Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].CO.[CH:14]1[CH2:18][CH:17]=[CH:16][CH:15]=1.C1COCC1>CC(CC(C)=O)C>[CH:18]1([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][C:2]=2[OH:11])[CH2:17][CH2:16][CH:15]=[CH:14]1
Reactant: Oc1ccc2ccccc2c1
Reactant: C1=CCC=C1
Solvent: CO
Solvent: CC(=O)CC(C)C
Solvent: C1CCOC1
Product: Oc1ccc2ccccc2c1C1C=CCC1
Temperature: 25 °C

Procedure:
Into a 2-liter flask having a stirrer, a condenser and a thermometer, 144 g of 2-naphthol, 200 g of methanol and 40 g of PTS were introduced, and a solution of mixture of 66 g of cyclopentadiene and 60 g of methanol was added dropwise over a period of 3 hours while stirring the mixture at room temperature, followed by further stirring for 4 hours at room temperature. To the reaction solution thus obtained, THF and MIBK were added, and the resultant solution was washed with 200 ml of an aqueous 10% sodium hydroxide solution five times, and thereafter further washed with water until it turned neutral, followed by removal of the solvent using an evaporator. The results of analysis by GPC thereof are shown in FIG. 11. Its yield determined by GPC was 90% (area ratio). An NMR spectrum of the 1-(2-penten-1-yl)-2-naphthol obtained is shown in FIG. 12.
Reaction SMILES: [C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.[CH2:23](Br)[C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:25].O>C(OCC)(=O)C.CCOCC>[CH2:23]([O:11][C:10](=[O:12])[C@@H:9]1[CH2:13][CH2:14][CH2:15][N:8]1[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:25]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)O
Reactant: O=C(CBr)c1ccccc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)OCC(=O)c1ccccc1
Reaction time: 8 h
Yield: 81.9 %

Procedure:
Boc-proline (1.00 g, 4.65 mmol) was dissolved in ethyl acetate (29.4 mL), triethylamine (0.46 g, 0.63 mL) and phenacyl bromide (0.93 g, 4.68 mmol) were added and, within a few minutes, a precipitate formed. The mixture was stirred overnight, water and ether were added and the two layers separated. The organic layer was washed with 0.1N HCl, saturated sodium bicarbonate, and brine, then dried over MgSO4. Evaporation of the solvent provided the desired compound (1.27 g, 83%); FABMS 334.2 (M+H), 234.1 (M+2H-Boc), 667.3 (2M+H); HRFABMS calcd for C18H23NO5 (M+H) 334.1654, found 334.1665.
Reaction SMILES: FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.O[C:17]1[C:25]([CH3:26])=[C:24]2[C:20]([C:21](=[O:27])[O:22][CH2:23]2)=[C:19]([O:28][S:29]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[C:18]=1[CH2:39]/[CH:40]=[C:41](\[CH3:48])/[CH2:42][CH2:43][C:44]([O:46][CH3:47])=[O:45].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:26][C:25]1[C:17]([O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])=[C:18]([CH2:39]/[CH:40]=[C:41](\[CH3:48])/[CH2:42][CH2:43][C:44]([O:46][CH3:47])=[O:45])[C:19]([O:28][S:29]([C:32]2[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=2)(=[O:31])=[O:30])=[C:20]2[C:24]=1[CH2:23][O:22][C:21]2=[O:27]
Reactant: COC(=O)CC/C(C)=C/Cc1c(O)c(C)c2c(c1OS(=O)(=O)c1ccc(C)cc1)C(=O)OC2
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COC(=O)CC/C(C)=C/Cc1c(OS(=O)(=O)C(F)(F)F)c(C)c2c(c1OS(=O)(=O)c1ccc(C)cc1)C(=O)OC2

