Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([Cl:9])[N:3]=1.[CH2:10]([O:12][C:13](=[O:17])[CH:14](Br)[CH3:15])[CH3:11].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[CH2:10]([O:12][C:13](=[O:17])[CH:14]([O:8][C:7]1[C:2]([Cl:1])=[N:3][C:4]([Cl:9])=[CH:5][CH:6]=1)[CH3:15])[CH3:11]
Reactant: CCOC(=O)C(C)Br
Reactant: Oc1ccc(Cl)nc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: CCOC(=O)C(C)Oc1ccc(Cl)nc1Cl

Procedure:
164 g (1 mole) of 2,6-dichloro-3-pyridinol, 1500 ml of acetonitrile, 253.4 g (1.4 moles) of 2-bromopropionic acid ethyl ester and 127.2 (1.2 moles) of sodium carbonate are refluxed for 3 hours. The reaction mixture is then cooled, filtered, and concentrated in a rotary evaporator. The residue is taken up in ether and washed with 2N sodium hydroxide solution. After drying with magnesium sulphate, the solution is concentrated by evaporation and distilled in vacuo; a clear oil distills at 110°-140°/0.1 torr; yield: 200 g; i nD25 : 1.5200. Crystallisation from benzene/petroleum ether yields a product having a melting point of 41°-46°;
Reaction SMILES: C(OC([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:18](=O)[CH3:19])[C:16]#[N:17])=[CH:11][CH:10]=1)=O)(C)(C)C.C(O)C.C(O[CH:27](OCC)[CH2:28][NH:29][NH2:30])C.[ClH:34]>O1CCOCC1.C(OCC)(=O)C>[ClH:34].[NH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:18]([CH3:19])=[N:30][N:29]3[CH:28]=[CH:27][NH:17][C:16]=23)=[CH:13][CH:14]=1
Reactant: CC(=O)C(C#N)c1ccc(NC(=O)OC(C)(C)C)cc1
Reactant: CCOC(CNN)OCC
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1nn2cc[nH]c2c1-c1ccc(N)cc1

Procedure:
A mixture of 2.5 g of 2-(4-t-butoxycarbonylamino-phenyl)-3-oxobutyronitrile, 20 ml of ethanol and 1.4 g of 2,2-diethoxyethylhydrazine was heated under reflux for 2 hours. 20 ml of 4N hydrogen chloride in dioxane were added, and then the whole mixture was heated under reflux for a further 30 minutes. After the mixture had been cooled, ethyl acetate was added to precipitate crystals. These crystals were collected by filtration and recrystallized from ethanol to give 1.4 g of the title compound as pale brown plates melting at 180°-190° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][C:14](=[O:16])[NH:13][C:12](=[O:17])[CH2:11]2)=[CH:6][CH:5]=1)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:11][C:12](=[O:17])[NH:13][C:14](=[O:16])[CH2:15]2)=[CH:8][CH:9]=1
Reactant: O=C1CC(c2ccc([N+](=O)[O-])cc2)CC(=O)N1
Agent: [Pd]
Solvent: CO
Product: Nc1ccc(C2CC(=O)NC(=O)C2)cc1
Yield: 61.7 %

Procedure:
A solution of 197 mg (0.841 mmol) of 4-(4-nitro-phenyl)-piperidine-2,6-dione (as prepared in the previous step) in methyl alcohol (MeOH) (15 mL) was hydrogenated over 10% Pd/C at 20 psi for 5 h at RT. The mixture was filtered through Celite, the filter cake was washed with MeOH, and the solvents were evaporated in vacuo to afford 106 mg (62%) of the title compound as an off-white solid: Mass spectrum (ESI, m/z): Calcd. for C11H12N2O2, 205.1 (M+H), found 205.1.
Reaction SMILES: [C:1]1([C:7]2([CH2:29][C:30]([O:32]CC)=[O:31])[CH2:9][CH:8]2[C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[CH2:25][CH2:24][CH2:23][NH:22][C:21]=4[N:20]=3)=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>C(O)C>[C:1]1([C:7]2([CH2:29][C:30]([OH:32])=[O:31])[CH2:9][CH:8]2[C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[CH2:25][CH2:24][CH2:23][NH:22][C:21]=4[N:20]=3)=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)CC1(c2ccccc2)CC1c1ccc(OCCc2ccc3c(n2)NCCC3)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)CC1(c2ccccc2)CC1c1ccc(OCCc2ccc3c(n2)NCCC3)cc1
Reaction time: 24 h
Yield: 53.3 %

