Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH2:7])=[O:6].C[O:12][C:13](OC)([CH3:15])[CH3:14].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O>[CH3:14][C:13]1([CH3:15])[NH:7][C:5](=[O:6])[C:4]2[CH:3]=[CH:2][CH:10]=[CH:9][C:8]=2[O:12]1
Reactant: COC(C)(C)OC
Reactant: NC(=O)c1cccc(O)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)=O
Product: CC1(C)NC(=O)c2ccccc2O1
Yield: 86 %

Procedure:
To a solution of 3-hydroxy-benzamide (50 g, 0.36 mol) in acetone (300 mL) was added 2,2-dimethoxy-propane (100 mL) and p-toluene sulfonic acid (5 g, 0.03 mol) and the mixture was heated to reflux overnight. The solvent was evaporated under vacuum to give crude 2,2-dimethyl-2H-benzo[e][1,3]oxazin-4(3H)-one (55 g, 86%) that was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 7.91 (dd, J=1.8, 7.8 Hz 1H), 7.44 (t, J=7.8 Hz 1H), 7.35 (brs, 1H), 7.05 (t, J=7.8 Hz 1H), 6.91 (d, J=8.1 Hz 1H), 1.65 (s, 6H).
Reaction SMILES: O=C(Cl)[O:3][C:4](Cl)(Cl)Cl.[CH2:9]([O:11][C:12](=[O:15])[CH2:13][NH2:14])[CH3:10].C>O1CCOCC1>[N-:14]=[C:4]=[O:3].[CH2:9]([O:11][C:12](=[O:15])[CH2:13][NH2:14])[CH3:10]
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Agent: CCOC(=O)CN
Solvent: C1COCCO1
Product: [N-]=C=O

Procedure:
0.35 mol diphosgene is added dropwise over 1 hour to a mixture of 0.28 mol of glycine ethyl ester and 0.4 g activated charcoal in 400 mL dioxane under N2. The reaction mixture is then heated and stirred at reflux for 21/2 hours. The reaction mixture is then cooled, filtered, and concentrated to dryness by rotary evaporator, keeping exposure to moisture to a minimum. The crude product is re-dissolved in 100 mL THF, and the pH of the solution is adjusted to 5.5-6.0 by addition of pyridine. The product mixture is again filtered, and the product is purified by fractional distillation to give glycine ethyl ester isocyanate.
Reaction SMILES: [C:1]1([C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:8]2[C@@H:11]([S:12]([CH3:15])(=[O:14])=[O:13])[NH:10][C:9]2=[O:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:29]1(S([O-])=O)[CH:34]=[CH:33]C=[CH:31][CH:30]=1.[Na+].ClCCCl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:23]1([C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@H:8]2[CH:11]([S:12]([C:15]3[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=3)(=[O:14])=[O:13])[NH:10][C:9]2=[O:16])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CS(=O)(=O)[C@H]1NC(=O)[C@H]1C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=S([O-])c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCCl
Solvent: O
Product: O=C1NC(S(=O)(=O)c2ccccc2)[C@@H]1C(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 72.8 %

