Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH3:9])=[C:4]([OH:11])[CH:3]=1.C(N1C=CN=C1)([N:14]1C=CN=C1)=O.C(N(CC)CC)C>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]([CH3:9])=[N:14][O:11][C:4]=2[CH:3]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CC(=O)c1ccc(F)cc1O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1noc2cc(F)ccc12

Procedure:
A mixture of 4′-fluoro-2′-hydroxyacetophenone, oxime (47.0 g, 0.278 mol) in tetrahydrofuran is heated to just under reflux, treated with a solution of 1,1′-carbonyldiimidazole (55.0 g, 0.340 mol) and triethylamine (39.0 g, 0.390 mol) in tetrahydrofuran, refluxed for one hour, cooled, concentrated in vacuo, and poured into an ice-water mixture. The resultant aqueous mixture is extracted with ether. The organic extracts are combined, washed sequentially with saturated ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain an oil. Column chromatography of the oil using silica gel and a methylene chloride/hexanes solution (1:1) gives the title product as a yellow oil which is identified by 1H NMR spectral analysis.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-:13])=[O:12].IC.[CH3:17]S(C)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O>[CH3:1][O:2][C:3](=[O:14])[CH:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-:13])=[O:12])[CH3:17]
Reactant: COC(=O)Cc1ccccc1[N+](=O)[O-]
Reactant: CS(C)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CI
Solvent: O
Product: COC(=O)C(C)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A round bottom flask was charged with (2-nitro-phenyl)-acetic acid methyl ester (4.22 g, 21.6 mmol) (prepared as described in Organic Letters, 2009, 11, 1345-1348), iodomethane (2.8 mL, 45 mmol) and dry dimethyl sulfoxide (20 mL). Cesium carbonate (18 g, 56 mmol) was added and the mixture was stirred at room temperature under an atmosphere of nitrogen for 18 hours. Water (50 mL) was added and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with water (2×30 mL), saturated aqueous sodium chloride (30 mL), dried over magnesium sulfate, filtered and evaporated. 2-(2-Nitro-phenyl)-propionic acid methyl ester was isolated as a red oil (3.24 g, 71%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.93 (d, J=8.1 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.43 (t, J=7.7 Hz, 1H), 4.32 (q, J=7.0 Hz, 1H), 3.67 (s, 3H), 1.61 (d, J=7.0 Hz, 3H). MS=232 (MH)+.
Reaction SMILES: [C:1]([NH:4][C:5]1[N:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[C:6]=1[C:7]([OH:9])=O)(=[O:3])[CH3:2].[CH:16]1([CH2:19][N:20]2[C:28]3[N:27]=[C:26]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([NH:36][CH3:37])=[CH:32][CH:31]=4)[NH:25][C:24]=3[C:23](=[O:38])[N:22]([CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[F:46])[C:21]2=[O:47])[CH2:18][CH2:17]1>CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[NH:4]([C:5]1[N:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[C:6]=1[C:7]([N:36]([C:33]1[CH:34]=[CH:35][C:30]([CH2:29][C:26]2[NH:25][C:24]3[C:23](=[O:38])[N:22]([CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=4[F:46])[C:21](=[O:47])[N:20]([CH2:19][CH:16]4[CH2:18][CH2:17]4)[C:28]=3[N:27]=2)=[CH:31][CH:32]=1)[CH3:37])=[O:9])[C:1]([CH3:2])=[O:3]
Reactant: CC(=O)Nc1nc(C)cc(C)c1C(=O)O
Reactant: CNc1ccc(Cc2nc3c([nH]2)c(=O)n(Cc2ccccc2F)c(=O)n3CC2CC2)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Product: CC(=O)Nc1nc(C)cc(C)c1C(=O)N(C)c1ccc(Cc2nc3c([nH]2)c(=O)n(Cc2ccccc2F)c(=O)n3CC2CC2)cc1