Procedure:
A solution of ethyl 1-phenyl-2-{4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]phenyl}cyclopropylacetate (0.10 g ) in ethanol was added sodium hydroxide (10%, 5 mL) and was stirred for 24 h. The reaction mixture was concentrated and the residue was purified by hplc to afford 0.050 g of the desired product as its TFA salt. 1H NMR δ 7.58 (d, 1H, J=7.4 Hz), 7.39 (m, 2H), 7.28 (t, 2H, J=7.4 Hz), 7.22 (d, 2H, J=8.2 Hz), 7.16 (t, 1H, J=7.0 Hz), 6.88 (d, 2H, J=8.2 Hz), 6.72 (d, 1H, J=7.4 Hz), 4.27 (t, 2H, J=5.9 Hz), 3.49 (t, 2H, J=5.6 Hz), 3.14 (t, 2H, J=5.9 Hz), 2.81 (t, 2H, J=6.3 Hz), 2.44 & 1.93 (AB q, 2H, J=16.1 Hz), 2.30 (t, 1H, J=8.3 Hz), 1.91-1.94 (m, 2H), 1.42-1.54 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:35])[CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:27][CH2:26][N:25]([CH2:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[CH2:24][CH2:23]3)=[O:21])=[N:18][N:19]=2)(=[O:12])=[O:11])=[C:5]([CH3:36])[CH:4]=1.[CH3:37][C:38]1([CH3:41])[CH2:40][O:39]1>CN(C=O)C>[OH:39][C:38]([CH3:41])([CH3:40])[CH2:37][N:32]1[CH2:33][CH2:34][CH:29]([CH2:28][N:25]2[CH2:26][CH2:27][N:22]([C:20]([C:17]3[O:16][C:15]([CH2:14][N:13]([CH3:35])[S:10]([C:6]4[C:7]([CH3:9])=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[CH3:36])(=[O:11])=[O:12])=[N:19][N:18]=3)=[O:21])[CH2:23][CH2:24]2)[CH2:30][CH2:31]1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2nnc(C(=O)N3CCN(CC4CCNCC4)CC3)o2)c(C)c1
Reactant: CC1(C)CO1
Solvent: CN(C)C=O
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2nnc(C(=O)N3CCN(CC4CCN(CC(C)(C)O)CC4)CC3)o2)c(C)c1
Temperature: 70 °C

Procedure:
4-methoxy-N,2,6-trimethyl-N-[(5-{[4-(piperidin-4-ylmethyl)piperazin-1-yl]carbonyl}-1,3,4-oxadiazol-2-yl)methyl]benzenesulfonamide (34 mg, 0.066 mmol) and 2,2-dimethyloxirane (1 mL, 13.8 mmol) were dissolved in DMF (1 mL) and the reaction heated to 70° C. in a sealed tube for 6 h. The reaction was cooled and concentrated in vacuo and the crude product purified using prep method B to afford the title compound.
Reaction SMILES: C(OCC)(=O)CC(C)=O.[CH3:10][N:11]1[CH2:16][CH2:15][CH:14]([NH:17][NH2:18])[CH2:13][CH2:12]1.[CH:19]1([C:22]2N(C(C)C)N=[CH:24][C:23]=2[CH:30]=[O:31])CC1>>[CH3:19][C:22]1[N:17]([CH:14]2[CH2:15][CH2:16][N:11]([CH3:10])[CH2:12][CH2:13]2)[N:18]=[CH:24][C:23]=1[CH:30]=[O:31]
Reactant: CN1CCC(NN)CC1
Reactant: CC(C)n1ncc(C=O)c1C1CC1
Solvent: CCOC(=O)CC(C)=O
Product: Cc1c(C=O)cnn1C1CCN(C)CC1

