Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][N:10]=[CH:11][CH:12]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:13][CH:14]([OH:16])[CH3:15].[CH3:24][S:25](Cl)(=[O:27])=[O:26].C(OCC)(=O)C>O1CCCC1.O>[CH3:24][S:25]([O:16][CH:14]([CH2:13][CH:12]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:11]=[N:10][O:9][CH3:8])[CH3:15])(=[O:27])=[O:26]
Reactant: CS(=O)(=O)Cl
Reactant: CON=CC(CC(C)O)Oc1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: CON=CC(CC(C)OS(C)(=O)=O)Oc1ccccc1
Temperature: 15 °C
Reaction time: 1 h

Procedure:
3.3 mL of triethylamine was added to a solution of 3.6 g of 5-(methoxyimino)-4-phenoxypentan-2-ol in 36 mL of tetrahydrofuran, and thereafter, 1.2 mL of methanesulfonyl chloride was added to the mixture at a temperature of 0° C. to 10° C. The obtained mixture was stirred at 15° C. or lower for 1 hour. Thereafter, 200 mL of ethyl acetate and 200 mL of water were added to the reaction mixture, and the water layer was then removed. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was then distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1), so as to obtain 4.4 g of 5-(methoxyimino)-4-phenoxypentan-2-yl methanesulfonate in the form of a light yellow oily product.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[CH3:12][O:13][CH2:14][CH2:15]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:15][CH2:14][O:13][CH3:12])=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10]
Reactant: COCCBr
Reactant: CC(=O)c1cc(O)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COCCOc1ccc(O)c(C(C)=O)c1
Temperature: 25 °C
Yield: 50 %

Procedure:
To a solution (250 mL) of 1-(2,5-dihydroxyphenyl)ethanone (11.0 g) in acetonitrile were added 2-methoxyethylbromide (19.6 mL) and potassium carbonate (12.0 g) at room temperature, and the mixture was heated under reflux for 15 hr. The reaction mixture was allowed to cool to room temperature and filtered through celite, and the filtrate was concentrated under reduced pressure. Saturated aqueous ammonium chloride solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10, volume ratio) to give the title object compound (7.6 g, 50%) as a pale-yellow oil.
Reaction SMILES: [ClH:1].Cl.[NH2:3][C:4]1[CH:5]=[C:6]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1.[C:16]([N:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1)(=[O:18])[CH3:17].C([BH3-])#N.[Na+].C(OCC)(=O)C>CO.O>[ClH:1].[ClH:1].[C:16]([N:19]1[CH2:24][CH2:23][CH:22]([NH:3][C:4]2[CH:9]=[CH:8][CH:7]=[C:6]([N:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[CH:5]=2)[CH2:21][CH2:20]1)(=[O:18])[CH3:17]
Reactant: Nc1cccc(N2CCCCC2)c1
Reactant: CC(=O)N1CCC(=O)CC1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CO
Product: CC(=O)N1CCC(Nc2cccc(N3CCCCC3)c2)CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 132.1 %

Procedure:
To a solution of N-(3-aminophenyl)piperidine dihydrochloride (3.73 g) and 1-acetyl-4-piperidone (2.1 g) in methanol (30 ml) was added sodium cyano borohydride (1.9 g), followed by stirring at room temperature for 5 hours. To the mixture were added ethyl acetate ester (20 ml) and water (30 ml), the organic layer was dried over anhydrous sodium sulfate and then the solvent was distilled off. The residual oily compound was separated and purified by silica gel column chromatography (developing solvent: ethyl acetate ester). The oily compound was dissolved in dioxane (10 ml) and to the mixture was added 6N solution of hydrogen chloride in dioxane (2 ml). Then, the solvent was removed to obtain a colorless amorphous solid (3.7 g).
Reaction SMILES: [N:1]#[C:2]Br.[Br:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][C:6]=1[CH3:12]>C(OCC)C.C1COCC1>[Br:4][C:5]1[CH:11]=[CH:10][C:8]([NH:9][C:2]#[N:1])=[CH:7][C:6]=1[CH3:12]
Reactant: N#CBr
Reactant: Cc1cc(N)ccc1Br
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cc1cc(NC#N)ccc1Br
Yield: 26.4 %