Procedure:
This compound was prepared by a method similar to that described in example 79 except that 2-acetylamino-4,6-dimethylnicotinic acid was used in place of N-acetyl-6-amino-2-pyridine carboxylic acid, the reaction was performed using 1 equivalent of 3-cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dione and excess triethyl amine and a catalytic amount of 4-dimethylaminopyridine were added as the final reagents to the reaction mixture. The product was purified by chromatography using silica gel eluted with 93:7 chloroform/methanol. MS, m/z(M+)=624.4 and m/z(M−)=622.5.
Reaction SMILES: [CH:1](=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].[C-:9]#[N:10].[Na+]>C(OCC)(=O)C.O>[OH:8][CH:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7])[C:9]#[N:10]
Reactant: C=CCCCCC=O
Reactant: [C-]#N
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: C=CCCCCC(O)C#N
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Pyridinium chlorochromate (19.26 g, 0.088 mol) was added to a solution of hept-6-en-1-ol (5.0 g, 0.044 mol) and dichloromethane (600 mL). The resulting mixture was stirred at room temperature for 2 h, then diluted with diethyl ether, filtered through silica gel and concentrated in vacuo below room temperature to yield hept-6-enal as an oil, which was used in the next step without further purification. To a solution of hept-6-enal (4.9 g, 0.044 mol) in ethyl acetate (36 mL) was added a solution of sodium cyanide (6.4 g, 0.13 mol) in water (36 mL) and the resulting mixture was stirred at room temperature for 24 h. The layers were separated and the aqueous layer was extracted 2 times with ethyl acetate. The combined organic layers were dried (MgSO4) filtered and concentrated in vacuo to yield 2-hydroxyoct-7-enenitrile as a tan oil, which was used in the next step without further purification. A stream of HCl(g) was introduced into a solution of 2-hydroxyoct-7-enenitrile (6.0 g, 0.043 mmol) and methanol (130 mL) at −78° C. for 5 min. The resulting mixture was stored at −10° C. for 18 h, then concentrated in vacuo. The residue was diluted with ethyl acetate (106 mL) and water (106 mL) and the solution was stirred at room temperature overnight. The layers were separated, and the organic layer was dried with MgSO4, filtered, and concentrated in vacuo to yield methyl 2-hydroxyoct-7-enoate. 1H NMR (400 MHz, CDCl3) δ 5.48-5.82 (m, 1H), 4.89-5.08 (m, 2H), 4.31-4.52 (m, 1H), 3.79 (s, 3H), 2.78-3.12 (bs, 1H), 2.02-2.28 (m, 2H), 1.75-1.89 (m, 1H), 1.68-1.70 (m, 1H), and 1.38-1.52 (m, 4H).
Reaction SMILES: I[C:2]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:13]C1(C)CCCB(C)O1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.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>[CH3:13][C:2]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=1[NH2:4]
Reactant: CB1CCCC(C)(C)O1
Reactant: Nc1ccc(C(F)(F)F)cc1I
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: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(C(F)(F)F)ccc1N
Temperature: 100 °C

Procedure:
A mixture of 2-iodo-4-trifluoromethyl aniline (5.0 g, 17.42 mmol), trimethylboroxane (3.64 ml, 26.1 mmol), tetrakis(triphenylphosphine)palladium (1.0 g, 0.87 mmol) and potassium carbonate (4.82 g, 34.8) in DMF (10 ml) was heated to 100° C. for 48 h. The reaction was quenched with water (50 ml) and extracted with EtOAc (3×50 ml). The combined EtOAc layers were washed with brine and dried over sodium sulfate. The title compound was obtained after flash column using EtOAc:hexane/1:9 as the eluant. 1H NMR (CDCl3, 500 MHz): δ7.13 (s, 1H), 7.30 (d, J=8 Hz, 1H), 6.71 (d, J=8 Hz, 1H), 3.98 (br s, 2H), 2.21 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[N:9][NH:10]2.[CH3:20][N:21](C=O)C>[C-]#N.[Zn+2].[C-]#N>[Cl:19][C:17]1[CH:18]=[C:2]([CH:3]=[C:4]([O:5][C:6]2[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]3[C:7]=2[CH:8]=[N:9][NH:10]3)[CH:16]=1)[C:20]#[N:21]
Reactant: Clc1cc(Br)cc(Oc2c(Cl)ccc3[nH]ncc23)c1
Reactant: CN(C)C=O
Agent: [C-]#N
Agent: [Zn+2]
Product: N#Cc1cc(Cl)cc(Oc2c(Cl)ccc3[nH]ncc23)c1
Temperature: 90 °C

