Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:17](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]([CH3:17])[CH:8]2[CH2:9][CH2:10][C:11](=[O:14])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1
Reactant: O=C1CCC(NCc2ccc(Cl)cc2)CC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CN(Cc1ccc(Cl)cc1)C1CCC(=O)CC1
Reaction time: 8 h

Procedure:
8.4 g (35 mMol) of 4-[N-(4-chloro-benzyl)-amino]-cyclohexanone are dissolved in 50 ml of absolute dimethylformamide and, after the addition of 2.6 g (18.7 mMol) of potassium carbonate, 5.0 g (35 mMol) of methyliodide are added dropwise at 25°-30° C. After standing overnight the mixture is concentrated, mixed with water and extracted with chloroform. The extracts are dried and concentrated.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([Si:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9])=[CH:4][C:3]=1[CH2:14][OH:15].C(N(CC)CC)C.[C:23](Cl)(=[O:35])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>O1CCCC1>[C:23]([O:15][CH2:14][C:3]1[CH:4]=[C:5]([Si:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9])[O:6][C:2]=1[CH3:1])(=[O:35])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: CC[Si](CC)(CC)c1cc(CO)c(C)o1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCCCCC(=O)OCc1cc([Si](CC)(CC)CC)oc1C
Temperature: 25 °C

Procedure:
To a stirred solution of 5-methyl-2-triethylsilyl-4-furanmethanol (208 mg. 0.92 mmol) and triethylamine (121 mg, 1.20 mmol) in tetrahydrofuran (10 ml) at 0 degrees under argon was added lauroyl chloride 302 mg, 1.38 mmol). This solution was allowed to warm gradually to room temperature and quenched with a 10% aqueous HCl solution. The organics were extracted into hexanes and the combined fractions were washed with a saturated aqueous solution of sodium bicarbonate, H2O and brine. Evaporation of the dried (magnesium sulfate) extracts gave an oil which was purified by filtration through silica using 2% ethyl ether/hexanes to give the title compound.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[CH:10]1[CH:15]=[CH:14][C:13]([C@H:16]2[O:18][C@@H:17]2[CH2:19][OH:20])=[CH:12][CH:11]=1>O>[O:7]([C@@H:16]([C:13]1[CH:14]=[CH:15][CH:10]=[CH:11][CH:12]=1)[C@H:17]([OH:18])[CH2:19][OH:20])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OC[C@H]1O[C@@H]1c1ccccc1
Reactant: Oc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: OC[C@@H](O)[C@@H](Oc1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 38.1 %

Procedure:
A mixture of phenol (9.4 g), NaOH (1.33 g) and water (6.6 ml) was heated on a boiling water bath until the mixture became homogeneous. (2R, 3R)-3-Phenylglycidol (5.0 g) was added in small portions over a period of 10 minutes and the mixture was heated with stirring on a boiling water bath for 1 hr. The mixture was poured into a solution of NaOH (3.99 g) in ice water (75 ml) and extracted with ether (50 ml) 2 times. The ether solution was dried over anhydrous sodium sulfate and the solvent distilled off to obtain a white solid. Recrystallization from methylene chloride gave white crystals (3.1 g) of (2R, 3S)-3-phenoxy-3-phenylpropane-1,2-diol.
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:14](Br)([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:16])[CH3:15]>[N+](C)([O-])=O.C1(C)C=CC=CC=1.[Cl-].[Cl-].[Zn+2]>[CH3:19][C:18]([CH3:21])([CH2:17][CH:14]([CH3:16])[CH3:15])[CH2:20][C:3]1[CH:2]=[CH:1][C:13]2[NH:12][C:11]3[C:6]([C:5]=2[CH:4]=1)=[CH:7][C:8]([CH2:19][C:18]([CH3:21])([CH3:20])[CH2:17][CH:14]([CH3:16])[CH3:15])=[CH:9][CH:10]=3
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Reactant: CC(C)(C)CC(C)(C)Br
Agent: [Cl-]
Agent: [Zn+2]
Solvent: Cc1ccccc1
Solvent: C[N+](=O)[O-]
Product: CC(C)CC(C)(C)Cc1ccc2[nH]c3ccc(CC(C)(C)CC(C)C)cc3c2c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
ZnCl2 (36.8 g, 276 mmol) and carbazole (21.0 g, 126 mmol) are suspended in 600 mL nitromethane in a 1 qt jar in a glove-box. The t-octyl bromide (53.4 g, 276 mmol) is added dropwise to the gray-green suspension via addition funnel. The mixture turns into a black solution during the addition. The solution is allowed to stir at room temperature for two hours and then poured into 500 mL ice water. The product is extracted out of the mixture with 500 mL and 250 mL CH2Cl2. The combined organic portions are dried with MgSO4, filtered and rotovapped to yield a dark residue. This residue is taken up in 200 mL toluene, passed through a plug of silica, and washed through with 150 mL toluene. The yellow solution is reduced to a solid on the rotovap. This material is recrystallized from 100 mL hexane at −13° C. 27 g (55%) of white crystals are collected. The crystallization only moderately improved the purity of the product. 1H NMR (CDCl3): δ 8.02 (d, JH-H=1.6 Hz, 2H), 7.80 (br s, 1H, NH), 7.42 (dd, JH-H=8.6, 1.8 Hz, 2H), 7.29 (d, JH-H=8.5 Hz, 2H), 1.83 (s, 4H, CH2), 1.49 (s, 12H, CMe2), 0.72 (s, 18H, CMe3).
Reaction SMILES: [N:1]1([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.FC(F)(F)S(O[CH2:23][C:24]([F:27])([F:26])[F:25])(=O)=O.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:10]([O:9][C:7]([N:1]1[CH2:6][CH2:5][N:4]([CH2:23][C:24]([F:27])([F:26])[F:25])[CH2:3][CH2:2]1)=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(OCc1ccccc1)N1CCNCC1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(OCc1ccccc1)N1CCN(CC(F)(F)F)CC1
Temperature: 60 °C
Reaction time: 2 h
Yield: 112.9 %

