Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=O)[CH:12](Br)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[SH:21][C:22]1[NH:23][CH:24]=[CH:25][N:26]=1.[OH-].[Na+].O>CCO>[C:13]1([C:12]2[S:21][C:22]3=[N:26][CH:25]=[CH:24][N:23]3[C:11]=2[C:8]2[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CS(=O)(=O)c1ccc(C(=O)C(Br)c2ccccc2)cc1
Reactant: Sc1ncc[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CS(=O)(=O)c1ccc(-c2c(-c3ccccc3)sc3nccn23)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 8 %

Procedure:
A mixture of the bromoketone of step 2 of example 8 (141.2 mg, 4 mmol), 2-mercaptoimidazole (400 mg, 4 mmol) and NaOH (400 μL, 10 N) in EtOH (4 mL) was stirred at r.t. for 6 h. H2O was added and the precipitate that formed was filtered. The solid was washed with water and dried under vaccum. The dried solid residue (234 mg) was heated with P2O5 (900 mg) in PPA (3.5 mL) at 170 ° C. for 20 h. The mixture was quenched with ice and NH4OAc and extracted with EtOAc. The organic extracts were washed with brine, dried over MgSO4, filtered and concentrated to a solid. The solid residue was chromatographed on silica gel (eluted with 40 % EtOAc/Hexane) to give 113 mg of the title compound. 1H NMR (CD3COCD3): δ3.10 (s, 3H), 7.40-7.20 (m, 7H), 7.65 (d, 2H), 8.00 (d, 2H).
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[C:6]2=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=[C:5]2[O:4][CH2:3]1.CN(C=O)C.F[C:19]1[N:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[NH:28][N:27]=[C:26]2[CH3:31])=[CH:21][C:20]=1[CH3:32]>>[CH3:1][C:2]1([CH3:12])[C:6]2[C:7]([O:11][C:19]3[N:24]=[CH:23][C:22]([N:25]4[C:26]([CH3:31])=[N:27][NH:28][C:29]4=[O:30])=[CH:21][C:20]=3[CH3:32])=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1
Reactant: CC1(C)COc2cccc(O)c21
Reactant: Cc1cc(-n2c(C)n[nH]c2=O)cnc1F
Solvent: CN(C)C=O
Product: Cc1cc(-n2c(C)n[nH]c2=O)cnc1Oc1cccc2c1C(C)(C)CO2
Temperature: 110 °C
Reaction time: 16 h
Yield: 11 %

Procedure:
To a solution of 3,3-dimethyl-2H-benzofuran-4-ol (WO2012/076877 Intermediate 50, 30 mg, 0.18 mmol) in dry DMF (0.5 mL) dipotassium carbonate (50.5 mg, 0.365 mmol) and then 4-(6-fluoro-5-methyl-3-pyridyl)-3-methyl-1H-1,2,4-triazol-5-one (Intermediate 9, 38.0 mg, 0.18 mmol) were added and the reaction mixture was stirred for 16 hours at 110° C. The reaction was quenched with water (1 ml), diluted with brine (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and Dichloromethane/methanol from 99.5:0.5 to 95:5 as eluent affording the title compound (7 mg) as a yellow pale solid.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH3:8])[CH:7]=1.[Li]CCCC.[B:15](OC(C)C)([O:20]C(C)C)[O:16]C(C)C>C1COCC1>[F:9][C:5]1[CH:4]=[CH:3][C:2]([B:15]([OH:20])[OH:16])=[CH:7][C:6]=1[CH3:8]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Cc1cc(Br)ccc1F
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1cc(B(O)O)ccc1F
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 84 %

Procedure:
5-Bromo-2-fluorotoluene (6 g, 31.7 mmol) was dissolved in dry THF (50 mL) and cooled to −78° C. under N2. n-BuLi (14 mL, 2.5M solution in THF) was added slowly using a dry syringe. Cloudiness appeared. The reaction was stirred for 40 minutes at −78° C. Triisopropyl borate (22 mL, 95 mmol) was slowly added while stirring. The reaction was allowed to warm to room temperature. Stirring continued for an additional 2 hours. A pale yellow, cloudy solution formed. (TLC (1:2 ethyl acetate/hexanes)) indicated disappearance of the starting material. The reaction was quenched by adding 10% aqueous NaOH (200 mL). After stirring for 45 minutes, 10% citric acid solution (300 mL) was added until, pH ˜5.0. The product was extracted with ethyl acetate (500 mL). The organic phase was washed with brine and dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide an off white solid (yield: 4.1 g, 84%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]([CH3:13])[CH3:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:14][CH:15]1[CH2:20]CNC[CH2:16]1>>[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:13][CH2:16][CH:15]([CH3:20])[CH2:14][CH2:12]2)=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: CC1CCNCC1
Reactant: CN(C)c1ccc(N)c(C(N)=O)c1
Product: CC1CCN(c2ccc(N)c(C(N)=O)c2)CC1

