Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]1=[O:7].[CH2:8]1[O:10][CH:9]1[CH2:11]O.[H-].[Na+]>CN(C=O)C.[Cl-].[Na+].O>[O:10]1[CH2:8][CH:9]1[CH2:11][O:7][C:2]1[N:1]=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: OCC1CO1
Reactant: O=c1nccc[nH]1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: c1cnc(OCC2CO2)nc1
Yield: 30 %

Procedure:
A solution of 2 (1H)-pyrimidinone (0.61 g, 4 mmol) and glycidol (0.30 g, 4 mmol) in DMF (10 mL) was added dropwise to a stirred suspension of NaH (0.14 g, 6 mmol) in DMF (5 mL). The reaction mixture is stirred at r. t. until the reagents disappeared (TLC). The reaction mixture is taken up with brine and extracted with EtOAc (3×20 mL). The organic phases are separated, dried over Na2SO4 and evaporated under reduced pressure. The crude residue was chromatographed (Petroleum ether/AcOEt, 1:1, as eluent) to afford pure compound in 30% yield. 1H NMR (CDCl3): δ 2.60-2.70 (m, 2H), 3.16 (m, 1H), 3.89-4.04 (m, 2H), 4.17-4.28 (m, 1H), 4.50-4.65 (m, 1H), 7.00 (t, 1H, J=7.4 Hz), 8.56 (d, 2H, J=4.9 Hz).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9](=[O:16])[N:10]2[CH2:13][CH:14]=O)=[N:5][CH:4]=1.[O:17]1[C:26]2[CH:25]=[C:24]([CH2:27][N:28]([CH:36]3[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:23]=[CH:22][C:21]=2[O:20][CH2:19][CH2:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl.C(O)(=O)C.C(Cl)(Cl)Cl>[O:17]1[C:26]2[CH:25]=[C:24]([CH2:27][N:28]([CH:36]3[CH2:41][CH2:40][N:39]([CH2:14][CH2:13][N:10]4[C:11]5[C:6](=[N:5][CH:4]=[C:3]([NH:2][CH3:1])[CH:12]=5)[CH:7]=[CH:8][C:9]4=[O:16])[CH2:38][CH2:37]3)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:23]=[CH:22][C:21]=2[O:20][CH2:19][CH2:18]1
Reactant: CC(C)(C)OC(=O)N(Cc1cc2c(cn1)OCCO2)C1CCNCC1
Reactant: CNc1cnc2ccc(=O)n(CC=O)c2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: CC(=O)O
Product: CNc1cnc2ccc(=O)n(CCN3CCC(N(Cc4cc5c(cn4)OCCO5)C(=O)OC(C)(C)C)CC3)c2c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 31.7 %

Procedure:
To 76 mg of (7-(methylamino)-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde, a solution of 0.11 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate in 2.5 mL of dichloromethane and 19 μL of acetic acid were added, and the mixture was stirred at room temperature for 5 minutes. To the reaction mixture, 0.10 g of sodium triacetoxyborohydride was added, and the mixture was stirred at the same temperature for 2 hours 20 minutes. Thereto was added chloroform and the reaction mixture was adjusted to pH 8.3 with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was washed with water and a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by basic silica gel column chromatography using an eluent of chloroform:methanol=19:1 to obtain 55 mg of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-(methylamino)-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a light yellow oily substance.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:23]=[CH:22][C:15]([O:16][CH2:17][CH:18]([OH:21])[CH2:19][CH3:20])=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl.C(OCC)C>[Cl:11][C:12]1[CH:23]=[CH:22][C:15]([O:16][CH2:17][C:18](=[O:21])[CH2:19][CH3:20])=[CH:14][CH:13]=1
Reactant: CCC(O)COc1ccc(Cl)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: CCOCC
Product: CCC(=O)COc1ccc(Cl)cc1

