Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[O:11])[N:5]=[CH:4][C:3]=1[NH:20][CH:21]1[CH:28]2[CH2:29][CH:24]3[CH2:25][C:26]([O:31]COC)([CH2:30][CH:22]1[CH2:23]3)[CH2:27]2.[ClH:35].CO>>[ClH:35].[Br:1][C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[O:11])[N:5]=[CH:4][C:3]=1[NH:20][CH:21]1[CH:22]2[CH2:23][CH:24]3[CH2:25][C:26]([OH:31])([CH2:27][CH:28]1[CH2:29]3)[CH2:30]2
Reactant: COCOC12CC3CC(C1)C(Nc1cnn(CC(=O)NCc4ccncc4)c(=O)c1Br)C(C3)C2
Agent: Cl
Solvent: CO
Product: O=C(Cn1ncc(NC2C3CC4CC2CC(O)(C4)C3)c(Br)c1=O)NCc1ccncc1
Yield: 51 %

Procedure:
2-[5-Bromo-4-{[5-(methoxymethoxy)tricyclo[3.3.1.13,7]dec-2-yl]amino}-6-oxopyridazin-1(6H)-yl]-N-(pyridin-4-ylmethyl)acetamide (30 mg, 0.0563 mmol) in 10 mass % hydrogen chloride-methanol (3 mL) was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was evaporated under reduced pressure, and the resulting solid was collected by filtration and dried to give the desired product (51% yield).
Reaction SMILES: II.Br[CH2:4][CH2:5][CH:6]=[CH2:7].[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:10]=1/[CH:19]=[N:20]/[S:21]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:22]>C1COCC1>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:10]=1[C@@H:19]([NH:20][S:21]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:22])[CH2:7][CH2:6][CH:5]=[CH2:4]
Reactant: CC(C)(C)S(=O)/N=C/c1cc(C(F)(F)F)ccc1Br
Reactant: C=CCCBr
Agent: II
Solvent: C1CCOC1
Product: C=CCC[C@H](NS(=O)C(C)(C)C)c1cc(C(F)(F)F)ccc1Br
Temperature: 40 °C
Yield: 64.9 %

Procedure:
To a 100 mL three-neck RBF equipped with stir bar and condenser was added Mg (excess), catalytic iodine, THF (20 mL), followed by 4-bromobut-1-ene (4.55 g, 33.7 mmol) in small increments. The mixture was heated to 40° C. for 1 hour. The reaction was cooled to room temperature and the freshly made Grignard reagent was added via syringe into a 250 mL RBF with N-{(E)-[2-bromo-5-(trifluoromethyl)phenyl]methylidene}-2-methylpropane-2-sulfinamide (8.0 g, 22.5 mmol) in THF (100 mL). Upon completion, the reaction was quenched with saturated aqueous NH4Cl and partitioned with ethyl acetate. The organic was dried over sodium sulfate, filtered, concentrated and purified by column chromatography to yield N-{(1S)-1-[2-bromo-5-(trifluoromethyl)phenyl]pent-4-en-1-yl}-2-methylpropane-2-sulfinamide (6.0 g, 14.6 mmol). 1H NMR (500 MHz, CDCl3) δ7.72 (m, 2H), 7.42 (d, J=8.2 Hz, 1H), 5.87 (m, 1H), 5.13 (m, 2H), 5.02 (m, 1H), 2.24 (m, 1H), 2.18 (m, 1H), 2.08 (m, 1H), 1.98 (m, 1H), 1.27 (s, 9H).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([OH:15])([CH3:14])[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C=O)C>[CH2:20]([O:15][C:3]([CH3:14])([C:2]([F:16])([F:17])[F:1])[C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:5])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC(O)(C(=O)OCc1ccccc1)C(F)(F)F
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(OCc1ccccc1)(C(=O)OCc1ccccc1)C(F)(F)F
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A cooled (0° C.) solution of benzyl 3,3,3-trifluoro-2-hydroxy-2-methylpropanoate (Int. D1) (100 mg, 0.403 mmol) in DMF (4 ml) was treated with sodium hydride (16.11 mg, 0.403 mmol) followed by benzyl bromide (0.048 ml, 0.403 mmol) and stirred at 0° C. for 2 h. The reaction mixture was allowed to warm to room temperature and stirring continued for a further 3 hrs. The reaction mixture was partitioned between EtOAc and 0.1M HCl solution. The organic phase was washed with saturated brine, dried over magnesium sulfate and concentrated in vacuo to afford the title compound as an oil.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[C:6]([C:9]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:10]=1[N:11]([CH3:14])[CH:12]=[O:13])(=[O:8])[CH3:7].O>ClCCl>[Cl:4][CH2:7][C:6]([C:9]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:10]=1[N:11]([CH3:14])[CH:12]=[O:13])=[O:8]
Reactant: CC(=O)c1cc(F)ccc1N(C)C=O
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: CN(C=O)c1ccc(F)cc1C(=O)CCl
Reaction time: 8 h

