Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1([CH2:11][CH:12]=C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CSC.C(N(CC)CC)C.[Cl-].[NH4+].C[OH:27]>C(Cl)Cl>[C:1]([O:5][C:6]([C:8]1([CH2:11][CH:12]=[O:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CO
Reactant: C=CCC1(C(=O)OC(C)(C)C)CC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CSC
Product: CC(C)(C)OC(=O)C1(CC=O)CC1
Temperature: -72 °C
Yield: 56 %

Procedure:
6.9 g (36.34 mmol, 1 eq., 96% a % by GC) 1-allyl-cyclopropanecarboxylic acid tert-butyl ester were dissolved in 40 ml CH2Cl2 and 40 ml MeOH. The solution was cooled to −72° C. and the ozone was bubbled through the reaction mixture until a blue color was obtained. Then nitrogen was bubbled to remove excess ozone until a colorless solution was obtained. 10 ml (3.68 eq.) dimethyl sulfide and 14 ml (2.76 eq.) triethylamine were added. The reaction mixture was warmed to RT and stirred overnight at that temperature (peroxide test negative, pH 7-8). The yellowish reaction mixture was added to 100 ml sat. aq. ammonium chloride solution (exothermic) and extracted 3 times with 70 ml CH2Cl2. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude aldehyde, which was purified by filtration over SiO2 (CH2Cl2; TLC:EtOAc/heptane 1:2) to provide 3.90 g (96% GC, 56% yield) of the title compound as an oil.
Reaction SMILES: [H-].[Na+].[Br-].[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O.[CH3:34][C:35](=O)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>O>[CH3:34][CH:35]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]=[CH:5][OH:4]
Reactant: OCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCCCCCCCC(C)=O
Agent: [Br-]
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCCCCCC(C)CCCCC=CO
Temperature: 70 °C
Reaction time: 18 h
Yield: 49.5 %

Procedure:
Into a dried 5 L, 3 neck round bottom flask fitted with mechanical stirring, nitrogen inlet, dropping funnel, thermometer and nitrogen outlet is added 80 g of 60% sodium hydride (2.0 mol) in mineral oil. The mineral oil is removed by washing with hexanes. Anhydrous dimethyl sulfoxide (500 ml) is added to the flask and heated to 70° C. until evolution of hydrogen stops. The reaction mixture is cooled to room temperature followed by addition of 1 L of anhydrous tetrahydrofuran. (6-hydroxyhexyl) triphenylphosphonium bromide (443.4 g, 1 mol) is slurried with warm anhydrous dimethyl sulfoxide (50° C., 500 ml) and slowly added to the reaction mixture thru the dropping funnel while keeping the reaction at 25-30° C. The reaction is stirred for 30 minutes at room temperature at which time 2-decanone (171.9 g, 1.1 mol) is slowly added thru a dropping funnel. Reaction is slightly exothermic and cooling is needed to maintain 25-30° C. Mixture is stirred for 18 hrs. and then poured into a separatory funnel containing 600 ml of purified water and 300 ml of hexanes. After shaking the oil phase (top) is allowed to separate out and the water phase is removed. The extractions of the oil phase are continued using water until both phases are clear. The organic phase is collected, vacuum distilled and purified by liquid chromatography (90:10 hexanes:ethyl acetate, silica gel stationary phase) to obtain a clear, oily product (119.1 g).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(=O)([O-])[O-:16].[K+].[K+].[F:21][C:22]([F:27])([F:26])[CH2:23][CH2:24]I>C(#N)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([OH:16])[CH2:14][CH2:13][N:12]([CH2:24][CH2:23][C:22]([F:27])([F:26])[F:21])[CH2:11][CH2:10]1
Reactant: O=C([O-])[O-]
Reactant: FC(F)(F)CCI
Reactant: Clc1cccc(C2CCNCC2)c1Cl
Agent: [K+]
Solvent: CC#N
Product: OC1(c2cccc(Cl)c2Cl)CCN(CCC(F)(F)F)CC1