Procedure:
Oxalylchloride (1.0 ml, 0.011 mmol) is added to a solution of dimethylsulfoxide (DMSO) (1.7 ml, 0.022 mol) in methylenechloride (20 ml) at −60° C. 1-(4-Chlorophenoxy)-butan-2-ol (2.0 g, 0.01 mol) is added in one portion. After 15 minutes triethylamine (7 ml, 0.05 mol) is added and the reaction temperature is allowed to warm up and reach 0° C. The mixture is diluted with diethylether and washed repeatedly with brine. The organic phase is dried, filtered evaporated to give the 1-(4-chlorophenoxy)-butane-2-one.
Reaction SMILES: [CH2:1]([S:8][C:9]1[C:14]2[N:15]=[C:16](Cl)[N:17]=[C:18]([N:19]3[CH2:24][CH2:23][S:22](=[O:25])[CH2:21][CH2:20]3)[C:13]=2[N:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:27][CH2:28][CH2:29][NH2:30]>O1CCOCC1>[CH2:1]([S:8][C:9]1[C:14]2[N:15]=[C:16]([NH:30][CH2:29][CH2:28][OH:27])[N:17]=[C:18]([N:19]3[CH2:24][CH2:23][S:22](=[O:25])[CH2:21][CH2:20]3)[C:13]=2[N:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCCO
Reactant: O=S1CCN(c2nc(Cl)nc3c(SCc4ccccc4)ncnc23)CC1
Solvent: C1COCCO1
Product: O=S1CCN(c2nc(NCCO)nc3c(SCc4ccccc4)ncnc23)CC1

Procedure:
20.3 gm (0.05 mol) of 8-benzylthio-2-chloro-4-(1-oxido-thiomorpholino)-pyrimido[5,4-d]pyrimidine (melting point: 188°-190° C.) were refluxed for about 45 minutes with 8 gm (0.13 mol) of 2-hydroxyethyl-amine in 400 ml of dioxane. Most of the solvent was distilled off in vacuo, and the residue was taken up in about 500 ml of water. The reaction product, which precipitated after standing for a little while, was filtered off, washed with water and dried at about 70° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH:4]([C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=1)[CH2:5][CH:6]=O.[CH3:17][O:18]C(=O)CC1C=CC(Cl)=C(Cl)C=1.COC(OC)CCBr.Cl>>[CH3:1][O:2][C:3](=[O:16])[CH:4]([C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=1)[CH2:5][CH2:6][CH:17]=[O:18]
Reactant: COC(=O)C(CC=O)c1ccc(Cl)c(Cl)c1
Reactant: COC(=O)Cc1ccc(Cl)c(Cl)c1
Agent: COC(CCBr)OC
Agent: Cl
Product: COC(=O)C(CCC=O)c1ccc(Cl)c(Cl)c1

Procedure:
In analogy to the procedure described for the synthesis of 2-(3,4-dichloro-phenyl)-4-oxo-butyric acid methyl ester (example 2, step 1) the title compounds was prepared from 3,4-dichloro-phenyl-acetic acid methyl ester (commercially available), and 3-bromopropionaldehyde dimethylacetal and subsequent treatment with HCl aq. MS (m/e): 274.1/276.1 (MH+).
Reaction SMILES: [C:1]([C:3]1[S:4][C:5]2[C:11]([C:12]#[N:13])=[C:10](/[N:14]=[CH:15]/[N:16](C)C)[CH:9]=[CH:8][C:6]=2[N:7]=1)#[N:2].N[C:20]1[CH:21]=[CH:22][C:23]2[NH:27][CH:26]=[N:25][C:24]=2[CH:28]=1.[K+].[Br-]>C(Cl)Cl.CO>[NH:25]1[C:24]2[CH:28]=[C:20]([NH:13][C:12]3[C:11]4[C:10](=[CH:9][CH:8]=[C:6]5[N:7]=[C:3]([C:1]#[N:2])[S:4][C:5]5=4)[N:14]=[CH:15][N:16]=3)[CH:21]=[CH:22][C:23]=2[N:27]=[CH:26]1
Reactant: Nc1ccc2[nH]cnc2c1
Reactant: CN(C)/C=N/c1ccc2nc(C#N)sc2c1C#N
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: N#Cc1nc2ccc3ncnc(Nc4ccc5nc[nH]c5c4)c3c2s1
Yield: 98 %