Procedure:
A solution of sulphuryl chloride (3.2 ml) in dichloromethane (20 ml) was added dropwise over a period of 10 minutes to the solution of 2'-acetyl-4'-fluoro-N-methylformanilide at 0° under a nitrogen atmosphere and the mixture stored overnight at 0 to 5°. Water (25 ml) was added whilst maintaining the temperature below 1 0°. The dichloromethane layer was separated, washed with water (1 25 ml) and dried over magnesium sulphate to give a solution of 2'-(2-chloroacetyl)-4'-fluoro-N-methylformanilide.
Reaction SMILES: C([O:3][C:4](=O)[C:5]([F:27])([F:26])[C@@:6]([C:18]1[C:23]([F:24])=[CH:22][CH:21]=[C:20]([Br:25])[N:19]=1)([NH:11][S@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH2:7][CH2:8][O:9][CH3:10])C.[BH4-].[Li+]>C1COCC1.C(OCC)(=O)C>[Br:25][C:20]1[N:19]=[C:18]([C@:6]([NH:11][S@:12]([C:14]([CH3:16])([CH3:15])[CH3:17])=[O:13])([CH2:7][CH2:8][O:9][CH3:10])[C:5]([F:27])([F:26])[CH2:4][OH:3])[C:23]([F:24])=[CH:22][CH:21]=1
Reactant: CCOC(=O)C(F)(F)[C@](CCOC)(N[S@@](=O)C(C)(C)C)c1nc(Br)ccc1F
Agent: [BH4-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COCC[C@@](N[S@@](=O)C(C)(C)C)(c1nc(Br)ccc1F)C(F)(F)CO
Temperature: 25 °C
Reaction time: 6 h
Yield: 68.4 %

Procedure:
To a solution of (R)-3-(6-bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-5-methoxy-3-((S)-2-methyl-propane-2-sulfinylamino)-pentanoic acid ethyl ester (2.4 g, 4.90 mmol) in THF (38 ml) was added lithiumborohydride (214 mg, 9.81 mmol) in 2 portions. The slightly exothermic reaction was stirred for 6 hours at room temperature. Crushed ice was added carefully and the reaction mixture was diluted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The crude yellowish resin (2.05 g) was chromatographed over silica gel (Redisep column 40 g, cyclohexane/ethyl acetate 4:6) to give the title compound as a colourless resin. 1.50 g (68.4% yield).
Reaction SMILES: [Br:1][C:2]1[O:6][CH:5]=[C:4]([C:7]([OH:9])=O)[CH:3]=1.O.O[N:12]1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.N>CN(C=O)C>[Br:1][C:2]1[O:6][CH:5]=[C:4]([C:7]([NH2:12])=[O:9])[CH:3]=1
Reactant: On1nnc2ccccc21
Reactant: O=C(O)c1coc(Br)c1
Agent: CCN=C=NCCCN(C)C
Agent: N
Solvent: O
Solvent: CN(C)C=O
Product: NC(=O)c1coc(Br)c1
Temperature: 0 °C
Reaction time: 5 h
Yield: 78.9 %

Procedure:
A solution of 5-bromo-furan-3-carboxylic acid (0.364 g, 1.92 mmol), 3-hydroxybenzotriazole hydrate (0.28 g, 2.11 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (0.40 g, 2.11 mmol) in DMF (11 mL) is stirred at room temperature for 2 hours. The reaction mixture is then cooled to 0° C. and aq. NH3 (0.22 mL) is added. The mixture is stirred at room temperature for an additional 5 hours, then the solvent is removed in vacuo and the residue dissolved in EtOAc, washed with 1N NaOH, and 1N HCl. The organic layers are combined, dried over MgSO4 and concentrated to afford the title compound (0.288 g, 79%). HPLC (254 nm): Rt 2.17 min (85.3%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1.CN(C=O)C>O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:20][C:21]1[CH:22]=[CH:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=1)[CH:6]=[CH:5]2
Reactant: CS(=O)(=O)c1ccc(CCl)cc1
Reactant: O=c1[nH]ccc2cc(Br)ccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccc(Cn2ccc3cc(Br)ccc3c2=O)cc1
Temperature: 50 °C
Yield: 38.1 %