Procedure:
Benzyl 1-piperazinecarboxylate (2.0 g, 9.08 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.5 g, 10.8 mmol) and triethylamine (1.9 mL, 13.8 mmol) were dissolved in 50 mL of tetrahydrofuran, and the reaction mixture was stirred at 60° C. for two hours. After cooling to room temperature, the reaction mixture was mixed with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate twice. The combined organic layers were sequentially washed with water and brine in this order. The mixture was dried over anhydrous sodium sulfate and evaporated. The resulting residue was purified by silica gel column chromatography (Fuji Silysia, NH Silica gel; ethyl acetate:hexane=50:50) to give 4-(2,2,2-trifluoroethyl)piperazin-1-carboxylic acid benzyl ester (3.1 g) as a colorless oil.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[S:3])[NH2:2].[Cl:14][C:15]1[CH:16]=[C:17]([CH:22]=[CH:23][CH:24]=1)[C:18](=O)[CH2:19]Br>>[Cl:14][C:15]1[CH:16]=[C:17]([C:18]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[S:3][CH:19]=2)[CH:22]=[CH:23][CH:24]=1
Reactant: O=C(CBr)c1cccc(Cl)c1
Reactant: COC(=O)c1ccc(C(N)=S)cc1
Product: COC(=O)c1ccc(-c2nc(-c3cccc(Cl)c3)cs2)cc1
Yield: 72 %

Procedure:
In the same manner as in Example 28, methyl 4-thiocarbamoylbenzoate was reacted with 3-chlorophenacyl bromide to obtain methyl 4-[4-(3-chlorophenyl)-2-thiazolyl]benzoate. The product was recrystallized from ethanol. Yield: 72%. Pale yellow prisms. Melting point: 150 to 151° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[N:8]([CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:5]2=[N:6][CH:7]=1.[CH3:22][CH:23]([SH:25])[CH3:24]>>[C:11]([C:9]1[N:8]([CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:5]2=[N:6][CH:7]=[C:2]([S:25][CH:23]([CH3:24])[CH3:22])[CH:3]=[C:4]2[N:10]=1)([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)c1nc2cc(Br)cnc2n1CC1CCOCC1
Reactant: CC(C)S
Product: CC(C)Sc1cnc2c(c1)nc(C(C)(C)C)n2CC1CCOCC1

Procedure:
The title compound was prepared according to the procedure described in Step E of Example 32 from 6-bromo-2-tert-butyl-3-(tetrahydro-2H-pyran-4-ylmethyl)-3H-imidazo[4,5-b]pyridine (Step F of Example 47) and 2-propanethiol (TCI Tokyo Kasei Kogyo Co., Ltd.).
Reaction SMILES: C[O:2][C:3]1[CH:10]=[C:9]([CH:11]([CH3:22])[CH:12]([CH3:21])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH:8]=[C:5]([O:6]C)[CH:4]=1.C(O)(=O)C.Br>O>[CH3:22][CH:11]([C:9]1[CH:10]=[C:3]([OH:2])[CH:4]=[C:5]([CH:8]=1)[OH:6])[CH:12]([CH3:21])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCC(C)C(C)c1cc(OC)cc(OC)c1
Agent: Br
Solvent: CC(=O)O
Solvent: O
Product: CCCCCCCCC(C)C(C)c1cc(O)cc(O)c1
Reaction time: 12 h

