Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8](=[O:15])[NH:7][CH:6]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.[CH:27]1(I)[CH2:31][CH2:30][CH2:29][CH2:28]1>O>[CH:27]1([N:7]2[CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]2=[O:15])[CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: IC1CCCC1
Reactant: COC(=O)c1c[nH]c(=O)c2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cn(C2CCCC2)c(=O)c2ccccc12
Temperature: 25 °C
Reaction time: 4 h
Yield: 23.3 %

Procedure:
To a solution of methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxylate (780 mg, 3.8 mmol, Bionet), potassium carbonate (650 mg, 4.7 mmol, Aldrich), and 6 mL of DMF was added cyclopentyl iodide (0.52 mL, 4.5 mmol, Aldrich). The solution was stirred at RT for 4 h, then diluted with 50 mL of water. The solids were filtered and washed with CH2Cl2 and EtOAc. The filtrate was concentrated in vacuo and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0% to 15% EtOAc:hexane to give 240 mg (23%) of methyl 2-cyclopentyl-1-oxo-1,2-dihydroisoquinoline-4-carboxylate as an off-white solid. MS m/z: 272.3(M+1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[OH-].[K+].[I:20]I.O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[I:20]
Reactant: Fc1cccc(F)c1-c1ccc2[nH]ncc2c1
Reactant: II
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: Fc1cccc(F)c1-c1ccc2[nH]nc(I)c2c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 72.4 %

Procedure:
To a solution of 5-(2,6-difluoro-phenyl)-1H-indazole (40.8 g, 176.46 mmol) in DMF (441.1 mL) was added KOH (14.8 g, 246.69 mmol) and I2 (98.5 g, 388.21 mmol) at RT. The reaction mixture was stirred for 6 h at RT. Water was added to the reaction mass and extracted with EtOAc (2×500 mL). Organic layer was washed with brine and dried over Na2SO4. The organic layer was concentrated and purified by column using silica (100-200 mesh) and 0-15 EtOAc-hexane to provide 5-(2,6-difluoro-phenyl)-3-iodo-1H-indazole (45.5 g, 72.4% yield). MS (ESI, pos. ion) m/z: 357.1 (M+1).
Reaction SMILES: C(N1CCN(C2N=C(Br)C=C3C=CSC=23)CC1)C.[CH2:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[N:28]=[C:29]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][CH2:44][O:45]C(=O)C)=[C:38]([Cl:49])[CH:37]=3)[CH:30]=[C:31]3[CH:35]=[CH:34][S:33][C:32]=23)[CH2:23][CH2:22]1)[CH3:20].Cl>C(OCC)(=O)C>[CH2:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[N:28]=[C:29]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][CH2:44][OH:45])=[C:38]([Cl:49])[CH:37]=3)[CH:30]=[C:31]3[CH:35]=[CH:34][S:33][C:32]=23)[CH2:23][CH2:22]1)[CH3:20]
Reactant: CCN1CCN(c2nc(-c3ccc(OCCOC(C)=O)c(Cl)c3)cc3ccsc23)CC1
Agent: CCN1CCN(c2nc(Br)cc3ccsc23)CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: CCN1CCN(c2nc(-c3ccc(OCCO)c(Cl)c3)cc3ccsc23)CC1
Reaction time: 0.75 h