Procedure:
A mixture of 30 g of (3R-cis)-3-triphenylmethyl-4-methylsulfonyl-2-azetidinone, 40 g of sodium benzenesulfinate, 25 g of tetra-n-butylammonium bromide, 400 ml of 1,2-dichloroethane, and 100 ml of water were refluxed under nitrogen for 30 minutes. The dichloroethane was removed in vacuo and the residue was extracted with 700 ml of ethyl acetate. The extract was washed with saturated aqueous sodium bicarbonate solution, then water, then saturated aqueous sodium chloride solution. The extract was dried over sodium sulfate and evaporated. The residue was chromatographed on a 50×280 mm silica gel column eluted with 1000 ml 1:4 ethyl acetate:hexane, then 1000 ml 1:1 ethyl acetate:hexane. (3R)-3-triphenylmethyl-4-phenylsulfonyl-2-azetidinone (25.3 g) was obtained as a mixture of cis and trans isomers.
Reaction SMILES: [ClH:1].C([O:6][C:7]([CH2:9][O:10][N:11]=[C:12]([C:43]1[N:44]=[C:45]([NH2:48])[S:46][CH:47]=1)[C:13]([NH:15][CH:16]1[C:41](=[O:42])[N:18]2[C:19]([C:25]([O:27]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:26])=[C:20]([CH:23]=[CH2:24])[CH2:21][S:22][C@H:17]12)=[O:14])=[O:8])(C)(C)C.C(OC(C)C)(C)C>C(O)=O>[ClH:1].[C:7]([CH2:9][O:10][N:11]=[C:12]([C:43]1[N:44]=[C:45]([NH2:48])[S:46][CH:47]=1)[C:13]([NH:15][CH:16]1[C:41](=[O:42])[N:18]2[C:19]([C:25]([OH:27])=[O:26])=[C:20]([CH:23]=[CH2:24])[CH2:21][S:22][C@H:17]12)=[O:14])([OH:8])=[O:6]
Reactant: C=CC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)C(=NOCC(=O)OC(C)(C)C)c3csc(N)n3)[C@H]2SC1
Agent: Cl
Solvent: CC(C)OC(C)C
Solvent: O=CO
Product: C=CC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=NOCC(=O)O)c3csc(N)n3)[C@H]2SC1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 73.6 %

Procedure:
Conc. hydrochloric acid (0.18 g) was added to a solution of benzhydryl 7-[2-(tert-butoxycarbonylmethoxyimino]-2-(2-aminothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer)(3.0 g) in formic acid (12 ml) at 10° C. and stirred for 2.5 hours at ambient temperature. The reaction mixture was poured into diisoproply ether (100 ml). The precipitates were collected by filtration, washed with diisopropyl ether and dried to give 7-[2-carboxymethoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylic acid mono-hydrochloride (syn isomer)(1.6 g).
Reaction SMILES: [C:1]1(=[CH:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H]>CCO.[Pd]>[CH:1]1([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: [H][H]
Reactant: COc1ccccc1C=C1CCCC1
Agent: [Pd]
Solvent: CCO
Product: COc1ccccc1CC1CCCC1
Yield: 93.6 %

Procedure:
A mixture of 1-cyclopentylidenemethyl-2-methoxybenzene (408 mmol, 76.7 g) and 10% Pd on carbon (7.67 g, 10% by weight) in absolute EtOH (767 mL) was shaken at room temperature under 54 psig of hydrogen pressure for 2.5 hours. Additional H2 was added to the vessel as necessary to maintain the initial pressure. The volatiles were removed in vacuo and the residue vacuum distilled to afford the title compound as a colorless oil (72.7 g, 94%). The desired fraction comes over at 85°-95° at 2.0-2.5 mm Hg and is used as such in the subsequent transformation.
Reaction SMILES: [N+:1]([C:4]1[C:9]2[N:10]=[C:11]([CH2:13][N:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[O:12][C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[H][H]>CO.[Pd]>[NH2:1][C:4]1[C:9]2[N:10]=[C:11]([CH2:13][N:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[O:12][C:8]=2[CH:7]=[CH:6][CH:5]=1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2nc3c([N+](=O)[O-])cccc3o2)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCN(Cc2nc3c(N)cccc3o2)CC1
Reaction time: 1 h
Yield: 90.6 %