Procedure:
A solution of 30.6 g. of 5-(1,2-dimethyldecyl)-resorcinol dimethyl ether in 350 ml. of glacial acetic acid and 150 ml. of 48% hydrogen bromide is refluxed eight hours, then stirred at 25° for 12 hours. The reaction mixture is diluted with water and extracted three times with ether. The combined extracts are washed with saturated aqueous sodium bisulfite and saturated aqueous sodium bicarbonate, dried (MgSO4), concentrated and distilled to give 5-(1,2-dimethyldecyl)resorcinol.
Reaction SMILES: [CH3:1][O:2][C:3]([O:5][C@@H:6]1[C@H:10]([O:11][C:12]([O:14][CH3:15])=[O:13])[C@@H:9]([CH3:16])[O:8][C@H:7]1[N:17]1[CH:24]=[C:23]([F:25])[C:21]([NH2:22])=[N:20][C:18]1=[O:19])=[O:4].N1C=CC=CC=1.Cl[C:33]([O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:34].Cl>ClCCl>[CH3:1][O:2][C:3]([O:5][C@@H:6]1[C@H:10]([O:11][C:12]([O:14][CH3:15])=[O:13])[C@@H:9]([CH3:16])[O:8][C@H:7]1[N:17]1[CH:24]=[C:23]([F:25])[C:21]([NH:22][C:33]([O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:34])=[N:20][C:18]1=[O:19])=[O:4]
Reactant: COC(=O)O[C@@H]1[C@H](OC(=O)OC)[C@@H](C)O[C@H]1n1cc(F)c(N)nc1=O
Reactant: CCCCCOC(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCCCOC(=O)Nc1nc(=O)n([C@@H]2O[C@H](C)[C@@H](OC(=O)OC)[C@H]2OC(=O)OC)cc1F
Temperature: -2.5 °C
Yield: 91.1 %

Procedure:
35.8 g (0.099 mole) of the compound obtained in Example 2 was mixed with 163 ml of dichloromethane and 11 ml (0.136 mole) of pyridine, and stirred. After cooling the resulting mixture to −5 to 0° C., 15.7 ml (0.109 mole) of n-pentyl chloroformate was added dropwise thereto while maintaining the temperature of the reaction mixture at less than 0° C., followed adding the resulting mixture was warmed to room temperature and stirred for 2 hrs, 1 N HCl thereto. The organic layer was separated, successively washed with 163 ml of saturated sodium bicarbonate and 163 ml of water, dried over anhydrous sodium sulfate, and concentrated under a reduced pressure, to obtain 42.9 g of the title compound.
Reaction SMILES: [C:1]1([CH3:9])[C:2]([CH:7]=O)=[CH:3][CH:4]=[CH:5][CH:6]=1.[N:10]([CH2:13][C:14]([O:16][CH3:17])=[O:15])=[N+:11]=[N-:12]>>[CH3:9][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[C:13]([N:10]=[N+:11]=[N-:12])[C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)CN=[N+]=[N-]
Reactant: Cc1ccccc1C=O
Product: COC(=O)C(=Cc1ccccc1C)N=[N+]=[N-]