Procedure:
A mixture of cyanogen bromide (0.550 g, 5.19 mmol), and (4-bromo-3-methylaniline (2.04 g, 11 mmol) (Aldrich Chemical Company) in diethyl ether/THF (8 mL) was stirred for 3 days under nitrogen. The reaction was filtered, the filtrate evaporated, and the residue flash chromatographed on silica gel using 9/1 Hexane/acetone to give (4-bromo-3-methylphenyl)cyanamide (0.289 g, 13%). HRMS: calcd for 2 C8H7BrN2+H+, 420.96579; found (ESI-FT/MS, [2M+H]+), 420.966.
Reaction SMILES: [CH2:1]([NH:5]C(=O)OC(C)(C)C)[CH2:2][C:3]#[CH:4].[N:13]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[N+:14]=[N-:15].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].Cl.[Na+].[Cl-]>C(O)(C)(C)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.O>[CH2:16]([N:13]1[CH:4]=[C:3]([CH2:2][CH2:1][NH2:5])[N:15]=[N:14]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C#CCCNC(=O)OC(C)(C)C
Reactant: [N-]=[N+]=NCc1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CC(C)(C)O
Solvent: O
Product: NCCc1cn(Cc2ccccc2)nn1

Procedure:
A reaction mixture comprising tert-butyl but-3-yn-1-ylcarbamate (306 mg, 1.808 mmol), (azidomethyl)benzene (241 mg, 1.808 mmol), copper (II) acetate (32.8 mg, 0.181 mmol) and Sodium L-ascorbate (71.6 mg, 0.362 mmol) in tert-butanol (25 ml)/water (25 ml) was stirred for 18 hours at room temperature. The reaction mixture was acidified to pH1 using 6M HCl and then saturated with solid NaCl. The reaction mixture was concentrated under reduced pressure. The remaining mixture was diluted with ethyl acetate. The organics were separated and dried over MgSO4, filtered, and the solvent concentrated under reduced pressure to afford an orange oil. The oil was loaded on to a 10 g SCX2 cartridge. The cartridge was washed with water and methanol. Product was then eluted with 2M ammonia in methanol. The solution was then concentrated under pressure to afford the title compound.
Reaction SMILES: [C:1]1([C:7]2[C:8](=[O:13])O[C:10](=[O:12])[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([NH:21][NH2:22])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)(=O)C>[CH2:14]([N:21]1[C:10](=[O:12])[CH:11]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]([OH:13])=[N:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NNCc1ccccc1
Reactant: O=C1C=C(c2ccccc2)C(=O)O1
Solvent: CC(=O)O
Product: O=c1cc(-c2ccccc2)c(O)nn1Cc1ccccc1
Yield: 344 %

Procedure:
3-Phenylfuran-2,5-dione (2.00 g, 11.5 mmol), benzylhydrazine (3.36 g, 17.2 mmol) and acetic acid (2 mL) were heated to 140° C. for 3 h in a 20 mL heavy-walled sealed tube under microwave irradiation. Upon cooling, a white precipitate formed which was filtered and washed three times with hexane and DCM. The white solid was dried under reduced pressure to give the title compound (11.01 g). LCMS m/z=279.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 5.13 (s, 2H), 7.00 (s, 1H), 7.42-7.26 (m, 5H), 7.49-7.43 (m, 3H), 7.66-7.60 (m, 2H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=O)[CH3:2].CO.C([BH3-])#[N:13].[Na+].[OH-].[Na+]>N.C(O)(=O)C>[N:6]1[CH:7]=[CH:8][CH:9]=[C:4]([CH:1]([NH2:13])[CH3:2])[CH:5]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)c1cccnc1
Agent: N
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: CC(N)c1cccnc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 44 %