Procedure:
To a solution of tert-butyl 4((4-nitrobenzo[d]oxazol-2-yl)methyl)-piperazine-1-carboxylate (5.97 g, 16.6 mmol, 1.0 equiv) in MeOH (49 mL) was added Pd/C (10% Pd, wet, 2.99 g). The resulting suspension was fixed with a hydrogen balloon and sparged with hydrogen while stirring was maintained. After 1 h, the mixture was filtered through a pad of celite and concentrated in vacuo to provide the title compound as an off-white solid (5.0 g, 91%).
Reaction SMILES: N#N.C[O:4][C:5]([C:7]1[N:8]=[CH:9][O:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][OH:19])[CH:13]=1)=[O:6].[OH-].[Na+].Cl>C1COCC1>[OH:19][CH2:18][C:14]1[CH:13]=[C:12]([C:11]2[O:10][CH:9]=[N:8][C:7]=2[C:5]([OH:6])=[O:4])[CH:17]=[CH:16][CH:15]=1
Reactant: COC(=O)c1ncoc1-c1cccc(CO)c1
Agent: Cl
Agent: N#N
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(O)c1ncoc1-c1cccc(CO)c1
Reaction time: 1.5 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 5-(3-hydroxymethyl-phenyl)-oxazole-4-carboxylic acid methyl ester (265 mg, 1.13 mmol) in THF (11.0 mL) was treated with a 1N NaOH (5.5 mL). The resulting mixture was stirred for 1.5 h then acidified with 1N HCl, extracted twice with EA (2×25 mL) and the combined organic phases were washed with brine (10 mL). The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure to give the title compound as a white solid. LC-MS-conditions 02: tR=0.67 min, [M+AcCN+N+H]+=261.29.
Reaction SMILES: [OH-].[K+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:13]([C:15]2[CH:23]=[C:22]3[C:18]([CH:19]=[CH:20][NH:21]3)=[CH:17][CH:16]=2)=[O:14])[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1.I[CH3:25]>CN(C=O)C.CCOCC>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:13]([C:15]2[CH:23]=[C:22]3[C:18]([CH:19]=[CH:20][N:21]3[CH3:25])=[CH:17][CH:16]=2)=[O:14])[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1
Reactant: COc1cc(OC)cc(C(=O)c2ccc3cc[nH]c3c2)c1
Reactant: CI
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COc1cc(OC)cc(C(=O)c2ccc3ccn(C)c3c2)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 73.1 %

Procedure:
Potassium hydroxide (0.21 g, 3.7 mmol) was added to a mixture of (3,5-dimethoxy-phenyl)-(1H-indol-6-yl)-methanone (0.69 g, 2.5 mmol) in DMF (7 mL) at 0° C. followed by addtion of iodomethane (0.2 mL, 2.7 mmol) and stirred at 0° C. for 2 hours. The mixture was diluted with ether (15 mL) and washed with brine (2×10 mL). The organic phase was dried over MgSO4, concentrated and purified via flash column chromatography (EtOAc/Hexane) to give (3,5-dimethoxy-phenyl)-(1-methyl-1H-indol-6-yl)-methanone as an off-white solid (0.54 g, 75% yield): 1H NMR (DMSO-d6) δ 3.80 (s, 6H, 20CH3), 3.85 (s, 3H, NCH3), 6.55 (d, J=3 Hz, 1H, Ar), 6.78 (t, J=2 Hz, 1H, Ar), 6.83 (d, J=2 Hz, 2H, Ar), 7.47 (d, J=2 Hz, 1H, Ar), 7.61 (d, J=3 Hz, 1H, Ar), 7.68 (d, J=8 Hz, 1H, Ar), 7.90 (brs, 1H, Ar). The product was used in the next step without further purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[CH2:18][C:17]3[CH:19]=[C:20](B4OC(C)(C)C(C)(C)O4)[CH:21]=[CH:22][C:16]=3[O:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][S:40]([CH3:43])(=[O:42])=[O:41])=[CH:35][N:34]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[CH2:18][C:17]3[CH:19]=[C:20]([C:33]4[CH:38]=[CH:37][C:36]([CH2:39][S:40]([CH3:43])(=[O:41])=[O:42])=[CH:35][N:34]=4)[CH:21]=[CH:22][C:16]=3[O:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cc1ccc(Cl)nc1
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(B4OC(C)(C)C(C)(C)O4)ccc3O2)CC1
Product: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(-c4ccc(CS(C)(=O)=O)cn4)ccc3O2)CC1