Procedure:
Preparation according to Example 2: 4-(2,3-dichlorophenyl)piperidine (0.02 g, 0.081 mmol), acetonitrile (2 ml), potassium carbonate (0.02 g, 0.14 mmol), 1,1,1-trifluoro-3-iodopropane (0.010 ml, 0.082 mmol). MS m/z (relative intensity, 70 eV) 343 (M+, 10), 341 (M+, 15), 260 (52), 258 (82), 152 (54), 42 (bp).
Reaction SMILES: [Cl:1][C:2]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([O:11][CH2:12][CH3:13])[C:3]=1[CH:4]=[O:5].[Br:14][C:15]1[CH:16]=[C:17]2[C:21](=[N:22][CH:23]=1)[NH:20][CH:19]=[CH:18]2.[OH-].[K+].[CH3:26]O>>[Br:14][C:15]1[CH:16]=[C:17]2[C:18]([CH:4]([C:3]3[C:6]([O:11][CH2:12][CH3:13])=[CH:7][CH:8]=[C:9]([F:10])[C:2]=3[Cl:1])[O:5][CH3:26])=[CH:19][NH:20][C:21]2=[N:22][CH:23]=1
Reactant: CCOc1ccc(F)c(Cl)c1C=O
Reactant: Brc1cnc2[nH]ccc2c1
Reactant: CO
Agent: [K+]
Agent: [OH-]
Product: CCOc1ccc(F)c(Cl)c1C(OC)c1c[nH]c2ncc(Br)cc12

Procedure:
A solution of 2-Chloro-6-ethoxy-3-fluorobenzaldehyde (2.0 g, 9.8 mmol), 5-bromo-7-azaindole (1.8 g, 8.9 mmol) and KOH (797 mg, 14.2 mmol) in methanol (30 mL) was stirred for 48 h at room temperature. The reaction mixture was concentrated to dryness and diluted with saturated aq. ammonium chloride. The aq. layer was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried (Na2SO4) and concentrated to give a residue that was purified by column chromatography (5/95, methanol/DCM) to give the title compound as foamy solid. 1H NMR (CDCl3, 400 MHz): δ=1.35 (t, 3H, J=7.2 Hz), 3.43 (s, 3H), 4.0 (q, 1H, J=7.2 Hz), 4.07 (q, 1H, J=7.2 Hz), 6.39 (s, 1H), 6.81 (dd, 1H, J=4.0, 9.2 Hz), 7.01 (t, 1H, J=8.4 Hz), 8.06 (d, 1H, J=2.0 Hz), 8.29 (d, 1H, J=2.0 Hz), 9.49 (s, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1C=C(O)[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[CH2:12]([O:14][C:15](=[O:31])[C:16]([C:29]#[N:30])=[CH:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([Br:28])[CH:19]=1)[CH3:13]>C1(C)C=CC=CC=1>[C:29]([C:16]1[C:15](=[O:31])[O:14][C:12]2[C:6]([C:17]=1[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([Br:28])[CH:19]=1)=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:13]=2)#[N:30]
Reactant: CCOC(=O)C(C#N)=Cc1cc(Br)c(OC)c(OC)c1
Reactant: COc1cccc(O)c1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc2c(-c3cc(Br)c(OC)c(OC)c3)c(C#N)c(=O)oc2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 1.7 %

