Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[N+:11]([O-])=O)[NH:7][C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[S:19]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)(=[O:21])=[O:20].Cl>C(O)C.[Zn]>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[NH2:11])[NH:7][C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[S:19]([N:22]1[CH2:23][CH2:24][O:25][CH2:26][CH2:27]1)(=[O:20])=[O:21]
Reactant: CCOC(=O)c1[nH]c2cc([N+](=O)[O-])c(Br)cc2c1S(=O)(=O)N1CCOCC1
Agent: Cl
Agent: [Zn]
Solvent: CCO
Product: CCOC(=O)c1[nH]c2cc(N)c(Br)cc2c1S(=O)(=O)N1CCOCC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Ethyl 5-bromo-6-nitro-3-(morpholin-4-ylsulfonyl)-1H-indole-2-carboxylate (256 mg, 0.55 mmol, 1.0 equiv) was suspended in 10 mL of absolute ethanol. 1.5 mL of concentrated aqueous HCl was added, followed Zn dust (362 mg, 5.5 mmol, 10 equiv), and the reaction was stirred at ambient temperature for 1 hour. The mixture was partitioned between ethyl acetate and water, which was extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 30% ethyl acetate/dichloromethane) provided the titled compound. Proton NMR for the product was consistent with the titled compound. 1H NMR (500 MHz, DMSO-d6): δ 12.38 (s, 1H), 8.15 (br s, 1H), 8.05 (br s, 1H), 7.91 (s, 1H), 6.94 (s, 1H), 3.62 (m, 4H), 2.87 (m, 4H) ppm. ESI+MS: 431.2 [M+H]+.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C(O[C:15](=O)[NH:16][CH2:17][CH:18]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[N:27][NH:28][CH:29]=2)=[CH:21][CH:20]=1)C1C=CC=CC=1>O1CCCC1>[F:36][C:33]1[CH:32]=[CH:31][C:30]([CH:18]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:29]=[N:28][NH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:17][NH:16][CH3:15])=[CH:35][CH:34]=1
Reactant: O=C(NCC(c1ccc(F)cc1)c1ccc(-c2cn[nH]c2)cc1)OCc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CNCC(c1ccc(F)cc1)c1ccc(-c2cn[nH]c2)cc1
Temperature: 25 °C
Reaction time: 51 h

Procedure:
Lithium aluminium hydride (5.3 ml, 5.30 mmol, 1M in tetrahydrofuran) was slowly added to {2-(4-Fluoro-phenyl)-2-[4-(1H-pyrazol-4-yl)-phenyl]-ethyl}-carbamic acid benzyl ester (439 mg, 1.06 mmol) in tetrahydrofuran (5 ml) at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature, stirred for 51 hours and quenched with water (5 ml), aqueous sodium hydroxide (2N, 5 ml) and ethyl acetate (10 ml). The aqueous layer was separated, extracted with ethyl acetate (2×20 ml). The combined organic liquors were washed with saturated aqueous brine then dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (SiO2), eluting with dichloromethane:methanol:acetic acid:water (120:15:3:2) gradient to (90:18:3:2) to afford the title compound, which was subsequently converted to the hydrochloride salt (100 mg, 32%). LC/MS: (PS-A2) Rt 1.87 [M+H]+ 296. 1H NMR (Me-d3-OD) δ 8.20 (2H, s), 7.57 (2H, d), 7.34-7.29 (4H, m), 7.02 (2H, t), t), 4.32 (1H, t), 3.67 (2H, d), 2.65 (3H, s).
Reaction SMILES: [ClH:1].[CH2:2]([C:5]1[N:9]2[CH2:10][CH2:11][CH2:12][N:13]=[C:8]2[S:7][C:6]=1[C:14]([O:16]CC)=[O:15])[CH2:3][CH3:4].Cl>[OH-].[Na+]>[ClH:1].[CH2:2]([C:5]1[N:9]2[CH2:10][CH2:11][CH2:12][N:13]=[C:8]2[S:7][C:6]=1[C:14]([OH:16])=[O:15])[CH2:3][CH3:4]
Reactant: CCCC1=C(C(=O)OCC)SC2=NCCCN21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CCCC1=C(C(=O)O)SC2=NCCCN21
Yield: 58.9 %

