Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[O:3]1[CH2:7][CH2:6][NH:5][C:4]1=[O:8].CN(C=O)C.[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[C:15]1([CH2:14][N:5]2[CH2:6][CH2:7][O:3][C:4]2=[O:8])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: BrCc1ccccc1
Reactant: O=C1NCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: O=C1OCCN1Cc1ccccc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A cold (ice-bath) suspension of sodium hydride (0.55 mole, hexane washed) in 100 mL of dry THF was stirred under a nitrogen atmosphere while a solution of 2-oxazolidinone in 500 mL of 10:1 THF:DMF was added dropwise. The resulting gray suspension was warmed to room temperature and stirred for 24 hour. Benzyl bromide (66 mL, 0.056 mole) was added to the resulting white suspension and stirred at ambient temperature 24 hour. The reaction was quenched by careful addition of 26 mL water and the resulting mixture was concentrated and poured into 500 mL of water. After extraction with methylene chloride, the combined extracts were washed with water and brine and dried over magnesium sulfate. Concentration in vacuo afforded 104 g of a yellow oil which was purified by Kugelrohr distillation (bp 100°/0.1 mm) to give 81 g (92% yield) of the product as a colorless liquid which solidified on standing at room temperature to a colorless solid, m.p. 76°-78°.
Reaction SMILES: [OH-].[Na+].[CH2:3]([N:6]1[C:10]2=[N:11][CH:12]=[C:13]([C:22]([O:24]CC)=[O:23])[C:14]([NH:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[C:9]2[CH:8]=[N:7]1)[CH2:4][CH3:5]>C(O)C.O>[CH2:3]([N:6]1[C:10]2=[N:11][CH:12]=[C:13]([C:22]([OH:24])=[O:23])[C:14]([NH:15][CH:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[C:9]2[CH:8]=[N:7]1)[CH2:4][CH3:5]
Reactant: CCCn1ncc2c(NC3CCOCC3)c(C(=O)OCC)cnc21
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCn1ncc2c(NC3CCOCC3)c(C(=O)O)cnc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.5 %

Procedure:
2M-Sodium hydroxide solution (0.7 ml) was added to a stirred suspension of Intermediate 38 (0.23 g) in ethanol (5 ml) and water (1.5 ml). After stirring overnight at room temperature, a further quantity of 2M-sodium hydroxide solution (0.7 ml) was added, and the reaction mixture was heated at 43° C. for 2.5 hours. The reaction solution was concentrated, diluted with water (5 ml) and acidified with 2M-hydrochloric acid. The resulting precipitate was collected by filtration, washed with water and dried to give Intermediate 39 as a white solid (0.14 g). LCMS showed MH+=305; TRET=2.42 min.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([CH3:18])[C:14]([O:16]C)=[O:15])[CH:7]=[CH:6]2.CO.[OH-].[K+].O>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([CH3:18])[C:14]([OH:16])=[O:15])[CH:7]=[CH:6]2
Reactant: COC(=O)C(C)c1ccc2cc(OC)ccc2c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1ccc2cc(C(C)C(=O)O)ccc2c1

Procedure:
The crude methyl 2-(6-methoxy-2-naphthyl)propionate is hydrolyzed with methanol/potassium hydroxide/water until TLC indicates no remaining ester. Then the reaction mixture is poured into water and extracted with methylene chloride and acidified with hydrochloric acid. The mixture is filtered and the organic and aqueous layers are separated. The aqueous layer then is acidified and filtered to yield 13.5 g of 2-(6-methoxy-2-naphthyl)propionic acid (melting point: 153°-155° C.).
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:3]2[CH:2]=[CH:8][C:6]([NH2:7])=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=2)=[CH:15][CH:14]=1
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: Nc1ccc(-c2ccc(Cl)cc2)cc1[N+](=O)[O-]
Temperature: 95 °C
Reaction time: 4 h
Yield: 69.4 %