Procedure:
The title compound is prepared from 4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid tert-butyl ester and 2-chloro-5-methanesulfonylmethyl-pyridine following a procedure analogous to that described in Example 1. LC (method 6): tR=1.17 min; Mass spectrum (ESI+): m/z=473 [M+H]+.
Reaction SMILES: C([O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][C@@H:18]3[F:23])([CH3:16])[CH:14]=[CH:13][CH2:12]4)[C@H:9]([CH3:24])[CH2:8][C:7]=2[CH:6]=1)(=O)C.BrN1C(=[O:31])CCC1=O.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C>CS(C)=O.O.C(OCC)(=O)C>[F:23][C@H:18]1[CH2:17][C@@:15]2([CH3:16])[C@@H:11]([CH2:12][C@H:13]([OH:31])[CH2:14]2)[C@H:10]2[C@H:19]1[C:20]1[CH:21]=[CH:22][C:5]([OH:4])=[CH:6][C:7]=1[CH2:8][C@H:9]2[CH3:24]
Reactant: CC(=O)Oc1ccc2c(c1)C[C@@H](C)[C@@H]1[C@@H]2[C@@H](F)C[C@]2(C)C=CC[C@@H]12
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Solvent: O
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: C[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1C[C@H](O)C[C@@]1(C)C[C@@H]2F
Temperature: 0 °C

Procedure:
A solution of 1.67 g (5.22 mmol) of 3-acetyloxy-11βfluoro-7α-methylestra-1,3,5(10),16-tetraene in 30 ml of DMSO and 2.4 ml of water is replaced in portions with 1.36 g of N-bromosuccinimide while being stirred at 0° C., the cold bath is removed after the addition of NBS is completed, and it is stirred for 45 more minutes at room temperature. For working-up, the reaction mixture is poured into ice water, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The crude bromohydrin (2.3 g) is then taken up in 25 ml of dry tetrahydrofuran, mixed with 5 ml (18.6 mmol) of tributyl tin hydride, a first spatula tip full of AIBN (a total of 200 mg dispersed over the reaction time), and stirred for 10 hours at a bath temperature of 80° C. under an argon atmosphere. For working-up, it is diluted with ethyl acetate, the organic phase is washed with dilute hydrochloric acid and water and dried on sodium sulfate. For saponification, the crude product is dissolved in 50 ml of methanol and 5 ml of dichloromethane, and it is mixed with 2.0 g of potassium carbonate. The reaction mixture is stirred for 1.5 hours under argon and poured into ice water for working-up. It is made hydrochloric with dilute acid, and it is extracted with ethyl acetate. The organic phase is washed with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (chloroform-tert-butylmethylether, gradient of up to 95:5), yield 1.16 g (75%), melting point 239–240° C. while decomposing, [α]D+96.8° (c 0.51 methanol).
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]=[CH:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.C1([Hg][C:22](Br)([Cl:24])[Cl:23])C=CC=CC=1>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH:7]2[CH:8]([C:9]([O:11][CH3:12])=[O:10])[C:22]2([Cl:24])[Cl:23])=[CH:13][CH:14]=1
Reactant: COC(=O)C=COc1ccc(Cl)cc1
Reactant: ClC(Cl)(Br)[Hg]c1ccccc1
Solvent: c1ccccc1
Product: COC(=O)C1C(Oc2ccc(Cl)cc2)C1(Cl)Cl
Reaction time: 4 h

Procedure:
A mixture of methyl 3-(4-chlorophenoxy)-2-propenoate (30 mmol), phenyl(bromodichloromethyl)mercury (30 mmol) and 50 ml benzene are heated under reflux, with stirring, for 4 hr, followed by TLC of the product. The mixture is then filtered and the solvent removed, giving methyl 3-(4-chlorophenoxy)-2,2-dichlorocyclopropanecarboxylate, which is then hydrolyzed and reacted with m-phenoxybenzyl bromide to give m-phenoxybenzyl 3-(4-chlorophenoxy)-2,2-dichlorocyclopropanecarboxylate.
Reaction SMILES: C1(O)C=CC=CC=1.B(F)(F)F.[CH2:12]1[CH:16]2[CH:17]3[CH:21]=[CH:20][CH:19]([CH:15]2[CH:14]=[CH:13]1)[CH2:18]3.C=CC(=C)C.C1CC=CC=1>C(Cl)(Cl)(Cl)Cl>[CH2:12]1[CH:16]2[C@@H:17]3[CH:21]=[CH:20][C@H:19]([CH:15]2[CH:14]=[CH:13]1)[CH2:18]3
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: C1=CCC=C1
Agent: FB(F)F
Solvent: C=CC(=C)C
Solvent: ClC(Cl)(Cl)Cl
Solvent: Oc1ccccc1
Product: C1=CC2C(C1)[C@@H]1C=C[C@H]2C1
Temperature: 55 °C