Procedure:
Following the general procedure of PREPARATION 61 and making non-critical variations but starting with o-tolualdehyde (5.0 g), methyl azidoacetate (19.2 g), the title compound is obtained, NMR (300 MHz, CDCl3) 7.96, 7.26-7.18, 7.13, 3.92 and 2.36 δ.
Reaction SMILES: [C@@H:1]1(C(O)=O)[CH2:6][CH2:5][CH2:4][CH2:3][C@H:2]1[C:7]([OH:9])=[O:8].C(Cl)(Cl)Cl.[N-:17]=[N+]=[N-].[Na+].CCOCC>S(=O)(=O)(O)O>[NH2:17][C@@H:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C@H:2]1[C:7]([OH:9])=[O:8]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(O)[C@@H]1CCCC[C@H]1C(=O)O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: N[C@@H]1CCCC[C@H]1C(=O)O
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
Trans-cyclohexane-1,2-dicarboxylic acid (8.105 g; racemic modification) is dissolved in conc. sulfuric acid (25 ml) and chloroform (50 ml) and kept at a temperature of 45° C., to which is added sodium azide (3.6 g) in one hour. After this, the solution is stirred for 90 minutes, added with ice water (25 ml) and is added with ether to remove chloroform. Barium carbonate (90 g) is added to the water layer of the solution to effect the neutralization. Barium sulfate is removed from the solution by filtration and the filtrate is concentrated to dryness to result in needle crystals of rac-trans-2-aminocyclohexanecarboxylic acid (referred to as A) having the following characteristics. When a corresponding rac-cis-compound is used as starting material, there is obtained the corresponding cis-compound i.e. rac-cis-aminocyclohexanecarboxylic acid, referred to as B).
Reaction SMILES: [CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([CH3:11])[CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH:12]=[O:13].[CH:14]1([Mg]Br)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.[Cl-].[NH4+]>O1CCCC1>[CH:14]1([CH:12]([C:3]2[O:4][C:5]3[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:6]=3[C:2]=2[CH3:1])[OH:13])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: Cc1ccc2oc(C=O)c(C)c2c1
Reactant: Br[Mg]C1CCCCC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cc1ccc2oc(C(O)C3CCCCC3)c(C)c2c1
Reaction time: 1 h
Yield: 76 %

Procedure:
To a solution (20 mL) of 3,5-dimethyl-1-benzofuran-2-carbaldehyde (1.00 g) synthesized above in tetrahydrofuran was added a 1.0M solution (8.61 mL) of cyclohexylmagnesium bromide in tetrahydrofuran at 0° C., and the mixture was stirred for 1 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, tetrahydrofuran was evaporated in an evaporator, and the residue was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (25% ethyl acetate/hexane) to give the title object compound (1.13 g, 76%) as a pale-yellow solid.
Reaction SMILES: C(O)(=O)CCCCCCCCCCC.S(Cl)(Cl)=O.Cl.[Br:20]Br.[CH3:22][O:23][C:24](=[O:58])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]C1C(=CC=C(O)C=1CCCCCCCCCCCC(O)=O)O>>[CH3:22][O:23][C:24](=[O:58])[CH:25]([Br:20])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35]
Reactant: COC(=O)CCCCCCCCCCCc1c(O)ccc(O)c1CCCCCCCCCCCC(=O)O
Reactant: BrBr
Agent: CCCCCCCCCCCC(=O)O
Agent: Cl
Solvent: O=S(Cl)Cl
Product: CCCCCCCCCCC(Br)C(=O)OC
Reaction time: 2.5 h

Procedure:
Initially, α-bromolauric acid methyl ester was prepared as follows. Pure lauric acid (100 gm 0.5 mol) was dissolved in thionyl chloride (89 gm, 0.75 mol) at 55° C. under nitrogen. A large amount of hydrogen chloride gas was generated. When all the lauric acid was converted to acid chloride and there was no more HCl gas being generated after stirring for 2.5 hours, bromine (89.25 gm, 0.65 mol) was slowly added to the solution at room temperature. The reaction mixture was stirred for another 8 hours at 45° C. The reaction was then stopped by evaporating additional bromine at 80° C. by bubbling in nitrogen. The crude product, α-bromolauric acid chloride, was cooled to 0° under nitrogen. Pure methanol was then added very slowly to the acid chloride solution at 0° C. The temperature was not allowed to exceed 15° C. during this process. The final crude product, α-bromolauric acid methyl ester, was washed with water several times. The final product was extracted twice with hexane. The NMR results showed that the product was completely pure. The yield of the reaction was about 98% and may be summarized as follows: ##STR7## B. Preparation of Hydroquinone Bislauric Acid Methyl Ester (2)
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:18]([C:20]1[CH:42]=[CH:41][C:23]([O:24][C:25]2[CH:26]=[C:27]([NH2:40])[CH:28]=[C:29]([O:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)[CH:30]=2)=[CH:22][CH:21]=1)#[N:19]>>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][C@@H:12]([C:15](=[O:17])[NH:40][C:27]2[CH:28]=[C:29]([O:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)[CH:30]=[C:25]([O:24][C:23]3[CH:41]=[CH:42][C:20]([C:18]#[N:19])=[CH:21][CH:22]=3)[CH:26]=2)[CH2:13][CH2:14]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: N#Cc1ccc(Oc2cc(N)cc(Oc3ccc(C#N)cc3)c2)cc1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](C(=O)O)CC1
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](C(=O)Nc2cc(Oc3ccc(C#N)cc3)cc(Oc3ccc(C#N)cc3)c2)CC1
Yield: 65.4 %