Procedure:
To a solution of 5-bromoveratraldehyde (1.0 g, 4.1 mmol) and ethyl cyanoacetate (0.45 mL, 4.1 mmol) in ethanol (4 mL) was added piperidine (0.4 mL, 4.1 mmol). The mixture was stirred at room temperature for 0.5 h and precipitate was collected by filtration to yield the product (1.16 g) 3-(3-bromo-4,5-dimethoxy-phenyl)-2-cyano-acrylic acid ethyl ester as a solid. To a solution of 3-methoxyphenol (0.11 mL, 1 mmol) in toluene (10 mL) was added sodium hydride (60 mg, 1.5 mmol, 60%) and the mixture was stirred at room temperature for 0.5 h. To the mixture was added 3-(3-bromo-4,5-dimethoxy-phenyl)-2-cyano-acrylic acid ethyl ester (340 mg, 1 mmol) as a solid, then the mixture was refluxed for 2 h. The solvent was evaporated and the residue was purified by chromatography on silica gel with ethyl acetate and hexane (1:2) as eluant, yielding 7 mg (1.7%) of the title compound. 1H NMR (CDCl3): 7.34 (d, J=9.6, 1H), 7.21 (d, J=1.8, 1H), 6.98 (d, J=1.8, 1H), 6.91-6.90 (m, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 3.93 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]([OH:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[C:26]2[S:39][CH:38]=[CH:37][C:27]=2[N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:29]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O>ClCCl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[O:24])[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[C:26]2[S:39][CH:38]=[CH:37][C:27]=2[N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:29]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)n1nc(-c2cc3cc(C(O)c4ccccc4)ccc3n2C(=O)OC(C)(C)C)c2sccc21
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)n1nc(-c2cc3cc(C(=O)c4ccccc4)ccc3n2C(=O)OC(C)(C)C)c2sccc21
Temperature: 25 °C
Yield: 69.2 %

Procedure:
To a solution of 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(hydroxy-phenyl-methyl)-indole-1-carboxylic acid tert-butyl ester [640 mg, 1.17 mmol, Intermediate (12)] in Dichloromethane (25 mL) is added Dess-Martin Periodinane (677 mg, 1.69 mmol) and stirred at room temperature. After 30 minutes water (5 mL) is added and stirred for 10 minutes. The reaction mixture is diluted with dichloromethane (50 mL) and washed twice with a mixture of 10% Na2S2O3/saturated NaHCO3 (5 mL), NaHCO3 (10 mL), water (10 mL), brine and dried over sodium sulfate. The residue is chromatographed on 35 g silica gel cartridge, eluting with 30% ethyl acetate/Heptane to afford 5-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [440 mg, 69%, Intermediate (13)] as a white solid; LC/MS: 544 (M+H). Step 2. A mixture of 5-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [122 mg, 0.224 mmol, Intermediate (13)] in tetrahydrofuran (9 mL) and 1M KOH(aqueous, 2 mL) is heated at 60° C. oil bath overnight. The solvent is removed and added water (5 mL). The water layer is neutralized with 3N hydrochloric acid and extracted three times with ethyl acetate (20 mL). The combined ethyl acetate phases are washed with brine and dried over sodium sulfate. The residue is chromatographed on 10 g silica gel cartridge, eluting with 50 to 100% ethyl acetate gradient in heptane to afford phenyl-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-methanone (58 mg, 75%, Example 25) as a pale yellow solid; 1H NMR [(CD3)2SO)]: δ 13.38 (1H, s), 12.09 (1H, s), 8.05 (1H), 7.78 (8H, m), 7.23 (1H, d, J=5.2 Hz), 6.87 (1H); LC/MS: 344 (M+H).
Reaction SMILES: C(OC(=O)C[C:8]1[C:9]([Cl:17])=[N:10][C:11]([NH2:16])=[N:12][C:13]=1[C:14]#N)(C)(C)C.[I-].[Na+].Cl[Si](C)(C)C.[C:26](#[N:28])C>>[NH2:16][C:11]1[N:10]=[C:9]([Cl:17])[CH:8]=[C:13]([CH2:14][C:26]#[N:28])[N:12]=1
Reactant: CC#N
Reactant: CC(C)(C)OC(=O)Cc1c(Cl)nc(N)nc1C#N
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Product: N#CCc1cc(Cl)nc(N)n1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
2-amino-4-chloro-6-cyano-pyrimidylacetate-t-butyl ester (100 g, 372.5 mmol) was suspended in dry acetonitrile (1.2 l) containing sodium iodide (55.84 g, 372.5 mmol) and warmed to 40° C. until the mixture became homogeneous. Then chlorotrimethylsilane (200 ml) was added and the orange suspension was heated at reflux. After 1 hour, TLC analysis (elute with 1:1 ethyl acetate/hexanes) indicated a complete reaction and the reaction was filtered and the filtrate was concentrated. The residue was diluted with ethyl acetate and washed with water and sodium bicarbonate solution and dried with magnesium sulfate. The crude product was slurried in activated carbon, filtered and concentrated to give 38.46 g of a green solid. This was again dissolved in ethyl acetate and passed through a 4-inch pad of silica gel and then concentrated to give the desired subject as a green solid, m.p. 110°-115° C. NMR (200 mHz) D6-acetone δ 6.8 (s, 1 H), 6.8-6.6 (bs, 1 H), 3.95 (s, 2 H).
Reaction SMILES: [C:1](=[O:22])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.CCN(CC)CC.Cl.Cl.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)=[CH:35][CH:34]=1>CN(C=O)C>[NH3:5].[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([N:39]2[CH2:44][CH2:43][N:42]([C:1]([O:2][CH2:3][CH2:4][N:5]3[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]3)=[O:22])[CH2:41][CH2:40]2)=[CH:37][CH:38]=1
Reactant: CN1CCN(CCOC(=O)Oc2ccc([N+](=O)[O-])cc2)CC1
Reactant: Clc1ccc(N2CCNCC2)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN1CCN(CCOC(=O)N2CCN(c3ccc(Cl)cc3)CC2)CC1
Product: N
Temperature: 25 °C
Reaction time: 24 h
Yield: 158.1 %