Procedure:
In 110 ml of 1N sodium hydroxide aqueous solution was suspended 9.96 g of ethyl 3-propyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidine-2-carboxylate hydrochloride obtained in Example 11, followed by reflux under heating for 90 minutes. After cooling, the reaction mixture was made acidic with concentrated hydrochloric acid. The precipitated crystals were collected by filtration and washed with acetone to obtain 5.3 g of the titled compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1C=O.[C:15]1([NH2:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1C=CC=CC=1>[CH3:1][O:2][CH:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=[N:21][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Nc1ccccc1
Reactant: COc1ccc2ccccc2c1C=O
Solvent: c1ccccc1
Product: COC1C=Cc2ccccc2C1=Nc1ccccc1
Yield: 102.2 %

Procedure:
2-Methoxy-1-naphthaldehyde [50.0 gm. 0.27 mole] and phenylamine [25 gm., 0.27 mole] were refluxed with benzene [100 ml] for 4 hours. The benzene was evaporated to an oil, dissolved in chloroform, the chloroform dried over sodium sulfate and evaporated to a green semisolid of the 2-methoxy-1-naphthylidene-phenylamine [68.8 gm., 97% yield]
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]3[N:14]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[F:33])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[Cl:23])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:34]([F:37])([F:36])[F:35].[CH:38](=O)[CH3:39]>C1(C)C=CC=CC=1.C(O)(=O)C>[Cl:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:16]=1[C:15](=[O:24])[N:14]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[F:33])[C:13]([C:11]1[S:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][CH2:38][CH3:39])=[C:3]([C:34]([F:37])([F:36])[F:35])[CH:4]=3)=[CH:9][CH:10]=1)=[CH:22]2
Reactant: Nc1ccc(-c2ccc(-c3cc4cccc(Cl)c4c(=O)n3Cc3ccc(F)cc3F)s2)cc1C(F)(F)F
Reactant: CC=O
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CCNc1ccc(-c2ccc(-c3cc4cccc(Cl)c4c(=O)n3Cc3ccc(F)cc3F)s2)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 34 %

Procedure:
To a solution of 3-[5-(4-amino-3-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one (28 mg, 51 μmol) in toluene (1 mL) was added one drop of acetic acid, and a molar excess of acetaldehyde. The mixture was stirred for 20 minutes at ambient temperature and then concentrated under reduced pressure. The residue was taken up in 25% HOAc/MeOH (1 mL), and a molar excess of NaCNBH3 was added. After stirring for 16 hours at ambient temperature there was still starting material present. Additional acetaldehyde was added. After 30 minutes a yellow solid appeared in the reaction. This solid was collected by filtration and was purified by silica gel column chromatography eluting with a gradient from 0% to 20% ethyl acetate/hexane on silica. The product peak was collected to afford 8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-ethylamino-3-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one (10 mg, 34% yield) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ 7.62-7.60 (1H, m), 7.55-7.51 (3H, m), 7.44-7.40 (1H, m), 7.05-6.98 (2H, m), 6.85 (1H, d, J=3.8 Hz), 6.82-6.72 (3H, m), 6.67 (1H, s), 5.36 (2H, s), 4.40 (1H, s), 3.29-3.22 (2H, m), 1.32 (3H, t, J=7.1 Hz) ppm.
Reaction SMILES: Cl.Br[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][N:4]=1.Cl.[CH3:13][O:14][C:15]1[N:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:13][O:14][C:15]1[N:20]=[CH:19][C:18]([C:3]2[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][N:4]=2)=[CH:17][CH:16]=1
Reactant: COc1ccc(B(O)O)cn1
Reactant: O=C(O)c1ccc(Br)nc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: COc1ccc(-c2ccc(C(=O)O)cn2)cn1