Procedure:
A mixture of intermediate 1 (3.0 g), potassium carbonate (3.70 g), 1-(chloromethyl)-4-(methylsulfonyl)benzene (2.74 g) and DMF (20 mL) was heated at 50° C. for 24 hours. The mixture was allowed to cool then poured into water (50 mL) and extracted with dichloromethane (100 mL). The extracts were combined, evaporated under reduced pressure and the residue purified (SiO2 chromatography, eluting with 2% methanol in dichloromethane) to give the sub-titled compound (2.0 g).
Reaction SMILES: I[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[O:10]=[C:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:12]1.C(OCC)(=O)C>C1COCC1>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([C:11]2([OH:10])[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:13][CH2:12]2)=[CH:3][CH:4]=1)#[N:7]
Reactant: CC(C)(C)OC(=O)N1CCCC(=O)CC1
Reactant: N#Cc1ccc(I)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCC(O)(c2ccc(C#N)cc2)CC1
Temperature: -40 °C
Reaction time: 2 h

Procedure:
A solution of 4-iodobenzonitrile (510 mg, 2.22 mmol, 1.1 equiv) in THF (3 mL) was added to a 10 mL round-bottom flask and the system purged with nitrogen. The mixture was cooled to −40° C. then isopropylmagnesium chloride (1.16 mL of a 2.0 M soln in THF, 2.32 mmol, 1.15 equiv) was added dropwise over 20 minutes. The resulting mixture was stirred at −40° C. for 2 hours then tert-butyl 4-oxoazepane-1-carboxylate (431 mg, 2.02 mmol, 1.0 equiv) in THF (0.5 mL) was added dropwise over 15 minutes. The resulting mixture was stirred at −40° C. for 1 hour then diluted into ethyl acetate (15 mL) and washed with 0.2 M HCl (10 mL), 0.1 M HCl (5 mL), saturated sodium bicarbonate (5 mL) then brine (5 mL). The organics were dried (Na2SO4), filtered and evaporated. To remove remaining ketone and aldol by-product, the residue was dissolved in acetonitrile (3 mL) then hydrazine (0.2 mL) was added and heated at 60° C. for 4 hours. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL), followed by 0.5 M phosphoric acid (3×20 mL), saturated sodium bicarbonate (10 mL) and brine (10 mL). The organics were dried (Na2SO4), filtered and evaporated. The residue was purified by silica column chromatography (hexanes/ethyl acetate) to obtain the title compound as a pink oil which solidified upon standing (303 mg, 47%). m/z (ES+) 317 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[N:12][CH:13]=2)=[CH:4][CH:3]=1.C(OO)(=[O:21])C.Cl>O.[OH-].[Na+]>[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]2[CH:13]=[N+:12]([O-:21])[C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: CC(=O)OO
Reactant: O=C(O)c1ccc(NCc2ccc(F)cc2)cn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)c1ccc(NCc2ccc(F)cc2)c[n+]1[O-]
Temperature: 25 °C

Procedure:
5.77 g of 5-(p-fluorobenzylamino)-pyridine-2-carboxylic acid are dissolved in 40 ml of water and 20 ml of 2 N aqueous sodium hydroxide. The solution is stirred at room temperature and 3.6 g of 40% aqueous peracetic acid are added. The solution becomes green and within less than a minute a solid separates. Another 3.6 g of said peracetic acid are added and the mixture is stirred for 4 hours. The pH of the mixture is adjusted to 4 with hydrochloric acid and filtered after cooling. The solid is collected and recrystallized from 90% aqueous acetonitrile, to yield the 5-(p-fluorobenzylamino)-pyridine-2-carboxylic acid N-oxide melting at 206°-209°.
Reaction SMILES: [CH2:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[O:6][C:5](=[O:16])[NH:4]1)[CH3:2].[Cl:17][C:18]1[CH:23]=[C:22](Cl)[N:21]=[C:20]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:19]=1>CN(C=O)C>[Cl:17][C:18]1[N:19]=[C:20]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:21]=[C:22]([N:4]2[C@@H:3]([CH2:1][CH3:2])[C@H:7]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=3)[O:6][C:5]2=[O:16])[CH:23]=1
Reactant: CC[C@H]1NC(=O)O[C@@H]1c1ccc(OC)cc1
Reactant: Clc1cc(Cl)nc(N2CCOCC2)n1
Solvent: CN(C)C=O
Product: CC[C@H]1[C@H](c2ccc(OC)cc2)OC(=O)N1c1cc(Cl)nc(N2CCOCC2)n1
Temperature: 85 °C
Reaction time: 0.33 h
Yield: 91 %

