Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.[H-].[Na+].CS(O[CH:14]1[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15]1)(=O)=O>CN(C=O)C>[I:1][C:2]1[CH:3]=[N:4][N:5]([CH:14]2[CH2:15][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17]2)[CH:6]=1
Reactant: CC(C)(C)OC(=O)N1CC(OS(C)(=O)=O)C1
Reactant: Ic1cn[nH]c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC(n2cc(I)cn2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61.1 %

Procedure:
At 0° C., a solution of 4-iodopyrazole (3.0 g, 15.46 mmol) in DMF (40 mL) was treated with NaH (60% mineral oil dispersion, 1.11 g, 46.39 mmol) in portions. The mixture stirred for 30 minutes, followed by the slow addition of 1-(tert-butoxycarbonyl)azetidin-3-yl methanesulfonate (5.0 g, 20.1 mmol). The reaction mixture was warmed to RT and then heated at 100° C. for 5 hours. The reaction mixture was poured into ice cold water, stirred for 30 minutes, and resulting precipitate collected by filtration and dried. The resulting residue washed with pentane and dried to obtain tert-butyl 3-(4-iodo-1H-pyrazol-1-yl)azetidine-1-carboxylate (3.3 g, 62% yield); 1H-NMR (400 MHz, CDCl3): 7.58 (s, 1H), 7.57 (s, 1H), 5.07-5.0 (m, 1H), 4.39-4.34 (m, 2H), 4.29-4.25 (dd, 2H), 1.45 (s, 9H).
Reaction SMILES: Cl.[F:2][C:3]([F:16])([F:15])[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH:12]([NH2:14])[CH3:13])[CH:9]=[CH:10][CH:11]=1.[NH2:17][C:18]1[N:23]=[C:22]([C:24](O)=[O:25])[CH:21]=[CH:20][N:19]=1>>[NH2:17][C:18]1[N:23]=[C:22]([C:24]([NH:14][CH:12]([C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][C:3]([F:15])([F:16])[F:2])[CH:7]=2)[CH3:13])=[O:25])[CH:21]=[CH:20][N:19]=1
Reactant: Nc1nccc(C(=O)O)n1
Reactant: CC(N)c1cccc(OCC(F)(F)F)c1
Agent: Cl
Product: CC(NC(=O)c1ccnc(N)n1)c1cccc(OCC(F)(F)F)c1
Yield: 42 %

Procedure:
The title compound is prepared in 42% yield (102 mg, a white solid) from 1-(3-(2,2,2-trifluoroethoxy)phenyl)ethanamine hydrochloride (139 mg, 0.72 mmol, Amine-16, single enantiomer) and 2-aminopyrimidine-4-carboxylic acid (100 mg, 0.72 mmol) by the similar manner in Step-1 of Example 8.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:30])=[C:6]([C:8]([CH3:29])([CH3:28])[CH2:9][C:10]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH2:11][N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[CH:14]=[CH:13]2)[CH:7]=1.I[CH2:32][CH3:33].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH2:32]([O:30][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][C:6]=1[C:8]([CH3:28])([CH3:29])[CH2:9][C:10]([OH:27])([C:23]([F:25])([F:26])[F:24])[CH2:11][N:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[CH:14]=[CH:13]1)[CH3:33]
Reactant: CC(C)(CC(O)(Cn1ccc(=O)c2ccccc21)C(F)(F)F)c1cc(F)ccc1O
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOc1ccc(F)cc1C(C)(C)CC(O)(Cn1ccc(=O)c2ccccc21)C(F)(F)F
Temperature: 80 °C