Procedure:
The title compound is prepared as described in EXAMPLE 31, Part I, but with 6-bromonicotinic acid hydrochloride and 6-methoxypyridin-3-ylboronic acid hydrochloride as starting materials, and 10 molar equivalents of 0.4M aqueous sodium carbonate. 1H NMR (DMSO) δ 13.40 (br s, 1H), 9.10 (d, 1H), 8.95 (d, 1H), 8.43 (dd, 1H), 8.28 (dd, 1H), 8.09 (d, 1H), 6.95 (d, 1H), 3.91 (s, 3H). ESI MS (M+1)+: 231.
Reaction SMILES: [CH:1]1([CH:7]([C:9]2[C:10]([CH3:24])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:13]=2)O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([NH:34][CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[O:33])=[CH:28][CH:27]=1>>[CH:1]1([CH:7]([NH:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][CH:31]=2)[C:9]2[C:10]([CH3:24])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)CCNC(=O)c1ccc(N)cc1
Reactant: Cc1nn(-c2ccc(C(F)(F)F)cc2)cc1C(O)C1CCCCC1
Product: Cc1nn(-c2ccc(C(F)(F)F)cc2)cc1C(Nc1ccc(C(=O)NCCC(=O)O)cc1)C1CCCCC1
Yield: 13.8 %

Procedure:
Using cyclohexyl{3-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}methanol (0.36 g) synthesized above and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (0.38 g) synthesized in Example 1(2) and in the same manner as in Example 1(7), the title object compound (77.5 mg, 7%) was obtained as a white solid.
Reaction SMILES: [F:1][C@H:2]1[C@@H:6]([O:7][C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[C:15]([C:18]2[N:22]4[CH:23]=[CH:24][C:25]([O:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:26][C:21]4=[N:20][CH:19]=2)[CH:14]=[CH:13]3)[CH2:5][N:4](C(OCC2C=CC=CC=2)=O)[CH2:3]1.[ClH:42]>[Pd].C(O)C>[ClH:42].[F:1][C@H:2]1[CH2:3][NH:4][CH2:5][C@H:6]1[O:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]1[N:22]3[CH:23]=[CH:24][C:25]([O:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:26][C:21]3=[N:20][CH:19]=1)[CH:14]=[CH:13]2
Reactant: COCCOc1ccn2c(-c3ccc4cccc(O[C@H]5CN(C(=O)OCc6ccccc6)C[C@H]5F)c4n3)cnc2c1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: COCCOc1ccn2c(-c3ccc4cccc(O[C@@H]5CNC[C@@H]5F)c4n3)cnc2c1
Reaction time: 18 h

Procedure:
Crude (cis)-benzyl 3-fluoro-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate (1.0 g, 2.0 mmol) and palladium on carbon (1 g, 50% on a molar basis) were added to a mixture of ethanol and 1% HCl (v/v) and placed under hydrogen in a balloon with vigorous stirring. After 18 hours, the crude mixture was passed through Celite, rinsed several times with ethanol, and the collected filtrate was evaporated. The crude material was purified on silica gel using a 6% solution of ammonium hydroxide in methanol and dichloromethane to yield free base product, which, when subjected to HCl in dichloromethane and subsequent precipitation in diethyl ether yielded 150 mg (16% isolated yield) of highly pure product. MS APCI (+) m/z 423.3 (M+1) detected.
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=[S:16])[C:5]([C:14]#[N:15])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1.[CH3:17][O:18][CH2:19][CH2:20]Br.CC[O-].[Na+]>C(O)C>[NH2:1][C:2]1[N:3]=[C:4]([S:16][CH2:20][CH2:19][O:18][CH3:17])[C:5]([C:14]#[N:15])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1
Reactant: N#Cc1c(-c2ccccc2)nc(N)[nH]c1=S
Reactant: COCCBr
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: COCCSc1nc(N)nc(-c2ccccc2)c1C#N

