Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.C([Li])CCC.CCCCCC.[CH3:21][C:22]1[CH:23]=[C:24]([O:27][C:28]=1[CH3:29])[CH:25]=[O:26].O>O1CCCC1>[CH3:21][C:22]1[CH:23]=[C:24]([CH:25]([C:2]2[CH:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=2)[OH:26])[O:27][C:28]=1[CH3:29]
Reactant: COc1ccc(Br)cn1
Reactant: Cc1cc(C=O)oc1C
Agent: [Li]CCCC
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1ccc(C(O)c2cc(C)c(C)o2)cn1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
3-Bromo-6-methoxypyridine (1.67 g) was dissolved in tetrahydrofuran (40 ml) under an argon atmosphere to prepare a solution. A 1.6 M n-butyllithium/hexane solution (5.7 ml) was added dropwise to the solution at −78° C., and the mixture was then stirred at −78° C. for 30 min. A solution of 4,5-dimethylfurfural (1.00 g) in tetrahydrofuran (20 ml) was added dropwise thereto, and the temperature of the mixture was raised to room temperature while stirring. Water was added to the reaction solution to stop the reaction, and the solvent was removed by distillation under the reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using hexane-ethyl acetate to give (4,5-dimethylfuran-2-yl)-(6-methoxypyridin-3-yl)-methanol (1.24 g, yield 60%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:48]=[CH:47][C:12]([CH2:13][C@H:14]([NH:35][C:36](=[O:46])[O:37][C@H:38]2[C@H:45]3[C@H:41]([O:42][CH2:43][CH2:44]3)[O:40][CH2:39]2)[C@H:15]([OH:34])[CH2:16][N:17]([CH2:30][CH:31]([CH3:33])[CH3:32])[S:18]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[C:51](OC)([CH3:53])[CH3:52].C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][C@H:14]2[C@@H:15]([CH2:16][N:17]([CH2:30][CH:31]([CH3:33])[CH3:32])[S:18]([C:21]3[CH:22]=[CH:23][C:24]([N+:27]([O-:29])=[O:28])=[CH:25][CH:26]=3)(=[O:19])=[O:20])[O:34][C:51]([CH3:53])([CH3:52])[N:35]2[C:36]([O:37][C@H:38]2[C@H:45]3[C@H:41]([O:42][CH2:43][CH2:44]3)[O:40][CH2:39]2)=[O:46])=[CH:47][CH:48]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(C)(C)OC
Reactant: CC(C)CN(C[C@@H](O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)O[C@@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Product: CC(C)CN(C[C@H]1OC(C)(C)N(C(=O)O[C@@H]2CO[C@H]3OCC[C@H]32)[C@H]1Cc1ccc(OCc2ccccc2)cc1)S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Yield: 64.5 %

Procedure:
To a solution of (3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-{isobutyl[(4-nitrophenyl)sulfonyl]amino}propylcarbamate (1.00 g, 1.5 mmol) in 20 mL of dichloromethane was added 2,2-dimethoxypropane (1.5 g, 14.6 mmol) and p-toluenesulfonic acid (0.09 g, 0.5 mmol). The solution was refluxed for 12 hours, and the solvent was removed under reduced pressure. The residue was purified on silica gel using ethyl acetate-hexanes (3.5:6.5) as eluent to provide 0.70 g (70%) of the title compound. 1H-NMR (CDCl3): δ 0.85 (3H,d), 0.90 (3H,d), 1.35,1.44 (3H,s)*,1.55,1.61 (3H,s)*, 1.84-2.00 (3H,m,b), 2.61-2.91 (4H,m), 2.91-3.08 (3H,m), 3.17,3.33 (1H,d)*, 3.56 (1H,t), 3.80-3.86 (2H,m), 3.91-3.98(1H,m), 4.23-4.27 (2H, m), 5.02-5.16 (2H,s), 5.67 (1H,d), 6.91 (2H,d), 7.03 (1H,d), 7.14 (1H,d), 7.31 (1H,d), 7.38 (2H,m), 7.45 (2H,d), 7.67 (2H,d), 8.25 (2H,d).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].Br[C:15]1[S:23][C:22]2[C:21]([NH:24][C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][CH:33]=3)[NH:30][CH:29]=[CH:28]4)=[N:20][CH:19]=[N:18][C:17]=2[CH:16]=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[S:23][C:22]3[C:21]([NH:24][C:25]4[CH:26]=[C:27]5[C:31](=[CH:32][CH:33]=4)[NH:30][CH:29]=[CH:28]5)=[N:20][CH:19]=[N:18][C:17]=3[CH:16]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: Brc1cc2ncnc(Nc3ccc4[nH]ccc4c3)c2s1
Reactant: COc1ccc(B(O)O)cc1OC
Product: COc1ccc(-c2cc3ncnc(Nc4ccc5[nH]ccc5c4)c3s2)cc1OC