Procedure:
A mixture of 1-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one (0.053 g), iodoethane (0.011 mL) and powdered potassium carbonate (0.090 g) in 1 mL of anhydrous DMF was heated at 80° C. for 18 hours, cooled to room temperature, and diluted with water and filtered. The solid was purified with flash silica gel chromatography using ethyl acetate as the eluent. The product rich fraction were concentrated in vacuo and provided 1-[4-(2-ethoxy-5-fluorophenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one, m.p. 195° C.-196° C.
Reaction SMILES: [F:1][C:2]1[C:11]([F:12])=[CH:10][C:9]2[O:13][CH2:14][CH:15]([CH3:16])[N:7]3[C:8]=2[C:3]=1[C:4](=[O:20])[C:5]([C:17]([OH:19])=[O:18])=[CH:6]3.[B:21](F)([F:23])[F:22]>>[B:21]([F:23])([F:22])[O:18][C:17]([C:5]1[C:4](=[O:20])[C:3]2[C:8]3=[C:9]([O:13][CH2:14][CH:15]([CH3:16])[N:7]3[CH:6]=1)[CH:10]=[C:11]([F:12])[C:2]=2[F:1])=[O:19]
Reactant: FB(F)F
Reactant: CC1COc2cc(F)c(F)c3c(=O)c(C(=O)O)cn1c23
Product: CC1COc2cc(F)c(F)c3c(=O)c(C(=O)OB(F)F)cn1c23

Procedure:
From 1.0 g of 8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid (for preparation see Journal of Medicinal Chemistry 1992, 35 (4), 611) and 1.51 g (3 eq.) of BF3 etherate, by the same method as described for Example 38A, 1.0 g (85% of theory) of the title compound is isolated.
Reaction SMILES: [N:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:6][CH:5]=1)=[C:2]=[S:3].[H-].[Na+].[NH2:18][C:19]1[C:24](=[O:25])[N:23]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])[CH2:22][CH2:21][C:20]=1[C:37](OCC)=[O:38].Cl>CN(C)C=O>[CH3:36][O:35][C:28]1[CH:29]=[C:30]([O:33][CH3:34])[CH:31]=[CH:32][C:27]=1[CH2:26][N:23]1[CH2:22][CH2:21][C:20]2[C:37](=[O:38])[N:1]([C:4]3[CH:5]=[CH:6][C:7]([O:10][CH2:11][C:12]([F:13])([F:15])[F:14])=[CH:8][CH:9]=3)[C:2](=[S:3])[NH:18][C:19]=2[C:24]1=[O:25]
Reactant: CCOC(=O)C1=C(N)C(=O)N(Cc2ccc(OC)cc2OC)CC1
Reactant: FC(F)(F)COc1ccc(N=C=S)cc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(CN2CCc3c([nH]c(=S)n(-c4ccc(OCC(F)(F)F)cc4)c3=O)C2=O)c(OC)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 29.9 %

Procedure:
To a solution of 1-isothiocyanato-4-(2,2,2-trifluoroethoxy)benzene (115 mg) in N,N-dimethylformamide (2 ml) was added sodium hydride (60% in oil, 45 mg), and a solution of ethyl 5-amino-1-(2,4-dimethoxybenzyl)-6-oxo-1,2,3,6-tetrahydropyridine-4-carboxylate (150 mg) in N,N-dimethylformamide (2 ml) was added dropwise thereto over 5 min under ice-cooling. The mixture was stirred for 10 min, allowed to be warmed to room temperature, and stirred for 30 min. The reaction mixture was poured into 0.5M hydrochloric acid (4 ml) under ice-cooling, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained yellow solid was washed with diethyl ether to give the title compound (70 mg) as beige fine needle crystals.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C@H:8]([CH2:17][CH2:18][CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[O:5][N:4]=1.N1C(C)=CC=CC=1C.[CH:34]([S:37](Cl)(=[O:39])=[O:38])([CH3:36])[CH3:35]>C(Cl)Cl>[CH:20]1([CH2:19][CH2:18][CH2:17][C@@H:8]([C:6]2[O:5][N:4]=[C:3]([CH2:2][NH:1][S:37]([CH:34]([CH3:36])[CH3:35])(=[O:39])=[O:38])[N:7]=2)[CH2:9][C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1
Reactant: CC(C)S(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CN)no1
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CC(C)S(=O)(=O)NCc1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 56.2 %