Procedure:
The resulting compound and 7-(1-ethylpiperazin-4-yl)-5-bromothieno[2,3-c]pyridine (0.19 g) were reacted in the same manner as in Example 300-4, to give a reaction solution containing 7-(4-ethylpiperazin-1-yl)-5-[4-(2-acetoxyethoxy)-3-chlorophenyl]thieno[2,3-c]pyridine. Ethyl acetate and 2N hydrochloric acid were added to the reaction solution, and the resulting insoluble matters were filtered off. The aqueous layer was separated, while the organic layer was extracted with 2N hydrochloric acid. The resulting aqueous layers were combined and washed with ethyl acetate twice. The pH of the resulting solution was adjusted to pH 10 by adding a 8N aqueous solution of sodium hydroxide, and then the solution was extracted with ethyl acetate twice. The extract was washed with brine, dried over magnesium sulfate, and the solvent was evaporated. Methanol (6 ml) was added to the resulting residue and dissolved, followed by the addition of a 8N aqueous solution of sodium hydroxide (0.75 ml). The resulting mixture was left as it was at room temperature for 45 min, and then the solvent was evaporated. Water was added to the resulting residue, and then the mixture was extracted with ethyl acetate thrice. The extract was washed with brine, dried over magnesium sulfate, and the solvent was evaporated. The resulting residue was purified by NH silica gel column chromatography (ethyl acetate/n-hexane system), to give the title compound (0.03 g) as a colorless viscous oil.
Reaction SMILES: [CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=1)[CH:2]=[CH2:3].C([Mg]Cl)(C)C.C(C(CC=C)CO[SiH2]C1C=CC([Mg]Cl)=CC=1)C=C.[CH3:41][Sn:42](Cl)([CH3:44])[CH3:43]>O.C1COCC1>[CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11]([Sn:42]([CH3:44])([CH3:43])[CH3:41])=[CH:10][CH:9]=1)[CH:2]=[CH2:3]
Reactant: C=CCC(CC=C)CO[SiH2]c1ccc(I)cc1
Reactant: C[Sn](C)(C)Cl
Agent: C=CCC(CC=C)CO[SiH2]c1ccc([Mg]Cl)cc1
Agent: CC(C)[Mg]Cl
Solvent: O
Solvent: C1CCOC1
Product: C=CCC(CC=C)CO[SiH2]c1ccc([Sn](C)(C)C)cc1
Temperature: 25 °C
Reaction time: 13 h
Yield: 96 %

Procedure:
At first, a THF solution (2 mL) of the 4-(diallylethoxysilyl)iodobenzene (202 mg, 0.56 mmol) obtained in Example 2 was added dropwise with 2 mol/L of i-PrMgCl (0.59 mL (solvent: THF), 1.18 mmol) at −30° C. Then, the resultant solution was stirred under a nitrogen atmosphere at −30° C. for 1.5 hours to obtain a THF solution containing 4-(diallylethoxysilyl)phenylmagnesium chloride (Grignrad solution). Subsequently, the obtained Grignrad solution was added dropwise with 1 mol/L of trimethyl tin chloride (Me3SnCl: 1.18 mL (solvent: THF), 1.18 mmol) at −30° C. to obtain a reaction mixture. Thereafter, the reaction mixture was stirred under a nitrogen atmosphere at room temperature for 13 hours, and added with distilled water to terminate the reaction. After that, the organic layer was separated from the reaction mixture, and the aqueous layer was extracted with ether to collect the organic layer. Subsequently, the organic layer thus collected was washed with sat.NaHCO3 and sat.NaCl, dried with MgSO4, filtered, and concentrated to obtain a crude product. Thereafter, the crude product thus obtained was separated and purified by silica gel column chromatography (hexane/EtOAc=5/1), and thereby 4-(diallylethoxysilyl)phenyl-trimethyltin was obtained (214 mg, 96% yield).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=O)=[C:12]([CH3:16])[N:11]=[C:10]([CH3:17])[N:9]=2)=[CH:4][CH:3]=1.CC1C([P+]([O:38][C:39]([CH3:41])=[O:40])(C2C=CC=CC=2)C2C=CC=CC=2)=CC=CC=1.Cl[CH2:43]Cl>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=[CH:41][C:39]([O:38][CH3:43])=[O:40])=[C:12]([CH3:16])[N:11]=[C:10]([CH3:17])[N:9]=2)=[CH:4][CH:3]=1
Reactant: CC(=O)O[P+](c1ccccc1)(c1ccccc1)c1ccccc1C
Reactant: ClCCl
Reactant: Cc1nc(C)c(C=O)c(-c2ccc(F)cc2)n1
Product: COC(=O)C=Cc1c(C)nc(C)nc1-c1ccc(F)cc1