Procedure:
The title compound was prepared from 3,4-dimethoxybenzeneboronic acid and (6-bromo-thieno[3,2-d]pyrimidin-4-yl)-(1H-indol-5-yl)-amine by a procedure analogous to example 2. M.P. 171-178° C.; LC-MS: 403 (MH+); HPLC RT: 4.11 minutes.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([OH:10])=[N:2]1.[CH2:11]([N:18]1C(=O)O[C:21](=[O:22])[C:20]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:19]12)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([NH:18][C:19]1[CH:29]=[CH:28][CH:27]=[CH:26][C:20]=1[C:21]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([OH:10])=[N:2]1)=[O:22])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: Oc1n[nH]c2ccccc12
Reactant: O=c1oc(=O)n(Cc2ccccc2)c2ccccc12
Product: O=C(c1ccccc1NCc1ccccc1)n1nc(O)c2ccccc21
Yield: 71.5 %

Procedure:
1H-Indazol-3-ol was reacted with N-benzylisatoic anhydride according to the general procedure A above and afforded the desired amine as a yellow solid in 71.5% yield; m.p. 163°-165° C.
Reaction SMILES: ClC1C=C[CH:5]=[C:4]([C:8]([O:10]O)=O)[CH:3]=1.[C:12]([O:16][C:17]([NH:19]C=C(C)C)=[O:18])([CH3:15])([CH3:14])[CH3:13]>C(Cl)(Cl)Cl>[C:12]([O:16][C:17]([NH:19][CH:8]1[O:10][C:4]1([CH3:3])[CH3:5])=[O:18])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)=CNC(=O)OC(C)(C)C
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)NC1OC1(C)C

Procedure:
A solution of 27.18 g of m-chloroperbenzoic acid in chloroform is cooled to circa 10° under argon and treated, by dropwise addition, with a chloroform solution of 17.1 g of 3-(N-tert.-butoxycarbonylamino)-2-methyl-prop-2-ene over a period of 1 hour maintaining the temperature below 15° with external cooling. About 30 minutes after the addition is complete and a white precipitate begins to form. Completeness of the reaction can be judged by chromatographic analysis. When the reaction is complete, the suspension is diluted with chloroform and washed with 3×300 ml of a 10% aqueous solution of sodium bisulphite followed by 3×300 ml of a 10% aqueous solution of sodium bicarbonate. Drying of the organic layer and removal of the solvent in vacuo afforded 3-(N-tert.-butoxycarbonylamino)-2-methyl-2,3-epoxypropane as a colourless oil; 1H-NMR (CDCl3): δ (ppm)=3.3 (2H, t, CH2N), 2.65 (2H, ABq, CH2) 1.43 (9H, s, tBu), 1.33 (3H, s, CH3).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][C:7]2([CH2:11][CH2:10][CH2:9][CH2:8]2)[C:6]1=[O:17])=[O:4].O.O.[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].Cl>CO.[Cl-].[Na+].O.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]([CH3:15])([CH3:16])[CH2:12][C:7]2([CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]1[OH:17])=[O:4]
Reactant: COC(=O)C1CC(C)(C)CC2(CCCC2)C1=O
Agent: Cl
Agent: [BH4-]
Agent: [Ca+2]
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: COC(=O)C1CC(C)(C)CC2(CCCC2)C1O
Yield: 75.1 %

