Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([Br:11])[CH:10]=1)[C:5]([Cl:7])=[O:6].[C:12]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[CH:14][CH:13]=1.[Sb:26]([Cl:31])([Cl:30])([Cl:29])([Cl:28])[Cl:27]>C(Cl)(Cl)Cl>[C:12]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:13]=[CH:14][C:15]([C:18]2[N:19]=[C:18]([C:15]3[CH:16]=[CH:17][C:12]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:13][CH:14]=3)[O+:6]=[C:5]([C:4]3[CH:3]=[C:2]([Br:1])[CH:10]=[C:9]([Br:11])[CH:8]=3)[N:19]=2)=[CH:16][CH:17]=1.[Cl:27][Sb-:26]([Cl:7])([Cl:31])([Cl:30])([Cl:29])[Cl:28]
Reactant: Cl[Sb](Cl)(Cl)(Cl)Cl
Reactant: O=C(Cl)c1cc(Br)cc(Br)c1
Reactant: N#Cc1ccc(-c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: Brc1cc(Br)cc(-c2nc(-c3ccc(-c4ccccc4)cc3)nc(-c3ccc(-c4ccccc4)cc3)[o+]2)c1
Product: Cl[Sb-](Cl)(Cl)(Cl)(Cl)Cl
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
2.98 g of 3,5-dibromobenzoyl chloride and 3.58 g of 4-biphenylcarbonitrile were dissolved in 40 mL of chloroform. The obtained solution was cooled to 0° C., and 2.99 g of antimony pentachloride was added dropwise to the cooled solution. The obtained mixed liquid was stirred at room temperature for 10 minutes, and then, heated under reflux for 14 hours. The obtained reaction mixture was cooled to room temperature, and then distilled under a reduced pressure to remove chloroform to give 4,6-bis(4-biphenylyl)-2-(3,5-dibromophenyl)-1,3,5-oxadiazin-1-ium=hexachloroantimonate as a red solid.
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:20]([Br:24])(Br)(Br)Br.[F:25][C:26]1[CH:31]=[C:30]([O:32][Si:33]([CH:40]([CH3:42])[CH3:41])([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35])[CH:29]=[C:28]([F:43])[C:27]=1[CH2:44]CO>C(Cl)Cl>[Br:24][CH2:20][CH2:44][C:27]1[C:26]([F:25])=[CH:31][C:30]([O:32][Si:33]([CH:40]([CH3:42])[CH3:41])([CH:34]([CH3:36])[CH3:35])[CH:37]([CH3:38])[CH3:39])=[CH:29][C:28]=1[F:43]
Reactant: CC(C)[Si](Oc1cc(F)c(CCO)c(F)c1)(C(C)C)C(C)C
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)[Si](Oc1cc(F)c(CCBr)c(F)c1)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 67.1 %