Procedure:
4-(4-Fluorophenyl)-2,6-dimethyl-5-pyrimidinecarboxaldehyde (31 g, 0.134 mol) and methyl(triphenylphosphoranylidene) acetate (46.6 g, 0.139 mol) in 500 mL of dichlormethane were stirred at room temperature for twenty-four hours. The solution was then concentrated and flash chromatographed on silica gel, eluting with 20% ethyl acetate/hexane, to give 36.3 g of methyl 3-[4-(4-fluorophenyl)-2,6-dimethyl-5-pyrimidinyl]-2-propenoate.
Reaction SMILES: [Cl:1][CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9](=[O:16])[NH:8][C:7]2[CH:17]=[CH:18][CH:19]=[N:20][C:6]1=2)=[O:4].C(=O)([O-])[O-].[Na+].[Na+].[CH3:27][C:28]([CH3:37])=[CH:29][CH2:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>C(O)(C)C>[ClH:1].[ClH:1].[CH3:27][C:28]([CH3:37])=[CH:29][CH2:30][N:31]1[CH2:36][CH2:35][N:34]([CH2:2][C:3]([N:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:9](=[O:16])[NH:8][C:7]3[CH:17]=[CH:18][CH:19]=[N:20][C:6]2=3)=[O:4])[CH2:33][CH2:32]1
Reactant: O=C1Nc2cccnc2N(C(=O)CCl)c2ccccc21
Reactant: CC(C)=CCN1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)O
Product: CC(C)=CCN1CCN(CC(=O)N2c3ccccc3C(=O)Nc3cccnc32)CC1
Product: Cl

Procedure:
8.62 gm of 11-chloroacetyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepin-6-one, 3.5 gm of sodium carbonate and 5.07 gm of 1-(3-methyl-but-2-enyl)-piperazine [R1 =--CH2 --CH=C(CH3)2 ] were refluxed in 100 ml of isopropanol for 2.5 hours. Then, the reaction mixture was suction-filtered while still hot, and the filtrate evaporated to a volume of 40 ml and cooled. The precipitated crystals were dissolved, while heating, in 100 ml of absolute ethanol, and the calculated quantity of concentrated hydrochloric acid was added. Upon cooling, the dihydrochloride crystallized out.
Reaction SMILES: [C:1]1([CH:7]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:8]2[CH:9]=[CH:10][C:11](=[O:27])[N:12]([CH2:14][CH2:15][N:16]3C(=O)C4C(=CC=CC=4)C3=O)[CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCO.O.NN>C1COCC1>[NH2:16][CH2:15][CH2:14][N:12]1[CH:13]=[C:8]([CH:7]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:9]=[CH:10][C:11]1=[O:27]
Reactant: O=C1c2ccccc2C(=O)N1CCn1cc(C(c2ccccc2)c2ccccc2)ccc1=O
Agent: NN
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: NCCn1cc(C(c2ccccc2)c2ccccc2)ccc1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.5 %

Procedure:
To a solution of 2-{2-[5-(diphenylmethyl)-2-oxo-1(2H)-pyridinyl]ethyl}-1H-isoindole-1,3(2H)-dione (295 mg) in mixed solvent (EtOH:THF=4.4 mL:2.2 mL) was added hydrazine hydrate (329 μL) and the mixture was stirred at ambient temperature for 1 hour. The resulting mixture was evaporated in vacuo and the residue was diluted with chloroform (10 mL). The mixture was filtered and the filtrate was evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform:MeOH=99:1-96:4) to afford 1-(2-aminoethyl)-5-(diphenylmethyl)-2(1H)-pyridinone (154 mg) as colorless crystals.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:14][CH2:13]3)=[N:9][C:10]=2[I:11])[CH:5]=[CH:6][N:7]=1.[NH3:28]>CC(O)C>[NH2:28][C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:14][CH2:13]3)=[N:9][C:10]=2[I:11])[CH:5]=[CH:6][N:7]=1
Reactant: O=C(OCc1ccccc1)N1CCC(c2nc(I)c3c(Cl)nccn23)CC1
Reactant: N
Solvent: CC(C)O
Product: Nc1nccn2c(C3CCN(C(=O)OCc4ccccc4)CC3)nc(I)c12
Temperature: -78 °C