Procedure:
To a reactor equipped as in Example 1-A were added 2823 gms (30 moles) of phenol and 16.1 gms of BF3 etherate in 20 gms of carbon tetrachloride. The mass was heated to 55° C. and 1201.2 gms (9.09 moles) of a 99.9% reactive C10 hydrocarbon stream consisting mainly of dicyclopentadiene and cyclopentadiene isoprene codimers was added over a 4 hour (14400 s) period. The temperature of the reaction mass was 80° C. after the hydrocarbon addition period. The reactor was heated to 150° C. over a 7 hour (25200 s) period and a vacuum distillation begun. The reaction was finished at 245° C. and 1 mm Hg. The resin had an equivalent weight of 187, a melt point of 115° C. and an average functionality of 2.95.
Reaction SMILES: F[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15]([C:19]([OH:21])=[O:20])=[CH:14][CH:13]=[CH:12]3)[CH:5]=[CH:4][N:3]=1.[NH4+:22].[OH-]>>[NH2:22][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15]([C:19]([OH:21])=[O:20])=[CH:14][CH:13]=[CH:12]3)[CH:5]=[CH:4][N:3]=1
Reactant: O=C(O)c1cccc2cc(Oc3ccnc(F)n3)ccc12
Reactant: [NH4+]
Agent: [OH-]
Product: Nc1nccc(Oc2ccc3c(C(=O)O)cccc3c2)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
6-(2-Fluoropyrimidin-4-yloxy)-1-naphthoic acid (1.2 g, 4.2 mmol) was dissolved in NH4OH (37% water, 20 mL) and stirred at RT for 3 h. Solvent was evaporated. A little bit of MeOH was added to the slurry followed by ether until the compound crashed out. Solid was filtered.
Reaction SMILES: [N+:1]([C:4]1[CH:26]=[CH:25][C:7]([C:8]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[O:9])=[CH:6][CH:5]=1)([O-])=O.C(OCC)(=O)C>[Pt].ClCCl>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[O:9])=[CH:25][CH:26]=1
Reactant: CCCCCCCCCCCCCCOC(=O)c1ccc([N+](=O)[O-])cc1
Agent: [Pt]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCCCOC(=O)c1ccc(N)cc1
Yield: 65.2 %

Procedure:
Under a nitrogen purge, 10% platinum on carbon (2.5 grams) was added to a mixture of tetradecyl 4-nitrobenzoate (25 grams, 69 mmol) and ethyl acetate (250 milliliters) in a Parr vessel. The vessel was placed under hydrogen pressure (49 psi, 3.3×105 Pa) for sixteen hours. Dichloromethane was added and the reaction mixture was filtered through a layer of CELITE filter aid. The filtrate was concentrated under reduced pressure to a tan solid. The solid was recrystallized from ethanol to obtain 15 grams of tetradecyl 4-aminobenzoate as light tan needles.
Reaction SMILES: [CH2:1](C(O)(CCCCCCC)CC)C.[CH2:14]([C:16]([OH:28])([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:17][CH3:18])C>>[CH3:14][C:16]([OH:28])([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:17][CH2:18][CH3:1]
Reactant: CCCCCCCC(O)(CC)CC
Reactant: CCCCCCCCCC(O)(CC)CC
Product: CCCCCCCCCC(C)(O)CCC