Procedure:
5-Methyl-1-(1-methyl-piperidin-4-yl)- 1 H-pyrazole-4-carbaldehyde was prepared from ethyl acetoacetate and (1-methyl-piperidin-4-yl)-hydrazine in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49).
Reaction SMILES: [C:1]1([CH:7]2[O:12][CH2:11][CH:10]([OH:13])[CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[C:19]([S:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[F:33])[N:18]=1>O1CCCC1.O>[Cl:16][C:17]1[CH:22]=[C:21]([O:13][CH:10]2[CH2:11][O:12][CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][CH2:9]2)[N:20]=[C:19]([S:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[F:33])[N:18]=1
Reactant: OC1COC(c2ccccc2)OC1
Reactant: Fc1cccc(CSc2nc(Cl)cc(Cl)n2)c1F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Fc1cccc(CSc2nc(Cl)cc(OC3COC(c4ccccc4)OC3)n2)c1F

Procedure:
To a solution of 2-phenyl-1,3-dioxan-5-ol (484 mg) in anhydrous tetrahydrofuran (10 ml) at 0° C. was added 60% sodium hydride (110 mg) and the mixture was heated to reflux for 25 minutes. On allowing to cool to ambient temperature 4,6-Dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (the product of step (ii) (75 mg) was added and the reaction was heated to reflux for a further 90 minutes. The reaction mixture was allowed to cool, diluted with water and extracted with ethyl acetate (×3). The combined organic layers were dried with magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica using a 95:5 to 90:10 mixture of iso-hexane and ethyl acetate as eluent to give the sub-title compound as a white solid. Yield: 350 mg
Reaction SMILES: [CH2:1]([OH:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH:8]=[CH2:9].[CH2:11]=[CH:12][CH2:13]CC>C1COCC1>[CH2:1]([OH:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]/[CH:8]=[CH:9]\[CH2:11][CH2:12][CH3:13]
Reactant: C=CCCC
Reactant: C=CCCCCCCCO
Solvent: C1CCOC1
Product: CCC/C=C\CCCCCCCO
Reaction time: 4 h
Yield: 73 %

Procedure:
In a glovebox, a 20 mL vial was charged with 8-nonenol (0.58 g, 4.1 mmol), 1-pentene (4 mL), and THF (4 mL). A solution of 1 (0.026 g, 1 mol %) in THF (0.5 mL) was added, and the mixture was stirred in an open vial for 4 hours. The vial was removed from the glovebox, the reaction was quenched with excess ethyl vinyl ether, and the solvent was removed in vacuo. Flash chromatography of the residue (SiO2, using a gradient of hexanes to 20% EtOAc in hexanes) provided 12 (0.56 g, 73% yield, 86% Z as determined by 1H-NMR) as a colorless oil; 1H NMR (CDCl3): δ 5.36 (2H, m), 3.64 (2H, br t, J=5.3 Hz), 2.01 (4H, m), 1.36 (2H, m), 1.28-1.40 (11H, m), 0.90 (3H, t, J=7.4 Hz); 13C NMR (CDCl3): δ 130.0, 129.7, 63.1, 32.8, 29.3 (4C), 27.2, 25.7, 22.9, 13.8; HRMS (EI): 184.1805, [C12H24O]+ requires 184.1827.
Reaction SMILES: [C:1]([CH:4]1[C:9](=[O:10])[CH2:8][CH:7]([CH2:11][CH:12]([S:14][CH2:15][CH3:16])[CH3:13])[CH2:6][C:5]1=[O:17])(=O)[CH3:2].C(O)(=O)C.[Cl:22]/[CH:23]=[CH:24]/[CH2:25][O:26][NH2:27].[OH-].[Na+]>O.CCCCCC>[Cl:22]/[CH:23]=[CH:24]/[CH2:25][O:26][NH:27][C:1](=[C:4]1[C:9](=[O:10])[CH2:8][CH:7]([CH2:11][CH:12]([S:14][CH2:15][CH3:16])[CH3:13])[CH2:6][C:5]1=[O:17])[CH3:2]
Reactant: NOC/C=C/Cl
Reactant: CCSC(C)CC1CC(=O)C(C(C)=O)C(=O)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Solvent: CCCCCC
Product: CCSC(C)CC1CC(=O)C(=C(C)NOC/C=C/Cl)C(=O)C1