Procedure:
A solution of tert-butyl (3R)-3-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate (preparation 18) (216 mg, 0.61 mmol) and 2,6-lutidine (180 μl, 1.50 mmol) in DCM (3 ml) was treated with isopropanesulphonylchloride (100 μl, 0.90 mmol) and stirred at room temperature for 18 hours. Reaction was complete but it was left for 12 days before purification commenced. The reaction mixture was diluted with DCM and washed with 1M HCl (2×20 ml), sat. NaHCO3 solution and brine. The organic extract was dried over anhydrous MgSO4, filtered and the solvent removed under reduced pressure. The residue was purified on a silica column eluting with a solvent gradient of pentane:EtOAc (90:10) gradually changing to (50:50) to afford the title compound as a colourless oil (157 mg, 56%).
Reaction SMILES: [CH3:1][NH2:2].[Br:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[F:12])[CH2:7]Br>CO>[Br:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[F:12])[CH2:7][CH2:1][NH2:2]
Reactant: Fc1ccc(CBr)cc1Br
Reactant: CN
Solvent: CO
Product: NCCc1ccc(F)c(Br)c1
Reaction time: 91 h
Yield: 58.9 %

Procedure:
To 40% solution of methylamine in methanol (100 ml) with being stirred under ice cooling was added dropwise 3-bromo-4-fluorobenzylbromide (13.04 g; 48.7 mmol) in methanol (10 ml). The mixture was brought to room temperature, and stirred for 91 hours. The reaction mixture was concentrated under reduced pressure, and the residue was taken up in water. The mixture was alkalinized with sodium hydroxide, followed by extraction with ether (160 ml). The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=1:0→10:1), to thereby yield 6.25 g of the target compound (yield: 58.9%).
Reaction SMILES: Cl.[CH2:2]([O:14][C:15](=[O:22])[C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][NH:17]1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].C(=O)([O-])O.[Na+].[C:28](Cl)(=[O:44])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>O1CCOCC1.O>[CH2:2]([O:14][C:15](=[O:22])[C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][N:17]1[C:28](=[O:44])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCCCCCOC(=O)[C@@H]1C[C@@H](O)CN1
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CCCCCCCCCCCCCCCC(=O)N1C[C@H](O)C[C@H]1C(=O)OCCCCCCCCCCCC

Procedure:
trans-4-Hydroxy-L-proline dodecyl ester hydrochloride (10 g, 29.8 mmol) was dissolved in 1,4-dioxane (125 ml) and water (125 ml); with stirring, sodium hydrogencarbonate (10.4 g, 123.8 mmol) was firstly added, followed by 1-hexadecanoyl chloride (9 ml, 8.19 g, 29.8 mmol). The reaction mixture was stirred for 1 hour at room temperature. The suspension was adjusted to pH 1 to 1.5 and then filtered. The residue was washed with water until neutral and dried under reduced pressure in the melt. Yield: 15.1 g (28 mmol, 94% of theory, 97 to 100% purity [HFLC]) of a white waxy crystalline mass, m.p.: 39 to 44° C. 1H-NMR (CDCl3)δ=0.89 (6H, t), 1.2 to 1.4 (40H, m), 1.5 to 1.7 (61-1, m), 2.05 to 2.40 (4H, dm), 3.79 (1H, dd), 4.12 (2H, m), 4.5 to 4.6 ppm (2H, m); 13C-NMR (CDCl3)δ=172.50 (s), 172.48 (s), 70.4 (d), 65.4 (t), 57.6 (d), 55.1 (t), 37.9 (t), 34.6 (t), 32.0, 29.72 (2C), 29.70 (2C), 29.68 (4C), 29.66, 29.62, 29.56 (2C), 29.48, 29.40, 29.38 (2C,), 29.28, 28.56, 25.85, 24.68, 22.70 (2C), 14.1 (2C, q,q). Elemental analysis: calc.: C 73.7%, H 11.8%, N 2.6%, O 11.9%; found: C 73.5%, H 11.8%, N 2.5%, O 12.2%.
Reaction SMILES: [CH2:1]([NH:4][S:5](Cl)(=[O:7])=[O:6])[CH2:2][CH3:3].[NH2:9][C:10]1[C:11]([F:21])=[C:12]([C:17]([F:20])=[CH:18][CH:19]=1)[C:13]([O:15][CH3:16])=[O:14]>C(Cl)Cl>[F:21][C:11]1[C:10]([NH:9][S:5](=[O:7])(=[O:6])[NH:4][CH2:1][CH2:2][CH3:3])=[CH:19][CH:18]=[C:17]([F:20])[C:12]=1[C:13]([O:15][CH3:16])=[O:14]
Reactant: CCCNS(=O)(=O)Cl
Reactant: COC(=O)c1c(F)ccc(N)c1F
Solvent: ClCCl
Product: CCCNS(=O)(=O)Nc1ccc(F)c(C(=O)OC)c1F
Temperature: 25 °C