Procedure:
2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 740 mg, 2.4 mmol) was dissolved in DMF (20 mL). NEt3 (1.2 mL, 8.6 mmol) and 4-(4-chlorophenyl)piperazine dihydrochloride (691 mg, 2.6 mmol) were added and the reaction mixture was stirred at room temperature for 24 hours, and the reaction mixture was then concentrated in vacuo. The resulting residue was dissolved in EtOAc (50 mL) and washed with 1M aq Na2CO3 solution (5×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 100:8:1 mixture of DCM:EtOH:NH3) to give 2-(4-methylpiperazin-1-yl)-ethyl 4-(4-chlorophenyl)piperazine-1-carboxylate (696 mg, 79%) as a colourless oil which crystallized on standing to give a white solid.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.C(N(CC)C(C)C)(C)C.[CH3:15][O:16][CH2:17][CH2:18][O:19][CH2:20]Cl.C(=O)([O-])O.[Na+]>ClCCl>[CH3:15][O:16][CH2:17][CH2:18][O:19][CH2:20][N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: COCCOCCl
Reactant: c1cn[nH]c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCCOCn1cccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.7 %

Procedure:
To a solution of 1H-pyrazole (13.6 g, 200 mmol) and N,N-diisopropylethylamine (68 mL, 400 mmol) in dichloromethane (150 mL), 2-methoxyethoxymethyl chloride (24.9 mL, 220 mmol) was added with cooling on ice. The reaction solution was stirred at room temperature for 2 hours, and an aqueous sodium hydrogencarbonate solution (500 mL) was then added to the reaction solution, followed by extraction three times with dichloromethane (500 mL). The organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography (hexane/ethyl acetate=1:1) to yield the title compound (29.9 g, 96%) as a colorless oil.
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[N+:8]([O-:11])(O)=[O:9].[CH:12]1[CH2:16]C=C[CH:13]=1>>[C:5]([O:4][CH:1]1[CH2:16][CH:12]([N+:8]([O-:11])=[O:9])[CH:13]=[CH:2]1)(=[O:7])[CH3:6]
Reactant: O=[N+]([O-])O
Reactant: C1=CCC=C1
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OC1C=CC([N+](=O)[O-])C1
Temperature: 25 °C

Procedure:
To 0.6 Mol of acetic anhydride were added at 25° C. 0.163 Mol 90% HNO3 over 45 minutes. The mixture was stirred for an additional 20 minutes before 0.1 Mol cyclopentadiene was added over a 1 hour period, maintaining the temperature at 25° C. The reaction mixture was stirred for an additional hour before it was poured onto ice water and extracted with methylene chloride. An oily residue (120% weight yield) was obtained. An aliquot was purified via Kugelrohr distillation removing first acetic acid/acetic anhydride followed by the product.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:8][CH2:9][C:10](=O)[CH2:11]Cl>C(#N)C>[Cl:8][CH2:9][C:10]1[N:1]=[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]2[CH:11]=1
Reactant: Nc1ccccn1
Reactant: O=C(CCl)CCl
Solvent: CC#N
Product: ClCc1cn2ccccc2n1
Yield: 34 %