Procedure:
3-Acetylpyridine (2.4 g, 20 mmol, Aldrich) was dissolved in 2M ammonia solution in methyl alcohol (50 mL, 100 mmol, Aldrich) and acetic acid (15 mL, J. T. Baker) was slowly added at 0 C. After stirring for 3 h at room temperature, the sodium cyanoborohydride (5.0 g, 80 mmol, Aldrich) was added to the solution at 0 C. The mixture was stirred under nitrogen at room temperature for overnight then the reaction was cooled at ice bath and quenched with aqueous 5 N sodium hydroxide (30 mL, 150 mmol, J. T. Baker). The methyl alcohol was removed from the mixture via vacuo. The residue was extracted by diethyl ether (30 mL×4). The combined organic phases were dried over anhydrous magnesium sulfate and concentrated via vacuo to give crude 1-pyridin-3-yl-ethylamine as light yellow oil in 44% yield (1.07 g, 8.8 mmol).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:26][S:27][C:28]1[S:29][C:30]2[CH:36]=[C:35]([CH:37]=O)[CH:34]=[CH:33][C:31]=2[N:32]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH2:37][C:35]2[CH:34]=[CH:33][C:31]3[N:32]=[C:28]([S:27][CH3:26])[S:29][C:30]=3[CH:36]=2)=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1
Reactant: CSc1nc2ccc(C=O)cc2s1
Reactant: Nc1ccc(Br)cc1[N+](=O)[O-]
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CSc1nc2ccc(CNc3ccc(Br)cc3[N+](=O)[O-])cc2s1
Reaction time: 0.17 h
Yield: 76.2 %

Procedure:
To a stirred mixture of 4-bromo-2-nitroaniline (694 mg, 3.2 mmol) in TFA (5 mL) at −15° C. under argon was added NaBH(OAc)3 (1.1 g, 5.3 mmol) portionwise. The mixture was stirred for 10 min. To the stirred mixture was added dropwise 2-(methylthio)benzo[d]thiazole-6-carbaldehyde (735 mg, 3.5 mmol) from Step 1 of this Example in CH2Cl2 (3 mL). The mixture was stirred for 1 h and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 100% hexanes to 100% EtOAc to afford 4-bromo-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline (1.0 g, 77%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.84 (t, J=6.0 Hz, 1H), 8.19 (d, J=2.4 Hz, 1H), 7.98 (s, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.56 (dd, J=2.4, 9.3 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 6.88 (d, J=9.2 Hz, 1H), 4.75 (d, J=6.0 Hz, 2H), 2.77 (s, 3H). LCMS (ESI) m/z 410 and 412 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH:7]([CH2:12][OH:13])[CH2:6]2.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]([F:14])([F:15])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH:7]([CH:12]=[O:13])[CH2:6]2
Reactant: OCC1Cc2ccc(C(F)(F)F)cc2C1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: O=CC1Cc2ccc(C(F)(F)F)cc2C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98 %

Procedure:
The above 5-trifluoromethyl-indan-2-yl-methanol (216 mg, 1 mmol) was dissolved in methylene chloride (15 mL) and the solution was cooled in an ice bath. To this solution was added Dess-Martin reagent (450 mg, 1.06 mmol) in four portions. The mixture was warmed to room temperature and stirred for 1 hr. The mixture was evaporated to dryness and the residue was triturated with petroleum ether (14 mL) and ether (7 mL). The precipitate was filtered out and the filtrate was extracted with ether and sodium bicarbonate solution. The organic layer was dried over sodium sulfate and solvents were evaporated to give 5-trifluoromethyl-indan-2-carbaldehyde (210 mg) as pale green oil. 1H-NMR (CDCl3) □ 9.78 (s, 1H), 7.48 (s, 1H), 7.43 (d, 1H), 7.32 (d, 1H), 3.33-3.38 (m, 3H), 3.15-3.27 (m, 2H).
Reaction SMILES: [H-].[Na+].[I-].[CH3:4][O:5][C:6]1[CH:28]=[CH:27][CH:26]=[CH:25][C:7]=1[CH2:8][O:9][C:10]1[C:11]2[N:12]([C:16]([CH2:20][N+](C)(C)C)=[C:17]([CH3:19])[N:18]=2)[CH:13]=[CH:14][CH:15]=1>C(O)C#C>[CH3:4][O:5][C:6]1[CH:28]=[CH:27][CH:26]=[CH:25][C:7]=1[CH2:8][O:9][C:10]1[C:11]2[N:12]([C:16]([CH2:20][O:5][CH2:6][C:7]#[CH:8])=[C:17]([CH3:19])[N:18]=2)[CH:13]=[CH:14][CH:15]=1
Reactant: COc1ccccc1COc1cccn2c(C[N+](C)(C)C)c(C)nc12
Agent: C#CCO
Agent: [H-]
Agent: [I-]
Product: C#CCOCc1c(C)nc2c(OCc3ccccc3OC)cccn12
Temperature: 0 °C
Reaction time: 1 h
Yield: 149.9 %