Procedure:
PPh3 (1.11 g, 4.24 mmol) was added to a cooled (0° C.) solution of CBr4 (0.92 g, 237 mmol) in DCM (15 mL). After stirring for 15 minutes, a solution of PMW04155 (0.70 g, 2.12 mmol) in DCM (5 mL) was added and the reaction mixture was stirred for 1 h, then allowed to warm to room temperature and stirred for 2 h. The solvent was removed in vacuo and the residue was purified using the Combiflash system (EtOAc/PE) to give the title compound (0.56 g, 67%) as a colourless oil; 1H NMR (270 MHz, CDCl3) 1.05-1.32 (21H, m, 6×CH3,3×CH), 3.13 (2H, t, J=7.7, CH2), 3.48 (2H, t, J=7.7, CH2), 6.34-6.45 (2H, m, ArH).
Reaction SMILES: B(Br)(Br)[Br:2].Br.[NH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:27])[C:15]1[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[C:18]([OH:24])=[C:17]([O:25]C)[CH:16]=1>C(Cl)Cl>[BrH:2].[NH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:27])[C:15]1[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[C:18]([OH:24])=[C:17]([OH:25])[CH:16]=1
Reactant: BrB(Br)Br
Reactant: COc1cc(C(=O)NCCCCCCN)cc([N+](=O)[O-])c1O
Agent: Br
Solvent: ClCCl
Product: NCCCCCCNC(=O)c1cc(O)c(O)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
1.25 g of boron tribromide are added -20° to a suspension of 392.3 mg of N-(6-aminohexyl)-4-hydroxy-5-nitro-m-anisamide hydrobromide in 25 ml of dry methylene chloride. After the addition the mixture is stirred at -20° for 1 hour and subsequently at room temperature for 17 hours. The reaction mixture is then evaporated, the residue is treated with 10 ml of water and stirred at room temperature for 1 hour. After evaporating the water the residue is chromatographed on Sephadex LH 20 with toluene/ethanol (1:1). There is obtained N-6-aminohexyl-3,4-dihydroxy-5-nitrobenzamide hydrobromide of m.p. 205°-207° (from ethanol).
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:22]5[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]5)=[N:19][C:18]4=[O:29])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:32]([F:35])([F:34])[F:33])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:42][C:43]([F:51])([F:50])[CH2:44]OS(C)(=O)=O>CS(C)=O>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:22]5[CH2:28][CH2:27][CH2:26][N:25]([CH2:44][C:43]([F:51])([F:50])[F:42])[CH2:24][CH2:23]5)=[N:19][C:18]4=[O:29])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:32]([F:35])([F:34])[F:33])[CH:3]=1
Reactant: CS(=O)(=O)OCC(F)(F)F
Reactant: O=C1N=C(N2CCCNCC2)SC1=Cc1ccc2c(cnn2Cc2ccc(Cl)cc2C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: O=C1N=C(N2CCCN(CC(F)(F)F)CC2)SC1=Cc1ccc2c(cnn2Cc2ccc(Cl)cc2C(F)(F)F)c1
Temperature: 70 °C
Reaction time: 1 h

Procedure:
A solution of 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[1,4]diazepan-1-yl-thiazol-4-one (0.051 g, 0.098 mmol) in DMSO (2.2 mL) was treated with potassium carbonate (0.045 g, 0.32 mmol) and methanesulfonic acid 2,2,2-trifluoro-ethyl ester (0.06 g, 0.32 mmol). Reaction mixture was stirred at 70° C. for 1 hour and partitioned between dichloromethane and water. The dichloromethane layer was dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude solid. The crude solid was purified using semi-preparative reverse phase HPLC (YMC ODS A, 100×30 mm, 50 μM I.D., 0.05% TFA acetonitrile/0.05% TFA water=30/70 to 100/0) to yield the title compound as a flocculent solid.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2.Br[CH2:14][CH:15]([CH3:17])[CH3:16].O>CN(C)C=O>[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:14][CH:15]([CH3:17])[CH3:16])[N:8]=[CH:7]2.[Br:3][C:4]1[CH:12]=[CH:11][C:10]2[C:6](=[CH:7][N:8]([CH2:14][CH:15]([CH3:17])[CH3:16])[N:9]=2)[CH:5]=1
Reactant: CC(C)CBr
Reactant: Brc1ccc2[nH]ncc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)Cn1cc2cc(Br)ccc2n1
Product: CC(C)Cn1ncc2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 1.25 h

Procedure:
Sodium hydride (80% suspension in oil, 0.7 g, 0.023 mol) was suspended in N,N-dimethylformamide (DMF) (10 ml) and then a solution of 5-bromoindazole (4.1 g, 0.021 mol) in DMF (40 ml) was added dropwise over 30 minutes. Once the addition was complete the mixture was stirred at ambient temperature for 75 minutes and then a solution of 1-bromo-2-methylpropane (3.7 g, 0.027 mol) in DMF (25 ml) was added over 10 minutes. The mixture was stirred for 5 hours and was then allowed to stand at ambient temperature overnight. The mixture was poured into water, extracted with diethyl ether and then the organic extract was washed further with water, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with 1:1 diethyl ether:hexane to give 5-bromo-1-(2-methylpropyl)indazole (2.67 g) and 5-bromo-2-(2-methylpropyl)indazole (1.49 g), each as an orange oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:11][C:12](=[O:17])[CH:13]=[C:14]([NH2:16])[CH3:15])[CH3:10])=[CH:5][CH:4]=1.[Br:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([O:28][CH2:29][CH3:30])[C:26]=1[OH:27])[CH:22]=O.[CH2:31]([CH:34]1[CH2:39][C:38](=[O:40])[CH2:37][C:36](=O)[CH2:35]1)[CH2:32][CH3:33]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]([NH:11][C:12]([C:13]2[CH:22]([C:21]3[CH:24]=[C:25]([O:28][CH2:29][CH3:30])[C:26]([OH:27])=[C:19]([Br:18])[CH:20]=3)[C:37]3[C:38](=[O:40])[CH2:39][CH:34]([CH2:31][CH2:32][CH3:33])[CH2:35][C:36]=3[NH:16][C:14]=2[CH3:15])=[O:17])[CH3:10])=[CH:7][CH:8]=1
Reactant: CCOc1cc(C=O)cc(Br)c1O
Reactant: COc1ccc([C@H](C)NC(=O)C=C(C)N)cc1
Reactant: CCCC1CC(=O)CC(=O)C1
Solvent: CCO
Product: CCCC1CC(=O)C2=C(C1)NC(C)=C(C(=O)N[C@@H](C)c1ccc(OC)cc1)C2c1cc(Br)c(O)c(OCC)c1
Temperature: 80 °C
Reaction time: 18 h