Procedure:
According to the preparation of 25, 4-methylpiperidine was used to afford 28 (0.8 g) as brown liquid;
Reaction SMILES: O[C:2]1([C:8]2[N:9]=[C:10]([CH3:13])[S:11][CH:12]=2)[O:7][CH2:6][CH2:5][NH:4][CH2:3]1.[OH:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](=O)[CH3:26])=[CH:20][CH:19]=1>>[OH:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH:25]([N:4]2[CH2:5][CH2:6][O:7][CH:2]([C:8]3[N:9]=[C:10]([CH3:13])[S:11][CH:12]=3)[CH2:3]2)[CH3:26])=[CH:20][CH:19]=1
Reactant: CC(=O)Cc1ccc(OCCO)cc1
Reactant: Cc1nc(C2(O)CNCCO2)cs1
Product: Cc1nc(C2CN(C(C)Cc3ccc(OCCO)cc3)CCO2)cs1

Procedure:
Prepared by analogy to Example 13 by reaction of 2-hydroxy-2-(2-methyl-thiazol-4-yl)morpholine with 1-[4-(2-hydroxyethyoxy)phenyl]propan-2-one followed by purification on a silica gel column using methylene chloride as eluant.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH3:10])=[C:4]([CH3:11])[CH:3]=1.CCCCCC.C([O:22][B:23](OCCCC)[O:24]CCCC)CCC>O1CCCC1>[CH3:11][C:4]1[CH:3]=[C:2]([B:23]([OH:24])[OH:22])[CH:7]=[C:6]([CH3:8])[C:5]=1[O:9][CH3:10]
Reactant: COc1c(C)cc(Br)cc1C
Reactant: CCCCOB(OCCCC)OCCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1c(C)cc(B(O)O)cc1C
Temperature: -78 °C
Reaction time: 1 h
Yield: 82 %

Procedure:
4-Bromo-2,6-dimethylanisole (5 g, 1 eq, Acros) in tetrahydrofuran (100 mL) was cooled to −78° C. under nitrogen. N-Butyl lithium in hexane (1.6 M, 19 mL, 1.3 eq) was added dropwise over 10 min. The mixture was stirred at −78° C. for 1 h. Tributylborate (31 mL, 5 eq) was added to the solution and stirred at −78° C. for 1 h. The mixture was allowed to warm to room temperature and stirred for 16 h. Reaction was quenched with hydrochloric acid (1M, 20 mL). The solvent was evaporated and the residual aqueous solution was acidified to pH 1 using concentrated hydrogen chloride. The mixture was extracted with diethyl ether (2×100 mL). The combined organic phase was extracted with aqueous sodium hydroxide (1M, 2×100 mL). The combined aqueous phase was acidified with concentrated hydrogen chloride to pH 1. The resulting precipitates were collected by filtration to afford 3,5-dimethyl-4-methoxybenzene boronic acid (3.43 g, 82%) as a white solid: 1H NMR (CDCl3) five peaks for 2H: 7.87 (s), 7.60 (weak s), 7.85 (s), 7.26 (s) 6.98 (weak s); five signal for 3H: 3.80 (s), 3.76 (weak s), 3.74 (s), 3.69 (weak s), 3.67 (weak s); four signals for 6H: 2.40 (s), 2.54 (weak s), 2.51 (s), 2.25 (weak s). (I.b.) 3,5-Dimethyl-benzene boronic acid.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1Br.C([Li])CCC.C([O:20][B:21](OC(C)C)[O:22]C(C)C)(C)C>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[B:21]([OH:22])[OH:20]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: COCCc1ccccc1Br
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COCCc1ccccc1B(O)O
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of 2-(2-bromophenyl)ethyl methyl ether (V.2; 1 eq.) in THF (0.16M) at −78° C. was added n-butyllithium (2.5M; 1.1 eq.). The reaction mixture was stirred for 1 h at −78° C. then tri-iso-propylborate (1.2 eq.) was added and the final mixture was allowed to warm slowly to room temperature and stirred for 1 h. The reaction was quenched with the addition of aqueous HCl (1N) and extracted with EtOAc. The organic extract was washed with brine, dried over Na2SO4, filtered and concentrated to afford the desired material as a foam which was used as such.
Reaction SMILES: [CH3:1][NH2:2].S(C1C=CC(C)=CC=1)(O[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1)(=O)=O>O1CCCC1>[CH3:1][NH:2][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1
Reactant: CN
Reactant: Cc1ccc(CCOS(=O)(=O)c2ccc(C)cc2)cc1
Solvent: C1CCOC1
Product: CNCCc1ccc(C)cc1
Yield: 180.8 %