Procedure:
To a suspension of 4-(3-bromo-5-chlorophenoxy)-5-chloro-1H-indazole (40 g, 112 mmol) and zinc cyanide (15.74 g, 134 mmol) in DMF (400 mL) was added palladium tetrakis triphenylphosphine (38.7 g, 33.5 mmol) and heated to 90° C. for 1 hour. After this time, the reaction was cooled to room temperature and partitioned between saturated aq. NH4Cl (500 mL), water (500 mL) and EtOAc (2×1000 mL). The combined extracts were dried over MgSO4, absorbed onto silica gel (200 g) and the solvent removed in vacuo. This solid was purified on a silica gel (1000 g) column (0-10% EtOAc/CH2Cl2) to give the title compound as a white solid. LRMS (M+1)=303.9
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][CH2:6]O.C(Br)(Br)(Br)[Br:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][CH2:6][Br:12]
Reactant: OCCc1cccc(F)c1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Fc1cccc(CCBr)c1
Reaction time: 0.5 h
Yield: 100.5 %

Procedure:
To a solution of 3-(fluoro)phenethyl alcohol (3.8 g, 27.0 mmol), in anhydrous dichloromethane (100 ml), cooled to 0° C., was added carbon tetrabromide (11.25 g, 34.0 mmol) and triphenylphosphine (10.62 g, 41.0 mmol). After stirring for 0.5 h the solvent was removed in vacuo and diethyl ether (100 ml) was added to the residue. The resultant precipitate was removed by filtration, the filtrate evaporated under reduced pressure and the crude product chromatographed on silica-gel eluting with ethyl acetate/hexane (1:1) to give 3-(fluoro)phenethyl bromide (5.51 g, 100%), δ (250 MHz, CDCl3) 3.16 (2H, t, J=7.4 Hz, CH2), 3.57 (2H, t, J=7.4 Hz, CH2), 6.91-7.01 (3H, m, Ar--H), 7.24-7.33 (1H, m, Ar--H).
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[CH:8][S:9][C:10]=1[S:11][CH2:12][CH2:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15])=O)C.[BH4-].[Li+].CO>C1COCC1>[OH:3][CH2:4][C:6]1[N:7]=[CH:8][S:9][C:10]=1[S:11][CH2:12][CH2:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15]
Reactant: CCOC(=O)c1ncsc1SCCS(=O)(=O)c1ccccc1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CO
Product: O=S(=O)(CCSc1scnc1CO)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.4 %

Procedure:
To a solution of 4-ethoxycarbonyl-5-[2-(phenylsulfonyl)ethylthio]thiazole (702 mg, 2 mmol) in 20 ml of THF was added lithium borohydride (2M, 1 ml) and methanol (0.16 ml, 4 mmol) at -30° C. The reaction mixture was allowed slowly warm up to room temperature and stirred overnight. The solvent was removed under reduced pressure and the crude residue was subjected to chromatography by using dichloromethane and methanol as the eluent to give the title compound (400 mg, 65%). 1H NMR (CDCl3) δ 2.55 (s, 1H), 3.00 (t, 2H, J=6), 3.40 (t, 2H, J=6), 4.71 (s, 2H), 7.6 (t, 2H, J=7), 7.68 (t, 1H, J=7), 7.82 (d, 2H, J=7), and 8.80 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.N1C=CC=CC=1.[C:15](Cl)(=[O:19])[CH:16]([CH3:18])[CH3:17]>C(Cl)Cl>[Br:8][C:6]1[CH:7]=[C:2]([NH:1][C:15](=[O:19])[CH:16]([CH3:18])[CH3:17])[CH:3]=[N:4][CH:5]=1
Reactant: CC(C)C(=O)Cl
Reactant: Nc1cncc(Br)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)C(=O)Nc1cncc(Br)c1
Temperature: 0 °C
Reaction time: 15 h
Yield: 71 %