Procedure:
To a solution of sodium hydride (63.6% in mineral oil dispersion, 0.282 g) in 2-propynyl alcohol (14 ml) was added 8-(2-methoxybenzyloxy)-2-methyl-3-trimethylammoniomethylimidazo[1,2-a]pyridine iodide (3.43 g) and the mixture was heated at 90°-95° C. with stirring for 1 hour. After being cooled, the mixture was poured into ice-water and the resulting precipitate was collected by filtration and dissolved in methylene chloride. The solution was treated successively with silica gel (1 g) and activated charcoal and evaporated in vacuo. The crystalline residue was recrystallized from a mixture of ethyl acetate and n-hexane to give 8-(2-methoxybenzyloxy)-2-methyl-3-(2-propynyloxymethyl)imidazo[1,2-a]pyridine (1.85 g).
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([CH2:9][CH2:10][C:11]2[CH:25]=[CH:24][N:14]3[C:15](=[O:23])[C:16]([C:19](OC)=[O:20])=[CH:17][N:18]=[C:13]3[CH:12]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].[H-].C([Al+]C(C)C)(C)C.[Cl-].[NH4+].Cl>O1CCCC1>[CH:1]([C:4]1[N:5]=[C:6]([CH2:9][CH2:10][C:11]2[CH:25]=[CH:24][N:14]3[C:15](=[O:23])[C:16]([CH:19]=[O:20])=[CH:17][N:18]=[C:13]3[CH:12]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]
Reactant: COC(=O)c1cnc2cc(CCc3nc(C(C)C)cs3)ccn2c1=O
Agent: CC(C)[Al+]C(C)C
Agent: Cl
Agent: [Cl-]
Solvent: C1CCOC1
Product: CC(C)c1csc(CCc2ccn3c(=O)c(C=O)cnc3c2)n1
Reaction time: 2 h
Yield: 64.5 %

Procedure:
The methyl 8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-4-oxo-4H-pyrido[1,2-a]-pyrimidin-3-carboxylate (660 mg) obtained in (A) was dissolved in tetrahydrofuran (30 ml), added dropwise with diisopropylaluminum hydride (1 M solution in tetrahydrofuran, 9.2 ml) at −78° C., and then the mixture was stirred for 2 hours at the same temperature. The reaction mixture was added with saturated aqueous ammonium chloride (1 ml), then added with 12% aqueous hydrochloric acid, and stirred at room temperature for 1 hour. After insoluble solids were removed by filtration through a Celite layer, the solvent of the filtrate was evaporated, and the residue was dissolved in methylene chloride. This solution was added with active manganese dioxide (1.2 g) and stirred at room temperature for 16 hours. Then, insoluble matters were removed by filtration to obtain the title compound (390 mg) as yellow powder.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[N:10]=1)[C:5]([OH:7])=O.[C:12]([O:16][C:17]([NH:19][NH2:20])=[O:18])([CH3:15])([CH3:14])[CH3:13].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CC(=O)OCC.C(OCC)C>[C:12]([O:16][C:17]([NH:19][NH:20][C:5]([C:4]1[CH:8]=[C:9]([CH3:11])[N:10]=[C:2]([CH3:1])[CH:3]=1)=[O:7])=[O:18])([CH3:15])([CH3:14])[CH3:13]
Reactant: Cc1cc(C(=O)O)cc(C)n1
Reactant: CC(C)(C)OC(=O)NN
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cc(C(=O)NNC(=O)OC(C)(C)C)cc(C)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.2 %