Procedure:
To a solution of 9,9-dimethyl-6-oxo-spiro[4.5]decane-7-carboxylic acid methyl ester (450 mg) obtained in Step 1 in methanol (4.5 mL) was added calcium chloride dihydrate (417 mg), followed by stirring under ice-cooling for 15 minutes. Then, to the reaction mixture was added sodium borohydride (90 mg) in three portions, followed by stirring the reaction mixture under ice-cooling for 1.5 hours. To the reaction mixture were added successively 2N aqueous hydrochloric acid solution, toluene and saturated brine, and the mixture was stirred for 5 minutes, followed by separation of the aqueous layer. The organic layer was washed successively with water and saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:19 to 1:6) to give 6-hydroxy-9,9-dimethyl-spiro[4.5]decane-7-carboxylic acid methyl ester (341 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([Br:8])[C:5]([F:9])=[CH:4][C:3]=1[S:10](Cl)(=[O:12])=[O:11].[NH2:14][C:15]1[C:16]([CH3:22])=[N:17][N:18]([CH3:21])[C:19]=1[CH3:20]>N1C=CC=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([F:1])[C:3]([S:10]([NH:14][C:15]2[C:16]([CH3:22])=[N:17][N:18]([CH3:21])[C:19]=2[CH3:20])(=[O:12])=[O:11])=[CH:4][C:5]=1[F:9]
Reactant: O=S(=O)(Cl)c1cc(F)c(Br)cc1F
Reactant: Cc1nn(C)c(C)c1N
Solvent: c1ccncc1
Product: Cc1nn(C)c(C)c1NS(=O)(=O)c1cc(F)c(Br)cc1F
Yield: 72.5 %

Procedure:
Prepared from 2,5-difluoro-4-bromobenzenesulfonyl chloride (2 g, 6.9 mmol) and 4-amino-1,3,5-trimethyl-1H-pyrazole (858 mg, 6.9 mmol) in pyridine (30 ml) according to the method of intermediate 1, to give the title compound as a pale yellow solid (1.9 g, 5.0 mmol, 73%). δH (D-6 DMSO, 300K) 9.77 (1H, s), 8.12 (1H, dd, J=5.5 Hz 9.0 Hz), 7.55 (1H, dd J 6.Hz 7.5 Hz), 3.58 (3H, s), 1.92 (3H, s), 1.74 (3H, s). m/z (ES+, 70V) 380.0 (MH+).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[N:9][S:10][C:11]=2[C:12](=[S:14])[NH2:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:16][C:17](=O)[C:18]([O:20][CH3:21])=[O:19].C(=O)([O-])O.[Na+]>ClC1C=CC=CC=1>[C:1]1([C:7]2[N:8]=[N:9][S:10][C:11]=2[C:12]2[S:14][CH:16]=[C:17]([C:18]([O:20][CH3:21])=[O:19])[N:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)C(=O)CBr
Reactant: NC(=S)c1snnc1-c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Clc1ccccc1
Product: COC(=O)c1csc(-c2snnc2-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 48.8 %

Procedure:
In 20 ml of chlorobenzene were dissolved 1.1 g (5.0 mmol) of 4-phenyl-1,2,3-thiadiazole-5-carbothioamide and 0.92 g (5.0 mmol) of methyl bromopyruvate. The solution thus obtained was stirred for 3 hours with heating under reflux. After the reaction was completed, the reaction mixture was cooled to room temperature, a saturated aqueous solution of sodium hydrogen carbonate was added thereto, and the objective product was extracted with ethyl acetate. The solvent was distilled off from the extract solution under a reduced pressure, and the residue was purified by silica gel column chromatography using 3:1 mixture of n-hexane and ethyl acetate. Thus, 0.74 g of the objective compound was obtained.
Reaction SMILES: C([Si](C)(C)[O:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[C:14](=[O:21])[NH:13][C:12]1=[O:22])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[CH:16]=[C:15]([C:17]([F:18])([F:19])[F:20])[C:14](=[O:21])[NH:13][C:12]1=[O:22]
Reactant: CC(C)(C)[Si](C)(C)OCCCCn1cc(C(F)(F)F)c(=O)[nH]c1=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=c1[nH]c(=O)n(CCCCO)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.7 %