Procedure:
Trifluoromethanesulfonic anhydride (10.57 g) was added to a solution of methyl (E) 6-(1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-toluenesulfonyloxyisobenzofuran-5-yl)-4-methyl-4-hexenoate in methylene chloride (500 ml) amd pyridine (5 ml) at 0° C. After 6 hours the reaction was added to excess aqueous sodium bicarbonate. The organic solution was dried and evaporated to afford methyl (E) 6-(1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6-trifluoromethanesulfonyloxyisobenzofuran-5-yl)-4-methyl-4-hexenoate.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([CH3:12])[CH2:10][OH:11])[C:5]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:36])(=[N:27][C:28](=[O:35])[NH:29][CH:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:26])=[CH:21][CH:20]=1>>[CH:30]1([NH:29][C:28]([N:27]=[S:25]([C:22]2[CH:21]=[CH:20][C:19]([NH:18][C:2]3[N:7]=[C:6]([NH:8][C@H:9]([CH3:12])[CH2:10][OH:11])[C:5]([C:13]4[S:14][CH:15]=[CH:16][CH:17]=4)=[CH:4][N:3]=3)=[CH:24][CH:23]=2)([CH3:36])=[O:26])=[O:35])[CH2:31][CH2:32][CH2:33][CH2:34]1
Reactant: C[C@H](CO)Nc1nc(Cl)ncc1-c1cccs1
Reactant: CS(=O)(=NC(=O)NC1CCCC1)c1ccc(N)cc1
Product: C[C@H](CO)Nc1nc(Nc2ccc(S(C)(=O)=NC(=O)NC3CCCC3)cc2)ncc1-c1cccs1
Yield: 18 %

Procedure:
In the reaction of (R)-2-(2-chloro-5-(2-thienyl)pyrimidine-4-ylamino)propan-1-ol (103.4 mg, 0.38 mmol) with (RS)—S-(4-aminophenyl)-N-(cyclopentylcarbamoyl)-S-methylsulphoximide (98 mg, 0.35 mmol) according to procedure 5c, the desired product is obtained in 18% yield (33 mg) after chromatographic purification (silica gel, dichloromethane/ethanol (0%-20% ethanol)).
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28][CH:29]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])=[C:15](OS(C(F)(F)F)(=O)=O)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Sn](C)(C)[C:46]1[CH:47]=[CH:48][C:49]2[C:50](=[O:61])[C:51]3[C:56]([C:57]=2[CH:58]=1)=[CH:55][CH:54]=[C:53]([CH2:59][OH:60])[CH:52]=3>CN1CCCC1=O.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28][CH:29]([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[O:27])=[C:15]([C:46]4[CH:47]=[CH:48][C:49]5[C:50](=[O:61])[C:51]6[C:56]([C:57]=5[CH:58]=4)=[CH:55][CH:54]=[C:53]([CH2:59][OH:60])[CH:52]=6)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[Sn](C)(C)c1ccc2c(c1)-c1ccc(CO)cc1C2=O
Reactant: O=C(Cc1ccccc1)N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(OS(=O)(=O)C(F)(F)F)CS[C@H]12
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: O=C(Cc1ccccc1)N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(c3ccc4c(c3)-c3ccc(CO)cc3C4=O)CS[C@H]12
Reaction time: 0.75 h
Yield: 61.2 %

Procedure:
Benzhydryl 7β-phenylacetamido-3-trifluormethanesulfonyloxy-ceph-3-em-4-carboxylate (1.26 g) was dissolved in N-methylpyrrolidone (NMP) and treated with 3-trimethylstannyl-7-hydroxymethyl-9-fluorenone (0.742 g). Zinc chloride (4.0 ml, 1.0M solution in ether) was added followed by Pd2(dba)3 ·CHCl3 (60 mg) and the reaction mixture was stirred under nitrogen for 45 min. The reaction mixture was diluted with ethyl acetate and washed with water five times, then with saturated sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was crystallized from hot ethyl acetate/hexane to give 0.844 g of the desired product in the first crop and a further 0.170 g in the second crop of crystals.
Reaction SMILES: [C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][C:4]([CH2:7][C:8](=[O:10])[CH3:9])=[CH:3][CH:2]=1.[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.[OH-].[Na+].C(OCC)C>O>[C:1]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:2]=[CH:3][C:4]([CH:7]([CH2:22][C:21]2[CH:24]=[CH:25][C:18]([Cl:17])=[CH:19][CH:20]=2)[C:8](=[O:10])[CH3:9])=[CH:5][CH:6]=1
Reactant: CC(=O)Cc1ccc(-c2ccccc2)cc1
Reactant: ClCc1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: O
Product: CC(=O)C(Cc1ccc(Cl)cc1)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Yield: 53.2 %