Procedure:
To a solution of 2,6-dimethyl-isonicotinic acid (1.59 g, 10.5 mmol), hydrazinecarboxylic acid tert-butyl ester (1.42 g, 10.7 mmol) and DIPEA (6.06 g, 31.5 mmol) in DMF (33 mL), TBTU (4.05 g, 12.6 mmol) is added. The suspension is stirred at rt for 2 h before it is diluted with EA:diethyl ether 1:1 and washed with 1 N aq. NaOH solution. The washing is extracted three times with DCM, acidified and extracted again with DCM. The combined org. extracts are dried over MgSO4, filtered and concentrated to give crude N′-(2,6-dimethyl-pyridine-4-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (2.79 g) as a brown oil. This material is dissolved 5 M HCl in dioxane (14 mL) and the resulting solution is stirred at rt for 3 h. The solvent is removed in vacuo and the residue is purified by MPLC on RP-C18 silica gel to give 2,6-dimethyl-isonicotinic acid hydrazide hydrochloride (1.71 g) as a beige solid; LC-MS: tR=0.15 min, [M+1]+=166.10.
Reaction SMILES: [Cl:1][C:2]1[C:3](B(O)O)=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.Br[C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[C:21]([F:24])([F:23])[F:22]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[Cl:1][C:2]1[C:3]([C:16]2[CH:17]=[C:18]([Cl:20])[CH:19]=[CH:14][C:15]=2[C:21]([F:22])([F:23])[F:24])=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1
Reactant: FC(F)(F)c1ccc(Cl)cc1Br
Reactant: COc1cc(B(O)O)c(Cl)cn1
Agent: Cl[Pd+]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: NCCc1[c-]cccc1
Product: COc1cc(-c2cc(Cl)ccc2C(F)(F)F)c(Cl)cn1

Procedure:
443 mg (2.20 mmol) of 5-chloro-2-methoxypyridin-4-ylboronic acid and 571 mg (2.20 mmol) of 2-bromo-4-chloro-1-(trifluoromethyl)benzene in the presence of XPhos precatalyst were reacted according to General Method 2B. Yield: 193 mg (purity 93%, 25% of theory)
Reaction SMILES: [CH:1]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=[C:2]=1>[Pd]>[CH:1]1=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1
Reactant: C1=CCCCCCCCC=1
Agent: [Pd]
Agent: C1=C/CCCCCCCC/1
Product: C1=CCCCCCCCC1

Procedure:
Moore, J.Am.Chem.Soc. (84) 3788 discloses the hydrogenation of 1,2-cyclodecadiene using a 10% Pd on charcoal catalyst to produce 17-32% trans-cyclodecene.
Reaction SMILES: [C:1](=[O:13])([S:11][CH3:12])[O:2][CH:3]([O:5][C:6](=[O:10])[CH:7]([CH3:9])[CH3:8])C.Cl[C:15](OCCl)=O.C(O)(=O)C(C)(C)C>>[C:1](=[O:13])([S:11][CH3:12])[O:2][CH2:3][O:5][C:6](=[O:10])[C:7]([CH3:15])([CH3:9])[CH3:8]
Reactant: CSC(=O)OC(C)OC(=O)C(C)C
Reactant: O=C(Cl)OCCl
Agent: CC(C)(C)C(=O)O
Product: CSC(=O)OCOC(=O)C(C)(C)C

Procedure:
Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing 1-chloroethyl chloroformate with chloromethyl chloroformate in Step A and replacing isobutyric acid with pivalic acid in Step B affords O-(pivaloyloxymethyl) S-methyl thiocarbonate (9) as an oil.
Reaction SMILES: C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:22]1[C:27]2[CH:28]=[CH:29][C:30]([C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=3)=O)=[CH:31][C:26]=2[O:25][CH2:24][CH2:23]1.O>C1COCC1>[O:22]1[C:27]2[CH:28]=[CH:29][C:30]([C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=3)=[CH:9][C:10]#[N:11])=[CH:31][C:26]=2[O:25][CH2:24][CH2:23]1
Reactant: COc1cccc(C(=O)c2ccc3c(c2)OCCO3)c1
Reactant: CCOP(=O)(CC#N)OCC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1cccc(C(=CC#N)c2ccc3c(c2)OCCO3)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 77.9 %