Procedure:
Prepared from VII and 6-aminobenzimidazole. Flash chromatography eluent (DCM-MeOH 8:2). Yield: 98%; yellow solid; mp>260° C.; IR (KBr) νmax/cm−1 3084, 2226, 1615, 1557, 1464, 1376, 1347, 1248, 1147, 967, 939, 809; 1H NMR (300 MHz, DMSO-d6) δ 8.48 (d, 1H, J=8.7 Hz), 8.15-8.10 (m, 2H), 8.02 (m, 1H), 7.75 (d, 1H, J=8.7 Hz), 7.56 (m, 1H), 7.04 (m, 1H); HRMS calcd for C17H10N7S (M+H+): 344.0718, found 344.0705.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.[O:14]1[C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16][CH2:15]1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:21]2([OH:24])[CH2:22][CH2:23][C:18]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:19][CH2:20]2)=[N:3][CH:4]=1
Reactant: O=C1CCC2(CC1)OCCO2
Reactant: Brc1ccc(Br)nc1
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: OC1(c2ccc(Br)cn2)CCC2(CC1)OCCO2
Temperature: -78 °C
Reaction time: 2.5 h

Procedure:
To a solution of 2,5-dibromopyridine (4.10 g, 17 mmol) in anhydrous toluene (250 mL) at −78° C. was dropwise added n-BuLi (1.6 M, 12 mL). After stirred at −78° C. for 2.5 hours, a solution of 1,4-dioxa-spiro[4.5]decan-8-one (2.73 g, 17 mmol) in methylene chloride (25 mL) was added into the reaction mixture, and the resulting mixture was stirred for additional one hour and allowed to warm up to room temperature slowly. The reaction mixture was poured into aqueous NaHCO3 (200 mL) and then extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with saline solution (2×50 mL), dried over MgSO4, and concentrated in vacuo. The resulting solid was triturated with ether and the solid was collected by filtration. The ether solution was concentrated and the solid was chromatographed on silica gel, eluting with hexane/ethyl acetate (2 to 1) to give a pale yellow solid. Weight of combined solids:
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]([NH2:14])=[O:13])=[N:4][C:5](S(C)(=O)=O)=[N:6][CH:7]=1.[CH3:15][C@H:16]1[CH2:24][C:23]2[C:18](=[CH:19][C:20]([CH3:25])=[CH:21][CH:22]=2)[C@@H:17]1[NH2:26].C(N(CC)CC)C>CN(C)C(=O)C>[Cl:1][C:2]1[C:3]([C:12]([NH2:14])=[O:13])=[N:4][C:5]([NH:26][C@H:17]2[C:18]3[C:23](=[CH:22][CH:21]=[C:20]([CH3:25])[CH:19]=3)[CH2:24][C@@H:16]2[CH3:15])=[N:6][CH:7]=1
Reactant: CS(=O)(=O)c1ncc(Cl)c(C(N)=O)n1
Reactant: Cc1ccc2c(c1)[C@H](N)[C@@H](C)C2
Solvent: CC(=O)N(C)C
Solvent: CCN(CC)CC
Product: Cc1ccc2c(c1)[C@H](Nc1ncc(Cl)c(C(N)=O)n1)[C@@H](C)C2
Yield: 17.4 %