Procedure:
9.2 g of methylamine are condensed at −20° C. into a solution of 5.8 g of 2-p-tolylethyl tosylate in 15 ml of abs. tetrahydrofuran and the mixture is stirred overnight at room temperature in a pressure vessel. After the pressure vessel has been opened at −20° C., it is allowed to come to room temperature in order to allow excess methylamine to evaporate. The reaction solution is taken up in ether, washed with water and saturated sodium chloride solution, dried over magnesium sulphate and concentrated to dryness in vacuo. 5.39 g of methyl-(2-p-tolylethyl)amine are obtained, which is reacted further as a crude product.
Reaction SMILES: C([O:4][C:5]1[C:6]([CH3:20])=[C:7]([CH:17]=[CH:18][CH:19]=1)[C:8]([O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])=[O:9])C=C.CN1C[CH2:25][CH2:24][C:23]1=O>>[CH2:25]([C:19]1[CH:18]=[CH:17][C:7]([C:8]([O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:15])[CH3:16])=[O:9])=[C:6]([CH3:20])[C:5]=1[OH:4])[CH:24]=[CH2:23]
Reactant: CN1CCCC1=O
Reactant: C=CCOc1cccc(C(=O)OCC[Si](C)(C)C)c1C
Product: C=CCc1ccc(C(=O)OCC[Si](C)(C)C)c(C)c1O
Temperature: 220 °C