Procedure:
A solution of 1-[4-(tert-butyl-dimethyl-silanyloxy)-butyl]-5-trifluoromethyl-1H-pyrimidine-2,4-dione (Prep22, 260 mg, 0.71 mmol) in DCM (15 mL) was cooled at 0° C. and then TFA (820 μl, 1.1 mmol) was added. The mixture was stirred for 1 hour at room temperature and the solvent was evaporated. The crude was purified by flash chromatography with ethyl acetate-petroleum ether (7-3) to afford the title compound (132 mg, 74% yield).
Reaction SMILES: [CH2:1]([N:5]1[C:9]([CH2:10][CH2:11][S:12]([CH2:15][CH2:16][CH3:17])(=[O:14])=[O:13])=[CH:8][C:7]([C:18]([O:20]CC)=[O:19])=[N:6]1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>C(O)C>[CH2:1]([N:5]1[C:9]([CH2:10][CH2:11][S:12]([CH2:15][CH2:16][CH3:17])(=[O:13])=[O:14])=[CH:8][C:7]([C:18]([OH:20])=[O:19])=[N:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1nc(C(=O)OCC)cc1CCS(=O)(=O)CCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCn1nc(C(=O)O)cc1CCS(=O)(=O)CCC
Reaction time: 2 h
Yield: 100.7 %

Procedure:
To a solution of ethyl 1-butyl-5-[2-(propylsulfonyl)ethyl]-1H-pyrazole-3-carboxylate (5.00 g, 15.1 mmol) in ethanol (76 mL) at ambient temperature was added 6 M aqueous sodium hydroxide (5.0 mL, 30 mmol). The solution was stirred for 2 hours, then the volatiles were removed under reduced pressure and the resulting oil was dissolved in water (100 mL). The aqueous solution was washed with dichloromethane (50 mL) and then the pH was adjusted with 1 M hydrochloric acid to pH 4. A precipitate formed and the mixture was stirred for 1 hour. The solid was isolated by filtration, washed with water, and dried to provide 4.6 g of 1-butyl-5-[2-(propylsulfonyl)ethyl]-1H-pyrazole-3-carboxylic acid as a white powder.
Reaction SMILES: [C:1]([C:3]1[C:4]([C:20]([F:23])([F:22])[F:21])=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13](=[NH:16])[NH:14][OH:15])[C:7]([CH2:17][CH2:18][CH3:19])=[CH:6]2)#[N:2].[Cl:24][C:25]1[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:26]=1[C:27](Cl)=O.C(N(CC)CC)C>C(#N)C>[Cl:24][C:25]1[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:26]=1[C:27]1[O:15][N:14]=[C:13]([CH2:12][N:8]2[C:9]3[C:5](=[C:4]([C:20]([F:22])([F:23])[F:21])[C:3]([C:1]#[N:2])=[CH:11][CH:10]=3)[CH:6]=[C:7]2[CH2:17][CH2:18][CH3:19])[N:16]=1
Reactant: O=C(Cl)c1cc(I)ccc1Cl
Reactant: CCCc1cc2c(C(F)(F)F)c(C#N)ccc2n1CC(=N)NO
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCc1cc2c(C(F)(F)F)c(C#N)ccc2n1Cc1noc(-c2cc(I)ccc2Cl)n1
Temperature: 150 °C
Yield: 21.6 %