Procedure:
3-Amino-5-bromo pyridine (XVIII) (1 eq) was dissolved in DCM and cooled to 0° C. before adding pyridine (2.2 eq) and isobutyryl chloride (XIX) (1.1 eq). The reaction mixture was stirred at r.t. for 15 h until TLC showed the reaction was complete. The reaction mixture was diluted with DCM and washed with water. The organic extract was dried, concentrated and purified by column chromatography using silica gel (100-200 mesh) to afford N-(5-bromopyridin-3-yl)isobutyramide (XX) as a off white solid, (71% yield). 1H NMR (CDCl3) δ ppm 8.55-8.35 (m, 3H), 7.32 (s, 1H), 2.59-2.48 (m, 1H), 1.28-1.27 (d, 6H); ESIMS found C9H11BrN2O m/z 243.05 (M+H).
Reaction SMILES: Cl.[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][NH2+:18]3)=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1.[OH:23][C:24]1[CH:32]=[N:31][CH:30]=[CH:29][C:25]=1[C:26](O)=O>>[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][N:18]3[CH2:26][C:25]3[CH:29]=[CH:30][N:31]=[CH:32][C:24]=3[OH:23])=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:9])(=[O:10])[N:8]=1
Reactant: O=C(O)c1ccncc1O
Reactant: NC1=NS(=O)(=O)Nc2cccc(OC[C@H]3CCCC[NH2+]3)c21
Agent: Cl
Product: NC1=NS(=O)(=O)Nc2cccc(OC[C@H]3CCCCN3Cc3ccncc3O)c21

Procedure:
Prepared as in Example 15 from (R)-2-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidinium hydrochloride (Example 15a) and 3-hydroxyisonicotinic acid. 1H NMR (400 MHz, DMSO-d6) δ 1.45 (m, 1H), 1.52-1.74 (m, 4H), 1.84 (m, 1H), 3.19 (m, 2H), 4.18 (dd, 1H, J=10.2, 4.0 Hz), 4.64 (t, 1H, J=10.0 Hz), 5.25 (m, 1H), 6.61 (d, 1H, J=8.2 Hz), 6.87 (d, 1H, J=8.2 Hz), 7.08 (d, 1H, J=5.5 Hz), 7.46 (t, 1H, J=8.2 Hz), 7.84 (br s, 1H), 8.07 (d, 1H, J=5.5 Hz), 8.19 (s, 1H), 8.29 (br s, 1H), 10.28 (s, 1H), 10.9 (br s, 1H). MS 432 (MH+).
Reaction SMILES: [Br-].[CH2:2]([C@H:5]1[CH2:10][CH2:9][C@H:8]([CH2:11][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:7][CH2:6]1)[CH2:3][CH3:4].CC([O-])(C)C.[K+].[C:37]([C:39]1[CH:46]=[CH:45][C:42]([CH:43]=O)=[CH:41][CH:40]=1)#[N:38].O>O1CCCC1>[CH2:2]([C@H:5]1[CH2:10][CH2:9][C@H:8]([CH:11]=[CH:43][C:42]2[CH:45]=[CH:46][C:39]([C:37]#[N:38])=[CH:40][CH:41]=2)[CH2:7][CH2:6]1)[CH2:3][CH3:4]
Reactant: N#Cc1ccc(C=O)cc1
Reactant: CCC[C@H]1CC[C@H](C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CCC[C@H]1CC[C@H](C=Cc2ccc(C#N)cc2)CC1
Temperature: -20 °C
Reaction time: 1 h