Procedure:
Propylsulfamoyl chloride (0.379 mL, 2.40 mmol) was added to methyl 3-amino-2,6-difluorobenzoate (0.150 mL, 0.802 mmol), TEA (0.335 mL, 2.40 mmol) in DCM (1.5 mL) at 0° C. The solution was allowed to warm to room temperature overnight. The solids were filtered, and the supernate was concentrated to provide crude methyl 2,6-difluoro-3-(N-propylsulfamoylamino)benzoate, which was used directly in next step.
Reaction SMILES: [C:1]([N:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)(=[O:3])[CH3:2].[C:17](Cl)(=[O:19])[CH3:18].[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(Cl)Cl>[C:17]([C:7]1[CH:8]=[CH:9][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:4]([C:1](=[O:3])[CH3:2])[C:5]=2[CH:6]=1)(=[O:19])[CH3:18]
Reactant: CC(=O)Cl
Reactant: CC(=O)n1c2ccccc2c2ccccc21
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(=O)c1ccc2c3ccccc3n(C(C)=O)c2c1
Temperature: -78 °C
Yield: 55.5 %

Procedure:
9-Acetyl-carbazole (41.85 g, 0.2 mol) was dissolved in 1 L methylene chloride and 28.5 mL acetylchloride (0.4 mol) and 120 g aluminum chloride (0.9 mol) were added and the solution refluxed for 1.5 h. The solution was cooled to −78° C. and 6N HCl was added slowly while stirring and allowed to warm to room temperature. Methylene chloride was added to dissolve the precipitate and the solution was extracted, and the organics dried over Na2SO4, decolorized with charcoal, filtered and concentrated. Recrystallization from benzene/hexane gave 27.9 g 2,9-diacetylcarbazole.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]#[N:11])=[CH:4][CH:3]=1.C([Sn]([N:53]=[N+:54]=[N-:55])(CCCCCCCCCCCC)CCCCCCCCCCCC)CCCCCCCCCCC>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([C:10]3[N:55]=[N:54][NH:53][N:11]=3)=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(-c2ccccc2C#N)cc1
Reactant: CCCCCCCCCCCC[Sn](CCCCCCCCCCCC)(CCCCCCCCCCCC)N=[N+]=[N-]
Solvent: Cc1ccccc1
Product: Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
Temperature: 120 °C
Reaction time: 37.5 h
Yield: 82.3 %