Procedure:
0.30 g (1.27 mmol) of 5-chloro-2-(methylsulfonyl)pyrimidine-4-carboxamide, 0.25 g (1.53 mmol) of (1R,2S)-2,6-dimethyl-2,3-dihydro-1H-indene-1-amine and 0.28 g (2.54 mmol) of triethylamine in 1.5 ml of N,N-dimethylacetamide are heated in a closed cuvette in the microwave at 120° C. for 45 minutes (Biotage Initiator, http://www.biotage.com/DynPage.aspx?id=22001). The crude mixture obtained in this manner is applied to silica gel and purified by column chromatography using the mobile phase heptane/ethyl acetate. Concentration gives initially 0.07 g of 5-chloro-2-{[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]amino}pyrimidine-4-carboxamide (wax-like) and then 0.252 g of 5-{[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]amino}-2-(methylsulfonyl)pyrimidine-4-carboxamide (yield 52% at a purity of 95%).
Reaction SMILES: C([O:3][CH:4]=[CH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[N:14]=2)[CH:11]=1)C.O.[Br:25]N1C(=O)CCC1=O>O1CCCC1>[Br:25][CH:5]([C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[N:14]=2)[CH:11]=1)[CH:4]=[O:3]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC=Cc1ccc2nc(C(=O)Nc3ccccc3)cn2c1
Solvent: C1CCOC1
Solvent: O
Product: O=CC(Br)c1ccc2nc(C(=O)Nc3ccccc3)cn2c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 168 mg of 6-(2-ethoxyvinyl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in 5.1 mL of tetrahydrofuran are added 1.4 mL of water followed by addition, after cooling to 0° C., of a solution of 97 mg of N-bromosuccinimide in 0.7 mL of tetrahydrofuran. The reaction mixture is stirred for 3 hours at room temperature. The 6-(1-bromo-2-oxoethyl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide formed is not isolated from the reaction mixture, which is treated with 42 mg of thiourea and stirred for a further 16 hours after allowing the temperature to return to 20° C. The solid formed is filtered off by suction, washed with water and then with methanol and dried to give 51 mg of 6-(2-aminothiazol-5-yl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in the form of a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10][CH3:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].S(Cl)(Cl)(=O)=[O:13].CCO>C(Cl)Cl>[CH3:11][S:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[O:13]
Reactant: CSc1cccc([N+](=O)[O-])c1
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: CCO
Product: CS(=O)c1cccc([N+](=O)[O-])c1
Temperature: -20 °C
Reaction time: 4 h
Yield: 90.3 %

Procedure:
A solution of 3-nitro thioanisol (96 g, 568 mmol) in DCM (100 mL) was added dropwise to a cooled solution of sulfuryl chloride (96 g, 711 mmol) in DCM (600 mL) at −60° C. The mixture was stirred for 4 h at −20° C., then cooled to −60° C., and 350 mL of EtOH were carefully added. The reaction was then allowed to warm up to rt, subsequently, most of the solvent was evaporated, the residue was poured in sat. aq. NaHCO3, and the solid product was filtered off and carefully washed with hexane on the filter, then air-dried to give the desired sulfoxide (95 g, 90% yield).
Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([NH:15][NH:16][C:17]([C@@H:19]1[CH2:25][CH2:24][C@@H:23]2[CH2:26][N:20]1[C:21](=[O:32])[N:22]2[O:27][S:28]([OH:31])(=[O:30])=[O:29])=[O:18])=[O:14])(C)(C)C.[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35]>C(Cl)Cl.CCOCC>[F:37][C:36]([F:39])([F:38])[C:34]([OH:40])=[O:35].[NH2:7][C@@H:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([NH:15][NH:16][C:17]([C@@H:19]1[CH2:25][CH2:24][C@@H:23]2[CH2:26][N:20]1[C:21](=[O:32])[N:22]2[O:27][S:28]([OH:31])(=[O:30])=[O:29])=[O:18])=[O:14]
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCC[C@H]1C(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OS(=O)(=O)O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: N[C@@H]1CCC[C@H]1C(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OS(=O)(=O)O
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a solution of compound 288 (0.1 g, 0.2 mmol) in DCM (10 mL) at 0° C. was added TFA (0.5 mL) dropwise. After addition, the mixture was stirred at 0° C. for 3 h then diluted with 50 mL of ether. The solid was collected by filtration and washed with additional ether and dried to afford the title compound Compound 40 (Table 2) as a white solid (0.07 g, 72%)
Reaction SMILES: [F:1][C:2]1([F:20])[C:8]2([CH2:9][O:10]CC3C=CC(OC)=CC=3)[CH:3]1[CH2:4][CH2:5][CH2:6][CH2:7]2.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N.S([O-])([O-])(=O)=O.[Na+].[Na+]>ClCCl.O>[F:1][C:2]1([F:20])[C:8]2([CH2:9][OH:10])[CH:3]1[CH2:4][CH2:5][CH2:6][CH2:7]2
Reactant: COc1ccc(COCC23CCCCC2C3(F)F)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: OCC12CCCCC1C2(F)F
Reaction time: 3 h
Yield: 62.4 %