Procedure:
To a solution of 2-[5-cyano-2-propyl-4-(trifluoromethyl)-1H-indol-1-yl]-N-hydroxyethanimidamide (Example 275A) (0.05 g, 0.154 mmol) in anhydrous acetonitrile (10.0 mL) under N2, was added 2-chloro-5-iodobenzoyl chloride (0.159 g, 0.528 mmol) and triethylamine (0.5 mL, 6.81 mmol). The mixture was then heated in a microwave at 150° C. for 30 min. Upon cooling, the mixture was poured onto a biotage prepak column and the mixture was purified by flash chromatography (0-25% EtOAc-hexanes gradient) to give 0.019 g (22% yield) of pure product: MS (ES) m/z 570 (M+1).
Reaction SMILES: Cl[C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[O:7])=[C:4]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[N:3]=1.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>CO>[F:27][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[CH2:20][CH2:19][NH:18][C:4]1[N:3]=[C:2]([N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[CH:17]=[CH:16][C:5]=1[C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:7]
Reactant: O=C(NCc1cccnc1)c1ccc(Cl)nc1NCCc1cccc(F)c1
Reactant: C1CCNC1
Solvent: CO
Product: O=C(NCc1cccnc1)c1ccc(N2CCCC2)nc1NCCc1cccc(F)c1
Temperature: 150 °C

Procedure:
A mixture of 6-chloro-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide (50 mg, 0.13 mmol) and pyrrolidine (94 mg, 1.3 mmol) in a sealed tube was heated to 150° C. for 10 min. LC/MS indicated the reaction was complete. The crude was diluted with MeOH, filtered, and purified on RP-HPLC using a mixture of acetonitrile and H2O to a give 2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)-6-(pyrrolidin-1-yl)nicotinamide (20.2 mg, 37%). LRMS (M+H+) m/z 420.2.
Reaction SMILES: Br[C:2]1[S:6][C:5]([NH2:7])=[N:4][CH:3]=1.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:2]2[S:6][C:5]([NH2:7])=[N:4][CH:3]=2)=[CH:12][CH:11]=1
Reactant: COc1ccc(S)cc1
Reactant: Nc1ncc(Br)s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(Sc2cnc(N)s2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 73 %

Procedure:
A solution of 5-bromo-thiazol-2-ylamine (70a, 10.0 g, 38.5 mmol), 4-methoxy-benzenethiol (4.70 ml, 38.5 mmol) and K2CO3 (21.0 g, 151 mmol) in DMF (100 mL) was heated at 80° C. for 1.0 hour and stirred further 16 hours at room temperature. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4(s), and concentrated under reduced pressure to give 5-(4-methoxy-phenylsulfanyl)-thiazol-2-ylamine (70b, 6.70 g).
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([O:27][CH3:28])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[CH2:29]([N:8]1[C:9](=[O:26])[C:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)=[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:6]=[C:7]1[O:27][CH3:28])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: CCCCc1nc(OC)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCc1nc(OC)n(Cc2ccccc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Yield: 50 %

Procedure:
A solution of 4′-[(4-butyl-2-methoxy-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1.5 g), benzyl bromide (0.53 mL) and cesium carbonate (1.4 g) in N,N-dimethylformamide (15 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (0.93 g, 50%) as a colorless liquid.
Reaction SMILES: [C:1]([OH:26])(=[O:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[CH2:27](O)[CH2:28][CH2:29][OH:30].[PH2](O)=O>>[C:1]([O:26][CH2:3][CH2:2][CH2:1][O:25][C:29](=[O:30])[CH2:28][CH2:27][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]/[CH:13]=[CH:12]\[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH3:4])(=[O:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: OCCCO
Reactant: CCCCCCCC/C=C\CCCCCCCCCCCCCC(=O)O
Agent: O=[PH2]O
Product: CCCCCCCC/C=C\CCCCCCCCCCCCCC(=O)OCCCOC(=O)CCCCCCCCCCCCC/C=C\CCCCCCCC
Temperature: 160 °C
Reaction time: 6 h