Procedure:
A mixture of (S)-3-amino-but-2-enoic acid [1-(4-methoxy-phenyl)-ethyl]-amide (10 g), 3-bromo-5-ethoxy-4-hydroxy-benzaldehyde (10.4 g) and 5-propylcyclohexane-1,3-dione (6.5 g) in ethanol (150 ml) was stirred at 80° C. for 18 hr. The mixture was concentrated in vacuo. The residue was dissolved in toluene (100 ml) and dichloromethane (50 ml) and evaporated until a precipitated formed. The solid obtained was then crystallized in EtOAc.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[O:26]([CH2:33][C:34](Cl)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.O>ClCCl>[O:26]([CH2:33][C:34]([NH:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C:14](=[O:15])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C(Cl)COc1ccccc1
Reactant: Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: O=C(COc1ccccc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 34 %

Procedure:
To a stirred solution of [4-(6-aminopyridazin-3-yl)-piperazin-1-yl]-(2-trifluoromethyl-phenyl)methanone (105 mg, 0.300 mmol) in dichloromethane (10 mL) was added phenoxyacetyl chloride (56 mg, 0.32 mmol) followed by the addition of triethylamine (0.15 mL) at 0° C. The mixture was stirred at ambient temperature overnight. Water was added and the mixture was extracted with ethyl acetate (2×15 mL). The combined organic layer was washed sequentially with diluted HCl, sodium bicarbonate and brine solution, then dried with Na2SO4, concentrated. The residue was re-dissolved in small amount of dichloromethane and purified by column chromatography. The title compound was isolated as a white solid in 34% yield (50 mg). 1H NMR (300 MHz, CDCl3) δ 9.28, 8.38, 7.75, 7.64, 7.56, 7.35, 7.04, 4.65, 4.01, 3.68, 3.34.
Reaction SMILES: [NH2:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[O:19][C:18]([C:20]([NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][C:3]=1[F:29].C(N(CC)C(C)C)(C)C.ClC(O[C:44](=[O:50])OC(Cl)(Cl)Cl)(Cl)Cl.[CH3:51][CH:52]([CH3:55])[CH2:53][NH2:54]>ClCCl>[C:23]([NH:22][C:20]([C:18]1[O:19][C:15]([CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:6](=[O:7])[C:5]3[CH:27]=[CH:28][C:2]([NH:1][C:44]([NH:54][CH2:53][CH:52]([CH3:55])[CH3:51])=[O:50])=[C:3]([F:29])[CH:4]=3)[CH2:13][CH2:12]2)=[CH:16][CH:17]=1)=[O:21])([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)CN
Reactant: CC(C)(C)NC(=O)c1ccc(CN2CCN(C(=O)c3ccc(N)c(F)c3)CC2)o1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)CNC(=O)Nc1ccc(C(=O)N2CCN(Cc3ccc(C(=O)NC(C)(C)C)o3)CC2)cc1F
Reaction time: 0.5 h
Yield: 21.7 %