Procedure:
To a solution of 5-chloro-2-nitroaniline (2 g, 11.59 mmol) in dioxane (100 ml) and water (10 ml) was added (4-chlorophenyl)boronic acid (3.6 g, 23.02 mmol), K3PO4 (5.01 g, 23.18 mmol) and Pd(PPh3)4 (0.7 g, 0.58 mmol) with stirring for 4 h at 95° C. maintained with an inert atmosphere of nitrogen. Then the resulting mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column with 2% to 5% ethyl acetate in petroleum ether to afford 4-(4-chlorophenyl)-2-nitroaniline as a yellow solid (2.0 g, 69%). Next, to a solution of 5-(4-chlorophenyl)-2-nitroaniline (300 mg, 1.21 mmol) in ethanol (10 ml) was added hydrogen chloride (0.5 ml, 3.63 mmol) and Zn powder (800 mg, 12.3 mmol) in portions at room temperature and stirred for 2 h at 85° C. The resulting mixture was concentrated under vacuum to give a residue and dissolved in water (100 ml), adjusted to pH 8 with aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate (3×100 ml) and dried and concentrated under vacuum to give a residue, which was purified by a silica gel column with 10% to 20% ethyl acetate in petroleum ether to produce 4-(4-chlorophenyl)benzene-1,2-diamine as an off-white solid (200 mg, 76%). Finally, a solution of 4-(4-chlorophenyl)benzene-1,2-diamine (150 mg, 0.69 mmol) in heptafluorobutanoic acid (2 ml) was stirred for 8 h at 120° C. Then the reaction was quenched with water (50 ml), adjusted to pH 7 with sodium bicarbonate and extracted with ethyl acetate(3×100 ml). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 5% to 10% ethyl acetate in petroleum ether to produce 6-(4-chlorophenyl)-2-(heptafluoropropyl)-1H-1,3-benzodiazole as a white solid (49.5 mg, 18%).
Reaction SMILES: [CH:1]1[C:15](=[O:16])[N:14]=[C:13]2[N:3]([C@@H:4]3[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]3[O:12]2)[CH:2]=1.C1C=CN=CC=1.[FH:23].C([O-])([O-])=O.[Ca+2]>O1CCOCC1>[F:23][C@@H:5]1[C@H:6]([OH:11])[C@@H:7]([CH2:9][OH:10])[O:8][C@H:4]1[N:3]1[CH:2]=[CH:1][C:15](=[O:16])[NH:14][C:13]1=[O:12]
Reactant: O=c1ccn2c(n1)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
Reactant: F
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2F)c(=O)[nH]1
Temperature: 0 °C
Yield: 79 %

Procedure:
The title compound is prepared via a modification of a literature procedure, J. Fox, et al., J. Org. Chem., Vol. 29, pp. 558-564 (1964). Thus, 2,2′-cyclouridine (5.65 g, 25 mmol) is treated with a solution of 70% hydrogen fluoride/pyridine (65 mL) in anhydrous dioxane (500 mL) at 120° C. in a sealed steel vessel for twenty hours. The reaction mixture is cooled to ice temperature, poured into ice (400 mL), and the pH is adjusted to 7 by addition of solid CaCO3. After the solvent is evaporated in vacuo (1 torr), the residue is dissolved in methanol, adsorbed onto silica gel, and purified by column chromatography using silica and ethyl acetatemethanol (v/v, 20:1) as eluent to give 2′-deoxy-2′-fluoro-uridine as a white solid (4.81 g, 79%). The 5′-DMT and 3′-cyanoethoxy-diisopropyl phosphoramidite derivatized nucleoside are obtained in accordance with the procedures of examples 65 and 66.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[C:10]3[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:11]=3[S:12][C:3]=12.C(OCCO)C.Cl.N1C=CC=CC=1.[Br:33][C:34]1[CH:35]=[C:36]([CH:38]=[CH:39][CH:40]=1)[NH2:37]>>[Br:33][C:34]1[CH:35]=[C:36]([CH:38]=[CH:39][CH:40]=1)[NH:37][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[C:10]3[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:11]=3[S:12][C:3]=12
Reactant: Nc1cccc(Br)c1
Reactant: N#Cc1cnc2c(sc3ccc([N+](=O)[O-])cc32)c1Cl
Agent: Cl
Solvent: CCOCCO
Solvent: c1ccncc1
Product: N#Cc1cnc2c(sc3ccc([N+](=O)[O-])cc32)c1Nc1cccc(Br)c1
Yield: 61.9 %