Procedure:
To a solution of cyanomethylphosphonic acid diethyl ester (2.1 mL, 13.5 mmol) in anhydrous THF (15 mL) was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 13.5 mL, 13.5 mmol) at 0° C. and stirred for 30 min at room temperature followed by addition of (2,3-dihydro-benzo[1,4]dioxin-6-yl)-(3-methoxy-phenyl)-methanone (2.0 g crude, 6.7 mmol) in THF (15 mL) and refluxed for 30 min. The reaction mixture was poured into water (50 mL), extracted with CH2Cl2 (2×50 mL). The combined organic phases were washed with brine (50 mL), dried over MgSO4, and purified via flash column chromatography (EtOAc, Hexane) to give 3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-3-(3-methoxy-phenyl)-acrylonitrile as an off-white solid (1.53 g, 77% yield): mp, 64-66° C.; 1H NMR (DMSO-d6) δ 3.77 and 3.78 (2s, 3H, OCH3), 4.24-4.36 (m, 4H, CH2CH2), 6.19 and 6.24 (2s, 1H, CH), 6.77-7.09 (m, 6H, Ar), 7.33-7.36 (m, 1H, Ar); 13C NMR (DMSO-d6) δ 55.2, 55.2, 64.0, 64.0, 64.2, 64.3, 94.3, 95.2, 113.7, 114.6, 114.9, 115.8, 116.7, 117.1, 117.2, 117.9, 118.3, 120.9, 121.2, 121.7, 122.5, 129.7, 129.8, 129.8, 130.6, 138.5, 139.7, 143.1, 143.3, 144.8, 145.6, 159.1, 159.2, 160.8, 160.9. Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.48; H, 4.84; N, 4.64.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[N:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]2=[N:6][C:5]=1[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1.[Cl:20][C:21]1[CH:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH2:28])[N:22]=1>>[Cl:20][C:21]1[CH:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH:28][CH2:3][C:4]2[N:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]3=[N:6][C:5]=2[C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[N:22]=1
Reactant: Cc1cc(Cl)nc(N)n1
Reactant: ClCc1c(-c2ccc(Cl)cc2)nc2ccccn12
Agent: Cl
Product: Cc1cc(Cl)nc(NCc2c(-c3ccc(Cl)cc3)nc3ccccn23)n1

Procedure:
The title compound was prepared according to Method A and the experimentals described for compound 139 from 3-(chloromethyl)-2-(4-chlorophenyl)imidazo[1,2-a]pyridine hydrochloride and 4-chloro-6-methylpyrimidin-2-amine. M/e+, 384.1, 386 for C19H15C12N5. 1H-NMR (400 MHz, CDCl3, δ) 8.25 (m, 1H), 7.74 (d, J=6.598 Hz, 2H), 7.63 (m, 1H), 7.42 (d, J=6.599 Hz, 2H), 7.24 (m, 1H), 6.84 (m, 1H), 6.55 (s, 1H), 5.41 (s, NH), 5.05 (d, J=5.13 Hz, 2H, D, CH2), 2.318 (s, 3H, D, CH3) ppm.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]([C:13](=[O:18])N(OC)C)[C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].[Li][CH3:21]>C1COCC1>[C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]([C:13](=[O:18])[CH3:21])[C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:2])([CH3:3])[CH3:4]
Reactant: [Li]C
Reactant: CON(C)C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C
Solvent: C1CCOC1
Product: CC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 80.9 %

Procedure:
[1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic acid-tert-butyl ester (2.0 g, 7.3 mmol) was dissolved in, freshly distilled THF under an argon atmosphere. The solution was cooled to −78° C. whereupon MeLi (15.6 mL, 1.4 M in diethyl ether, 21.9 mmol, 3 eqv) was added dropwise maintaining an internal temperature <−70° C. The reaction was stirred at −70° C. for 30 minutes before warming to −30° C. for a further 30 minutes. After this time TLC analysis indicated the complete consumption of starting material. Saturated aqueous ammonium chloride solution (10 mL) was added and the reaction allowed to warm to room temperature. The aqueous phase was extracted with ethyl acetate (3×30 mL). The organic phases were washed with water (3×50 mL) and brine (50 mL), dried over MgSO4, filtered and the solvents removed in vacuo to give a crude yellow oil. Purification by column chromatography (SiO2, 20% ethyl acetate in hexanes) afforded the title compound as a colourless oil (1.355 g, 84%).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[NH:11]1[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CCOC(=O)C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCOC(=O)C1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Temperature: 100 °C
Reaction time: 8 h
Yield: 84.3 %

Procedure:
In a solution of 1-fluoro-4-nitro benzene (3.00 g, 21.3 mmol) in DMSO (30 mL) was added ethyl piperidine-4-carboxylate (5.01 g, 31.9 mmol) and K2CO3 (5.87 g, 42.5 mmol). The resulting mixture was stirred at 100° C. for 8 h. After cooling to rt, the reaction was quenched with H2O (70 mL). The resulting mixture was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc/petroleum ether (1:2 v/v) to obtain compound 18a as a yellow solid (5.00 g, 80% yield). Mass Spectrum (LCMS, ESI pos.): Calcd. for C14H18N2O4: 279.1 (M+H). Found 279.1.