Procedure:
5-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylfuran-2-carboxamide (Example 3; 0.05 g, 0.124 mmol) and N,N-diisopropylethylamine (0.028 mL) were dissolved in dichloromethane (5 mL). Bis(trichloromethyl)carbonate (0.014 g, 0.046 mmol) was added dropwise and the reaction was left to stir for 30 minutes. N,N-diisopropylethylamine (0.094 mL) was added to the reaction followed by 2-methylpropan-1-amine (0.018 g, 0.248 mmol, 0.025 mL) and the reaction was stirred for a further 2 hours. The reaction mixture was washed with water and flushed through a hydrophobic frit. The organic phase was concentrated under vacuum and purified by basic reverse phase HPLC to afford the title compound (5 mg).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[C:3]=1[CH2:22][C:23]([O:25][CH3:26])=[O:24].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:37]1[CH2:41]OC[CH2:38]1.ICCC>CN(C=O)C>[CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[C:3]=1[CH:22]([CH2:38][CH2:37][CH3:41])[C:23]([O:25][CH3:26])=[O:24]
Reactant: C1CCOC1
Reactant: COC(=O)Cc1c(C)nc2sc3c(c2c1-c1ccccc1Cl)CCCC3
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCCI
Product: CCCC(C(=O)OC)c1c(C)nc2sc3c(c2c1-c1ccccc1Cl)CCCC3
Yield: 73.1 %

Procedure:
This compound was prepared according to the procedure C from methyl [2-methyl-4-(2-chlorophenyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate (0.300 g; 0.78 mmol), LHMDS 1N in THF (0.86 mL; 0.86 mmol), 1-iodopropane (0.114 mL; 1.17 mmol) in DMF (3.1 mL) for 4 h. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (2-30%) in heptane furnished 0.244 g (74%) of the title compound as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:26])=[O:25])[C:11](=[O:33])[C@:10]([CH2:35][C:36]([OH:38])=[O:37])([CH3:34])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:39][Si](C=[N+]=[N-])(C)C.C(OCC)C>CO.C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:28][CH2:29]3)(=[O:25])=[O:26])[C:11](=[O:33])[C@:10]([CH2:35][C:36]([O:38][CH3:39])=[O:37])([CH3:34])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC[C@@H](CN(C)S(=O)(=O)C1CC1)N1C(=O)[C@@](C)(CC(=O)O)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: c1ccccc1
Solvent: CCOCC
Product: CC[C@@H](CN(C)S(=O)(=O)C1CC1)N1C(=O)[C@@](C)(CC(=O)OC)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid (0.055 g, 0.095 mmol; Example 141) in 1 mL of MeOH and 4 mL of benzene was added a 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether (0.095 mL, 0.189 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 h and was then concentrated. The crude material was purified by reverse phase preparatory HPLC (eluent: 10 to 90% acetonitrile, water, 0.1% TFA, gradient elution) to provide the title compound as a white powder after lyophilization of the pooled collected fractions.
Reaction SMILES: N(C(C1C=C(C=CC=1)C(C)=C)(C)C)=C=O.OCCCCCCOC([C:26]1[C:27](=[O:41])[O:28][C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[C:31](N(CC)CC)[CH:30]=2)=O.C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC>C(Cl)Cl>[O:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:35]=[CH:26][C:27]1=[O:41]
Reactant: CCN(CC)c1ccc2cc(C(=O)OCCCCCCO)c(=O)oc2c1
Agent: C=C(C)c1cccc(C(C)(C)N=C=O)c1
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Solvent: ClCCl
Product: O=c1ccc2ccccc2o1

Procedure:
In this scheme, m-(2-isocyanatoprop-2-yl)-α-methylstyrene (23) and m/p-methylstyrene (24) are polymerised under the action of AIBN as free-radical initiator in toluene at 100 to 110° C. to yield the copolymer (25). The preferred molar proportion x of comonomer (23) is between 0 and 60%. The copolymer (25) obtainable in this manner reacts with 3-(6-hydroxyhexoxycarbonyl)-7-diethylaminocoumarin (26) in the presence of catalytic quantities of dibutyltin dilaurate (DBZD) in refluxing methylene chloride, wherein the copolymer (27) may be obtained with a lateral coumarin luminophore (Et=ethyl).
Reaction SMILES: C([O:8][C@H:9]1[C@H:15]([O:16]CC2C=CC=CC=2)[C@@H:14]([O:24]CC2C=CC=CC=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:52]([OH:54])[CH3:53])[CH2:11][O:12]2)C1C=CC=CC=1.ClC1C=CC=CC=1Cl>[Pd].CO.O1CCCC1>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C@@:13]23[O:32][C@@:10]([CH:52]([OH:54])[CH3:53])([CH2:11][O:12]2)[C@@H:9]([OH:8])[C@H:15]([OH:16])[C@H:14]3[OH:24])=[CH:34][C:35]=1[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][C:48]([F:50])([F:49])[F:51])=[CH:43][CH:42]=1
Reactant: CC(O)[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(OC(F)(F)F)cc4)c3)(O1)[C@H](OCc1ccccc1)[C@@H](OCc1ccccc1)[C@@H]2OCc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: Clc1ccccc1Cl
Solvent: C1CCOC1
Product: CC(O)[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(OC(F)(F)F)cc4)c3)(O1)[C@H](O)[C@@H](O)[C@@H]2O
Temperature: 25 °C
Reaction time: 2 h
Yield: 28.2 %

