaction SMILES: [C:1]([NH:5][CH2:6][CH:7]([OH:21])[CH2:8][O:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[C:12]([Cl:20])=[C:13]([CH3:19])[NH:14]2)([CH3:4])([CH3:3])[CH3:2].[C:22](O)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(OC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.N.C(O)(=O)CC(O)=O>CCOCC.O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[C:22]([O:21][CH:7]([CH2:6][NH:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:8][O:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[C:12]([Cl:20])=[C:13]([CH3:19])[NH:14]2)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Cc1[nH]c2cccc(OCC(O)CNC(C)(C)C)c2c1Cl
Reactant: O=C(O)c1ccccc1
Agent: N
Agent: O=C(O)CC(=O)O
Agent: O=C(OC(=O)c1ccccc1)c1ccccc1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cc1[nH]c2cccc(OCC(CNC(C)(C)C)OC(=O)c3ccccc3)c2c1Cl
Temperature: 25 °C
Reaction time: 15 h

Procedure:
3.1 g of 1-tert.butylamino-3-(3-chloro-2-methyl-indol-4-yloxy)-2-propanol, 6.1 g of benzoic acid and 12 ml of hexamethyl phosphoric acid triamide are heated on a steam bath until all of the benzoic acid is dissolved. After cooling to room temperature, 2.9 g of benzoic acid anhydride are added and stirring is effected for 15 hours. The resulting clear yellow solution is poured onto ice, 250 ml of ether are added and stirring effected for 1 hour. After making the liquid alkaline with concentrated ammonia, the ether phase is separated, shaken out with tartaric acid, made alkaline while cooling with ice, with concentrated ammonia and extracted with methylene chloride. After evaporating the methylene chloride, the residual title compound is crystallised with 1 mol of malonic acid from tetrahydrofuran and ether. M.p. of hydrogen malonate form: 176°-177°.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[CH:9])=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][SH:16])=[CH:13][CH:12]=1.[Na]>>[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]\[CH:15]([S:16][CH:15](/[CH:9]=[CH:8]\[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:14]2[CH:17]=[CH:18][C:11]([Cl:10])=[CH:12][CH:13]=2)[C:14]2[CH:17]=[CH:18][C:11]([Cl:10])=[CH:12][CH:13]=2)=[CH:4][CH:3]=1
Reactant: C#Cc1ccc(F)cc1
Reactant: SCc1ccc(Cl)cc1
Agent: [Na]
Product: Fc1ccc(/C=C\C(SC(/C=C\c2ccc(F)cc2)c2ccc(Cl)cc2)c2ccc(Cl)cc2)cc1

Procedure:
A solution of 4-fluorophenylacetylene (0.02 mol) and 4-chlorobenzyl mercaptan (0.02 mol) and metallic sodium (0.02 g atom) was subjected to the General Procedure to form Z-4-fluorostyryl 4-chlorobenzylsulfide. The title compound was obtained in 82% yield following oxidation. 1HNMR (CDC13) δ4.60 (2H, s), 6.68 (1H, d, JH,H=11.84), 7.18-7.60 (8H aromatic+1H ethylenic).