Procedure:
From 2-amino-4-phenyl-6-thioxo-1,6-dihydro-pyrimidine-5-carbonitrile, 2-methoxyethyl bromide and sodium ethylate in ethanol. EI-MS m/e (%): 286 (M+, 6), 228 ([M—MeOCH═CH2]+, 100).
Reaction SMILES: C(O[C:9](=O)[NH:10][C@H:11]1[CH2:16][CH2:15][C@@H:14]([F:17])[CH2:13][CH2:12]1)C1C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[F:17][C@@H:14]1[CH2:15][CH2:16][C@H:11]([NH:10][CH3:9])[CH2:12][CH2:13]1
Reactant: O=C(N[C@H]1CC[C@@H](F)CC1)OCc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: CN[C@H]1CC[C@@H](F)CC1

Procedure:
The title compound was prepared from (cis)-(4-fluoro-cyclohexyl)-carbamic acid benzyl ester by lithium aluminum hydride reduction under standard conditions in 91% yield.
Reaction SMILES: C(OC(=O)[NH:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:17]=2)=[CH:11][N:10]=1)=S)C.[Cl-].O[NH3+].C([N:38](CC)C(C)C)(C)C.C(O)C>CO>[NH2:38][C:6]1[N:8]=[C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([NH:23][C:24](=[O:25])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH:17]=3)=[CH:11][N:10]2[N:5]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: CCOC(=O)NC(=S)Nc1ccc(Oc2ccc(Cl)c(NC(=O)OC(C)(C)C)c2)cn1
Agent: [Cl-]
Agent: [NH3+]O
Solvent: CO
Solvent: CCO
Product: CC(C)(C)OC(=O)Nc1cc(Oc2ccc3nc(N)nn3c2)ccc1Cl
Yield: 94.2 %

Procedure:
In the same manner as in Example 23-1 and using ethyl{[(5-{3-[(tert-butoxycarbonyl)amino]-4-chlorophenoxy}pyridin-2-yl)amino]carbonothioyl}carbamate (7.23 g, 15.5 mmol), hydroxylammonium chloride (7.64 g, 0.110 mol), N,N-diisopropylethylamine (13.5 mL, 77.4 mmol), ethanol (50 mL) and methanol (50 mL) as starting materials, the title compound (5.49 g, 92%) was obtained as a white solid.
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)=[CH:9][C:8]=1[CH3:18].C[O:20][B:21](OC)[O:22]C.Cl.[OH-].[Na+].P([O-])(O)(O)=O.[Na+]>C1COCC1>[CH3:18][C:8]1[CH:9]=[C:10]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[CH:11]=[CH:12][C:7]=1[B:21]([OH:22])[OH:20]
Reactant: COB(OC)OC
Reactant: Cc1cc(-n2cccn2)ccc1Br
Agent: Cl
Agent: O=P([O-])(O)O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1cc(-n2cccn2)ccc1B(O)O
Temperature: -25 °C
Reaction time: 16 h
Yield: 86.6 %

Procedure:
n-Butyllithium (7.9 mL of a 2.5 M solution in hexanes, 20 mmol) was added to a solution of compound 2b (4.7 g, 20 mmol) in 100 mL THF at −78° C. The mixture was allowed to warm to −25° C. over 1 hr, then the mixture was cooled to −78° C. Trimethylborate (3.4 mL, 30 mmol) was added and the reaction was allowed to warm to RT. Hydrochloric acid (1N, 100 mL) was then added and the mixture was stirred for 16 hr. The pH of the aqueous layer was adjusted to 3-4 using sodium hydroxide and sodium dihydrogen phosphate solution, then the mixture was extracted with ethyl acetate. The organic layer was concentrated, then the residue was partitioned between ether and 0.5 N sodium hydroxide solution. The aqueous layer was extracted with two additional portions of ether and was then acidified to pH 3-4 using concentrated hydrochloric acid. The mixture was extracted with ethyl acetate, and the combined ethyl acetate extracts were dried over sodium sulfate, filtered, and evaporated to afford 2-methyl-4-(pyrazol-1-yl)phenylboronic acid (compound 2c, 3.5 g) as an amber gum.
Reaction SMILES: [H-].[Na+].[C:3]1([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.I[CH3:18]>CN(C)C=O>[CH2:10]([N:9]([CH3:18])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CI
Reactant: c1ccc(CNc2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(Cc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 39.5 %