Procedure:
To a mixture of 25.0 g (0.11 mol) of trans-4-propylcyclohexylmethyltriphenylphosphonium bromide and 100 ml of tetrahydrofuran (THF) was added 12.2 g (0.10 mol) of t-BuOK while maintaining a temperature of lower than −20° C., and stirred for 1 hour. Subsequently, 70 ml of solution of 12.9 g (0.10 mol) of 4-cyanobenzaldehyde in THF was added dropwise to the solution while maintaining a temperature of lower than −20° C., and stirred at the same temperature for 2 hours to react. After finishing of the reaction, 50 ml of water was added to the reaction product and then extracted with 100 ml of toluene. The organic layer thus obtained was washed with water thrice and then dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: toluene) to obtain 12.1 g of a crude 4-(2-(trans-4-propylcyclohexyl)vinyl)benzonitrile.
Reaction SMILES: [CH2:1]([C:5]1[S:9][C:8]([C:10]2[O:14][C:13]([C:15]3[CH:26]=[C:25]([CH3:27])[C:18]([O:19][CH2:20][CH:21]([OH:24])[CH2:22][OH:23])=[C:17]([CH3:28])[CH:16]=3)=[N:12][N:11]=2)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[OH:24][CH:21]([CH2:20][O:19][C:18]1[C:25]([CH3:27])=[CH:26][C:15]([C:13]2[O:14][C:10]([C:8]3[S:9][C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:6][CH:7]=3)=[N:11][N:12]=2)=[CH:16][C:17]=1[CH3:28])[CH2:22][O:23][S:39]([CH3:38])(=[O:41])=[O:40]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cc(-c2nnc(-c3ccc(CC(C)C)s3)o2)cc(C)c1OCC(O)CO
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cc(-c2nnc(-c3ccc(CC(C)C)s3)o2)cc(C)c1OCC(O)COS(C)(=O)=O
Reaction time: 1 h
Yield: 29.3 %

Procedure:
To a solution of 3-{4-[5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol (627 mg, 1.56 mmol) and DIPEA (311 mg, 2.41 mmol) in DCM (10 mL), methanesulfonyl chloride (207 mg, 1.81 mmol) is added. The mixture is stirred at rt before another portion of DIPEA (40 mg, 0.31 mmol) and methanesulfonyl chloride (36 mg, 0.31 mmol) is added. Stirring is continued for 1 h before the reaction is quenched by adding water. The mixture is extracted with DCM. The org. extract is washed with water, dried over MgSO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 7:3 to give methanesulfonic acid 2-hydroxy-3-{4-[5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenoxy}-propyl ester (220 mg) as a colourless oil; LC-MS: tR=1.08 min, [M+1]+=481.09.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].C([S:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19](=[O:21])[CH3:20])C1C=CC=CC=1>C1C=CC=CC=1>[SH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19](=[O:21])[CH3:20]
Reactant: CC(=O)c1ccccc1SCc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: c1ccccc1
Product: CC(=O)c1ccccc1S
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.4 %

Procedure:
To a stirred suspension of aluminium chloride (10.50 g, 78.8 mmol) in dry benzene (200 mL) was added a solution of 1-[2-(benzylsulfanyl)phenyl]ethan-1-one (11.93 g, 49.2 mmol) in dry benzene (100 mL) dropwise in an ice bath under argon atmosphere. After the reaction mixture being stirred at room temperature overnight, the reaction was quenched by the cautious addition of ice-water. The separated organic layer was washed with water and extracted with 5% aqueous solution of sodium hydroxide (300 mL). The aqueous layer was acidified to about pH 3 with concentrated hydrochloric acid (12 N) and extracted with dichloromethane (300 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo to afford 6.47 g of the crude product 1-(2-sulfanylphenyl)ethanone.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([CH:12]2[CH:16]=[N:15][N:14]=[N:13]2)=[CH:8][C:4]=1[C:5](O)=[O:6].C(Cl)(=O)C([Cl:20])=O>CN(C)C=O.ClCCl>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([CH:12]2[CH:16]=[N:15][N:14]=[N:13]2)=[CH:8][C:4]=1[C:5]([Cl:20])=[O:6]
Reactant: COc1ccc(C2C=NN=N2)cc1C(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1ccc(C2C=NN=N2)cc1C(=O)Cl
Reaction time: 4 h