Procedure:
In this example, 29.5 g (0.1151 mol) of 2-acetyl-5-(2-ethylthiopropyl)cyclohexane-1,3-dione; 1.7 g (0.0277 mol) of acetic acid, and 19.7 g (0.1369 mol) of 3-trans-chloroallyloxyamine in 62 ml of water were admixed to 37 ml of hexane. Aqueous 5 wt. % sodium hydroxide was slowly added dropwise over about 15 minutes until 5.5 g (0.1369 m+small excess) of sodium hydroxide had been added yielding a reaction mixture pH of about 6. The mixture was heated to and maintained at 40° C. for 21/2 hours and then cooled to room temperature. The organic (i.e., hexane) phase was separated and washed with 16 ml of aqueous 5 wt. % hydrochloric acid and then aqueous 6.25 wt. % sodium hydroxide added until pH12. The aqueous phase was separated and admixed with 35 ml of hexane at about 0° C. (ice bath) and the pH adjusted to 5 by the dropwise addition of aqueous 36 wt. % hydrochloric acid over an ice bath. A few mls of methylene chloride was then added. The organic phase was separated, dried over magnesium sulfate and then concentrated by evaporation affording 35.2 g of a crude product as an oil. The crude product was purified by column chromatography over silica gel eluting with hexane:methylene chloride mixtures affording 17.4 g of the purified title compound also as an oil. Elemental analysis carbon calculated 55.56%, found 54.43%; Hydrogen calculated 6.99%, found 6.53%; Nitrogen 4.05%, found 4.31%.
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]([F:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[N:17]=[C:16]2Cl)=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].[CH3:28][CH2:29][O-:30].[Na+]>C(O)C>[CH2:29]([O:30][C:16]1[N:15]([C:11]2[C:12]([F:14])=[CH:13][C:2]([Cl:1])=[C:3]([CH:10]=2)[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5])[C:20](=[O:21])[C:19]([F:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[N:17]=1)[CH3:28]
Reactant: CC(C)OC(=O)c1cc(-n2c(Cl)nc(C(F)(F)F)c(F)c2=O)c(F)cc1Cl
Reactant: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOc1nc(C(F)(F)F)c(F)c(=O)n1-c1cc(C(=O)OC(C)C)c(Cl)cc1F

Procedure:
using isopropyl 2-chloro-5-[2-chloro-5-fluoro-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-4-fluorobenzoate and sodium ethylate in ethanol there is obtained isopropyl 5-[2-ethoxy-5-fluoro-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-2-chloro-4-fluorobenzoate, 1H-NMR (CDCl3, 400 MHz): 7.83 ppm (d,1H), 7.40 ppm (d,1H), 5.27 ppm (m,1H), 4.48 ppm (m,2H), 1.39 ppm (d,3H), 1.38 ppm (d,3H), 1.29 ppm (t,3H);
Reaction SMILES: [CH3:1][C:2]([C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)([CH3:7])[C:3]([O:5][CH3:6])=[O:4].C1C(=O)N([Br:22])C(=O)C1>CC(N=NC(C#N)(C)C)(C#N)C.C(Cl)(Cl)(Cl)Cl>[Br:22][CH2:14][C:11]1[CH:10]=[CH:9][C:8]([C:2]([CH3:1])([CH3:7])[C:3]([O:5][CH3:6])=[O:4])=[CH:13][CH:12]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)C(C)(C)c1ccc(C)cc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)C(C)(C)c1ccc(CBr)cc1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 62.4 %