Procedure:
Following the procedure of Example 9(e) cis-4-tert-butoxycarbonylamino-cyclo-hexanecarboxylic acid 1.0 g (4.15 mmol) and [3,5-bis-(4-cyano-phenoxy)-phenyl]-amine (1.34 g, 4.15 mmol) were used to afford 1.5 g of the required product. 1H NMR (DMSO-d6): δ 1.4 (9H, s), 2.3 (4H, m), 2.81 (1H, m), 3.15 (4H, m), 3.5 (1H, m), 6.71 (1H, s), 6.81 (1H, brs), 7.21 (6H, m), 7.92 (4H, d), 10.0 (1H, brs).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Cl[C:7]1[N:8]=[C:9]([NH:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[S:13][C:11]=2[N:12]=1>>[N:1]1([C:7]2[N:8]=[C:9]([NH:19][CH2:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:10]3[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[S:13][C:11]=3[N:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=[N+]([O-])c1cc2c(NCc3ccccc3)nc(Cl)nc2s1
Reactant: c1c[nH]cn1
Product: O=[N+]([O-])c1cc2c(NCc3ccccc3)nc(-n3ccnc3)nc2s1

Procedure:
Following the procedure of Example 97, the reaction of imidazole with 2-chloro-6-nitro-4-benzylamino-thieno-[2,3-d]-pyrimidine gives 2-(imidazol-1-yl)-6-nitro-4-benzylamino-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][NH:8][S:9]([C:12]2[CH:21]=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[CH:24]1([CH2:30]N)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[CH:24]1([CH2:30][N:8]([CH2:7][C:6]2[CH:22]=[CH:23][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[S:9]([C:12]2[CH:21]=[CH:20][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=2)(=[O:10])=[O:11])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: COC(=O)c1ccc(S(=O)(=O)NCc2ccc(OC)cc2)cc1
Reactant: NCC1CCCCC1
Product: COc1ccc(CN(CC2CCCCC2)S(=O)(=O)c2ccc(C(=O)O)cc2)cc1

Procedure:
Prepared as in example 5-10 from Methyl 4-(N-(4-methoxybenzyl)sulfamoyl)benzoate (Example 5-10b) and cyclohexylmethanamine. MS (M−H, 416.1); NMR (400 MHz, DMSO-d6): δ, ppm: 0.63 (m, 2H), 0.87 (m, 3H), 0.94 (m, 1H), 1.25-1.52 (m, 5H), 1.70 (m, 2H), 2.86 (m, 2H), 3.70 (s, 3H), 4.22 (s, 2H), 6.84 (m, 2H), 7.16 (m, 2H), 7.91 (m, 2H), 7.62 (m, 2H), 8.09 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([C:6]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13](=[O:18])[CH:12]=[C:11]3[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:35][CH:36]1[CH2:38][CH2:37]1>CN(C=O)C.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH2:35][CH:36]2[CH2:38][CH2:37]2)[C:13](=[O:18])[CH:12]=[C:11]3[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)=[O:7])=[CH:26][CH:27]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc2[nH]c(=O)cc(-c3cccc(Cl)c3)c2c1
Reactant: BrCC1CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2CC1CC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 67.7 %

Procedure:
A solution of 6-(4-Chloro-benzoyl)-4-(3-chloro-phenyl)-1H-quinolin-2-one (3.10 g, 7.87 mmol), prepared according to the methods described in PCT international patent application publication number WO 97/21701 (published Jun. 19, 1997), in DMF (28 mL) was treated with cesium carbonate (2.56 g, 7.87 mmol) and (bromomethyl)cyclopropane (2.13 g, 15.7 mmol). The reaction mixture was stirred at room temperature for 12 hours, diluted with dichloromethane (25 mL), and washed with 1N HCl (2×10 mL) and brine (20 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to give a black residue. Purification by flash column chromatography (silica, ethyl acetate:petroleum ether 1:9-3:7) gave 6-(4-Chloro-benzoyl)-4-(3-chloro-phenyl)-1-cyclopropylmethyl-1H-quinolin-2-one (2.39 g, 68%) as an off-white foam.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1([CH2:10][CH2:11][OH:12])[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.Cl[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].C(N(CC)CC)C>O1CCCC1>[CH2:17]([O:16][C:14]([N:7]1[CH2:8][CH2:9][C:4]([CH2:3][CH2:2][OH:1])([CH2:10][CH2:11][OH:12])[CH2:5][CH2:6]1)=[O:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: OCCC1(CCO)CCNCC1
Reactant: O=C(Cl)OCc1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(OCc1ccccc1)N1CCC(CCO)(CCO)CC1