Procedure:
A solution of 400 mg (1.38 mmol) of 4-chloro-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile in 8 mL of 2-ethoxyethanol containing 160 mg (1.38 mmol) of pyridine hydrochloride and 0.180 mL (1.65 mmol) of 3-bromoaniline is heated at reflux for 4 hours. The reaction mixture is filtered hot and the solid is stirred with methanol and ammonium hydroxide. The mixture is poured into water and the solid is collected, washing with ethyl acetate to give 363 mg (62%) of 4-(3-bromoanilino)-8-nitro[1]benzothieno[3,2-b]pyridine-3-carbonitrile as a brown solid, mp>300° C.
Reaction SMILES: [CH:1]12[CH:14]=[CH:13][CH:5]([CH:6]3[C:11](=[O:12])O[C:8](=[O:9])[CH:7]31)[CH:4]1[CH:2]2[CH2:3]1.[N+:15]([C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1)([O-:17])=[O:16].O>C(O)(=O)C>[N+:15]([C:18]1[CH:24]=[CH:23][C:21]([N:22]2[C:8](=[O:9])[CH:7]3[CH:6]([CH:5]4[CH:13]=[CH:14][CH:1]3[CH:2]3[CH:4]4[CH2:3]3)[C:11]2=[O:12])=[CH:20][CH:19]=1)([O-:17])=[O:16]
Reactant: Nc1ccc([N+](=O)[O-])cc1
Reactant: O=C1OC(=O)C2C3C=CC(C4CC34)C12
Solvent: O
Solvent: CC(=O)O
Product: O=C1C2C3C=CC(C4CC34)C2C(=O)N1c1ccc([N+](=O)[O-])cc1
Temperature: 60 °C

Procedure:
250 g of tricyclo-[3.2.2.02.4 ]-non-8-ene-6,7-dicarboxylic acid anhydride (prepared from cycloheptatriene and maleic acid anhydride, K. Alder, Ber. 86, 1528-39 (1953)) and 200 g of 4-nitroaniline are refluxed in 1500 ml of glacial acetic acid for 3 hours. The reaction mixture cooled to 60° C is poured into 2000 ml of hot water, whereupon the crude product precipitates. After cooling, the crude product is filtered off, dried, and recrystallised from ethyl acetate; M.P. 210°-212° C.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1F)[CH:11]=[O:12].[CH3:17][O:18][C:19]1[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1.O>CN(C=O)C>[F:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[O:25][C:21]1[CH:22]=[CH:23][CH:24]=[C:19]([O:18][CH3:17])[CH:20]=1)[CH:11]=[O:12]
Reactant: O=Cc1ccc(F)c(F)c1
Reactant: COc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cccc(Oc2ccc(C=O)cc2F)c1
Temperature: 120 °C
Yield: 57.7 %

Procedure:
Cesium carbonate (2.757 g, 8.44 mmol) was added to a solution of 3,4-difluoro-benzaldehyde (1.0 g, 7.037 mmol) and 3-methoxyphenol (875 mg, 7.05 mmol) dissolved in DMF (20 mL). The reaction was heated to 120° C. for 24 hours. The reaction mixture was then poured into 300 mL of water and extracted 3 times with 60 mL of ethyl acetate. The combined organic layers were washed with water (2 times), brine, and dried over sodium sulfate. The organic layer was filtered and concentrated under reduced pressure. 3-Fluoro-4-(3-methoxy-phenoxy)-benzaldehyde (1.0 g) was isolated using flash silica gel and eluting with 10% ethyl acetate and heptane.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH:13]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6]3=[CH:5][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:38][CH:39]([CH3:41])[CH3:40])=[C:34]([CH:37]=1)[C:35]#[N:36].O>CN(C=O)C>[C:35]([C:34]1[CH:37]=[C:30]([CH:31]=[CH:32][C:33]=1[O:38][CH:39]([CH3:41])[CH3:40])[CH2:29][O:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH:13]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6]3=[CH:5][C:4]=2[CH:3]=1)#[N:36]
Reactant: CC(C)Oc1ccc(CCl)cc1C#N
Reactant: CC(C)(C)OC(=O)CC1CCn2c1cc1cc(O)ccc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)Oc1ccc(COc2ccc3c(c2)cc2n3CCC2CC(=O)OC(C)(C)C)cc1C#N
Temperature: 60 °C
Yield: 65.4 %