Procedure:
To a solution of (4R*,5R*)-4-ethyl-5-(4-methoxyphenyl)oxazolidin-2-one (217 mg, 0.98 mmol) in DMF (2 mL) was added at room temperature under argon NaH (51.4 mg, 1.18 mmol). After 20 minutes, a suspension of 4-(4,6-dichloropyrimidin-2-yl)morpholine (230 mg, 0.98 mmol in DMF (1 mL) was added, and the reaction mixture was stirred at 85° C. for 20 minutes. The solution was quenched at 0° C. with aqueous NH4Cl, extracted with ethyl acetate, and the organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography using EtOAc in hexane from 0% to 20% in order to give the title compound as a white solid (375 mg, 91%). LC-MS: [M+H] 419.1; Rt 1.26 min; (LCMS method 1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:6]([NH:8][CH2:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[C:13]([OH:15])=O)=[O:7].[N:24]1([CH:30]2[CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[C:35]([NH2:39])[CH:36]=3)[CH2:31]2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CN(C=O)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:6]([NH:8][CH2:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:12]([C:13](=[O:15])[NH:39][C:35]2[CH:36]=[C:37]3[C:32](=[CH:33][CH:34]=2)[CH2:31][CH:30]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[CH2:38]3)[CH:11]=1)=[O:7]
Reactant: COc1ccc(C(=O)NCc2cccc(C(=O)O)c2)cc1OC
Reactant: Nc1ccc2c(c1)CC(N1CCOCC1)C2
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)NCc2cccc(C(=O)Nc3ccc4c(c3)CC(N3CCOCC3)C4)c2)cc1OC
Temperature: 25 °C
Reaction time: 20 h
Yield: 62.4 %

Procedure:
To a suspension of the 3-[(3,4-dimethoxy-benzoylamino)-methyl]-benzoic acid (100 mg, 0.32 mmol) and 2-morpholin-4-yl-indan-5-ylamine (84 mg, 0.38 mmol) 1.5 mL of DMF. To this was added TBTU (122 mg, 0.38 mmol), and the vial warmed until a clear solution was obtained. The solution was stirred at room temperature. Stirring continued for 20 h total. Diluted with EtOAc and washed with Na2CO3, water and brine. The organic layer was dried over MgSO4, evaporated and purified by column chromatography, CH2Cl2/MeOH gradient 1-10%, to give 103 mg of 3,4-dimethoxy-N-[3-(2-morpholin-4-yl-indan-5-ylcarbamoyl)-benzyl]-benzamide. MS, electrospray, 516, (M+H).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[C:12]([NH:19][C@H:20]([CH:28]=[CH2:29])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>C(Cl)Cl>[C:12]([NH:19][C@H:20]([C@@H:28]1[CH2:29][O:9]1)[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H]1CO1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 9.74 g of m-chloroperbenzoic acid in 50 ml of methylene chloride is added over the course of 15 min at from 0° to 5° C. to a solution of 1.45 g of N-Boc-1-phenyl-3-buten-2(S)-amine in 20 ml of methylene chloride. The batch is stirred for 18 h at that same temperature and is then stirred for a further 8 h, with heating to RT, to complete the reaction and poured onto ice-cold 10% sodium carbonate solution. The aqueous phase is extracted three times with ether. The combined organic phases are washed in succession three times with 10% sodium sulfite solution, three times with saturated sodium hydrogen carbonate solution, with sodium thiosulfate solution and with brine and dried over sodium sulfate. After concentrating the solvents, the title compound is purified by column chromatography (SiO2, hexane/ethyl acetate: 4/1) and recrystallised from hexane. M.p. 51°-52° C.; TLC Rf (C)=0.33; FAB-MS (M+H)+=264.
Reaction SMILES: Cl.[CH3:2][C@@H:3]1[NH:8][CH2:7][C@@H:6]([OH:9])[CH2:5][CH2:4]1.C(N(CC)CC)C.[C:17](Cl)([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>C(Cl)Cl>[OH:9][C@@H:6]1[CH2:7][N:8]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C@@H:3]([CH3:2])[CH2:4][CH2:5]1
Reactant: C[C@H]1CC[C@H](O)CN1
Reactant: O=C(Cl)OCc1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@H]1CC[C@H](O)CN1C(=O)OCc1ccccc1
Temperature: 0 °C