Procedure:
A 500-mL round bottom flask, with stirrer bar, was charged with methyl 2-methyl-2-(p-tolyl)propanoate (2.50 g, 13.0 mmol), NBS (2.31 g, 13.0 mmol), and carbon tetrachloride (240 mL). The resulting solution was heated at reflux and AIBN (0.043 g, 0.26 mmol) was added. After stirring for 3.5 h, the reaction was cooled to room temperature and the solids removed by filtration. The filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (100:0 to 80:20) as eluent as eluent to afford the title compound (2.20 g, 62%) as a colorless oil. MW=271.15. 1H NMR (CDCl3, 300 MHz) δ 7.39-7.28 (m, 4H), 4.48 (s, 2H), 3.65 (s, 3H), 1.57 (s, 6H).
Reaction SMILES: [CH3:1][N:2]([CH3:17])[C:3]1[NH:8][C:7]2=[N:9][CH:10]=[CH:11][C:6]2=[C:5]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)[N:4]=1.CCN(CC)CC.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1.CN(C1C=CN=CC=1)C>[C:25]([N:9]1[C:7]2[N:8]=[C:3]([N:2]([CH3:17])[CH3:1])[N:4]=[C:5]([C:12]3[O:13][CH:14]=[CH:15][CH:16]=3)[C:6]=2[CH:11]=[CH:10]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CN(C)c1nc(-c2ccco2)c2ccn(C(=O)c3ccccc3)c2n1
Yield: 28.6 %

Procedure:
A solution of N,N-dimethyl-4-(2-furyl)-1H-pyrrolo[2,3-d]pyrimidine-2-amine (181 mg, 0.8 mmol) in THF (3 mL) was treated with Et3N, (111 μL, 0.8 mmol), benzoyl chloride (93 μL, 0.8 mmol) and a catalytic amount of DMAP, stirred at room temperature for 16 h, quenched with water, extracted with EtOAc, dried (MgSO4), concentrated in vacuo and purified by chromatography (EtOAc:Heptane, 1:9 then Heptane:DCM, 2:1) to give the title compound (76 mg) as a yellow solid.
Reaction SMILES: [Na].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[C:5]=1[NH:14][S:15]([C:18]1[N:22]=[C:21]([NH2:23])[NH:20][N:19]=1)(=[O:17])=[O:16].[C:24](OC)(=[O:30])[CH2:25][C:26](OC)=[O:27]>C(O)C>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:12])([F:13])[F:11])[C:5]=1[NH:14][S:15]([C:18]1[N:22]=[C:21]2[N:23]=[C:24]([OH:30])[CH:25]=[C:26]([OH:27])[N:20]2[N:19]=1)(=[O:17])=[O:16]
Reactant: COc1cccc(C(F)(F)F)c1NS(=O)(=O)c1n[nH]c(N)n1
Reactant: COC(=O)CC(=O)OC
Agent: [Na]
Solvent: CCO
Product: COc1cccc(C(F)(F)F)c1NS(=O)(=O)c1nc2nc(O)cc(O)n2n1
Reaction time: 48 h

Procedure:
Sodium (5.90 g, 257 mmol) was added to 250 ml of absolute ethanol under nitrogen and allowed to react. A 28.67 g, 85.0 mmol sample of N-(2-methoxy-6-trifluoromethylphenyl)-5-amino-1,2,4-triazole-3-sulfonamide and 24.46 g (170 mmol) of dimethyl malonate were added and the mixture heated at reflux with stirring for two days. It was then cooled with an ice bath and the solids present were collected by filtration and washed with hexane. They were then dissolved in about 150 ml of ice water and acidified with conc. hydrochloric acid to obtain 11.95 g, the title compound, which was collected by filtration and dried. The ethanolic solution was concentrated by evaporation and dried by adding toluene and removing volatiles by evaporation under reduced pressure three times. The residue was taken up in ethanol and treated as before with sodium and 16.85 g of dimethyl malonate to obtain another 10.26 g of the title compound. A total of 22.21 g (64.5 percent of theory) of the title compound, which melts at 237°-243° C. with decomposition, was obtained.
Reaction SMILES: [Cl:1][SiH2:2][Cl:3].[CH:4]12[CH2:10][CH:7]([CH2:8][CH2:9]1)[CH:6]=[CH:5]2>C1(C)C(C)=CC=CC=1.[Pt]>[CH:4]12[CH2:10][CH:7]([CH2:8][CH2:9]1)[CH2:6][CH:5]2[Si:2]([CH:5]1[CH2:6][CH:7]2[CH2:10][CH:4]1[CH2:9][CH2:8]2)([Cl:3])[Cl:1]
Reactant: Cl[SiH2]Cl
Reactant: C1=CC2CCC1C2
Agent: [Pt]
Solvent: Cc1ccccc1C
Product: Cl[Si](Cl)(C1CC2CCC1C2)C1CC2CCC1C2
Temperature: 80 °C
Reaction time: 0.25 h
Yield: 94 %