Procedure:
tert-Butyl 2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.287 g, 1.000 mmol), cesium carbonate (0.489 g, 1.500 mmol) and 5-(chloromethyl)-2-isopropoxybenzonitrile (0.315 g, 1.500 mmol) were taken up in DMF (2.0 mL) and heated to 60° C. for 16 h in a 20 mL sealed scintillation vial. The reaction was cooled down to room temperature and poured into water and extracted into ether (2×5 mL). The organic layers were combined and washed with water (3×5 mL), saturated NaCl (1×5 mL), dried over MgSO4, and filtered by vacuum filtration through a glass fiber paper. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (0.301 g) as a light yellow solid. LCMS m/z=461.5 [M+H]+.
Reaction SMILES: N1C=CC=C(CNC(C2C=CC3NC(C4C(C(=O)NC(C)C)=CNN=4)=NC=3C=2)=O)C=1.[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[CH:34][C:35]2[N:39]=[C:38]([C:40]3[C:44]([NH2:45])=[CH:43][NH:42][N:41]=3)[NH:37][C:36]=2[CH:46]=1.C(N(C(C)C)CC)(C)C.[N:58]1([C:64](Cl)=[O:65])[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]1>O1CCCC1>[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[CH:34][C:35]2[N:39]=[C:38]([C:40]3[C:44]([NH:45][C:64]([N:58]4[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]4)=[O:65])=[CH:43][NH:42][N:41]=3)[NH:37][C:36]=2[CH:46]=1
Reactant: COc1cc2nc(-c3n[nH]cc3N)[nH]c2cc1Cl
Reactant: O=C(Cl)N1CCCCC1
Agent: CC(C)NC(=O)c1c[nH]nc1-c1nc2cc(C(=O)NCc3cccnc3)ccc2[nH]1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc2nc(-c3n[nH]cc3NC(=O)N3CCCCC3)[nH]c2cc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
By proceeding in a manner similar to Example 248(a) above but (i) treating a solution of 3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-ylamine [0.2 g, Example 233(e)] and diisopropylethylamine (392 mg, 4 eq) in tetrahydrofuran (25 mL) with piperidinecarbonyl chloride (450 mg, 4 eq), stirring overnight at ambient temperature, and evaporating the reaction mixture, (ii) triturating the reaction product with water (30 mL) and ethyl acetate (50 mL) and extracting with aqueous layer with ethyl acetate, (iii) combining the organic phases, drying over magnesium sulfate, then evaporating (iv) chromatographing the residue on silica gel (ethyl acetate), (v) triturating the partially purified material with ethyl acetate (15 mL) for 1.5 hours and filtering, and (vi) evaporating the filtrate and chromatographing the residue on silica gel (ethyl acetate/heptane gradient of 20-0%) there was prepared piperidine-1-carboxylic acid[3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-amide (50 mg) as a yellow solid, mp>310° C. LC-MS (Method E) RT=3.25 minutes, 374 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[S:5][CH:6]=1.Cl.[Br-:15].[K+].OO>C1(C)C=CC=CC=1>[Br:15][C:7]([C:4]1[S:5][CH:6]=[C:2]([CH3:1])[N:3]=1)([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: [Br-]
Reactant: CCOC(=O)C(C)c1nc(C)cs1
Agent: Cl
Agent: OO
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCOC(=O)C(C)(Br)c1nc(C)cs1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 96.6 %