Procedure:
A mixture of 2-aminopyridine (12.5 g), 1,3-dichloro-2-propanone (17.7 g) and acetonitrile (100 ml) was heated under reflux for 2 hours and concentrated. An aqueous saturated solution of sodium bicarbonate was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (3:2, v/v)-eluted fraction. Recrystallization from ethyl acetate-hexane gave 2-chloromethylimidazo[1,2-a]pyridine (7.52 g, yield 34%) as pale-yellow crystals. m.p. 93-94° C.
Reaction SMILES: [CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][NH:4][C:5]1[N:10]=[C:9](Cl)[CH:8]=[C:7]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[N:6]=1.[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][NH:4][C:5]1[N:10]=[C:9]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:8]=[C:7]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[N:6]=1
Reactant: CC(C)(C)CNc1nc(Cl)cc(N2CCCC2)n1
Reactant: C1CNCCN1
Product: CC(C)(C)CNc1nc(N2CCCC2)cc(N2CCNCC2)n1
Yield: 76 %

Procedure:
The reaction of 2-(2,2-dimethylpropylamino)-4-chloro-6-pyrrolidinopyrimidine with piperazine as described in Example 17 leads to the title compound in a yield of 76%, m.p.: 118°-120° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][C:16](F)=[CH:15][CH:14]=3)=[O:12])=[C:9]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:22][CH:21]=3)[S:8][C:7]=2[CH:34]=1.[CH3:35][N:36]([CH3:44])[C@H:37]1[CH2:42][CH2:41][CH2:40][CH2:39][C@H:38]1[OH:43]>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:43][C@@H:38]4[CH2:39][CH2:40][CH2:41][CH2:42][C@@H:37]4[N:36]([CH3:44])[CH3:35])=[CH:15][CH:14]=3)=[O:12])=[C:9]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:22][CH:21]=3)[S:8][C:7]=2[CH:34]=1
Reactant: COc1ccc2c(C(=O)c3ccc(F)cc3)c(-c3ccc(OCCN4CCCC4)cc3)sc2c1
Reactant: CN(C)[C@H]1CCCC[C@H]1O
Product: COc1ccc2c(C(=O)c3ccc(O[C@@H]4CCCC[C@@H]4N(C)C)cc3)c(-c3ccc(OCCN4CCCC4)cc3)sc2c1
Yield: 71 %

Procedure:
The title compound was prepared in 71% yield by essentially following the procedures outlined in Example 72, Part E, from 4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone (Example 59, Part A) and (±)-cis-2-(dimethylamino)cyclohexanol.
Reaction SMILES: [CH3:1][C:2](C)([O-])[CH3:3].[K+].[Br:7][C:8]1[CH:9]=[CH:10][C:11](=[O:14])[NH:12][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].BrC(C)C>COCCOC>[Br:7][C:8]1[CH:9]=[CH:10][C:11](=[O:14])[N:12]([CH:2]([CH3:3])[CH3:1])[CH:13]=1
Reactant: CC(C)(C)[O-]
Reactant: O=c1ccc(Br)c[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)Br
Solvent: COCCOC
Product: CC(C)n1cc(Br)ccc1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 62.2 %