Procedure:
9.93 g of 1-(4-biphenylyl)-2-propanone, 8.4 g of 4-chlorobenzyl chloride and 2.1 g of sodium hydroxide were mixed and heated for 5 hours with stirring on an oil bath of 80° to 90° C. The reaction solution was left to cool to room temperature. Then, ethyl ether and water were added thereto. The organic layer was collected by separation and then dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and then the solvent was distilled off under reduced pressure. The residue was recrystallized from hexane to obtain 8.42 g (yield: 53%) of the above-identified compound as colorless needles having a melting point of from 107° to 108.5° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([CH2:10][N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[CH:7]=[CH:6][C:5]=1[CH2:23][NH:24][C:25](=[O:27])[CH3:26])([O-])=O.O.O.NN>C(O)C.[Ni]>[NH2:1][C:4]1[CH:9]=[C:8]([CH2:10][N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:15][CH2:16]2)[CH:7]=[CH:6][C:5]=1[CH2:23][NH:24][C:25](=[O:27])[CH3:26]
Reactant: CC(=O)NCc1ccc(CN2CCN(c3ccccc3)CC2)cc1[N+](=O)[O-]
Agent: [Ni]
Agent: NN
Solvent: CCO
Solvent: O
Product: CC(=O)NCc1ccc(CN2CCN(c3ccccc3)CC2)cc1N
Temperature: 25 °C
Yield: 104.5 %

Procedure:
To a solution of N-(2-nitro-4-((4-phenylpiperazin-1-yl)methyl)phenylmethyl)acetamide (0.5 g) and water-containing Raney-nickel (0.5 g) in ethanol (8 ml) was added dropwise hydrazine monohydrate (0.7 ml) and the mixture was refluxed under heating at room temperature for 1 hr. Raney-nickel was removed by passing the mixture through Celite and the solvent was evaporated to give a white solid (0.48 g). The obtained white solid was crystallized from hexane/ethyl acetate (1:1, 100 ml) to give the title compound (45.5 g) as white crystals, m.p.=148-149° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1([CH2:8][NH2:9])[CH2:7][CH2:6][CH2:5][CH2:4]1.OO.[O-]Cl.[Na+]>O.CO>[CH2:2]1[C:3]2([CH2:7][CH2:6][CH2:5][CH2:4]2)[CH2:8][N:9]=[N:1]1
Reactant: NCC1(CN)CCCC1
Agent: OO
Agent: [Na+]
Agent: [O-]Cl
Solvent: CO
Solvent: O
Product: C1CCC2(C1)CN=NC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
C-(1-Aminomethyl-cyclopentyl)-methylamine (4.87 g) was taken up in a mixture of H2O (40 mL) and MeOH (10 mL), and cooled in an ice bath. Simultaneously, H2O2 (23.9 mL of a 30% solution. 6 equiv.) and NaClO (54.3 mL of a 10% solution, 2.4 equiv.) were added dropwise, the ice bath was removed, and the mixture was stirred for 2 h. at room temperature. Extraction with DCM, drying over Na2SO4 and evaporation under reduced pressure yielded 3.74 g of a clear, light-yellow liquid containing 90% of the anticipated product and 10% of the diamine starting material. This material was used in subsequent steps without further purification. 1H NMR (400 MHz, CDCl3) δ 1.48-1.57 (m, 4H), 1.62-1.69 (m, 4H), 4.26 (s, 4H).
Reaction SMILES: [C:1]([CH2:3][C:4](Cl)=[O:5])#[N:2].[CH3:7][NH:8][CH2:9][CH2:10][CH2:11][Si:12]([O:17][CH3:18])([O:15][CH3:16])[O:13][CH3:14].N1C=CC=CC=1>C(OCC)C>[CH3:7][N:8]([CH2:9][CH2:10][CH2:11][Si:12]([O:15][CH3:16])([O:17][CH3:18])[O:13][CH3:14])[C:4](=[O:5])[CH2:3][C:1]#[N:2]
Reactant: CNCCC[Si](OC)(OC)OC
Reactant: N#CCC(=O)Cl
Solvent: c1ccncc1
Solvent: CCOCC
Product: CO[Si](CCCN(C)C(=O)CC#N)(OC)OC
Temperature: 25 °C
Yield: 77.6 %