Procedure:
1-benzyloxycarbonyl-4,4-bis-(2-hydroxyethyl)piperidine is prepared by reaction of 4,4-bis-(2-hydroxyethyl)piperidine with benzyl chloroformate in tetrahydrofuran in the presence of triethylamine.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([Cl:12])[Cl:11].NC(N)=O.C(O)C>[Pt].C1(C)C=CC=CC=1>[CH2:1]([CH2:9][SiH:10]([Cl:12])[Cl:11])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C[SiH](Cl)Cl
Reactant: C=Cc1ccccc1
Agent: [Pt]
Agent: NC(N)=O
Solvent: CCO
Solvent: Cc1ccccc1
Product: Cl[SiH](Cl)CCCc1ccccc1
Yield: 61 %

Procedure:
Reaction between styrene and methyldichlorosilane with platinum catalyst in the presence of urea. 0.384 g Styrene and 0.435 g methyldichlorosilane were introduced into a glass tube, and an ethanol solution containing 0.255 mg urea (5.1 wt %) was added with a microsyringe. 1 mg Of a toluene solution of 0-valent platinum complex of divinylsiloxane (0.04 wt % platinum content) was added. The reaction tube was sealed with Teflon tape and a septum and placed in a 100° C. oil bath where it was heated for 20 minutes. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of 64% and a phenethylmethyldichlorosilane yield of 61%. The ratio between the phenethylmethyldichlorosilane and the (α-methylbenzyl)methyldichlorosilane was 102:1.
Reaction SMILES: [CH3:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:16]2[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=2)=[CH:10]3)=[CH:4][C:3]=1[C:24](=[O:26])[CH3:25].[CH3:27][N:28]([CH:30](OC)OC)[CH3:29]>>[CH3:27][N:28]([CH3:30])/[CH:29]=[CH:25]/[C:24]([C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][C:2]=1[CH3:1])[C:13]1[N:9]([CH:10]=[C:11]([C:16]3[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=3)[N:12]=1)[CH2:8][CH2:7][O:6]2)=[O:26]
Reactant: CC(=O)c1cc2c(cc1C)-c1nc(-c3ncnn3C(C)C)cn1CCO2
Reactant: COC(OC)N(C)C
Product: Cc1cc2c(cc1C(=O)/C=C/N(C)C)OCCn1cc(-c3ncnn3C(C)C)nc1-2
Temperature: 130 °C
Reaction time: 48 h
Yield: 82 %

Procedure:
A mixture of 1-{13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}ethan-1-one (250 mg, 0.720 mmol) and DMF-DMA (170 mg, 1.44 mmol) in xylenes (10 mL) was stirred at 130° C. for 48 h under nitrogen atmosphere. After concentration, the residue was purified by reverse phase combiflash eluting with a 0-40% gradient of CH3CN in 0.3% NH4HCO3 to afford (2E)-3-(dimethylamino)-1-{13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-12-yl}prop-2-en-1-one (240 mg, 77% yield). LCMS (ESI) m/z: 407.3 [M+H+].
Reaction SMILES: [K].[C:2]1(=[O:12])[NH:6][C:5](=[O:7])[C:4]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]12.Cl.Cl.[CH2:15]([O:17][C:18](=[O:24])[CH:19](Cl)[O:20][CH2:21][CH3:22])[CH3:16]>>[CH2:15]([O:17][C:18](=[O:24])[CH:19]([N:6]1[C:2](=[O:12])[C:3]2[C:4](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:5]1=[O:7])[O:20][CH2:21][CH3:22])[CH3:16]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CCOC(=O)C(Cl)OCC
Agent: Cl
Agent: [K]
Product: CCOC(=O)C(OCC)N1C(=O)c2ccccc2C1=O

Procedure:
According to general procedure A, phthalimide potassium salt was reacted with 2-chloro-2-ethoxyacetic acid ethyl ester dihydrochloride (CAS 172348-75-3) to give (RS)-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxy-acetic acid ethyl ester. Light yellow semisolid. MS 278.0 ([M+H]+)