Procedure:
A mixture of ±trans-6-methylpiperidin-3-ol hydrochloride (14.0 g, 0.092 mol) in CH2Cl2 (150 mL) was cooled to 0° C. Triethylamine (51.5 mL, 0.369 mol) was added slowly. CbzCl (13.59 mL, 0.092 mol) was added dropwise, keeping the temperature below 20° C. The reaction was allowed to warm overnight to room temperature. The reaction was quenched by addition of water and diluted further with additional CH2Cl2. The layers were separated and the organics were dried over MgSO4 and concentrated. The crude material was purified by silica gel gradient chromatography (0-75% ethyl acetate in hexanes), providing ±Benzyl trans-5-hydroxy-2-methylpiperidine-1-carboxylate.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH:11]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=3)[O:10][C:9]2=[O:24])=[CH:4][CH:3]=1.NC1C=CC(N2[CH2:36][CH:35](COC3C=CC(C(OC)=O)=CC=3)[O:34]C2=O)=CC=1>>[C:35]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH:11]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=3)[O:10][C:9]2=[O:24])=[CH:4][CH:3]=1)(=[O:34])[CH3:36]
Reactant: COC(=O)c1ccc(OCC2CN(c3ccc(N)cc3)C(=O)O2)cc1
Reactant: Nc1ccc(N2CC(COc3ccc(C(=O)O)cc3)OC2=O)cc1
Product: CC(=O)Nc1ccc(N2CC(COc3ccc(C(=O)O)cc3)OC2=O)cc1
Yield: 88 %

Procedure:
The same procedure of Example 10 was repeated except that 4-[3-(4-aminophenyl)-2-oxooxazolidin-5-yl]methoxy benzoic acid (compound 114) obtained Example 11 was used in lieu of methyl 4-[3-(4-aminophenyl)-2-oxooxazolidin-5-yl]methoxybenzoate to give the title compound (compound 115) in a yield of 88%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH2:9][CH:10]1[O:12][CH2:11]1.[NH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([NH2:23])=[O:22])=[CH:19][N:18]=1>C(O)(C)C>[C:21]([C:20]1[CH:24]=[CH:25][C:17]([O:16][CH2:15][CH2:14][NH:13][CH2:11][CH:10]([OH:12])[CH2:9][O:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[N:18][CH:19]=1)(=[O:22])[NH2:23]
Reactant: NCCOc1ccc(C(N)=O)cn1
Reactant: Clc1ccccc1OCC1CO1
Solvent: CC(C)O
Product: NC(=O)c1ccc(OCCNCC(O)COc2ccccc2Cl)nc1

Procedure:
9.2 g of 3-(2-chloro-phenyloxy)-1,2-epoxy-propane are added to a solution of 9.0 g of 6-(2-aminoethoxy)-nicotinic acid amide in 200 ml of isopropanol and the mixture is heated under reflux for 4 hours. After evaporating off the solvent under reduced pressure, 1-[2-(5-carbamoyl-2-pyridyloxy)ethyl-amino]-3-(2-chloro-phenoxy)-2-propanol is obtained; its hydrochloride melts at 202°-204° C. after recrystallisation from methanol.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[O:12])=[CH:9][CH:8]=1)[CH2:5][CH3:6].[C:15](OC(=O)C)(=[O:17])[CH3:16].C(N(CC)CC)C>ClCCl>[C:15]([O:1][CH2:2][CH2:3][N:4]([C:7]1[CH:8]=[CH:9][C:10]([CH:11]=[O:12])=[CH:13][CH:14]=1)[CH2:5][CH3:6])(=[O:17])[CH3:16]
Reactant: CCN(CCO)c1ccc(C=O)cc1
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCN(CCOC(C)=O)c1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred solution of 193.2 g (1 mole) of 4-(N-2-hydroxyethyl-N-ethylamino)benzaldehyde in dichloromethane are added 153.1 g (1.5 moles) of acetic anhydride, 151.8 g (1.5 moles) of triethylamine, and 8.5 g (7 mole %) of 4-N,N-dimethylaminopyridine. The reaction mixture is stirred at room temperature for 16 hours. The product solution then is washed with cold 2N HCl followed by saturated sodium bicarbonate, and the organic layer is filtered through cotton, and evaporated to dryness.
Reaction SMILES: Cl[C:2]1[C:3](=[O:15])[N:4]([CH:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Cl:8])[N:7]=1.[Br:16][C:17]1[CH:23]=[C:22]([CH3:24])[C:20]([NH2:21])=[C:19]([CH3:25])[CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(OCC)(=O)C>C1COCC1>[Br:16][C:17]1[CH:23]=[C:22]([CH3:24])[C:20]([NH:21][C:2]2[C:3](=[O:15])[N:4]([CH:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Cl:8])[N:7]=2)=[C:19]([CH3:25])[CH:18]=1
Reactant: Cc1cc(Br)cc(C)c1N
Reactant: CCC(COC)n1cc(Cl)nc(Cl)c1=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCC(COC)n1cc(Cl)nc(Nc2c(C)cc(Br)cc2C)c1=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 84.9 %