Procedure:
z-15-Tetracosenoic acid (available from Sigma Chemicals), (0.286 mol, 104.7 g), propane-1,3-diol (0.136, 10.3 g) and hypophosphorous acid (0.4 g) was heated with stirring to 160° C. under nitrogen. After 6 h, TLC (80:18:2 petroleum ether-ethyl ether-acetic acid) indicated that the reaction had gone to completion (Rf: 0.63). The mixture was cooled down to room temperature and petroleum ether (1500 mL) was added. The resulting solution was washed with saturated sodium bicarbonate (3×150 mL) and saturated sodium chloride (3×150 mL). It was then dried over anhydrous sodium sulphate and concentrated to dryness. Residual mono-ester and fatty acid were removed by distillation in vacuo (230° C., 10−2 mbar). The resulting oil was dissolved into petroleum ether to make up a 33% solution and was passed down a silica column. Hexane was finally removed to yield 1,3-di-(z-15-tetracosenoyloxy)propane as a colourless oil.
Reaction SMILES: [Si:1]([O:18][C@H:19]([CH3:28])[CH2:20][CH2:21][CH2:22][C:23](OCC)=[O:24])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[Si:1]([O:18][C@H:19]([CH3:28])[CH2:20][CH2:21][CH2:22][CH2:23][OH:24])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCC[C@@H](C)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C[C@H](CCCCO)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 99.5 %

Procedure:
To a solution of (R)-ethyl 5-((tert-butyldiphenylsilyl)oxy)hexanoate (10 g, 25.09 mmol) in THF (150 mL) at 0° C. was added dropwise 1M LAH in THF (31.4 mL, 31.4 mmol) and the resulting mixture was stirred for 30 min. at 0° C. and then 2 h at room temp. The reaction was quenched with 1 mL of water (stir for 10 min), 1 mL of 15% NaOH/water (stir for 10 min), and then 2 mL of water. After stirring for 1 h, the mixture was filtered through celite. The filtrate was concentrated in vacuo. The residue was dried under high vacuum for 16 h to afford (R)-5-((tert-butyldiphenylsilyl)oxy)hexan-1-ol (8.9 g, 24.96 mmol, 99% yield) as a clear viscous oil. 1H NMR (500 MHz, CDCl3) δ 7.72-7.67 (m, 4H), 7.50-7.36 (m, 6H), 3.92-3.84 (m, 1H), 3.61-3.50 (m, 2H), 1.55-1.41 (m, 4H), 1.37-1.31 (m, 2H), 1.21-1.15 (m, 1H), 1.11-1.09 (m, 3H), 1.08 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[Cl:11][C:12]1[C:13]([F:20])=[N:14][C:15](F)=[C:16]([F:18])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([O:10][C:15]2[C:16]([F:18])=[CH:17][C:12]([Cl:11])=[C:13]([F:20])[N:14]=2)[CH:3]=1)[C:8]#[N:9]
Reactant: N#Cc1cc(O)cc(Cl)c1
Reactant: Fc1cc(Cl)c(F)nc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cc(Cl)cc(Oc2nc(F)c(Cl)cc2F)c1
Temperature: 25 °C