Procedure:
Combine 2-methoxy-5-(4H-triazol-4-yl)benzoic acid (5 mmol) and dichloromethane (40 mL). Add dropwise oxalyl chloride (0.72 mL, 8.25 mmol) followed by dimethylformamide (3 drops). After 4 hours, evaporate invacuo and dry to give the title compound.
Reaction SMILES: [CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([OH:8])[CH:2]=1.[OH-].[Na+].CS(C)=O.Cl[CH2:16][CH2:17][CH2:18][Si:19]([O:24][CH3:25])([O:22][CH3:23])[O:20][CH3:21]>C1(C)C=CC=CC=1>[NH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:8][CH2:16][CH2:17][CH2:18][Si:19]([O:24][CH3:25])([O:22][CH3:23])[O:20][CH3:21])=[CH:2][CH:1]=1
Reactant: CO[Si](CCCCl)(OC)OC
Reactant: Nc1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: Cc1ccccc1
Product: CO[Si](CCCOc1ccc(N)cc1)(OC)OC
Temperature: 85 °C

Procedure:
A glass reactor was charged with 60 g (0.55 mole) p-aminophenol, 43.28 g of a 50% aqueous solution of sodium hydroxide (0.54 mole NaOH), 112 cc dimethylsulfoxide and 120 cc toluene. The resultant mixture was heated to the boiling point for six hours under a nitrogen atmosphere to remove all of the water present by azeotropic distillation. The reaction mixture was then allowed to cool to about 75° C., at which time 109 g (0.55 mole) of 3-chloropropyl trimethoxysilane was added dropwise while the reaction mixture was stirred. The temperature of the reaction mixture increased spontaneously to 85° C. during this addition. The temperature of the reaction mixture was maintained at from 75° to 85° C. by heating and control of the addition rate. Following completion of the addition, the reaction mixture was heated at 115° C. for 16 hours, following which the mixture was allowed to cool and was filtered to remove any solid material. The solvents were then removed under a pressure of about 15 mm of mercury at a temperature of about 60° C. The pressure was then reduced to from 3 to 4 mm of mercury and the material boiling from 170° to 180° C. was recovered. This fraction, which weighed 70 g, was distilled using a fractionating column and a 50 g portion boiling from 175° to 177° C. under a pressure of 3 mm of mercury, was collected. The colorless liquid was found to contain 10.19% silicon and 5.20% nitrogen. The calculated values for 3(p-aminophenoxy)propyl trimethoxy silane are 10.33% silicon and 5.17% nitrogen. The infrared and nuclear magnetic resonance spectra of the product were in agreement with the proposed structure.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[N:11][N:12]([CH2:14][CH2:15][OH:16])[CH:13]=1)C1C=CC=CC=1.[H][H]>C1COCC1.[Pd]>[OH:16][CH2:15][CH2:14][N:12]1[CH:13]=[C:9]([OH:8])[CH:10]=[N:11]1
Reactant: OCCn1cc(OCc2ccccc2)cn1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: OCCn1cc(O)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 169.3 %