Procedure:
60% dispersion of sodium hydride in mineral oil (2.37 g, 0.0592 mol) was added to a solution of N-phenyl-N-benzylamine (10.33 g, 0.0564 mol) in anhydrous N,N-dimethylformamide (200 mL) at 0° C. The reaction mixture was warmed up to ambient temperature and stirred for 45 min. Iodomethane (7.99 g, 0.0564 mol) was added dropwise and the stirring at ambient temperature was continued under an atmosphere of nitrogen for 20 hours. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate (250 mL) and water (200 mL). The organic phase was dried with magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica using ethyl acetate/n-heptane (2:98) as mobile phase to yield N-benzyl-N-methyl-N-phenylamine (4.4 g, 0.0223 mol) as a yellow oil.
Reaction SMILES: [C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:11]1[CH:19]2[CH:14]([CH2:15][CH2:16][CH2:17][CH2:18]2)[CH2:13][CH:12]1[C:20]([OH:22])=[O:21]>[OH-].[Na+]>[C:1]1([S:7]([N:11]2[CH:19]3[CH:14]([CH2:15][CH2:16][CH2:17][CH2:18]3)[CH2:13][CH:12]2[C:20]([OH:22])=[O:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: O=C(O)C1CC2CCCCC2N1
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)C1CC2CCCCC2N1S(=O)(=O)c1ccccc1
Reaction time: 24 h

Procedure:
29.8 mmol (3.8 ml) of benzenesulphonyl chloride and 7.4 ml of 4M sodium hydroxide solution are added in succession to a solution, cooled to 0° C., of 29.6 mmol (5 g) of 2-perhydroindolecarboxylic acid in 7.4 ml of 4M NaOH. The reaction mixture is left at room temperature, with stirring, for 24 hours. The mixture is then rendered acidic to pH 2-3 and filtered. The resulting solid is washed with ether to yield the expected product.
Reaction SMILES: C(OCC)(=O)C=C.O[CH:9]([CH2:15][CH:16](O)[CH2:17][CH3:18])[C:10]([O:12][CH2:13][CH3:14])=[O:11].C(C1OC(=O)C(O)C1)C>C(O)CC>[C:10]([O:12][CH2:13][CH3:14])(=[O:11])/[CH:9]=[CH:15]/[CH:16]=[CH:17]/[CH3:18]
Reactant: CCOC(=O)C(O)CC(O)CC
Agent: C=CC(=O)OCC
Agent: CCC1CC(O)C(=O)O1
Solvent: CCCO
Product: C/C=C/C=C/C(=O)OCC

Procedure:
For example, when n-propyl alcohol is allowed to react with ethyl acrylate, ethyl 2,4-dihydroxyhexanoate corresponding to Formula (4) and 4-ethyl-2-hydroxy-γ-butyrolactone corresponding to Formula (6) are formed under some conditions in addition to the target ethyl sorbate.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Cl[CH2:12][CH2:13][N:14]([CH2:16][CH2:17]Cl)[CH3:15].Cl>CS(C)=O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:17][CH2:16][N:14]([CH3:15])[CH2:13][CH2:12]2)=[CH:4][CH:3]=1
Reactant: N#CCc1ccc(I)cc1
Reactant: CN(CCCl)CCCl
Agent: Cl
Solvent: CS(C)=O
Product: CN1CCC(C#N)(c2ccc(I)cc2)CC1
Temperature: 20 °C
Reaction time: 0.33 h
Yield: 57 %