Procedure:
To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[4-[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 15q (102 mg, 0.13 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL) were added o-dichlorobenzene (95 mg, 0.65 mmol) and 10% Pd/C (41 mg, 0.39 mmol) at room temperature. The mixture was stirred under H2 at room temperature for 2 hours and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=1/5 to give the title compound 15 as a white solid (18 mg, 28.2%, HPLC: 96.2%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 535.2[M+HCOO]−; and 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.47 (d, 1H), 7.42 (d, 1H), 7.37-7.26 (m, 5H), 5.27 (d, 1H), 4.92 (m, 2H), 4.61 (d, 1H), 4.12 (s, 2H), 4.01 (dd, 1H), 3.81 (dd, 1H), 3.54 (d, 1H), 3.47-3.37 (m, 3H), 1.17 (d, 3H).
Reaction SMILES: [CH:1]1[N:6]=[C:5](Cl)[C:4]2[N:8]=[CH:9][N:10]([C@@H:11]3[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:3]=2[N:2]=1.Cl.[CH3:21][O:22][C:23]1[CH:32]=[C:31]2[C:26]([CH2:27][CH:28]([NH2:33])[CH2:29][O:30]2)=[CH:25][CH:24]=1.C([N:36](CC)CC)C>C(O)C>[CH3:21][O:22][C:23]1[CH:32]=[C:31]2[C:26]([CH2:27][CH:28]([NH:33][NH:36][C:5]3[C:4]4[N:8]=[CH:9][N:10]([C:3]=4[N:2]=[CH:1][N:6]=3)[C@@H:11]3[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[CH2:29][O:30]2)=[CH:25][CH:24]=1
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Reactant: COc1ccc2c(c1)OCC(N)C2
Reactant: CCN(CC)CC
Agent: Cl
Solvent: CCO
Product: COc1ccc2c(c1)OCC(NNc1ncnc3c1ncn3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O)C2
Yield: 40.3 %

Procedure:
A mixture of 0.56 g 6-chloropurine riboside, 0.5 g 7-methoxy-3-chromanylamine hydrochloride, and 0.48 g of triethylamine is refluxed in 25 ml ethanol under nitrogen for 20 hrs. Solvent is evaporated to dryness and residue is treated with cold water. The clear aqueous solution is decanted off, residue is dissolved in ethanol and volatiles are evaporated under vacuo. The crude solid is purified by flash-chromatography on silica-gel using 5% methanolchloroform as an eluant. Evaporation of solvent from pure fractions followed by crystallization from CHCl3 -hexane affords 0.35 g (42%) of N6 -[7-methoxy-3-chromanylamino]adenosine having a melting point of 205°-207° C.
Reaction SMILES: [BrH:1].[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][NH2:7].[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C(O)C>[BrH:2].[Br-:1].[NH2:7][CH2:6][CH2:5][CH2:4][CH2:3][N+:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: NCCCCBr
Reactant: c1ccncc1
Agent: Br
Solvent: CCO
Product: NCCCC[n+]1ccccc1
Product: [Br-]

Procedure:
A solution of 17.4 g of 4-bromobutanamine hydrobromide and 6.0 ml (5.9 g) of pyridine in 75 ml of ethanol was heated under reflux for 18 hours. The reaction was cooled and the resulting solid was collected and recrystallized from ethanol to give 3.4 g (15%) of the analytical sample as colorless crystals, 1-(4-aminobutyl)pyridinium bromide hydrobromide mp 219° (decomposition).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1>>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:20](=[O:21])[C:19]2[CH:23]=[CH:24][C:16]([CH3:15])=[CH:17][CH:18]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: Cc1ccc(C(=O)Cl)cc1
Product: Cc1ccc(C(=O)NC2CCN(Cc3ccccc3)CC2)cc1