Procedure:
Dichlorosilane (18.5 g, 0.18 mol) is condensed into a cold trap at −78° C. and dissolved in precooled xylene (200 ml). The temperature is −10° C. after the addition. First norbornene (34.5 g, 0.37 mol) and then the catalyst [COD]PtCl2 (1% solution in in CH2Cl2, 2.50 ml) are added, whereupon an exothermic reaction starts spontaneously. The temperature rises to 46° C. and an ice bath is used to reduce the temperature to 40° C. After 15 min, the temperature begins to fall again. According to GC (gas chromatography), about 50% of the norbornene is consumed. The reaction mixture is heated to 80° C. for 15 min, then held at 40° C. for a further 1.5 h. The conversion of the norbornene according to GC is >90%. The reaction mixture is fractionally distilled. The main fraction at b.p. 118° C./1 mbar consists of 49.8 g of dichlorodinorbornylsilane. Yield 94%. Purity 95.7% (GC).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1.[C:12]1([C:18]#[CH:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCCCCC.C(OCC)(=O)C>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:11][O:10][C:4]1[CH:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:19]#[C:18][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:3]=1
Reactant: C#Cc1ccccc1
Reactant: COc1cc(OC)nc(Cl)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CN(C)C=O
Product: COc1cc(OC)nc(C#Cc2ccccc2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 45.9 %

Procedure:
2-Chloro-4,6-dimethoxypyrimdine (500 mg, 2.9 mmol), PdCl2(PPh3)2 (200 mg, 0.28 mmol CuI (160 mg, 0.84 mmol), triethylamne (4.8 mL, 34 mmol), and n-Bu4NI (3.2 g, 8.7 mmol) were combined in DMF (24 mL). The mixture was cooled in an ice bath and then phenylacetylene (1.25 mL, 11.4 mmol) was added. The reaction mixture was allowed to warm to ambient temperature. After 2.5 h at ambient temperature the reaction mixture was heated to 45-50° C. After 2 h, additional phenylacetylene (1.0 mL, 9.1 mmol) was added. After an additional 17 h stirring at 45-50° C., the reaction mixture was filtered through a pad of Celite.™, and the filter pad was washed thoroughly with ethyl acetate. The combined filtrates were washed with brine (4.times.20 mL), dried over MgSO4, filtered and concentrated in vacuo. The resulting black oil was purified by column chromatography eluting with hexane, 90:10, then 85:15 hexane:ethyl acetate to afford product contaminated with an impurity. Careful column chromatography of this impure material eluting with hexane then 90:10 hexane:ethyl acetate afforded 4,6-dimethoxy-2-(phenylethynyl)pyrimdine (320 mg, 46% yield) as a yellow solid. This material was carried on to the salt formation without further purification.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CN(C)C=O.[F:12][CH:13]([F:23])[C:14]1[C:18]([C:19](O)=[O:20])=[CH:17][N:16]([CH3:22])[N:15]=1.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[NH2:38])=[CH:27][C:26]=1[F:39]>ClCCl.O>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[NH:38][C:19]([C:18]2[C:14]([CH:13]([F:23])[F:12])=[N:15][N:16]([CH3:22])[CH:17]=2)=[O:20])=[CH:27][C:26]=1[F:39]
Reactant: Cn1cc(C(=O)O)c(C(F)F)n1
Reactant: Nc1ccc(F)cc1-c1ccc(Cl)c(F)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O
Product: Cn1cc(C(=O)Nc2ccc(F)cc2-c2ccc(Cl)c(F)c2)c(C(F)F)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.3 %