Procedure:
To a 1 L reactor equipped with a thermometer, a condenser and a loading glass were added 200 mL of diethylether and 11 g of cyanoacetylchloride, followed by stirring at room temperature in the presence of nitrogen. To the reactor were slowly added 20 g of N-methylaminopropyl trimethoxysilane (0.104 mol) and 11 g of pyridine (0.14 mol) in 100 mL of diethylether by using the loading glass. The reaction mixture was stirred for 2 hours at room temperature and then the precipitated pyridine salt was eliminated. After removing the solvent and non-reactants, the reaction mixture was distilled under reduced pressure to give 21 g of N-methyl-N-(3-trimethoxysilylpropyl)cyanoacetamide (formula 3). The yield was 75%.
Reaction SMILES: [N:1]1[NH:2][N:3]=[N:4][C:5]=1[C:6]1[CH:7]=[C:8]2[N:14]=[CH:13][N:12]([CH2:15][C:16]3[CH:32]=[CH:31][C:19]4[N:20]=[C:21]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[S:22][C:18]=4[CH:17]=3)[C:9]2=[N:10][CH:11]=1.[C:33]([O-])([O-])=O.[Cs+].[Cs+]>CI>[CH3:33][N:3]1[N:2]=[N:1][C:5]([C:6]2[CH:7]=[C:8]3[N:14]=[CH:13][N:12]([CH2:15][C:16]4[CH:32]=[CH:31][C:19]5[N:20]=[C:21]([NH:23][C@@H:24]6[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]6[OH:30])[S:22][C:18]=5[CH:17]=4)[C:9]3=[N:10][CH:11]=2)=[N:4]1
Reactant: O[C@@H]1CCCC[C@H]1Nc1nc2ccc(Cn3cnc4cc(-c5nn[nH]n5)cnc43)cc2s1
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CI
Product: Cn1nnc(-c2cnc3c(c2)ncn3Cc2ccc3nc(N[C@@H]4CCCC[C@H]4O)sc3c2)n1
Temperature: 90 °C

Procedure:
To the remaining portion of the reaction mixture from Example 93 were added excess Cs2CO3 (300 mg) and excess MeI (200 μL). The resulting mixture was heated at 90° C. for 4 h. LCMS showed that the reaction was mostly completed. After cooling to rt, the mixture was purified by preparative HPLC using a mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(2-methyl-2H-tetrazol-5-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (8 mg) as a white powder. The regiochemistry assignment of the compound was consistent with the result from a NMR Nuclear Overhauser Effect (NOE) experiment. 1H NMR (300 MHz, MeOH-d4) δ 9.17 (s, 1H), 8.69 (s, 1H), 8.55 (s, 1H), 7.67 (s, 1H), 7.25-7.41 (m, 2H), 5.58 (s, 2H), 4.36-4.51 (m, 3H), 3.57 (d, J=9.6 Hz, 1H), 3.36-3.49 (m, 1H), 2.13 (d, J=11.3 Hz, 1H), 2.01 (br s, 1H), 1.71 (d, J=10.0 Hz, 2H), 1.12-1.48 (m, 4H). LCMS (ESI) m/z 462 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([CH:7]=O)=[CH:4][CH:3]=1.[C:9]([NH:12][CH2:13][C:14]([OH:16])=[O:15])(=O)[CH3:10].CC([O-])=O.[Na+]>CC(OC(C)=O)=O.[OH-].[Na+].C(Cl)Cl>[Cl:1][C:2]1[S:6][C:5]([CH:7]=[C:13]2[C:14](=[O:15])[O:16][C:9]([CH3:10])=[N:12]2)=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(Cl)s1
Reactant: CC(=O)NCC(=O)O
Agent: CC(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CC(=O)OC(C)=O
Product: CC1=NC(=Cc2ccc(Cl)s2)C(=O)O1
Temperature: 25 °C
Yield: 96.6 %