Procedure:
A mixture of 1.50 g of 2-(4-methylphenyl)benzonitrile, 19.5 g of tridodecyltin azide (tri-n-dodecyltin azide) and 7 ml of toluene was stirred for 37.5 hours at 120° C. The reaction mixture was, after cooling, concentrated, and there were added 18 ml of ethanol, 1 ml of methylene chloride and 2.4 g of sodium nitrite dissolved in 9 ml of water, whose pH was adjusted at 3.4 with conc. hydrochloric acid. To the mixture were added 2 ml of ethyl acetate and 100 ml of hexane. Insolubles were filtered off. The filtrate was shaken, then left standing to form two layers. The organic layer was subjected to extraction with 1N NaOH. The alkaline layer was adjusted at pH 3 with conc. hydrochloric acid, and then subjected to extraction with ethyl acetate. The extract was concentrated, and there were added ethyl acetate and hexane to cause crystallization. The crystals were collected by filtration, washed with hexane and dried to afford 1.51 g (yield 82.3%) of 5-[2-(4'-methylbiphenyl)]tetrazole. Spectrum data were in good agreement with those in Example 4.
Reaction SMILES: C([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([C:20](=[O:24])[CH:21](O)O)=[CH:11][CH:10]=1)C1C=CC=CC=1.[CH3:25][O:26][C:27]1[CH:37]=[CH:36][C:30]([CH2:31][C:32]2([NH2:35])[CH2:34][CH2:33]2)=[CH:29][CH:28]=1.FC(F)(F)C([O-])=O>>[OH:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([CH:20]([OH:24])[CH2:21][NH:35][C:32]2([CH2:31][C:30]3[CH:36]=[CH:37][C:27]([O:26][CH3:25])=[CH:28][CH:29]=3)[CH2:34][CH2:33]2)=[CH:11][CH:10]=1
Reactant: O=C1COc2c(C(=O)C(O)O)ccc(OCc3ccccc3)c2N1
Reactant: COc1ccc(CC2(N)CC2)cc1
Agent: O=C([O-])C(F)(F)F
Product: COc1ccc(CC2(NCC(O)c3ccc(O)c4c3OCC(=O)N4)CC2)cc1

Procedure:
Reaction of 329 mg (1 mmol) 5-benzyloxy-8-(2,2-dihydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one and 177 mg (1 mmol) 1-(4-methoxy-benzyl)-cyclopropylamine according to general method 3. Yield: 39 mg (8%, trifluoroacetate); mass spectroscopy: [M+H]+=385.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.S(OC(CC#C)C(=O)C)([C:19]1[CH:25]=[CH:24][C:22](C)=[CH:21][CH:20]=1)(=O)=O>C(O)C>[CH2:9]([O:8][C:7]1[C:2]2[N:3]([C:19]([CH2:20][C:21]#[CH:22])=[C:25]([CH3:24])[N:1]=2)[CH:4]=[CH:5][CH:6]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: C#CCC(OS(=O)(=O)c1ccc(C)cc1)C(C)=O
Reactant: Nc1ncccc1OCc1ccccc1
Solvent: CCO
Product: C#CCc1c(C)nc2c(OCc3ccccc3)cccn12
Yield: 31 %

Procedure:
A solution of 2-amino-3-benzyloxypyridine (2 g) and 3-tosyloxy-5-hexyn-2-one (2.66 g) in ethanol (15 ml) was stirred and refluxed for 24 hours and then evaporated in vacuo. To the residue was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The oily residue was purified by column chromatography on silica gel (50 g) using chloroform as an eluent to give a solid, which was recrystallized from a mixture of methylene chloride and diethyl ether to give 8-benzyloxy-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine (0.855 g).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[O:15][C:14]([CH2:16][CH2:17][C@@H:18]([NH:30]C(=O)OC(C)(C)C)[CH2:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=4)=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[O:15][C:14]([CH2:16][CH2:17][C@@H:18]([NH2:30])[CH2:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:29])[F:28])=[CH:22][CH:21]=4)=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1
Reactant: CC(C)(C)OC(=O)N[C@H](CCc1nnc(-c2ccc3cnccc3c2)o1)Cc1ccc(C(F)(F)F)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@H](CCc1nnc(-c2ccc3cnccc3c2)o1)Cc1ccc(C(F)(F)F)cc1
Yield: 90.9 %