Procedure:
To a solution of 7,7-difluoro-1-((4-methoxybenzyloxy)methyl)- bicyclo[4.1.0]heptane (2.50 g, 8.90 mmol) in dichloromethane (20 mL) and water (3.0 mL) was added DDQ (3.00 g, 13.3 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 3 hour. Water (1.5 mL) was added followed by sodium sulfate (10 g). The resulting suspension was filtered through a short pad of silica gel column with ethyl acetate in hexanes (30%) to afford the title compound as a colorless liquid (0.90 g, 62%).
Reaction SMILES: Cl.C[N:3]([CH2:15][CH2:16][N:17]1[N:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:27])[CH2:4][CH2:5]C1C=CC([N+]([O-])=O)=CC=1.NC1C=CC(CCN(CCN2N=CC3C(=CC=CC=3)C2=O)C)=CC=1.C(N(CCCl)CC)C1C=CC=CC=1.C1(=O)C2C(=CC=CC=2)C=NN1.[H-].[Na+]>CN(C)C=O>[CH2:4]([NH:3][CH2:15][CH2:16][N:17]1[N:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:27])[CH3:5]
Reactant: CN(CCc1ccc([N+](=O)[O-])cc1)CCn1ncc2ccccc2c1=O
Agent: CCN(CCCl)Cc1ccccc1
Agent: CN(CCc1ccc(N)cc1)CCn1ncc2ccccc2c1=O
Agent: Cl
Solvent: CN(C)C=O
Product: CCNCCn1ncc2ccccc2c1=O

Procedure:
N-Ethyl-2-(2H-phthalazin-1-on-2-yl)ethylamine was prepared similarly to the method of Preparation 1 parts (A) and (B) using N-benzyl-N-ethyl-2-chloroethylamine, 2H-phthalazin-1-one and sodium hydride in dimethylformamide.
Reaction SMILES: CN(C)C=O.[C:6](#[N:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[N-:14]=[N+:15]=[N-:16].[Na+].Cl>[Cl-].[Zn+2].[Cl-].O>[C:7]1([C:6]2[NH:16][N:15]=[N:14][N:13]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1ccccc1
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: c1ccc(-c2nnn[nH]2)cc1
Temperature: 25 °C
Yield: 90.1 %

Procedure:
Zinc chloride (3.3 g, 24.3 mmol, 0.5 eq) was added to 15 mL of N,N-dimethylformamide in small portions while maintaining the temperature below 60° C. The suspension of zinc chloride was cooled to room temperature and treated with 5.0 g of benzonitrile (48.5 mmol, 1.0 eq) followed by 3.2 g of sodium azide (48.5 mmol, 1.0 eq). The heterogeneous mixture was heated at 115° C. with agitation for 18 hours. The mixture was cooled to room temperature, water (30 mL) was added and the mixture acidified by the addition of 5.1 mL of concentrated hydrochloric acid. The mixture was cooled to 0° C. and aged for one hour, then filtered and the filter cake washed with 15 mL of cold 0.1N HCl then dried at 60° C. under vacuum to afford 6.38 g (43.7 mmol, 90%) of the product.
Reaction SMILES: [C:1]([C:4]1[C:5]([NH:13][C:14]([C:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[O:18][CH:17]=2)=O)=[CH:6][C:7]2[O:11][CH2:10][O:9][C:8]=2[CH:12]=1)(=[O:3])[CH3:2].CC(C)([O-])C.[K+].[Cl-].[NH4+].[K+].[Br-]>C(O)(C)(C)C>[O:18]1[CH:17]=[C:16]([C:14]2[CH2:2][C:1](=[O:3])[C:4]3[C:5](=[CH:6][C:7]4[O:11][CH2:10][O:9][C:8]=4[CH:12]=3)[N:13]=2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]1=2
Reactant: CC(=O)c1cc2c(cc1NC(=O)c1coc3ccccc13)OCO2
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [Cl-]
Solvent: CC(C)(C)O
Product: O=C1CC(c2coc3ccccc23)=Nc2cc3c(cc21)OCO3
Yield: 17 %