Procedure:
2-(4-(benzyloxy)-1H-pyrazol-1-yl)ethanol (1.81 g, 8.3 mmol) was dissolved in THF (15 mL) under nitrogen. Pd/C (0.22 g, 0.21 mmol) was added and the solution was placed under vacuum and charged with a hydrogen balloon. The mixture stirred at ambient temperature overnight under this hydrogen atmosphere. The solution was filtered through GF/F paper and concentrated to give 1-(2-hydroxyethyl)-1H-pyrazol-4-ol (1.8 g, quantitative).
Reaction SMILES: [CH:1]([CH:3]([CH2:9][CH3:10])[CH2:4][C:5]([O:7]C)=O)=O.[C:11]1([CH2:17][CH2:18][NH2:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(O)(=O)C>[CH2:9]([C:3]1[CH2:1][N:19]([CH2:18][CH2:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5](=[O:7])[CH:4]=1)[CH3:10]
Reactant: NCCc1ccccc1
Reactant: CCC(C=O)CC(=O)OC
Solvent: CC(=O)O
Product: CCC1=CC(=O)N(CCc2ccccc2)C1

Procedure:
4-Ethyl-1-phenethyl-1H-pyrrol-2(5H)-one is synthesized by a cyclocondensation between methyl 3-formylpentanoate and 2-phenylethylamine in glacial acetic acid at 70° C. according to a procedure of R. Fisher (DE 4127111, 1992)
Reaction SMILES: [CH3:1][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:18]([NH2:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].Cl[C:22]([CH3:26])([CH3:25])[C:23]#[CH:24]>CN(C)C=O.[Cu]>[CH3:3][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:8][CH2:9][N:10]([C:13]2[C:18]([NH:19][C:22]([CH3:26])([CH3:25])[C:23]#[CH:24])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:11][CH2:12]1)=[O:6])[CH3:1]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncccc2N)CC1
Reactant: C#CC(C)(C)Cl
Agent: [Cu]
Solvent: CN(C)C=O
Product: C#CC(C)(C)Nc1cccnc1N1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 16 h

Procedure:
To a mixture of 1-[1,1-dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 5.40 g), cuprous chloride (1.00 g), copper powder (1.00 g), and dry dimethylformamide (25 ml) under nitrogen at 0° is added a solution of 3-chloro-3-methyl-1-butyne (2.00 g) in dry dimethylformamide (5 ml) in 4 portions over 15 min. The resulting mixture is then stirred at 20°-25° for 16 hrs, concentrated, and diluted with methylene chloride (75 ml) and water (20 ml). The layers are separated and the aqueous phase is extracted with methylene chloride (25 ml). The combined organic phase is washed with saline (20 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a residue which is chromatographed on silica gel (70-230 mesh, 500 g), eluting with a gradient of ethyl acetate/hexane (10/90-20/80). Pooling of fractions giving an Rf =0.31 (ethyl acetate/hexane, 25/75) and removal of solvent under reduced pressure gives the title compound, NMR (CDCl3) 7.75, 7.47, 6.94, 4.61, 3.56, 3.00, 2.39, 1.64 and 1.48 δ.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]=[C:10]2[CH2:13][CH2:14][CH2:15][N:16]2C(=O)C3C(=CC=CC=3)C2=O)=[CH:5][CH:4]=1.O.NN>C(O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]=[C:10]2[CH2:13][CH2:14][CH2:15][NH2:16])=[CH:5][CH:4]=1
Reactant: COc1ccc2c(c1)C(CCCN1C(=O)c3ccccc3C1=O)=CCC2
Agent: NN
Solvent: O
Solvent: CCO
Product: COc1ccc2c(c1)C(CCCN)=CCC2
Yield: 77.1 %

Procedure:
A solution of 2-[3-(7-methoxy-3,4-dihydronaphthalen-1-yl)propyl]isoindole-1,3-dione (11.8 g, 34.0 mmol) and hydrazine monohydrate (5.1 g, 0.1 mol) in ethanol (150 ml) was refluxed for 1 hour and then cooled in an ice bath. The resulting insoluble material was removed by filtration and the solvent was removed in vacuo to afford the titled compound (5.7 g, yield 77%, oil). This compound was provided for the next reaction without further purification.