Procedure:
1.6 ml (18.4 mmol) of oxalyl dichloride and 0.2 ml of dimethylformamide are added to a mixture consisting of 2.96 g (16.8 mmol) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid in 100 ml of dichloromethane. After 2 hours at room temperature, a solution consisting of 3.83 g (16.0 mmol) of 4′-chloro-5,3′-difluorobiphenyl-2-yl-amine and 2.9 ml (20.8 mmol) in 100 ml of dichloromethane is added. The reaction mixture is stirred for 16 hours at room temperature. For work-up, the reaction mixture is poured into water, and the organic phase is separated, dried over magnesium sulphate and concentrated in vacuo. Column chromatography (petroleum ether/acetone 3:1) yields 5.94 g (93% of theory) of N-(4′-chloro-3′,5-difluorobiphenyl-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide with a logP (pH 2.3) of 3.05.
Reaction SMILES: [NH2:1][CH:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][S:10][C:11]3[N:15]([CH3:16])[N:14]=[N:13][N:12]=3)[CH2:7][S:8][C@H:3]12.S1C2C=CC=CC=2N=C1S[C:32](=[O:41])[C:33]([C:35]1[N:36]=[C:37]([NH2:40])[S:38][CH:39]=1)=[O:34].C(O)C>ClCCl>[NH2:40][C:37]1[S:38][CH:39]=[C:35]([C:33](=[O:34])[C:32]([NH:1][CH:2]2[C:20](=[O:21])[N:4]3[CH:3]2[S:8][CH2:7][C:6]([CH2:9][S:10][C:11]2[N:15]([CH3:16])[N:14]=[N:13][N:12]=2)=[C:5]3[C:17]([OH:19])=[O:18])=[O:41])[N:36]=1
Reactant: Cn1nnnc1SCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Reactant: Nc1nc(C(=O)C(=O)Sc2nc3ccccc3s2)cs1
Solvent: CCO
Solvent: ClCCl
Product: Cn1nnnc1SCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=O)c3csc(N)n3)C2SC1
Reaction time: 0.25 h

Procedure:
3.29 g of 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid are suspended in 25 ml of dichloromethane and mixed with 2.7 ml of N,O-bis-(trimethylsilyl)acetamide. After 15 minutes, a clear solution is present. This is cooled to -15°, and 3.9 g of 2-(2-aminothiazol-4-yl)-2-oxothioacetic-acid-S-benzothiazol-2-ylester are added. After stirring for four hours at -15°, the preparation is stirred into 100 ml of ethanol, whereby the end product precipitates. This is stirred for one hour at 0°, filtered, washed with ethanol and vacuum dried. Yield: 3.9 g, i.e. 80.7%. M.p.: from 145° (decomp.).
Reaction SMILES: [CH3:1][C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:7])[CH2:3][C:4](O)=[O:5].C(Cl)(=O)C([Cl:17])=O>ClCCl.CN(C)C=O>[CH3:1][C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:7])[CH2:3][C:4]([Cl:17])=[O:5]
Reactant: CC(C)(CC(=O)O)c1ccccc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(CC(=O)Cl)c1ccccc1
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
A solution of 3-methyl-3-phenylbutyric acid (0.508 g, 2.85 mmol) in dichloromethane (10 mL) at −78° C. was treated with oxalyl chloride (3.62, 28.5 mmol) and 1 drop of dimethylformamide. The reaction mixture was stirred at −78° C. for 10 min, and dry ice/acetone bath was removed to stir at room temperature over night. Solvent was removed under reduced pressure, and dried under high vacuum. The product was used directly for subsequent reaction without analysis.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]([OH:15])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].S(Cl)(Cl)=O.[CH3:20]O>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]([O:15][CH3:20])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(C=CC(=O)O)cc1OC
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)C=Cc1ccc(OC)c(OC)c1
Temperature: 60 °C
Reaction time: 12 h
Yield: 80 %

Procedure:
To a suspension of 3-(3,4-dimethoxyphenyl)-2-propenoic acid (21.8 g, 105 mmol) in methanol (220 ml) was added thionyl chloride (23.0 mL, 315 mmol) under ice cooling and the mixture was stirred at 60° C. for 12 hours. The resulting mixture was concentrated under reduced pressure, and the residue was added to water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to obtain 18.7 g (yield 80%) of the title compound. mp. 72–74° C.