Procedure:
To a solution of Intermediate 104 (7.57 g, 38.0 mmol) in toluene (100 mL) was added hydrochloric acid (3.43 mL, 41.8 mmol). The mixture was kept at room temperature for 10 minutes. The mixture was cooled to 0° C. and potassium bromide (PANREAC, 4.97 g, 41.8 mmol) and hydrogen peroxide (4.59 mL, 49.4 mmol) were added. Reaction mixture was stirred at 0° C. for 3 hours and then was quenched with 1N Na2S2O3 (150 mL) and saturated NaHCO3 aqueous solution (150 mL). Organic phase was separated and the aqueous phase was extracted with EtOAc (2×150 mL). Combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound (10.22 g, 36.7 mmol, 97% yield) as oil. 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.43 (m, 1H), 4.21-4.28 (q, 2H), 2.30-2.35 (m, 6H), 1.19-1.24 (m, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])[O:3]1.[N:11]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19](Cl)=[O:20])=[N+:12]=[N-:13]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[N:11]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([CH:5]1[C:6](=[O:8])[O:7][C:2]([CH3:10])([CH3:1])[O:3][C:4]1=[O:9])=[O:20])=[N+:12]=[N-:13]
Reactant: [N-]=[N+]=NCCCCCC(=O)Cl
Reactant: CC1(C)OC(=O)CC(=O)O1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC1(C)OC(=O)C(C(=O)CCCCCN=[N+]=[N-])C(=O)O1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (6.31 g, 43.8 mmol) and 4-dimethylaminopyridine (5.60 g, 45.9 mmol) in 100 ml of CH2Cl2 was added dropwise a solution of crude 6-azidohexanoic chloride (7.32 g, 41.7 mmol) in 30 ml of CH2Cl2 at 0° C. The mixture was stirred at 0° C. for 1 hr then at room temperature for 1 hr. The solution was washed with 0.5N aqueous HCl (100 ml), water (100 ml) followed by brine (100 ml) and dried over Na2SO4. After filtration and evaporation of solvent, 5-(6-azidohexanoyl)-2,2-dimethyl-1,3-dioxane-4,6-dione was obtained as a light red oil (12.0 g, 100%).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[N:4]([C:8]([S:11][CH3:12])=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.[I:13]N1C(=O)CCC1=O>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([S:11][CH3:12])=[N:9][C:10]=2[I:13])[CH:5]=[CH:6][N:7]=1
Reactant: CSc1ncc2c(Cl)nccn12
Reactant: O=C1CCC(=O)N1I
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CSc1nc(I)c2c(Cl)nccn12
Temperature: 55 °C
Reaction time: 6 h
Yield: 94 %

Procedure:
P To a solution of 8-chloro-3-methylsulfanyl-imidazo[1,5-a]pyrazine (1.75 g, 0.00876 mol) in DMF (15 mL) was added N-iodosuccinimide (3.94 g, 0.0175 mol), the resulting mixture was stirred at 55° C. for 6 hrs. The mixture was diluted with EtOAc (200 mL), washed with sat. aq. NaHCO3 (40 mL), water (2×40 mL), brine (40 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography to give the title compound as a yellow solid, 2.68 g, 94% yield. 1H NMR (CDCl3, 400 MHz): δ 2.72 (s, 3H), 7.36 (d, J=4.8 Hz, 1H), 7.76 (d, J=4.8 Hz, 1H).
Reaction SMILES: [NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].[C@@H:13]12[C:22](=O)[O:21][C:19](=[O:20])[C@@H:14]1[CH2:15][CH2:16][CH2:17][CH2:18]2>C(O)(=O)C>[C:22]1(=[O:21])[N:1]([CH:2]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:3][C:4]([OH:6])=[O:5])[C:19](=[O:20])[C@H:14]2[CH2:15][CH2:16][CH2:17][CH2:18][C@@H:13]12
Reactant: NC(CC(=O)O)c1ccccc1
Reactant: O=C1OC(=O)[C@@H]2CCCC[C@H]12
Solvent: CC(=O)O
Product: O=C(O)CC(c1ccccc1)N1C(=O)[C@H]2CCCC[C@H]2C1=O
Temperature: 25 °C
Yield: 58 %

Procedure:
A stirred mixture 3-amino-3-phenylpropionic acid and cis-1,2-cyclohexanedicarboxylic anhydride in 10 mL of acetic acid under nitrogen was heated to reflux for 4 h and then allowed to cool to room temperature. The resulting mixture was concentrated to an orange yellow oil. This oil was crystallized from a 1/1 mixture of ethyl acetate/hexane to afford 1.77 g (58%) of 3-(cis-hexahydrophthalimido)-3-phenylpropionic acid as white crystals: 1H NMR (DMSO-d6) δ12.45 (br s, 1H, COOH), 7.33 (m, 5H, Ph), 5.48 (dd, 1H, J=6.3, 9.6, CH), 3.41 (dd, 1H, J=16.5, 9.6 Hz), 3.14 (dd, 1H, J=16.5, 6.3 Hz), 2.50 (m, 2H), 1.8-1.1 (m, 8H); 13C NMR (DMSO-d6) δ179.3, 179.2, 171.7, 138.7, 128.4, 127.5, 126.8, 50.1, 38.7, 38.6, 35.2, 23.0, 22.9, 21.1. Anal. Calcd for C17H19NO4. Theory: C, 67.76; H, 6.36; N, 4.65. Found: C, 67.52; H, 6.20; N, 4.60.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[CH3:11][N:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1>>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]3[CH2:16][CH2:17][N:12]([CH3:11])[CH2:13][CH:14]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: Fc1ccc2cc[nH]c2c1
Reactant: CN1CCC(=O)CC1
Product: CN1CC=C(c2c[nH]c3cc(F)ccc23)CC1
Yield: 69.2 %

