Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:6][CH2:5][C:4](=O)[N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].CC(C[AlH]CC(C)C)C.[CH2:25]([C@@H:32]1[CH2:36][O:35][C:34](=[O:37])[N:33]1[C:38](=[O:47])[CH2:39][C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(C(C)C)CC)(C)C.COC1N(C(OC(C)(C)C)=O)C(C)(C)CC1>CCOCC.C1(C)C=CC=CC=1.ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[CH2:25]([C@@H:32]1[CH2:36][O:35][C:34](=[O:37])[N:33]1[C:38](=[O:47])[C@H:39]([C@H:4]1[N:3]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:2]([CH3:15])([CH3:1])[CH2:6][CH2:5]1)[C:40]1[CH:41]=[CH:42][C:43]([Cl:46])=[CH:44][CH:45]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1C(=O)CCC1(C)C
Reactant: O=C(Cc1ccc(Cl)cc1)N1C(=O)OC[C@H]1Cc1ccccc1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: CC(C)C[AlH]CC(C)C
Agent: COC1CCC(C)(C)N1C(=O)OC(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1[C@H]([C@@H](C(=O)N2C(=O)OC[C@H]2Cc2ccccc2)c2ccc(Cl)cc2)CCC1(C)C
Temperature: -78 °C
Reaction time: 2 h
Yield: 61.3 %

Procedure:
tert-Butyl 2,2-dimethyl-5-oxopyrrolidine-1-carboxylate (1.170 g, 5.4859 mmol) was dissolved in Et2O (15 mL) and cooled to −78° C. The solution was treated with DIBAL-H (3.7304 mL, 5.5956 mmol). The mixture was stirred at −78° C. for 2 hours and then warmed to ambient temperature overnight. The reaction was quenched by addition of an aliquot (7 mL) of a solution of p-toluenesulfonic acid hydrate (0.012 g) in MeOH (12 mL). The mixture was stirred at ambient temperature for 60 hours. The suspension was concentrated in vacuo and re-suspended in a mixture of Rochelle's salt (0.5N) and ethyl acetate. After separation, the aqueous portion was washed with ethyl acetate (2×). The combined organics were then washed with saturated NaCl, dried over Na2SO4 and concentrated in vacuo to a light oil (92%). A solution of titanium(IV) chloride (3.7128 ml, 3.7128 mmol) in toluene was cooled to 0° C. and treated with a solution of (R)-4-benzyl-3-(2-(4-chlorophenyl)acetyl)oxazolidin-2-one (1.1131 g, 3.3753 mmol) dissolved in dichloromethane (7 mL). After 5 minutes, diisopropylethylamine (0.64671 mL, 3.7128 mmol) was added. The resultant solution was stirred for 1 hour at 0° C. and then cooled to −20° C. A solution of tert-butyl 5-methoxy-2,2-dimethylpyrrolidine-1-carboxylate (1.090 g, 5.0630 mmol) in dichloromethane (7 mL) was added, and the mixture was stirred at −20° C. for 75 minutes. The reaction was quenched with saturated NH4Cl (about 4 mL) and diluted with water to dissolve the solids. After separation, the aqueous portion was washed with methylene chloride (3×). The combined organics were washed with water (2×), dried over Na2SO4 and concentrated in vacuo. The crude product was subjected to chromatography on SiO2 and eluted with 9:1 hexanes/ethyl acetate to produce (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (1.09 g, 61%). MS (ESI+) [M+H] 526.7/528.8
Reaction SMILES: [CH2:1]([C@H:3]1[C:8](=[O:9])[N:7]([CH2:10][CH3:11])[C:6]2[CH:12]=[CH:13][C:14]([C:16]([OH:18])=O)=[CH:15][C:5]=2[O:4]1)[CH3:2].S(Cl)([Cl:21])=O>>[CH2:1]([C@H:3]1[C:8](=[O:9])[N:7]([CH2:10][CH3:11])[C:6]2[CH:12]=[CH:13][C:14]([C:16]([Cl:21])=[O:18])=[CH:15][C:5]=2[O:4]1)[CH3:2]
Reactant: CC[C@@H]1Oc2cc(C(=O)O)ccc2N(CC)C1=O
Reactant: O=S(Cl)Cl
Product: CC[C@@H]1Oc2cc(C(=O)Cl)ccc2N(CC)C1=O

Procedure:
A mixture of (S)-2,4-diethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carboxylic acid (1.1 g) in thionyl chloride (15 ml) was stirred under reflux for 2 hours. Thionyl chloride was distilled off under reduced pressure to give (S)-2,4-diethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbonyl chloride (1.25 g).
Reaction SMILES: OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([NH:12][C:13](=[O:30])[CH2:14][NH:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:25]([F:28])([F:27])[F:26])[CH:23]=3)[N:18]([CH3:29])[N:17]=2)[CH2:9]1.[OH:31][C:32]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]1>>[OH:31][C:32]1([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:33][CH2:34][CH:35]([N:8]2[CH2:9][CH:10]([NH:12][C:13](=[O:30])[CH2:14][NH:15][C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([C:25]([F:27])([F:26])[F:28])[CH:23]=4)[N:18]([CH3:29])[N:17]=3)[CH2:11]2)[CH2:36][CH2:37]1
Reactant: O=C1CCC(O)(c2ccccc2)CC1
Reactant: Cn1nc(NCC(=O)NC2CNC2)c2cc(C(F)(F)F)ccc21
Solvent: O=C(O)C(F)(F)F
Product: Cn1nc(NCC(=O)NC2CN(C3CCC(O)(c4ccccc4)CC3)C2)c2cc(C(F)(F)F)ccc21