Procedure:
To a solution of 4-iodophenylacetonitrile (10 g, 41.1 mmol) in anhydrous DMSO (20 mL) was added NaNH2 (4.8 g, 123.3 mmol, 3 eq.) in one portion. The temperature of the reaction was maintained at 20° C. using a water bath. The mixture was stirred at 20° C. for 20 min to give a deep red solution then a solution of bis-(2-chloro-ethyl)-methyl-amine.HCl salt (7.92 g, 41.1 mmol, 1 eq.) in anhydrous DMSO (20 mL) was added in a drop-wise fashion. The resulting mixture was stirred at room temperature for 16 h then partitioned between EtOAc (250 mL) and H2O (250 mL). The organic layer was separated and washed with H2O (3×100 mL) and saturated brine (100 mL) then dried over Na2SO4, filtered and concentrated by rotary evaporation. The crude product was purified by flash column chromatography by eluting with 10% MeOH/EtOAc to yield 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carbonitrile as a brownish solid (7.6 g, 23.43 mmol, 57%). 1H NMR (300 MHz, CD3OD): δ 7.89 (d, 2H), 7.43 (d, 2H), 3.13 (d, 2H), 2.58 (td, 2H), 2.50 (s, 3H), 2.24 (m, 4H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([I:17])=[C:4]([CH2:11][CH2:12][O:13][C:14](=[O:16])[CH3:15])[C:5]([I:10])=[C:6]([NH2:9])[C:7]=1[I:8].[CH3:18][C:19]1([CH3:27])[O:23][CH:22]([C:24](Cl)=[O:25])[CH2:21][O:20]1>>[CH3:18][C:19]1([CH3:27])[O:23][CH:22]([C:24]([NH:9][C:6]2[C:5]([I:10])=[C:4]([CH2:11][CH2:12][O:13][C:14](=[O:16])[CH3:15])[C:3]([I:17])=[C:2]([NH:1][C:24]([CH:22]3[CH2:21][O:20][C:19]([CH3:27])([CH3:18])[O:23]3)=[O:25])[C:7]=2[I:8])=[O:25])[CH2:21][O:20]1
Reactant: CC(=O)OCCc1c(I)c(N)c(I)c(N)c1I
Reactant: CC1(C)OCC(C(=O)Cl)O1
Product: CC(=O)OCCc1c(I)c(NC(=O)C2COC(C)(C)O2)c(I)c(NC(=O)C2COC(C)(C)O2)c1I
Yield: 47 %

Procedure:
3,5-Diamino-2,4,6-triiodo-(2-acetoxyethyl)benzene was acylated with 2,2-dimethyl-1,3-dioxolane-4-carboxylic chloride (prepared in situ) according to the procedure in Example 29a. After work up, the product was purified by preparative HPLC and isolated in 47% yield.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:11][C:10]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[CH3:19][C:20]1[O:21][C:22]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]([F:38])([F:37])[F:36])[CH:29]=2)=[C:23]([C:25](O)=[O:26])[N:24]=1>>[C:2]([C:7]1[S:11][C:10]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:25]([C:23]3[N:24]=[C:20]([CH3:19])[O:21][C:22]=3[C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]([F:37])([F:36])[F:38])[CH:29]=3)=[O:26])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2ccc(Cn3cc(N)cn3)s2)OCCO1
Reactant: Cc1nc(C(=O)O)c(-c2cccc(OC(F)(F)F)c2)o1
Product: CC(=O)c1ccc(Cn2cc(NC(=O)c3nc(C)oc3-c3cccc(OC(F)(F)F)c3)cn2)s1

Procedure:
Following general procedure X followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-1H-pyrazol-4-ylamine and 2-methyl-5-(3-trifluoromethoxy-phenyl)-oxazole-4-carboxylic acid. LC-MS-conditions 05c: tR=0.81 min; [M+H]+=492.2.
Reaction SMILES: [CH2:1]([C:4]1[C:13]2[O:12][C:11]([C:14]3[NH:18][N:17]=[N:16][N:15]=3)=[CH:10][C:9](=[O:19])[C:8]=2[C:7]([O:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:6][CH:5]=1)[CH:2]=[CH2:3]>[Pd].C(O)C>[CH3:24][CH:23]([CH3:25])[CH2:22][CH2:21][O:20][C:7]1[C:8]2[C:9](=[O:19])[CH:10]=[C:11]([C:14]3[NH:18][N:17]=[N:16][N:15]=3)[O:12][C:13]=2[C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][CH:6]=1
Reactant: C=CCc1ccc(OCCC(C)C)c2c(=O)cc(-c3nnn[nH]3)oc12
Agent: [Pd]
Solvent: CCO
Product: CCCc1ccc(OCCC(C)C)c2c(=O)cc(-c3nnn[nH]3)oc12