Procedure:
A mixture of benzyl 4-(8-chloro-1-iodoimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate (0.500 g, 0.00101 mol) in IPA (20 mL) was cooled to at −78° C. and treated with a stream of ammonia gas over 3 minutes. The resulting solution was heated at 110° C. in a Parr vessel prior to concentration in vacuo, suspension in DCM and filtration through a bed of Celite. The filtrate was concentrated in vacuo to afford 0.504 g of desired product. 1H NMR (400 MHz, CDCl3): δ 1.88-2.02 (m, 2H), 2.99-3.10 (m, 3H), 4.24-4.41 (m, 2H), 5.15 s, 2H), 6.03 (br, 2H), 7.03 (d, J=4.8 Hz, 1H), 7.24 (d, J=5.2 Hz, 1H), 7.31-7.40 (m, 5H). MS (ES+): m/z 479.33 [MH+].
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]2[N:15]([CH2:16][C:17]([OH:19])=O)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[N:8]=2)=[CH:4][CH:3]=1.[C:20](N1C=CN=C1)([N:22]1C=CN=C1)=O.CN>O1CCCC1>[CH3:20][NH:22][C:17](=[O:19])[CH2:16][N:15]1[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[N:8]=[C:7]1[C:5]1[S:6][C:2]([CH3:1])=[CH:3][CH:4]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1ccc(-c2nc3cccnc3n2CC(=O)O)s1
Agent: CN
Solvent: C1CCOC1
Product: CNC(=O)Cn1c(-c2ccc(C)s2)nc2cccnc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 59.5 %

Procedure:
A solution of 2-(5-methyl-2-thienyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (5.0 g, 0.0183 mole) and 1,1'-carbonyldiimidazole (2.97 g, 0.0183 mole) in tetrahydrofuran (100 ml) was stirred at room temperature for 33/4 hours with a stream of nitrogen bubbling through it. A solution of methylamine (36 ml of a 3.03M solution in tetrahydrofuran, 0.1098 mole) was added and the reaction mixture was stirred at room temperature overnight under nitrogen. The solvents were removed under reduced pressure and the resulting solid was triturated in water (100 ml), collected by filtration, and rinsed twice with water, twice with a 5% potassium hydroxide solution, and twice again with water. The solid was dissolved in hot isopropyl alcohol, and filtered while hot. Addition of isopropyl ether caused solid to precipitate. The solid was collected by filtration, rinsed with isopropyl ether, and dried under high vacuum at room temperature overnight to give 3.12 g (60%) of title compound, mp 213°-216° C.
Reaction SMILES: [CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[CH2:21]([CH:23]([CH2:27][CH3:28])[CH2:24][CH2:25][NH2:26])[CH3:22].[BH4-].[Na+]>CO>[CH2:21]([CH:23]([CH2:27][CH3:28])[CH2:24][CH2:25][NH:26][CH2:1][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)[CH3:22]
Reactant: CCC(CC)CCN
Reactant: COc1cc(C=O)ccc1Oc1cnc(C(N)=O)cn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCC(CC)CCNCc1ccc(Oc2cnc(C(N)=O)cn2)c(OC)c1
Reaction time: 8 h
Yield: 31.7 %