Procedure:
tert-Butyl(R)-4-(5-(isoquinolin-6-yl)-1,3,4-oxadiazol-2-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate (0.060 g, 0.12 mmol) was stirred with 10 mL TFA in 10 mL DCM for 1 hour. After removing the solvent, the remaining residue was made basic with 2 M ammonia in MeOH and purified by chromatography on silica gel (4% 2M ammonia MeOH solution in DCM) to give the desired product as a white solid (0.045 g, 93%). LCMS (API-ES) m/z: 413 (M+H+); 1H NMR (400 MHz, CD3OD) δ ppm 1.87-1.97 (m, 1H), 2.17-2.27 (m, 1H), 2.63-2.79 (m, 2H), 2.91-2.98 (m, 1H), 3.12 (dd, J=13.40, 5.18 Hz, 1H), 4.18-4.25 (m, 1H), 7.50 (d, J=8.02 Hz, 2H), 7.64 (d, J=8.02 Hz, 2H), 7.92 (d, J=5.67 Hz, 1H), 8.14-8.19 (m, 1H), 8.22-8.27 (m, 1H), 8.50 (d, J=5.48 Hz, 1H), 9.30 (s, 1H), one H was obscured.
Reaction SMILES: S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12](O)([C:16]1[S:20][N:19]=[CH:18][CH:17]=1)[CH2:11][CH2:10][CH2:9]2>C1C=CC=CC=1>[Cl:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([C:16]1[S:20][N:19]=[CH:18][CH:17]=1)=[CH:11][CH2:10][CH2:9]2
Reactant: OC1(c2ccns2)CCCc2cc(Cl)ccc21
Solvent: c1ccccc1
Solvent: O=S(Cl)Cl
Product: Clc1ccc2c(c1)CCC=C2c1ccns1
Reaction time: 1.5 h

Procedure:
0.072 ml of thionyl chloride is added at room temperature to a solution of 132 mg of 6-chloro-1-hydroxy-1-(5-isothiazolyl)-1,2,3,4-tetrahydronaphthalene (Example 12) in 0.45 ml of benzene, and the mixture is then stirred at 75° for 1.5 hours. The mixture is concentrated under reduced pressure, 0.156 ml of morpholine is added to the resulting resin, and the mixture is stirred at 75° for 2.5 hours. The black suspension is cooled to 2° and treated with 5N HCl which has likewise been pre-cooled. The pH is then adjusted to 8 with solid NaHCO3 and extraction is carried out with chloroform. The organic phase is separated off, dried over sodium sulfate and concentrated. The crude title compound is purified by column chromatography (SiO2, hexane/ethyl acetate 4:1) and crystallisation from hexane; 1H-NMR (CDCl3): δ(ppm)=2.44 (m,2H), 2.85 (m,2H), 6.37 (t,1H), 7.14 (m, 2H), 7.19 (d,1H), 7.21 (s,1H), 8.49 (d,1H).
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([Cl:17])[CH:8]=2)=[N:4][CH:3]=1.[CH2:18]([C:20]1[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=[CH:24][C:21]=1[CH:22]=[O:23])[CH3:19].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.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:17][C:9]1[CH:8]=[C:7]([C:5]2[S:6][C:2]([C:27]3[C:20]([CH2:18][CH3:19])=[C:21]([CH:24]=[CH:25][CH:26]=3)[CH:22]=[O:23])=[CH:3][N:4]=2)[CH:12]=[CH:11][C:10]=1[O:13][CH:14]([CH3:16])[CH3:15]
Reactant: CCc1c(C=O)cccc1B1OC(C)(C)C(C)(C)O1
Reactant: CC(C)Oc1ccc(-c2ncc(Br)s2)cc1Cl
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: CN(C)C=O
Solvent: O
Product: CCc1c(C=O)cccc1-c1cnc(-c2ccc(OC(C)C)c(Cl)c2)s1
Temperature: 120 °C
Yield: 86.2 %