Procedure:
Into a suspension of 155 (2.95 mmol) in t-butyl alcohol (100 mL) was added potassium t-butoxide (1.66 g, 14.7 mmol). The mixture was refluxed under argon for 12 h, cooled, and poured into a 10% ammonium chloride solution (100 mL). The solid precipitate was collected and washed with EtOH. The crude product was purified by flash chromatography (silica gel, CH2Cl2: EtOH 16:1-10:1). Obtained as a pale-yellow solid from 155; yield 17%; mp>315° C.; ESI-MS (Positive mode): m/z 306 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): δ 6.12 (2H, s), 6.49 (1H, s), 7.13 (1H, s), 7.36-7.45 (3H, m), 7.69 (1H, d, J=8.0 Hz), 8.14 (1H, s), 8.52 (1H, s); IR (KBr): 1626 (C═O) cm−1; Anal. Calcd for C18H11NO4: C, 70.82; H, 3.63; N, 4.59. Found: C, 70.52; H, 3.95; N, 4.21.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[N:10]=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[N-:13]=[N+:14]=[N-:15].[Na+].[Cl-].[NH4+].Cl>CN(C)C=O>[N:6]1[NH:13][N:14]=[N:15][C:5]=1[C:4]1[C:3]([C:2]([F:11])([F:1])[F:12])=[N:10][CH:9]=[CH:8][CH:7]=1
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1cccnc1C(F)(F)F
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: FC(F)(F)c1ncccc1-c1nn[nH]n1
Temperature: 85 °C
Reaction time: 20 h

Procedure:
A mixture of 2-(trifluoromethyl)nicotinonitrile (0.43 g, 2.50 mmol), sodium azide (0.24 g, 3.75 mmol), and ammonium chloride (0.20 g, 3.75 mmol) in dimethylformamide (2.5 mL) was stirred at 85° C. for 20 hours. After cooling to room temperature, the reaction mixture was poured onto water (20 mL) and acidified with dilute hydrochloric acid. The resulting precipitate was collected, washed with water and dried to yield 3-(2H-tetrazol-5-yl)-2-(trifluoromethyl)pyridine, 0.484 g (90%).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.S(Cl)(Cl)=O.[C:10]1([S:16][CH2:17][C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[OH:26])=O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)Cl.C(N(CC)CC)C>[OH:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:18]([C:2]1[NH:1][CH:5]=[CH:4][N:3]=1)=[CH:17][S:16][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: c1c[nH]cn1
Reactant: O=C(CSc1ccccc1)c1ccccc1O
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Oc1ccccc1C(=CSc1ccccc1)c1ncc[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of 1.02 g of imidazole, 1.52 g of triethylamine and 30 ml of dry methylene chloride, 1.78 g of thionyl chloride was added with ice-cooling. The resultant mixture was stirred for 30 minutes, followed by addition of 2.44 g of 2-phenylthio-2'-hydroxyacetophenone and a solution consisting of 1.16 g of triethylamine and 5 ml of dry methylene chloride. The reaction mixture was stirred at room temperature for further 2 hours. Ice water was then added to the reaction mixture, followed by its extraction with methylene chloride. The organic, i.e., methylene chloride layer was washed with water, dried over magnesium sulfate, and then concentrated. The residue was dissolved in chloroform. The chloroform solution was subjected to chromatography on a silica gel column. Upon concentration of the resulting eluate, 0.2 g of Isomer A (Compound 61; m.p. 235.5°-237° C.) and 0.9 g of Isomer B (Compound 62; m.p. 152.5°-154° C.) of 1-(2-hydroxyphenyl)-1 -imidazolyl-2-phenylthioethylene were obtained respectively as colorless crystals.
Reaction SMILES: [C:1]([OH:7])(=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5].[C:8]1([CH2:14][CH2:15]O)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C([O-])(=O)C([O-])=O.[Sn+4].C([O-])(=O)C([O-])=O>[C:1]([O:7][CH2:15][CH2:14][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: OCCc1ccccc1
Reactant: CCCCC(=O)O
Agent: O=C([O-])C(=O)[O-]
Agent: [Sn+4]
Product: CCCCC(=O)OCCc1ccccc1
Temperature: 170 °C
Reaction time: 1 h
Yield: 74.7 %