Procedure:
A mixture consisting of 5-chlorothiophene-2-carboxaldehyde (1.00 g, 6.82 mmol), N-acetylglycine (0.96 g, 8.18 mmol), NaOAc (0.67 g, 8.18 mmol) in Ac2O (5 mL) is warmed at reflux for 16 hours. The reaction mixture is cooled to ambient temperature and diluted with dilute aqueous NaOH (0.5 M, 100 mL) and CH2Cl2 (100 mL). The layers are separated and the organic phase is washed with aqueous NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated to provide 1.5 g (100%) of the title compound as a colorless oil which is used without further purification in the next reaction. 1H NMR (300 MHz, CDCl3) δ2.39 (s, 3H), 6.94 (d, J=4.0 Hz, 1H), 7.21 (s, 1H), 7.26 (d, J=4.0 Hz, 1H) ppm.
Reaction SMILES: Cl.[CH2:2]([N:9]1[CH2:14][CH2:13][C:12]([C:16]2[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=2)(O)[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH4+:23].[OH-]>>[C:3]1([CH2:2][N:9]2[CH2:14][CH:13]=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([NH2:23])=[CH:18][CH:17]=3)[CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: [NH4+]
Reactant: OC1(c2ccc(Br)cc2)CCN(Cc2ccccc2)CC1
Agent: Cl
Agent: [OH-]
Product: Nc1ccc(C2=CCN(Cc3ccccc3)CC2)cc1
Temperature: 180 °C
Reaction time: 12 h

Procedure:
A mixture of 1-benzyl-4-(p-bromophenyl)-4-piperidinol hydrochloride (0.23 mol) and Cu2O (2 g) in NH4OH (500 ml) was stirred at 180° C. for 12 hours. The mixture was cooled, extracted with DCM and washed with water. The organic layer was dried, filtered off and evaporated, yielding 60 g of 4-[1,2,3,6-tetrahydro-1-(phenylmethyl)-4-pyridinyl]benzenamine (intermediate 47).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:10]C(=O)COC)[CH3:9])=[CH:4][CH:3]=1.P([O-])(O)(O)=O.[Na+].P([O-])(O)(O)=O.[Na+].[Na+].P([O-])(O)(O)=O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH2:10])[CH3:9])=[CH:4][CH:3]=1
Reactant: COCC(=O)NC(C)c1ccc(Cl)cc1
Agent: O=P([O-])(O)O
Agent: [Na+]
Product: C[C@@H](N)c1ccc(Cl)cc1
Temperature: 40 °C
Reaction time: 48 h

Procedure:
A mixture of 200 mg (0.88 mmol) of racemic N-[1-(4-chloro-phenyl)-ethyl]-methoxy-acetamide and 50 U of Candida antarctica lipase (Novozym 435®) was made up to a volume of 7 ml using a 50 mM aqueous solution of sodium dihydrogen phosphate/disodium dihydrogen phosphate buffer mixture. The reaction mixture, which had a pH value of 8, was shaken at 40° C. for 48 hours. The reaction mixture was then extracted three times with di-isopropyl-ether. The combined organic phases were concentrated under reduced pressure. The remaining residue was gas-chromatographically analysed by means of a chiral column. By these means, it was found that the reaction had proceeded with a conversion rate of 48%. The (R)-1-(4-chloro-phenyl)-ethyl-amine formed showed an ee value of 99%.
Reaction SMILES: [C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[Cl:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1>N1C=CC=CC=1>[Cl:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([CH:6]([OH:7])[C@H:5]2[O:8][C@@H:1]([N:9]3[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]3=[O:11])[CH2:2][C@@H:3]2[OH:4])=[O:24])=[CH:21][CH:20]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Solvent: c1ccncc1
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](C(O)C(=O)c3ccc(Cl)cc3)O2)c(=O)[nH]c1=O
Yield: 80 %