Procedure:
To (+/−)-3,5-dichloro-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone (300 mg) and 4-bromo-2,6-dimethylaniline (238 mg) in THF (anhydrous, 9.4 mL) at 0° C. was added sodium bis(trimethylsilyl)amide (1.0 M/THF, 2.6 mL). The mixture was stirred at 0° C. for 10 minutes. Ethyl acetate (100 mL) was added and washed with water (25 mL) and brine (25 mL). The organic layer was dried over MgSO4 and concentrated and the crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent. The product was then crystallized from ethyl acetate/hexane to afford the title compound (419 mg). Elemental analysis calcd. for C17H21N3O2BrCl: C, 49.23; H, 5.10; N, 10.13. Found: C, 49.33; H, 5.05; N, 10.09.
Reaction SMILES: [O:1]=[CH:2][C:3]#[C:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1.[N-:13]=[N+:14]=[N-:15].[Na+]>CS(C)=O>[CH:2]([C:3]1[C:4]([C:5]2[CH:6]=[CH:7][C:8]([C:9]#[N:10])=[CH:11][CH:12]=2)=[N:13][NH:14][N:15]=1)=[O:1]
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1ccc(C#CC=O)cc1
Agent: [Na+]
Solvent: CS(C)=O
Product: N#Cc1ccc(-c2n[nH]nc2C=O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 20.4 %

Procedure:
To a solution of 4-(3-oxoprop-1-ynyl)benzonitrile (500 mg, 3.22 mmol, 1.00 equiv) in DMSO (15 mL) was added NaN3 (314 mg, 4.83 mmol, 1.50 equiv) in portions. The resulting solution was stirred at room temperature for 1 h and then quenched by the addition of 1 mL of water. The resulting mixture was concentrated under vacuum and the residue was purified on a C18 flash column eluted with 0-15% of acetonitrile in water to give 130 mg (20%) of 4-(5-formyl-2H-1,2,3-triazol-4-yl)benzonitrile as a light yellow solid. LCMS (method C, ESI), RT=0.93 min, m/z=199.0 [M+1]+
Reaction SMILES: [CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH2:5].N1C=CC=CC=1.[CH3:13][C:14]([CH2:18][CH2:19][CH:20]=[C:21]([CH3:33])[CH2:22][CH2:23][CH:24]=[C:25]([CH3:32])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30])=[CH:15][CH2:16]Br>O1CCOCC1>[CH3:13][C:14]([CH2:18][CH2:19][CH:20]=[C:21]([CH3:33])[CH2:22][CH2:23][CH:24]=[C:25]([CH3:32])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30])=[CH:15][CH2:16][NH:5][CH2:4][CH2:3][N:2]([CH3:6])[CH3:1]
Reactant: CN(C)CCN
Reactant: CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCBr
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCNCCN(C)C
Temperature: 0 °C
Yield: 33.4 %

Procedure:
4.4 g of N,N-dimethylethylenediamine was dissolved in 40 ml of dioxane. 5 ml of pyridine was added to the solution. 17.6 g of 3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl bromide was added thereto and the mixture was heated under reflux for 2 h and poured in ice-water. After extraction with n-hexane followed by washing with water and concentration, the resulting reaction mixture was treated by alumina column chromatography to obtain 6 g (33%) of the title compound as a colorless oil.