Procedure:
Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719 Part A) (0.700 g, 2.56 mmol), 3-ethylpentylamine (Example 733, Part B) (0.310 g, 2.69 mmol) and 3 Å molecular sieves in a vial. Add methanol (12.8 mL), cap and stir overnight. Add NaBH4 (0.0969 g, 2.56 mmol) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes. Concentrate the fraction containing the product, then add EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2×25 mL), dry it over Na2SO4, filter and concentrate. Dissolve the product in ether:dichloromethane (5:1) (25 mL), add hexanes (20 mL), and then concentrate to about a quarter of the volume. Filter the precipitate to give the title compound (0.302 g, 31.7%): TOF MS ES+ 373.2 (M+H)+, HRMS calcd for C20H29N4O3 373.2240 (M+H)+, found 373.2247, time 0.39 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 0-20% over 5 min, 20-95% over 18], tR=12.0 min, 100% purity.
Reaction SMILES: CC1C(=[O:8])[C@@H](O)CC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/C1C(C)(C)C[C@H](O)C(=O)C=1C.CCN(C(C)C)C(C)C.Cl[C:55]([O:57]C(Cl)C(Cl)(Cl)Cl)=[O:56].[CH2:64]([OH:75])[C@H:65]([C@H:67]([C@@H:69]([C@@H:71]([CH2:73][OH:74])[OH:72])[OH:70])[OH:68])[OH:66]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CN(C=O)C>[C:55](=[O:56])([OH:8])[OH:57].[CH2:73]([OH:74])[C@H:71]([C@H:69]([C@@H:67]([C@@H:65]([CH2:64][OH:75])[OH:66])[OH:68])[OH:70])[OH:72]
Reactant: CC1=C(/C=C/C(C)=C/C=C/C(C)=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C2=C(C)C(=O)[C@@H](O)CC2(C)C)C(C)(C)C[C@H](O)C1=O
Reactant: O=C(Cl)OC(Cl)C(Cl)(Cl)Cl
Agent: CN(C)c1ccncc1
Agent: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(O)O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of astaxanthin 2E (0.100 g, 0.168 mmol) in DCM (4 mL) at 0° C. was added DIPEA (0.585 mL, 3.36 mmol), and 1,2,2,2-tetrachloroethyl chloroformate (0.103 mL, 0.672 mmol). The reaction mixture was stirred at 0° C. for 2 hours, then at room temperature for 1.5 hours, at which time (D)-mannitol (0.3060 g, 1.68 mmol), DMF (3 mL), and DMAP (0.2052 g, 1.68 mmol) were added to the reaction. The reaction mixture was stirred at room temperature for 24 hours, at which time the reaction was diluted with DCM, quenched with brine (20 mL), and then extracted with DCM. The combined organic layers were concentrated to yield mannitol monocarbonate (LVII) (10.19%) HPLC retention time: 9.474 min., 10.19% (AUC); LRMS (ESI) m/z (relative intensity): 827 (M++Na) (50), 804 (M+) (25), 725 (58), 613 (100), and astaxanthin 2E (53.73%).
Reaction SMILES: [CH:1]1(CN2C(=O)C3NC(C4C=CC(COCCOCCOCCOCCOCCOCCOCCOCCOCCOC)=CC=4)=NC=3N(CC3CCCCC3)C2=O)CCCCC1.[CH:62]1([CH2:68][N:69]2[C:77](=[O:78])[C:76]3[N:75]=[C:74]([C:79]4[CH:89]=[CH:88][C:82](/[CH:83]=[CH:84]/[C:85]([OH:87])=[O:86])=[CH:81][CH:80]=4)[NH:73][C:72]=3[N:71]([CH2:90][CH:91]3[CH2:96][CH2:95][CH2:94][CH2:93][CH2:92]3)[C:70]2=[O:97])[CH2:67][CH2:66][CH2:65][CH2:64][CH2:63]1.C(=O)([O-])[O-].[K+].[K+].CO>C(#N)C>[CH3:1][O:86][C:85](=[O:87])/[CH:84]=[CH:83]/[C:82]1[CH:81]=[CH:80][C:79]([C:74]2[NH:73][C:72]3[N:71]([CH2:90][CH:91]4[CH2:92][CH2:93][CH2:94][CH2:95][CH2:96]4)[C:70](=[O:97])[N:69]([CH2:68][CH:62]4[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67]4)[C:77](=[O:78])[C:76]=3[N:75]=2)=[CH:89][CH:88]=1
Reactant: COCCOCCOCCOCCOCCOCCOCCOCCOCCOCc1ccc(-c2nc3c([nH]2)c(=O)n(CC2CCCCC2)c(=O)n3CC2CCCCC2)cc1
Reactant: O=C(O)/C=C/c1ccc(-c2nc3c(=O)n(CC4CCCCC4)c(=O)n(CC4CCCCC4)c3[nH]2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CO
Product: COC(=O)/C=C/c1ccc(-c2nc3c(=O)n(CC4CCCCC4)c(=O)n(CC4CCCCC4)c3[nH]2)cc1
Temperature: 25 °C
Yield: 74 %