Procedure:
Reaction of thymidine with 4-chlorobenzoyl chloride in pyridine at 5° to 20° C. forms 5'-(4-chlorobenzoyl)thymidine (yield: 80%), which is then allowed to react with diethylaminosulfur trifluoride in methylene chloride at -78° C., thus giving 3'-deoxy-3'-fluorothymidine (yield: 19.9%) [Japanese Patent Kokai No. 68325 (1989)].
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([C:9](O)(O)[C:10](=[O:11])[C:4]2=[CH:3][CH:2]=1)=[O:8].Cl.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([NH:25][C:26](=[O:29])[NH:27][NH2:28])[CH:20]=[C:21]([O:23][CH3:24])[CH:22]=1>>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([NH:25][C:26](=[O:29])[NH:27][N:28]=[C:9]2[C:10](=[O:11])[C:4]3[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=3)[C:7]2=[O:8])[CH:20]=[C:21]([O:23][CH3:24])[CH:22]=1
Reactant: COc1cc(NC(=O)NN)cc(OC)c1
Reactant: O=C1c2ccccc2C(=O)C1(O)O
Agent: Cl
Product: COc1cc(NC(=O)NN=c2c(=O)c3ccccc3c2=O)cc(OC)c1

Procedure:
ninhydrin, 4-(3,5-dimethoxyphenyl)-semicarbazide hydrochloride
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH2:11]1C2C3C4C[CH:12]1CC1C4CC(CC12)C3>>[C:11]([C:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2)#[CH:12]
Reactant: C1C2CC3CC1CC(C2)C3
Reactant: C1C2CC3C4CC5CC(C14)C(C2)C3C5
Product: C#CC12CC3CC(CC(C3)C1)C2

Procedure:
The aluminum bromide catalyzed reaction of 1-bromodiamantane (see Gund, T.M.; Schleyer, P.v.R. Tetrahedron Lett. 1971, 1583) with vinyl bromide in methylene chloride followed by dehydrohalogenation of the adduct with potassium t-butoxide in DMSO gave a mixture of five components. This mixture was separated by column chromatography and components were identified as diamantane (5%), 1-(2-bromovinyl)diamantane (8%), 1-ethynyldiamantane (50%), 4-(2-bromovinyl)-9-ethynyldiamantane (9%), and 4,9-diethynyl-diamantane (30%). The formation of 2-bromovinyl compounds results from incomplete dehydrohalogenation, and indicates that the elimination is slower than that observed for the adamantane system. The presence of diamantane and 4,9-diethynyl derivatives indicates the facile disproportionation chemistry in this system. In 1-ethynyldiamantane the ethynyl group is on the girdle, whereas in the case of the 4,9- disubstituted derivative, the ethynyl groups are on the epical positions. Although reaction condition were not found to give pure 1-ethynyldiamantane (similar difficulty was encountered with 1-ethynyladamantane), yields were improved to greater than 55% by the use of ferric chloride as the catalyst and hexane/methylene chloride as the solvent.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH2:13])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][CH2:26][NH:27][C:28](=[O:42])[C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][N:38]=[C:37](Cl)[N:36]=4)=[CH:31][CH:30]=3)[CH:23]=2)[NH:18][CH:17]=1)#[N:15]>>[C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][CH2:26][NH:27][C:28](=[O:42])[C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][N:38]=[C:37]([NH:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[N:36]=4)=[CH:31][CH:30]=3)[CH:23]=2)[NH:18][CH:17]=1)#[N:15]
Reactant: N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(Cl)n4)cc3)cc12
Reactant: NCCCCCCN1CCOCC1
Product: N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(NCCCCCCN5CCOCC5)n4)cc3)cc12