Procedure:
The 1-benzyl-4-aminopiperidine prepared in Example 30 was treated with p-methylbenzoyl chloride in a similar manner to that described in the same example and the product converted to a salt.
Reaction SMILES: C(O[C:4]([C:6]1[N:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[C:15]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[N:16][O:17][C:18]=2[CH3:19])=[CH:10][CH:11]=1)=[O:5])C.[NH2:26][CH2:27][CH2:28][OH:29]>>[OH:29][CH2:28][CH2:27][NH:26][C:4]([C:6]1[N:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[C:15]([C:20]3[CH:21]=[CH:22][N:23]=[CH:24][CH:25]=3)=[N:16][O:17][C:18]=2[CH3:19])=[CH:10][CH:11]=1)=[O:5]
Reactant: NCCO
Reactant: CCOC(=O)c1ccc(OCc2c(-c3ccncc3)noc2C)nn1
Product: Cc1onc(-c2ccncc2)c1COc1ccc(C(=O)NCCO)nn1
Yield: 23 %

Procedure:
As described for example 69, 6-(5-methyl-3-pyridin-4-yl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid ethyl ester (100 mg, 0.29 mmol) was converted, using 2-aminoethanol instead of isopropylamine, to the title compound (24 mg, 23%) which was obtained as a light yellow solid. MS: m/e=356.3 [M+H]+.
Reaction SMILES: [C:1]1(=[O:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:9][C:10]#[N:11]>>[O:7]=[C:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:9][C:10]#[N:11]
Reactant: N#CCBr
Reactant: O=C1CCCCC1
Product: N#CCC1CCCCC1=O

Procedure:
Cyclohexanone is reacted with bromoacetonitrile by the method of Example 65 to generate the title compound.
Reaction SMILES: [Al].[O:2]=[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](O[Si](CC)(CC)CC)([C:13]([F:16])([F:15])[F:14])[CH:5]=[CH:4]1>O>[F:14][C:13]([F:15])([F:16])[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([OH:2])=[CH:4][CH:5]=1
Reactant: CC[Si](CC)(CC)OC1(C(F)(F)F)C=CC(=O)c2ccccc21
Agent: [Al]
Solvent: O
Product: Oc1ccc(C(F)(F)F)c2ccccc12
Temperature: 25 °C
Yield: 89.6 %

Procedure:
A strip of aluminum foil weighing 278 mg (10 mmol) was amalgamated by immersion in a solution of 2% mercuric chloride in water for 15 seconds, washed with absolute ethanol followed by diethyl ether, cut into small pieces, and added to a solution of 353 mg (1.0 mmol) of 1,4-dihydro-1-oxo-4-triethylsiloxy-4-trifluoromethylnaphthalene in 10 mL of 10% water - 90% tetrahydrofuran. The resulting mixture was heated at 70 C for 1.5 hours, allowed to cool to room temperature, and filtered. The filter cake was washed with diethyl ether. Concentration of the combined filtrates gave a residue which was poured into 25 mL of water. The aqueous mixture was extracted with three 10 mL portions of dichloromethane. Combination, drying (MgSO4), and concentration of the organic layers gave a residue which was purified by PTLC (one 2 mm silica gel plate eluted with dichloromethane), affording 190 mg (90% yield) of 4-trifluoromethyl-1-naphthol as a white solid. An analytical sample was obtained by recrystallization from dichloromethane-hexane: mp 132-133° C.; 1H NMR (CDCl3) δ 5.50 (broad s, 1H), 6.79 (d, 1H, J=8 Hz), 7.50-7.80 (m, 3H), 8.10-8.45 (m, 2H); 19F NMR (CDCl3, relative to CFCl3) -59.5 ppm (s); IR (KBr) 3327, 1580, 1385, 1355, 1327, 1260, 1251, 1241, 1195, 1178, 1146, 1120, 1111, 1101, 1056, 767, cm-1; mass spectrum (70 eV) m/z (relative intensity) 212 (100, M+), 133 (32), 115 (100). Anal. Calcd. for C11H7F3O: C, 62.27; H, 3.33. Found: C, 61.82; H, 3.50.