Procedure:
A solution of 1.0 parts of 5-[8-allyl-5-(3-methyl-n-butoxy)-4-oxo-4H-1-benzopyran-2-yl]tetrazole in 19 parts of ethanol was hydrogenated overnight at room temperature and pressure using 0.02 parts of 5% palladium on charcoal as catalyst. The reaction mixture was filtered and the solvent removed by evaporation. Crystallisation of the residue from ethanol gave 0.52 parts of 5-[5-(3-methyl-n-butoxy)-8-n-propyl-4-oxo-4H-1-benzopyran-2-yl]tetrazole, m.p. 202°-204°C.
Reaction SMILES: [CH:1]([S:4][C:5]1[NH:6][C:7](=[O:24])[C:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]=1[C:10]#[N:11])([CH3:3])[CH3:2].[H-].[Na+].Cl.[CH3:28][N:29]([CH2:31][CH2:32][CH2:33]Cl)[CH3:30]>O1CCOCC1>[CH:1]([S:4][C:5]1[N:6]([CH2:33][CH2:32][CH2:31][N:29]([CH3:30])[CH3:28])[C:7](=[O:24])[C:8]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:9]=1[C:10]#[N:11])([CH3:3])[CH3:2]
Reactant: CC(C)SC1=C(C#N)C(c2ccccc2)(c2ccccc2)C(=O)N1
Reactant: CN(C)CCCCl
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(C)SC1=C(C#N)C(c2ccccc2)(c2ccccc2)C(=O)N1CCCN(C)C
Reaction time: 1 h

Procedure:
A suspension of 10.0 g 2-isopropylthio-5-oxo-4,4-diphenyl-2-pyrroline-3-carbonitrile and 0.9 g sodium hydride (80%) in 150 ml dioxan is boiled for one hour, with stirring. Thereafter, one mixes with a further 0.9 g sodium hydride and 5.2 g dimethylaminopropyl chloride hydrochloride and boils further for 30 hours.
Reaction SMILES: [CH2:1]([O:19][C:20]1[O:24][CH:23]=[C:22]([C:25]([OH:27])=O)[CH:21]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].S(Cl)([Cl:30])=O>C(Cl)Cl>[CH2:1]([O:19][C:20]1[O:24][CH:23]=[C:22]([C:25]([Cl:30])=[O:27])[CH:21]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCCOc1cc(C(=O)O)co1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCCOc1cc(C(=O)Cl)co1
Reaction time: 5 h

Procedure:
To a cooled mixture of 40.0 g (0.106 mole) of 5-(cis-9-octadecen-1-yloxy)-3-furoic acid in methylene chloride is added 30 ml of thionyl chloride. The mixture is stirred for 5 hours. Then the solvent and excess thionyl chloride is removed under reduced pressure affording the crude 5-(cis-9-octadecen-1-yloxy)-3-furoyl chloride. A mixture of 11.6 g (0.100 moles) of methyl acetoacetate and 2.3 g of sodium in 1 liter of benzene is refluxed for 20 hours, then cooled, and the crude 5-(cis-9-octadecen-1-yloxy)-3-furoyl chloride is added over a two hour period. The mixture is refluxed for 6 hours, cooled by the addition of ice and mixed well. The benzene layer is separated, washed with 5% sodium bicarbonate solution and dried. The benzene is distilled off under reduced pressure yielding 2-[5-(cis-9-octadecen-1-yloxy)-3-furoyl]acetoacetic acid, methyl ester. To a solution of 3.3 g of ammonium chloride in 15 ml of water at 40° C is added 10 g of the above ester maintaining the temperature at 40° C for 15 minutes followed by rapid cooling. The solution is extracted with ether, the extract dried, and evaporated to dryness affording 2-[5-(cis-9-octadecen-1-yloxy)-3-furoyl]acetic acid methyl ester.