Procedure:
Beginning with 1.00 gm (7.4 mMol) 6-fluoro-1H-indole and 1.82 mL (14.8 mMol) 1-methyl-4-piperidone, 1.18 gm (70%) of the title compound were recovered as a colorless crystalline solid.
Reaction SMILES: [OH:1][CH:2]([C:5]1[CH:9]=[CH:8][S:7][C:6]=1[S:10][CH3:11])[CH2:3][CH3:4].[CH3:12][O:13][CH2:14][CH2:15][O:16][CH2:17]Cl.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:12][O:13][CH2:14][CH2:15][O:16][CH2:17][O:1][CH:2]([C:5]1[CH:9]=[CH:8][S:7][C:6]=1[S:10][CH3:11])[CH2:3][CH3:4]
Reactant: CCC(O)c1ccsc1SC
Reactant: COCCOCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCC(OCOCCOC)c1ccsc1SC
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.9 %

Procedure:
To a stirred solution of 3-(1-hydroxypropyl)2-methylthiothiophene (17.7 g, 0.094 mol) in dry methylene chloride (100 ml) was added methoxyethoxymethyl chloride (20.6 g, 0.165 mol) followed by N,N,-diisopropylethylamine (21.3 g, 0.165 mol). The mixture was stirred at room temperature overnight. The mixture was washed with water, dried over anhydrous Na2SO4, filtered and concentrated in vacuo at room temperature to give 24.4 g of amber oil (94% yield). NMR confirmed the structure and mass spectral analysis confirmed the molecular weight at 276.09.
Reaction SMILES: [Br:1][C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][C:9](Br)=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1.[C:19]1([NH:25][C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC(O)=O.CC(O)=O.[Pd]>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:16]3=[C:17]4[C:12](=[CH:11][CH:10]=[C:9]([N:25]([C:26]5[CH:35]=[CH:34][C:33]6[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=6)[CH:27]=5)[C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[C:8]4=[CH:7][CH:6]=2)[CH:13]=[CH:14][C:15]=13
Reactant: c1ccc(Nc2ccc3ccccc3c2)cc1
Reactant: Brc1ccc2ccc3c(Br)ccc4ccc1c2c43
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: Brc1ccc2ccc3c(N(c4ccccc4)c4ccc5ccccc5c4)ccc4ccc1c2c43
Temperature: 100 °C
Yield: 36.9 %

Procedure:
A mixture of 18 g (50 mmol) of 1,6-dibromopyrene, 11 g (50 mmol) of N-phenylnaphthalen-2-amine, 0.16 g (0.7 mmol) of Pd(OAC)2, 0.5 g (1.4 mmole) of tri-tert-butylphosine, 6 g (75 mmol) sodium tert-butoxide was stirred in 200 ml dry toluene, the reaction mixture was then heat to 100° C. for about overnight under nitrogen. The solution was filtered. The toluene solution was removed under reduced pressure from the filtrate. The residue was extracted three times with dichloromethane and water, dried with MgSO4 and filtered, and the dichloromethane was removed under reduced pressure. The product was purified by column chromatography to get 9.2 g of product (yield 37%).
Reaction SMILES: [C:1]([OH:11])(=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:12]1([SH:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Br>C(O)(=O)C.O>[C:4]1([CH:3]([S:18][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:2][C:1]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(O)C=Cc1ccccc1
Reactant: Sc1ccccc1
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)CC(Sc1ccccc1)c1ccccc1
Yield: 70.2 %

Procedure:
Cinnamic acid (30.0 g.), benzenethiol (24.0 g.) and 45% w/v hydrogen bromide in acetic acid (21.5 ml) were heated together at 100° for 7 hrs. The reaction mixture was diluted with water and steam distilled to remove unchanged thiol. The hot aqueous layer was decanted from the oily product, which was recrystallised from 60°-80° petrleum ether to give 3-phenyl-3-(phenylthio)propionic acid (36.7 g) m.pt. 85°-90°. A sample recrystallised again from 60°-80° petroleum ether had m.pt. 88°-90°.