Procedure:
3-ethyl-3-decanol; 3-ethyl-3-dodecanol;
Reaction SMILES: Cl[C:2]1[C:3]([F:22])=[CH:4][C:5]2[C:6]([CH:21]=1)=[N:7][C:8]1[N:9]([CH2:19][CH3:20])[CH:10]=[C:11]([C:16]([OH:18])=[O:17])[C:12](=[O:15])[C:13]=1[CH:14]=2.[OH:23][CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>N1C=CC=CC=1>[CH2:19]([N:9]1[C:8]2[N:7]=[C:6]3[CH:21]=[C:2]([N:29]4[CH2:30][CH2:31][N:26]([CH2:25][CH2:24][OH:23])[CH2:27][CH2:28]4)[C:3]([F:22])=[CH:4][C:5]3=[CH:14][C:13]=2[C:12](=[O:15])[C:11]([C:16]([OH:18])=[O:17])=[CH:10]1)[CH3:20]
Reactant: OCCN1CCNCC1
Reactant: CCn1cc(C(=O)O)c(=O)c2cc3cc(F)c(Cl)cc3nc21
Solvent: c1ccncc1
Product: CCn1cc(C(=O)O)c(=O)c2cc3cc(F)c(N4CCN(CCO)CC4)cc3nc21
Yield: 62.9 %

Procedure:
1-Ethyl-7-fluoro-8-[4-(2-hydroxyethyl)-1-piperazinyl]-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic acid is prepared under the conditions of Reference Example 5 but starting from 1.6 g of 8-chloro-1-ethyl-7-fluoro-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic acid and 2.6 g of 1-(2-hydroxyethyl)-piperazine in 16 cm3 of pyridine. 1.3 g of 1-ethyl-7-fluoro-8-[4-(2-hydroxyethyl)-1-piperazinyl]-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine-3-carboxylic acid are obtained in the form of a yellow solid melting at 264°-265° C.
Reaction SMILES: [CH:1]1[CH:10]=[C:9]2[C:11]([O:13][C:14](=O)[C:7]3=[C:8]2[C:3](=[C:4]([Br:16])[CH:5]=[CH:6]3)[CH:2]=1)=[O:12].Cl.[NH2:18][OH:19]>N1C=CC=CC=1>[Br:16][C:4]1[CH:5]=[CH:6][C:7]2[C:14](=[O:13])[N:18]([OH:19])[C:11](=[O:12])[C:9]3[C:8]=2[C:3]=1[CH:2]=[CH:1][CH:10]=3
Reactant: O=C1OC(=O)c2ccc(Br)c3cccc1c23
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: O=C1c2cccc3c(Br)ccc(c23)C(=O)N1O
Yield: 82.6 %

Procedure:
4-Bromo-1,8-naphthalic anhydride (1.6 g, 5.8 mmol) and hydroxylamine hydrochloride (0.8 g, 11.5 mmol) were reacted in pyridine (30 mL) following the procedure of Example 1 to give 1.4 g of the title compound , mp 248-251° C.;
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[S:8][C:9]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:11]=1.N1C=CC=CC=1>ClCCl>[CH3:1][S:2]([NH:6][C:7]1[S:8][C:9]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:11]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1nc(-c2ccccc2)c(-c2ccccc2)s1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1nc(-c2ccccc2)c(-c2ccccc2)s1
Temperature: 25 °C
Yield: 24.4 %