Procedure:
2-(Trimethylsilyl)ethyl 3-(allyloxy)-2-methylbenzoate (500 mg, 1.70 mmol) was dissolved in 1-methylpyrrolidine-2-one (1 ml) in a microwave vial, closed with a cap and subjected to microwave irradiation (CEM discover) with stirring at 220° C., maximum pressure 300 psi, run time 5 min, hold time 15 min. LCMS showed 3 peaks including a major peak with the expected product mass. After cooling, the crude mixture was directly loaded on a silica gel column (12 g) and purified using an ISCO system (hexane:EtOAc solvent mixture, product eluted ˜5% EtOAc in hexane) to give SKC-01-056. The above experiment was repeated several times in 1-2 g scale Total wt of the product isolated was 3.6 g.
Reaction SMILES: N#N.Cl[CH2:4][C:5]1[S:9][C:8]([C:10]2([CH3:15])[O:14][CH2:13][CH2:12][O:11]2)=[CH:7][CH:6]=1.[C-:16]#[N:17].[Na+].O>CS(C)=O>[CH3:15][C:10]1([C:8]2[S:9][C:5]([CH2:4][C:16]#[N:17])=[CH:6][CH:7]=2)[O:14][CH2:13][CH2:12][O:11]1
Reactant: CC1(c2ccc(CCl)s2)OCCO1
Reactant: [C-]#N
Agent: N#N
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC1(c2ccc(CC#N)s2)OCCO1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of [5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-2-yl]-methanol (10.00 g, 49.94 mmol) in dry CH2Cl2 (100 mL) was treated at 0° C. with Et3N (9.04 mL, 64.92 mmol) followed by DMAP (610 mg, 4.99 mmol) and Ms-Cl (4.65 mL, 59.92 mmol). After stirring at rt for 2 h, the reaction was quenched with water (200 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give crude 2-(5-chloromethyl-thiophen-2-yl)-2-methyl-[1,3]dioxolane as a yellow oil. In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of this crude 2-(5-chloromethyl-thiophen-2-yl)-2-methyl-[1,3]dioxolane in DMSO (400 mL) was treated with sodium cyanide (9.07 g, 185.09 mmol) and the reaction mixture was stirred at 80° C. for 1 h. Water (400 mL) was added to the cooled reaction mixture and the product was extracted with EA (2×500 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (60:40 hept-EA) gave the title compound: TLC: rf (60:40 hept-EA)=0.34. LC-MS-conditions 02: tR=0.89 min.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:25]2[C:30]([Cl:31])=[CH:29][N:28]=[C:27]([F:32])[CH:26]=2)=[N:4][C:5]([N:8]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][C:19]([CH3:24])([CH3:23])[CH2:18]2)C(=O)OC(C)(C)C)=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([C:25]2[C:30]([Cl:31])=[CH:29][N:28]=[C:27]([F:32])[CH:26]=2)=[N:4][C:5]([NH:8][CH2:16][CH:17]2[CH2:22][CH2:21][O:20][C:19]([CH3:23])([CH3:24])[CH2:18]2)=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N(CC1CCOC(C)(C)C1)c1ccc(Cl)c(-c2cc(F)ncc2Cl)n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1(C)CC(CNc2ccc(Cl)c(-c3cc(F)ncc3Cl)n2)CCO1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
tert-Butyl 3,5′-dichloro-2′-fluoro-2,4′-bipyridin-6-yl((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)carbamate (8 mg, 0.017 mmol), DCM (1 mL) and TFA (0.1 mL, 1.3 mmol) were combined in a 4 mL screw cap vial. The vial was capped and the reaction mixture was stirred at ambient temperature for 1 hour. The solvent was evaporated under vacuum and the residual material was converted to the free base using sodium bicarbonate. (5.8 mg, 91%). LCMS (m/z): 3484.2/386.1/388.2 (M+H), retention time=1.07 min.
Reaction SMILES: FC(F)(F)C(NC1CCN(CCCCCO[C:18]2[CH:42]=[CH:41][C:21]([C:22]([N:24]3[CH2:29][CH2:28][CH:27]([N:30]4[C:40]5[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=5)[CH2:34][CH2:33][C:31]4=[O:32])[CH2:26][CH2:25]3)=[O:23])=[CH:20][CH:19]=2)CC1)=O.[C:45](=[O:48])([O-])[O-:46].[K+].[K+]>CO>[NH2:30][CH:27]1[CH2:28][CH2:29][N:24]([CH2:22][CH2:21][CH2:20][CH2:19][C:45]([O:46][C:18]2[CH:42]=[CH:41][C:21]([C:22]([N:24]3[CH2:25][CH2:26][CH:27]([N:30]4[C:40]5[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=5)[CH2:34][CH2:33][C:31]4=[O:32])[CH2:28][CH2:29]3)=[O:23])=[CH:20][CH:19]=2)=[O:48])[CH2:25][CH2:26]1
Reactant: O=C(c1ccc(OCCCCCN2CCC(NC(=O)C(F)(F)F)CC2)cc1)N1CCC(N2C(=O)CCc3ccccc32)CC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: NC1CCN(CCCCC(=O)Oc2ccc(C(=O)N3CCC(N4C(=O)CCc5ccccc54)CC3)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 128.2 %

Procedure:
1-[1-{4-[5-(4-Trifluoroacetylamino-1-piperidinyl)pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (1.8 g) is dissolved in methanol (40 ml), and thereto is added potassium carbonate (0.8 g). The mixture is stirred at room temperature overnight. The reaction solution is concentrated and thereto is added water. The mixture is extracted with chloroform, dried over sodium carbonate, and purified by silica gel column chromatography (eluent; dichloromethane:methanol=10:1) to give 1-[1-{4-[5-(4-amino-1-piperidinyl)pentoyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (1 g) as colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[CH3:10][CH:11]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH2:12][CH2:13]Cl.[OH-].[K+]>C(O)C.[I-].[Na+]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:13][CH2:12][CH:11]([CH3:10])[CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])=[CH:5][CH:4]=1
Reactant: COc1ccc(O)cc1
Reactant: CC(C)CCCC(C)CCCl
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CCO
Product: COc1ccc(OCCC(C)CCCC(C)C)cc1
Temperature: 25 °C
Yield: 95.3 %