Procedure:
In the manner of Example 36, part (b), (E)-4-[1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6dioxo-9H-purin-8-yl]cinnamic acid was converted to (E)-1,3-bis(cyclohexylmethyl)-8-(3-(2-(1H-imidazol-1yxlcarbonyl)vinyl)phenyl)-9H-purin-2,6(1H,3H)-dione as a yellow powder. Such a sample (2.50 g, 4.62 mmol) was stirred at reflux in acetonitrile (75 ml) with potassium carbonate (1.28 g, 9.25 mmol) and methanol, (10 ml) for 24 hours. The mixture was cooled to room temperature and filtered and the filtrate-wash was adjusted to pH˜3 by addition of 6N hydrochloric acid. The resulting precipitate was filtered and washed with methanol and dried to give (E)-4-[1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]cinnamic acid methyl ester (1.70 g, 74%) as a white solid. 1H-NMR (300 MHz, DMSO-d6) δ: 8.16 (d, J=8.2 Hz, 2H, phenylCH), 7.83 (d, J=8.4 Hz, 2H, 2 phenylCH), 7.63 (d, J=15.9 Hz,1H, CH═), 6.70 (d, J=15.9 Hz, 1H, CH—), 3.95 (d, J=7.0 Hz, 2H, CH2N), 3.75 (d, J=6.8 Hz, 2H, CH2N), 3.70 (s, 3H, CH3), 2.0-1.50 and 1.20-0.80 (m, 22H, 2C6H11).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]3[N:12]=[C:13]([NH2:15])[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=2)=[CH:2]1.[C:16]([N:19]1[CH2:24][CH2:23][CH:22]([C:25](Cl)=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17]>>[C:16]([N:19]1[CH2:20][CH2:21][CH:22]([C:25]([NH:15][C:13]2[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=[C:6]([C:3]4[CH:4]=[CH:5][O:1][CH:2]=4)[N:11]3[N:12]=2)=[O:26])[CH2:23][CH2:24]1)(=[O:18])[CH3:17]
Reactant: Nc1nc2cccc(-c3ccoc3)n2n1
Reactant: CC(=O)N1CCC(C(=O)Cl)CC1
Product: CC(=O)N1CCC(C(=O)Nc2nc3cccc(-c4ccoc4)n3n2)CC1

Procedure:
The title compound was prepared following procedure and work up described for example 19, but starting from 5-(3-furyl)[1,2,4]triazolo[1,5-a]pyridin-2-amine ((A2), 50 mg; 0.25 mmol; 1.0 eq.) and 1-acetylpiperidine-4-carbonyl chloride (57 mg; 0.3 mmol; 1.2 eq.) as a white powder (41.3 mg, 46%). HPLC, Rt: 2.15 min. (purity 93.3%). LC/MS, M+(ESI): 354.4, M−(ESI): 352.4.
Reaction SMILES: [CH2:1]([C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[C:5]([N+:10]([O-:12])=[O:11])[CH:4]=1)[CH3:2].[Br:13]Br.O>C(O)(=O)C>[Br:13][C:8]1[CH:9]=[C:3]([CH2:1][CH3:2])[CH:4]=[C:5]([N+:10]([O-:12])=[O:11])[C:6]=1[NH2:7]
Reactant: BrBr
Reactant: CCc1ccc(N)c([N+](=O)[O-])c1
Solvent: O
Solvent: CC(=O)O
Product: CCc1cc(Br)c(N)c([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
To a solution of 4-ethyl-2-nitroaniline (28 g) in acetic acid (250 ml) was added bromine (9.64 ml) dropwise with stirring at room temperature. The reaction mixture was stirred for 1 hour, poured into water, and extracted with ethyl acetate (3×200 ml). The organic layer was washed with water (3×200 ml), brine (2×100 ml), dried over magnesium sulphate and evaporated to yield 2-bromo-4-ethyl-6-nitroaniline (38 g). This was dissolved in ethanol (200 ml), concentrated sulphuric acid (24 ml) was added dropwise, the mixture heated to reflux and solid sodium nitrate (27 g) added in small amounts over 30 minutes. The reaction mixture was refluxed for a further 1 hour, cooled and poured into ice water. The product was extracted into ethyl acetate which was washed with water (2×100 ml). brine (2×100 ml), dried over magnesium sulphate and evaporated to yield 3-bromo-5-ethyl-nitrobenzene (35.5 g), δ (60 MHz, CDCl3), 1.3 (3H, t, CH3), 2.8 (2H, q, CH2) 7.6 (1H, s, 4-H), 7.9 (1H, s. 6-H) and 8.0 (1H, s, 2H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=3)=[C:13]([CH3:22])[S:12][C:11]=2[CH:23]=1.[CH2:24]([NH:27][CH3:28])[CH:25]=[CH2:26]>>[CH2:24]([N:27]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=3)=[C:13]([CH3:22])[S:12][C:11]=2[CH:23]=1)[CH3:28])[CH:25]=[CH2:26]
Reactant: Cc1sc2cc(OCCCCBr)ccc2c1-c1ccc(Br)cc1
Reactant: C=CCNC
Product: C=CCN(C)CCCCOc1ccc2c(-c3ccc(Br)cc3)c(C)sc2c1