Procedure:
2.5 g of methanesulfonyl chloride was dropped into a solution of 5.0 g of 2-amino-4,5-diphenylthiazole and 3.3 ml of pyridine in dichloromethane under stirring at room temperature, and the resulting mixture was stirred as such overnight. Then the reaction mixture was successively washed with diluted hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and water in this order and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the reaction product was separated with a silica gel column by using isopropyl ether and ethyl acetate as a developer. The crystals thus obtained were recovered by filtration from isopropyl ether and washed with diethyl ether to give 1.6 g of 2-methanesulfonylamino-4,5-diphenylthiazole. The melting point of this product was from 225° to 227° C.
Reaction SMILES: [CH3:1][C:2]([CH3:14])([O:4][C:5]([N:7]1[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]1)=[O:6])[CH3:3].[CH2:15]([NH2:19])[CH2:16][CH2:17][CH3:18].C([BH3-])#N.[Na+].Cl>CO.C(O)(=O)C>[CH3:1][C:2]([CH3:14])([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([NH:19][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:9][CH2:8]1)=[O:6])[CH3:3]
Reactant: CCCCN
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CCCCNC1CCN(C(=O)OC(C)(C)C)CC1

Procedure:
A mixture of 1-(1,1-dimethylethoxycarbonyl)-4-piperidone (IX, 1.50 g) in methanol (15 ml) under nitrogen is cooled in an ice bath, treated with butylamine (X, 0.93 ml) and sodium cyanoborohydride (235 mg), adjusted to pH 5 with glacial acetic acid as determined on moistened pH test paper, and stirred at 20°-25° for 24 hrs during which additional sodium cyanoborohydride (115 mg) is added. The mixture is then adjusted to pH 3 using hydrochloric acid (3M) and concentrated under reduced pressure, the residue is diluted with water (20 ml) and extracted with ether (2×20 ml), and the organic phase is discarded. The aqueous phase is adjusted to pH 12 with potassium hydroxide, saturated with sodium chloride, and extracted with methylene chloride (3×25 ml). The combined organic phase is dried over sodium sulfate and concentrated under reduced pressure to give the title compound, Anal. Calcd for C14H28N2O2 : C=65.59, H=11.01, N=10.93, found: C=65.44, H=11.05, N=10.81.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[O:9][C:8]([CH2:10][OH:11])=[CH:7][CH:6]=1)[CH3:3].[Cl:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[S:20]([NH:23][C:24]1[C:29](Cl)=[N:28][C:27]([Cl:31])=[CH:26][N:25]=1)(=[O:22])=[O:21]>>[Cl:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[S:20]([NH:23][C:24]1[C:29]([O:11][CH2:10][C:8]2[O:9][C:5]([CH2:4][N:2]([CH3:1])[CH3:3])=[CH:6][CH:7]=2)=[N:28][C:27]([Cl:31])=[CH:26][N:25]=1)(=[O:22])=[O:21]
Reactant: O=S(=O)(Nc1ncc(Cl)nc1Cl)c1cccc(Cl)c1Cl
Reactant: CN(C)Cc1ccc(CO)o1
Product: CN(C)Cc1ccc(COc2nc(Cl)cnc2NS(=O)(=O)c2cccc(Cl)c2Cl)o1

Procedure:
Prepared by the method of Example 31 using (5-dimethylaminomethyl-2-furanyl)methanol (0.3 g) and 2,3-dichloro-N-(3,5-dichloro-2-pyrazinyl)benzenesulphonamide (Example 74) (0.4 g). Purified by silica gel chromatography eluting with methanol/dichloromethane mixtures. Yield 0.30 g.
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([C:11]([F:14])([F:13])[F:12])([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:19])([F:18])[F:17])[S:3]1.C(N(CC)CC)C.[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=[O:34]>C1(C)C=CC=CC=1>[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33]([NH:1][C:2]1[S:3][C:4](=[C:15]([F:20])[C:16]([F:17])([F:18])[F:19])[C:5]([C:7]([F:10])([F:9])[F:8])([C:11]([F:12])([F:13])[F:14])[N:6]=1)=[O:34]
Reactant: N=C1NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Reactant: COc1cccc(C(=O)Cl)c1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cccc(C(=O)NC2=NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S2)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
In toluene (10 ml) were dissolved 2-imino-4,4-bis(trifluoromethyl)-5-(tetrafluoroethylidene)-1,3-thiazolidine (1.0 g) and triethylamine (0.4 ml), and 3-methoxybenzoyl chloride (0.7 g) was gradually added thereto and the mixture was stirred at room temperature for 3 hours.