Procedure:
184.4 g (1.48 mol) of p-methoxyphenol, 275.9 g (1.56 mol, 1.05 eq) of 3,7-dimethyl-1-octyl chloride, 106.9 g of KOH (85% strength, 1.62 mol, 1.09 eq) and 15.04 g of sodium iodide were dissolved in 620 ml of dry ethanol in a 2 l four-necked round-bottomed flask fitted with dropping funnel, high-efficiency condenser, gas outlet and magnetic stirrer bar, and heated at the boil for 64 hours with magnetic stirring. The mixture was cooled to room temperature, and the reaction solution was decanted off from the solid formed. The reaction solution was evaporated in a rotary evaporator. The solid was taken up in 400 ml of 10% strength aqueous NaOH solution. This solution was extracted twice with 400 ml of toluene each time. The organic phases were combined, washed with 100 ml of 10% strength aqueous NaOH solution and dried using Na2SO4. The solvent was distilled off under reduced pressure in a rotary evaporator. The residue was distilled under reduced pressure (1 mbar, head temperature: 159-162° C.), giving 372.4 g (1.41 mol, 95%) of 1-methoxy-4-(3,7-dimethyloctyloxy)benzene as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[C:12]([O-])([O-])=O.[Cs+].[Cs+].CI>CN(C=O)C>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([CH3:12])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=C([O-])[O-]
Reactant: Clc1ncnc2[nH]cc(I)c12
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1cc(I)c2c(Cl)ncnc21
Temperature: 25 °C
Reaction time: 10 h
Yield: 61 %

Procedure:
To a mixture of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (Preparation 225, 30 g, 0.1 mol), Cs2CO3 (50 g, 0.15 mol) in DMF (150 mL), MeI (28.4 g, 0.2 mol) was added dropwise at 0° C. After addition, the mixture was stirred at room temperature for 10 hours. The reaction mixture was cooled to 0° C. and quenched by the addition of water (500 mL). Then the solid was collected by filtration and washed with Et2O (100 mL) to afford 4-chloro-5-iodo-7-methyl-7H-pyrrolo[2,3-d]pyrimidine as a brown solid in 61% yield, 20 g.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:6]([CH3:19])=[N:7][N:8]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:9]=1)=[O:4].[S-:20][C:21]#[N:22].[K+]>CC(C)=O.CCOC(C)=O>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:8]2[CH:9]=[C:5]([C:3](=[O:4])[CH2:2][S:20][C:21]#[N:22])[C:6]([CH3:19])=[N:7]2)=[CH:12][CH:13]=1
Reactant: COc1ccc(Cn2cc(C(=O)CBr)c(C)n2)cc1
Reactant: N#C[S-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: COc1ccc(Cn2cc(C(=O)CSC#N)c(C)n2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.8 %

Procedure:
According to Scheme 2, Step 3: To a solution of 2-bromo-1-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-4-yl)ethanone (9.28 mmol, 3.00 g) in acetone (19 mL) was added potassium thiocyanate (9.28 mmol, 0.90 g) and the reaction mixture was stirred overnight at room temperature. Then, the reaction mixture was diluted with EtOAc and the organic phase was washed with water. The organic phase was dried over MgSO4, was filtered and was concentrated. The crude residue was purified by flash chromatography over silica gel using cyclohexane/EtOAc (80:20 to 50:50) as eluent to yield 1-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-4-yl)-2-thiocyanatoethanone (6.57 mmol, 1.98 g, 71%).
Reaction SMILES: CC(C)[O-].[Nd+3].CC(C)[O-].CC(C)[O-].C(O[SiH](OCC)OCC)C.[C:24](OCC)(=[O:34])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].[SiH4].[OH-].[Na+]>C1COCC1>[CH2:24]([OH:34])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCCCCCCCCC(=O)OCC
Agent: CC(C)[O-]
Agent: CCO[SiH](OCC)OCC
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCCCCCO
Temperature: 60 °C
Reaction time: 7 h
Yield: 24 %

Procedure:
A dry Schlenk tube under argon was charged with 48 mg (0.15 mmol) of neodymium (III) isopropoxide. Triethoxysilane (1.4 mL, 7.5 mmol) and ethyl decanoate (696 μL, 3 mmol) were added and the reaction mixture was heated to 60° C. After 7 hours exposure of the reaction mixture to air caused a flame, presumably due to SiH4 gas evolution. After 29 hours, THF (8 mL) and aqueous NaOH (1 N, 15 mL) were added, and the mixture was stirred vigorously for 2.5 hours. The reaction was worked up as in Example 13. Purification by flash chromatography (ether:hexane=3:7) afforded 114 mg (24% yield) of pure decanol and 263 mg (44% yield) of recovered starting material (both >95% pure by 1H-NMR analysis).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[C:5]1([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]#[N:20])[CH2:13][CH2:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl.N1CCOCC1>N1CCOCC1>[C:5]1([N:11]2[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][C:19]3[NH:20][N:3]=[N:2][N:1]=3)[CH2:15][CH2:16]2)[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: N#CCCN1CCN(c2ccccc2)CC1
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: C1COCCN1
Product: c1ccc(N2CCN(CCc3nnn[nH]3)CC2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 60 %