Procedure:
A 2-L, 4-neck, round-bottom flask, fitted with a thermometer, mechanical stirrer, nitrogen inlet tube and Liebig condenser/receiving flask, was charged with 612.8 g (6.00 mol, 1.00 equiv) of pentanoic acid, 733.0 g (6.00 mol, 1.00 equiv) of 2-phenylethanol, and 2.50 g (0.2 wt. %) of tin oxalate (Fascat® 2001). The air was removed with three cycles of evacuation/nitrogen-fill using a mechanical vacuum pump (50-100 torr). The rate of stirring was set at ca. 200 rpm, the nitrogen sparge was set at 0.1 scfh, and the reaction mixture was heated to 170° C. After a 1-h hold, 159.3 g of distillate had been collected. It was not possible to get a clean separation; therefore, the organic layer was not returned to the reaction mixture. The temperature was increased to 180, 190, 200 and 210° C. and held for 1 h at each; the amounts of distillate were 21.4, 9.8, 4.9 and 2.2 g, respectively. The acid number was 2.88 mg KOH/g (99.0% conversion). The excess 2-phenylethanol (6.3% by GLC) was removed by vacuum distillation through a 15-cm Vigreux column at 140-165° C. (15-20 torr). The crude product was distilled at 150-155° C. (10 torr, 0.5 scfh nitrogen sweep) to afford 925 g (75%) of 2-phenylethyl pentanoate (99.3% pure by GLC): residual alcohol, 0.3% (GLC); APHA color, 13; acid number, 0.06 mg KOH/g; saponification number, 271 mg KOH/g (theor. 272 mg KOH/g).
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10][C:11]#[C:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrC1C=CC(C=O)=CC=1.O(CCCC#C)C1C=CC=CC=1>C(N(CC)CC)C.C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[O:1]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][OH:18])=[CH:19][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccc(C#CCCCOc2ccccc2)cc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: C#CCCCOc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: OCc1ccc(CCCCCOc2ccccc2)cc1

Procedure:
4-(5-Phenoxypent-1-ynyl)benzaldehyde--By the method of C. D. Perchonock, et al., J. Med. Chem., 29, 1442 (1986), 2.0 g 4-bromobenzaldehyde, 2.1 g (0.013 mole) 5-phenoxypent-1-yne, 0.76 g bis (triphenylphosphine) palladium (II) chloride, and 0.10 g copper (I) iodide in 7.0 mL dry triethylamine were stirred under argon for 17 hours. The mixture was diluted with ethyl acetate and washed with 2% H2SO4, then with water and finally with saturated aqueous NaCl. The resultant dark solution was treated with about 2 g activated carbon powder, dried over MgSO4 and then filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography using 3-6% ethyl acetate in hexane as eluant. The title compound was obtained as a tan solid (2.2 g, 78%).