Procedure:
Potassium tert-butoxide (16.80 g, 18.63 mL, 142.2 mmol) was added to a suspension of 5-bromo-1H-pyridin-2-one (25 g, 142.2 mmol) in DME (247.5 mL) and the mixture stirred at ambient temperature for 30 minutes. To the mixture was added potassium carbonate (13.76 g, 99.54 mmol) and 2-bromopropane (34.98 g, 26.70 mL, 284.4 mmol) and the reaction mixture heated at reflux for 64 hours. The reaction mixture was filtered to remove the resultant precipitate and the filtrate concentrated in vacuo. The residue was recrystalised from DCM/hexane to give the sub-title product as an off-white solid (19.1 g 62% Yield). 1H NMR (400.0 MHz, CDCl3) δ 1.36 (d, 6H), 5.22 (dt, 1H), 6.49 (d, 1H), 7.31 (dd, 1H) and 7.41 (d, 1H) ppm; MS (ES+) 217.3.
Reaction SMILES: [N:1]([CH2:4][CH2:5][NH:6]C(=O)CCCCCCCCCCCCC)=[N+:2]=[N-:3].[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[S:27](Cl)(=[O:29])=[O:28].N(CCN)=[N+]=[N-].C(N(CC)CC)C>ClCCl>[N:1]([CH2:4][CH2:5][NH:6][S:27]([C:23]1[S:22][CH:26]=[CH:25][CH:24]=1)(=[O:29])=[O:28])=[N+:2]=[N-:3]
Reactant: O=S(=O)(Cl)c1cccs1
Reactant: CCCCCCCCCCCCCC(=O)NCCN=[N+]=[N-]
Agent: [N-]=[N+]=NCCN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: [N-]=[N+]=NCCNS(=O)(=O)c1cccs1
Yield: 80 %

Procedure:
As in the synthesis of N-(2-azidoethyl)tetradecanamide, thiophene-2-sulfonyl chloride (0.218 g, 1.19 mmol) was reacted with 2-azidoethanamine (0.103 g, 1.19 mmol) and triethylamine (0.241 g, 2.39 mmol) in dichloromethane (5 mL) to give N-(2-azidoethyl)thiophene-2-sulfonamide (0.221 g, 80%). 1H NMR (300 MHz, CDCl3) δ 7.62 (d, 1H), δ 7.59 (d, 1H), 7.08 (t, 1H), 5.52 (s, 1H), 3.41 (t, 2H), 3.17 (q, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 140.6, 132.7, 132.6, 127.9, 50.9, 42.9 ppm; HRMS (ESI) calcd for C6H8N4O2S2 (M+) 232.0089. Found 232.0084.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][Cl:25]>C(OC(=O)C)C>[Cl:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][O:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1
Reactant: N#Cc1ccc(O)cc1
Reactant: ClCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: N#Cc1ccc(OCCCCCCl)cc1
Reaction time: 8 h
Yield: 90 %

Procedure:
While 70 g of 4-hydroxybenzonitrile (7) were added to 500 ml of acetonitrile and stirred, 85.3 g of potassium carbonate and 77.4 ml of 1-bromo-5-chloropentane were added. Subsequently, the temperature was gradually increased and stirring under reflux was continued for 8 hr, and then stirring was further continued at room temperature for 18 hr. After the reaction was completed, the resultant reaction mixture was added with 500 ml of ethylacetate and then washed with water. Thereafter, the ethylacetate layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The concentrated compound was dissolved in 280 ml of methanol, stirred at 0° C. for 2 hr, and then filtered, thus obtaining 118 g (yield: 90%) of a title compound as a white solid.
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH2:13]([C:17]1[N:18]=[C:19]([CH3:49])[N:20]([C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([O:47][CH3:48])[CH:40]=2)[C:21](=[O:38])[C:22]=1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[C:31]([C:36]#[N:37])=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:26][CH:25]=1)[CH2:14][CH2:15][CH3:16]>O.C(OCC)(=O)C>[CH2:13]([C:17]1[N:18]=[C:19]([CH3:49])[N:20]([C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([O:47][CH3:48])[CH:40]=2)[C:21](=[O:38])[C:22]=1[CH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]2[NH:3][C:4](=[O:7])[O:5][N:37]=2)=[CH:28][CH:29]=1)[CH2:14][CH2:15][CH3:16]
Reactant: O=C([O-])O
Reactant: CCCCc1nc(C)n(-c2ccc(OC)c(OC)c2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: CCCCc1nc(C)n(-c2ccc(OC)c(OC)c2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 58.6 %

Procedure:
A mixture of hydroxylammonium chloride (1.5 g), sodium hydrogen carbonate (2.3 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[4-butyl-1-(3,4-dimethoxyphenyl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (1.28 g) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was allowed to cool to room temperature, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (10 mL), N,N′-carbonyldiimidazole (0.63 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.58 mL) were added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.84 g, 59%).