Procedure:
To a solution of 5-bromo-2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazole (D71) (500 mg), 2-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (430 mg) and tripotassium phosphate (638 mg) in N,N-dimethylformamide (DMF) (12 mL) and water (2 mL) stirred under nitrogen at room temperature was added Pd(Ph3P)4 (174 mg) in one charge. The reaction vessel was sealed and heated under microwave at 120° C. for 15 min. After cooling the reaction, the reaction mixture was filtered and the filtrate was partitioned between ethyl acetate (250 mL) and saturated brine (50 mL). The organic phase was dried over sodium sulphate and evaporated in vacuo. The crude product was purified by column chromatography to give 3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylbenzaldehyde (D74) (500 mg) as a brown oil. MS (ES): C21H20ClNO2S requires 385. found 386.0 (M+H+).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)=[CH2:2].CC(C)=O>II.C(#N)C>[CH:2]#[C:1][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1
Reactant: C=Cc1ccc(O)cc1
Agent: II
Solvent: CC(C)=O
Solvent: CC#N
Product: C#Cc1ccc(O)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 16.6 %

Procedure:
51.0 g of the same p-vinylphenol fraction as used in Example 1, obtained by vacuum flash distillation was placed in a 300-ml flask together with 51.0 g of acetone. To the resulting mixture being stirred and cooled to 0° C. was dropwise added 1.0 ml of an acetonitrile solution containing 0.02 g of iodine. A polymerization reaction was conducted for 1 hour at 0° C. to obtain 8.3 g of a poly(p-vinylphenol). The polymer had a Mw of 13,800, a Mn of 11,200, a light transmittance at 248 nm, of 76.3% and a light transmittance at 450 nm, of 95.0%.
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=O.[C:17](OCC)(=[O:24])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].N1CCCCC1.C(OC(C)C)(C)C>>[Cl:16][C:13]1[CH:12]=[C:3]2[C:2](=[CH:15][CH:14]=1)[NH:1][C:17](=[O:24])[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:4]2[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1
Solvent: CC(C)OC(C)C
Solvent: C1CCNCC1
Product: CCOC(=O)c1c(-c2ccccc2)c2cc(Cl)ccc2[nH]c1=O
Temperature: 170 °C
Yield: 79.3 %

Procedure:
A mixture of 2-amino-5-chlorobenzophenone (6.93 g), diethyl malonate (7.2 g) and piperidine (0.3 ml) was heated at 170° C. for 4 hours. After cooling, isopropyl ether was added to the mixture to obtain crystals of ethyl 6-chloro-1,2-dihydro-2-oxo-4-phenyl-3-quinolinecarboxylate (7.77 g, 79.3%). The crystals was recrystallized from ethanol to give pale-yellowish needles. mp 223°-224° C.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([CH2:17][OH:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([CH2:17][O:18][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)N1CCCC(CO)C1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CS(=O)(=O)OCC1CCCN(C(=O)OCc2ccccc2)C1
Reaction time: 0.17 h

Procedure:
To a stirred solution of 1-benzyloxycarbonyl-3-hydroxymethyl-piperidine (1.29 g, 5.24 mmol, 1 eq) in CH2Cl2 (50 mL) at 0° C. was added diisopropylethylamine (2.7 mL, 15.72 mmol, 3 eq) followed by methanesulfonylchloride (0.61 mL, 7.86 mmol, 1.5 eq) via syringe. Let stir 10 minutes and removed the cooling bath. After 30 minutes the reaction was complete by thin layer chromatography analysis. Removed the CH2Cl2 under reduced pressure and used material crude in the next step.