Procedure:
Sodium azide (65 g; 1.0 mol), 4-phenyl-1-(2-cyanoethyl)-piperazine (215 g; 1.0 mol), and morpholine hydrochloride (124 g; 1.0 mol) were dissolved in 1 liter of morpholine, and heated at 120°-125° C with stirring for 4 hours. After the reaction mixture was allowed to cool to room temperature, it was filtered, and the solvent was removed in vacuo. The residue was mixed in water, and the pH of the resulting solution was adjusted to 5. Crude 5-[(4-phenyl-1-piperazyl)ethyl]tetrazole was collected by filtration and was dried; yield -- 170 g. The crude product was recrystallized from water and dried; yield -- 155 g (60% yield; m.p. 190°-194° C).
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[O:6][C@H:5]([CH2:7][O:8][N:9]2C(=O)C3=CC=CC=C3C2=O)[CH2:4][O:3]1.CNN>ClCCl>[CH3:1][C:2]1([CH3:20])[O:6][C@H:5]([CH2:7][O:8][NH2:9])[CH2:4][O:3]1
Reactant: CC1(C)OC[C@@H](CON2C(=O)c3ccccc3C2=O)O1
Agent: CNN
Solvent: ClCCl
Product: CC1(C)OC[C@@H](CON)O1
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.6 %

Procedure:
A mixture of (S)-N-(2,2-Dimethyl-1,3-dioxolan-4-ylmethoxy)phthalimide (10 g, 36 mmol), and N-methylhydrazine (3.32 g, 72 mmol) in dichloromethane (150 ml) was stirred at 25° C. for 2 h. The reaction was filtered, evaporated to dryness and the residue suspended in ether. The suspension was filtered and evaporated and the residue chromatographed in ethyl acetate affording (S)-2,2-Dimethyl-1,3-dioxolan-4-ylmethoxyamine (4.8 g, 91%) as a clear liquid [α]D25 -2.4° (0.49 in MeOH); υmax (film) 3550, 3300 and 1600 cm-1 ; δH (CDCl3)1.38(3H,S,CH3), 1.44(3H,S,CH3), 3.71 (3H,m,CH2ON+1H of CH2OCMe2), 4.05(1H,q,J6.3,8.2 Hz,1H of CH2OCMe2), 4.35(1H,m,CH) and 5.57(2H,br.s, D2O exchangeable, NH2); m/z 132 (M+ -CH3, 24%). Found: C, 48.76; H, 9.00; N, 9.56% C6H13NO3 requires C, 48.96; H, 8.90; N, 9.52%
Reaction SMILES: [Br:1][C:2]1[C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[C:10](I)[C:5]=2[S:4][CH:3]=1.[CH2:13]([O:15][CH:16]([O:28][CH2:29][CH3:30])/[CH:17]=[CH:18]/B1OC(C)(C)C(C)(C)O1)[CH3:14].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[C:10](/[CH:18]=[CH:17]/[CH:16]([O:28][CH2:29][CH3:30])[O:15][CH2:13][CH3:14])[C:5]=2[S:4][CH:3]=1
Reactant: Nc1ncc(I)c2scc(Br)c12
Reactant: CCOC(/C=C/B1OC(C)(C)C(C)(C)O1)OCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CCOC(/C=C/c1cnc(N)c2c(Br)csc12)OCC
Temperature: 25 °C
Yield: 75 %

Procedure:
A mixture of Example 21A (200 mg, 0.56 mmol), 2-[(1E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (175 mg, 0.67 mmol), Pd(PPh3)4 (40 mg, 0.03 mmol) and Na2CO3 (120 mg, 1.13 mmol) in 1,2-dimethoxyethane (10 mL) and water (5 mL) was heated in an 85° C. oil bath for 15 hours. The mixture was cooled to room temperature and concentrated under reduced pressure. The mixture was extracted with dichloromethane and the extract was dried (MgSO4), filtered, and concentrated. The residue was purified by flash column chromatography on silica gel to provide the desired product (150 mg, 75%). 1H NMR (DMSO-d6, 400 MHz) δ 8.02 (s, 1H), 7.88 (s, 1H), 6.74 (d, 1H), 6.09 (dd, 1H), 5.09 (d, 1H), 3.62 (m, 2H), 3.48 (m, 2H), 1.15 (t, 6H); MS m/e 357.1, 359.1 (M+H)+.