Procedure:
A solution of 3-chloro-5-cyanophenol (1-4; 218 mg; 1.41 mmol) and 3-chloro-2,5,6-trifluoropyridine (1-5; 250 mg; 1.49 mmol) in anhydrous DMF (2 mL) was cooled to −40° C. under a nitrogen atmosphere. The reaction mixture was then treated with 260 mg (1.94 mmol) of anhydrous potassium carbonate added in one portion, and the reaction mixture was vigorously stirred and allowed to warm to room temperature slowly over 90 minutes. The reaction mixture was then stirred for another hour at room temperature. The reaction mixture was diluted with a large excess of water, and a thick precipitate formed. After trituration, the suspension was filtered and the solid dried to give the title compound as an off white amorphous solid. 1H NMR (CDCl3): 7.91 (m, 2H), 7.99 (t, 1H), 8.60 (q, 1H). MS M+1=302.
Reaction SMILES: [CH2:1]([N:3]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:4]([C:6]1[C:7](=[O:20])[N:8]([CH3:19])[C:9]2[C:14]([C:15]=1[OH:16])=[C:13]([CH2:17][CH3:18])[CH:12]=[CH:11][CH:10]=2)=[O:5])[CH3:2].[OH-].[Na+].C(Cl)(Cl)Cl.O.O.C([O-])(=O)C.[Zn+2:39].C([O-])(=O)C>C(O)C.O>[Zn:39].[CH2:1]([N:3]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:4]([C:6]1[C:7](=[O:20])[N:8]([CH3:19])[C:9]2[C:14]([C:15]=1[OH:16])=[C:13]([CH2:17][CH3:18])[CH:12]=[CH:11][CH:10]=2)=[O:5])[CH3:2]
Reactant: [Zn+2]
Agent: CC(=O)[O-]
Agent: CCc1cccc2c1c(O)c(C(=O)N(CC)c1ccccc1)c(=O)n2C
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: [Zn]
Reaction time: 0.17 h

Procedure:
N-Ethyl-N-phenyl-5-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide (1.0 g, 2.85 mmol) was dissolved in a mixture of 1M NaOH (2.95 mmol, 2.95 ml) and ethanol (6.0 ml). Chloroform (20 ml) and water (40 ml) were added followed by addition of zinc acetate dihydrate (3.0 mmol, 660 mg). The two-phase mixture was stirred vigorously for 10 min, the organic phase was separated and dried with sodium sulphate and the solvents were removed. The residue was recrystallised from methanol to give the title compound (823 mg, 76% yield). Anal. Calcd for C42H42N4O6Zn: C, 66.01; H, 5.54; N, 7.33. Found C, 65.4; H, 5.68; N, 7.29. EDTA-titriometric determination of zinc gave a content of 8.45% (theoretical content is 8.50%), The solubility in water at room temperature was 0.3 mg/ml.
Reaction SMILES: N1C=CC=CC=1.Cl[C:8]([O:10][CH:11]([Cl:13])[CH3:12])=[O:9].[C:14]([O:19][CH2:20][CH2:21][OH:22])(=[O:18])[C:15]([CH3:17])=[CH2:16]>ClCCl>[C:8](=[O:9])([O:22][CH2:21][CH2:20][O:19][C:14](=[O:18])[C:15]([CH3:17])=[CH2:16])[O:10][CH:11]([Cl:13])[CH3:12]
Reactant: C=C(C)C(=O)OCCO
Reactant: CC(Cl)OC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: C=C(C)C(=O)OCCOC(=O)OC(C)Cl
Reaction time: 0.25 h
Yield: 74.4 %

Procedure:
Pyridine (0.89 ml, 11.00 mmol) is added dropwise to a solution of 1-chloroethyl chloroformate (1.20 ml, 11.00 mmol) and 2-hydroxyethyl methacrylate (1.22 ml, 10.00 mmol) in dichloromethane (12 ml) at 3° C. under a dry N2 atmosphere. After 15 min. at 3° C. and 17 hours at 20° C. the reaction mixture is transferred to a separating funnel with the aid of dichloromethane (10 ml). The reaction mixture is washed with hydrochloric acid (1.00M, 10 ml), saturated aqueous sodium hydrogen carbonate (10 ml) and water (2×10 ml). The organic phase is dried (MgSO4) and the solvent evaporated under reduced pressure to give 1.76 g (74%) of the title product. 1H NMR (60 MHz, CDCl3): δ 1.85 (3H, d, J=6 Hz, CH3 --CH), 1.96 (3H,d, J=2 Hz, CH3 --C=), 5.55 (1H, m, CH=), 6.10 (1H, m, CH=), 6.38 (1H, k, J=6 Hz, CH--CH3).