Procedure:
Using 6-morpholin-4-ylhexylamine (reference example 93i) and N-[2-(3-Cyano-1H-indol-5-yl)-ethyl]-4-[2-chloro-pyrimidin-4-yl]-benzamide (reference example 1az) as substrates MS (ion spray) m/z 552 (M+H)+.
Reaction SMILES: [OH-].[Na+].C([O:6][CH2:7][C@:8]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[F:25])([OH:17])[C@@H:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][N:12]=1)[CH3:10])(=O)C.O>CO>[F:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[C@@:8]([OH:17])([C@@H:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][N:12]=1)[CH3:10])[CH2:7][OH:6]
Reactant: CC(=O)OC[C@@](O)(c1ccc(F)cc1F)[C@H](C)c1ccncn1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: C[C@H](c1ccncn1)[C@@](O)(CO)c1ccc(F)cc1F
Reaction time: 0.25 h
Yield: 85.9 %

Procedure:
2N Sodium hydroxide solution (40 ml) was added with stirring over 0.25 hour to a solution of the product of part (ii) (23.3 g) in methanol (80 ml) and stirring was continued for a further 0.25 hour. Water (150 ml) was added and the mixture was cooled. The solid was filtered off, washed with water and dried to give the title compounds, (17.4 g), m.p. 148.5°-150.5°.
Reaction SMILES: [C:1]1([C:7]2([CH2:13][C:14]([NH:16][C:17]3[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=3[C:19]([NH2:21])=[O:20])=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CCO.[OH-].[Na+]>[C:1]1([C:7]2([CH2:13][C:14]3[NH:21][C:19](=[O:20])[C:18]4[C:17](=[CH:25][CH:24]=[CH:23][CH:22]=4)[N:16]=3)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC(=O)c1ccccc1NC(=O)CC1(c2ccccc2)CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=c1[nH]c(CC2(c3ccccc3)CCCCC2)nc2ccccc12
Yield: 95.5 %

Procedure:
The amide (73 mg, 0.217 mmol) in EtOH (1 mL) and 2N NaOH (1 mL) was heated at 80° C. for 1 h. The reaction mixture was concentrated, extracted with CH2Cl2 (3×) then dried over anhydrous sodium sulfate. Purification by flash chromatography (1:1, hexane-EtOAc) gave 2-(1-phenyl-cyclohexylmethyl)-3H-quinazolin-4-one (66 mg, 96%) as a white solid. Mass Spec [M+H]+=319.2.
Reaction SMILES: Br[CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:3]1.CC(C)=[O:21].O>[B-](F)(F)(F)F.[Ag+].CO>[OH:21][CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:3]1
Reactant: O=C(O)CCCCCCCCC1=CC(Br)CC1=O
Reactant: CC(C)=O
Agent: [Ag+]
Agent: F[B-](F)(F)F
Solvent: CO
Solvent: O
Product: O=C(O)CCCCCCCCC1=CC(O)CC1=O
Reaction time: 2 h

Procedure:
To a stirred solution of 57.2 g. of crude 4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one (Example 100) in 500 ml. of acetone and 325 ml. of water at 3°C. is added 44.1 g. (0.226 moles) of silver fluoborate during a 15 minute period. The mixture is stirred at 0°-3°C. for 2 hours and filtered. The filtrate is diluted with water, saturated with solid sodium chloride, and extracted with ether. The extract is washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. Partition chromatography of the residue on Celite gives white crystals, m.p. 58°-66°C., λ max.MeOH = 223 mμ (7800); ν max (KBR) = 3340 (hydroxyl groups), 1705 (carbonyl groups), and 1625 cm-1 (olefin group).