Procedure:
According to the method in example 31, 6-(4-Bromo-butoxy)-3-(4-bromo-phenyl)-2-methyl-benzo[b]thiophene and Allyl-methyl-amine were converted to yield Allyl-{4-[3-(4-bromo-phenyl)-2-methyl-benzo[b]thiophen-6-yloxy]-butyl}-methyl-amine, MS: 444 (MH+,1Br).
Reaction SMILES: CO[C:3]1[CH:14]=[CH:13][C:6]([CH2:7][C:8](=[O:12])[C:9]([O-:11])=[O:10])=[CH:5][CH:4]=1.[CH:15]1([CH2:21][Mg]Br)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.BrCC1CCCCC1.BrCCBr.C[CH2:37][O:38]CC>C1(C)C=CC=CC=1>[CH:6]1([CH2:7][CH:8]([OH:12])[C:9]([O:11][CH2:21][C:15]2[CH:20]=[CH:19][C:18]([O:38][CH3:37])=[CH:17][CH:16]=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:14][CH2:13]1
Reactant: CCOCC
Reactant: COc1ccc(CC(=O)C(=O)[O-])cc1
Reactant: Br[Mg]CC1CCCCC1
Agent: BrCC1CCCCC1
Solvent: Cc1ccccc1
Solvent: BrCCBr
Product: COc1ccc(COC(=O)C(O)CC2CCCCC2)cc1
Reaction time: 1 h
Yield: 26 %

Procedure:
A solution of 0.50 g (2.32 mmol) of 4-(methoxy)benzylglyoxylate (azeotropically dried with 2×25 mL of toluene) in 2 mL of ether at −78° C. was treated with 7 mL of 0.5 M of cyclohexylmethylmagnesium bromide (prepared from 1.0 mL (7.1 mmol) of bromomethylcyclohexane, 174 mg (7.1 mmol) of Mg, 0.1 mL (1.1 mmol) of 1,2-dibromoethane in 14 mL of ether) and the resulting mixture was stirred cold for 1 h. The reaction was quenched with 1 N NaHCO3 and the quenched mixture was partitioned between 100 mL of ether and 100 mL of sat'd NaHCO3. The aqueous layer was separated and extracted with 100 mL of ether. The combined organic layers were dried over MgSO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 180 mg (26%) of the title compound: RF: 0.32 (4:1 v/v hexanes/EtOAc); 1H NMR (300 MHz) δ 0.84-1.82 (m, 13H), 3.81 (s, 3H), 4.23 (m, 1H), 5.14 (s, 2H), 6.90 (d, J=8.7, 2H), 7.29 (d, J=8.7, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[NH:11][C:10](=[O:13])[CH2:9][CH2:8]2.[Cl:14][CH2:15][C:16](Cl)=[O:17].[Cl-].[Al+3].[Cl-].[Cl-]>[N+](C1C=CC=CC=1)([O-])=O>[Cl:14][CH2:15][C:16]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[C:12]2[C:7]=1[CH2:8][CH2:9][C:10](=[O:13])[NH:11]2)=[O:17]
Reactant: COc1cccc2c1NC(=O)CC2
Reactant: O=C(Cl)CCl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=[N+]([O-])c1ccccc1
Product: COc1ccc(C(=O)CCl)c2c1NC(=O)CC2
Reaction time: 15 h
Yield: 38.7 %

Procedure:
13 g of 8-hydroxy-3,4-dihydrocarbostyril (VII) and 20 g of chloroacetyl chloride were dissolved in 100 ml of nitrobenzene, and 40 g of aluminum chloride was added slowly to the mixture followed by stirring at a temperature of 70° to 75° C for 15 hours. The nitrobenzene was then steam-distilled. After allowing the mixture to cool, the precipitated crystals were filtered, washed with hot water and recrystallized from methanol to give 7.2 g of 5-chloroacetyl-8-hydroxy-3,4-dihydrocarbostyril (IV) as light yellow crystals having a melting point of 189° to 190° C.