Procedure:
The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-(1-methyl-5-trifluoromethyl-1H-indazol-3-ylamino)-acetamide TFA salt (as prepared in Example 18, Step D) and 4-hydroxy-4-phenyl-cyclohexanone using the procedure described in Step E of Example 1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:9][CH2:10]Br)=[CH:4][CH:3]=1.[OH:19][C:20]1([CH3:34])[C:24]2([CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[O:23][C:22](=[O:30])[N:21]1[CH2:31][CH2:32][CH3:33].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:9][CH2:10][N:27]2[CH2:28][CH2:29][C:24]3([O:23][C:22](=[O:30])[N:21]([CH2:31][CH2:32][CH3:33])[C:20]3([OH:19])[CH3:34])[CH2:25][CH2:26]2)=[CH:4][CH:3]=1
Reactant: CCCN1C(=O)OC2(CCNCC2)C1(C)O
Reactant: Fc1ccc(C(=CCBr)c2ccc(F)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCN1C(=O)OC2(CCN(CC=C(c3ccc(F)cc3)c3ccc(F)cc3)CC2)C1(C)O
Yield: 86 %

Procedure:
9.3 g of 3,3-bis(4-fluorophenyl)-2-propenyl bromide dissolved in 50 ml of acetone are portionwise added to a mixture containing 6.85 g of 4-hydroxy-4-methyl-2-oxo-3-n-propyl-1-oxa-3,8-diazaspiro[4,5]decane and 4.2 g of anhydrous potassium carbonate in 68 ml of anhydrous acetone at room temperature during 1 hour while stirring, then the reaction mixture is stirred at room temperature for an additional 1 hour. After filtering off the inorganic salts and evaporating the solvent under reduced pressure, the residue is taken up in benzene, washed with water, dried over anhydrous sodium sulfate and then the solution is evaporated to one tenth its volume under reduced pressure. The product is precipitated by adding n-hexane to the evaporation residue. The crystals are filtered off and dried to give the title compound in 86% yield, m.p.: 128°-129° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:5](O)=[O:6]>C1COCC1>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:5][OH:6])[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=1
Reactant: Cc1cc(C(=O)O)cc(C(F)(F)F)c1
Solvent: C1CCOC1
Product: Cc1cc(CO)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred suspension of 3-methyl-5-(trifluoromethyl)benzoic acid (1 g, 4.90 mmol) in THF (5 ml) at −78° C. under nitrogen was added dropwise over 10 mins borane tetrahydrofuran complex 1M in THF (24.49 ml, 24.49 mmol). The reaction mixture was then allowed to warm to RT over 20 hours. On cooling in an ice/water bath the reaction mixture was quenched dropwise with MeOH (10 ml) and then 1M HCl until effervescence ceased. Water was added and the reaction mixture stirred at RT for 30 mins and the THF was removed under reduced pressure. EtOAc was added and the organic portion dried over MgSO4, filtered and concentrated under reduced pressure. Purification was carried out by chromatography on silica using 0-50% EtOAc in Hexanes as eluent to afford the title product;
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[C:7](=[O:12])[CH:8]=[C:9]([SH:11])[S:10][C:5]=2[CH:4]=1.[H-].[Na+].[CH3:17]I.[Cl-].[NH4+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[C:7](=[O:12])[CH:8]=[C:9]([S:11][CH3:17])[S:10][C:5]=2[CH:4]=1
Reactant: CI
Reactant: COc1ccc2c(=O)cc(S)sc2c1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: COc1ccc2c(=O)cc(SC)sc2c1
Temperature: 0 °C
Reaction time: 12 h
Yield: 83.3 %

Procedure:
7-Methoxy-2-mercapto-4-oxo-4H-1-benzothiopyran (2.00 g, 8.92 mmol) was dissolved in DMF (15 ml) and gradually added with sodium hydride (505.8 mg, 11.59 mmol) over 30 minutes in the ice bath and under nitrogen atmosphere. After removal of the ice bath and stir for 12 hours, the solution was added with methyl iodide (0.83 ml, 13.37 mmol) and further stirred for 3 hours. The reaction liquid was injected into the cooled aqueous solution (100 ml) of saturated ammonium chloride. The precipitated crude crystals were filtrated and fully washed with water and dried in a desiccator under reduced pressure. The crude crystals were washed with the ether-hexane solution to obtain 1.77 g (yield: 83%) of 7-methoxy-2-methylthio-4-oxo-4H-1-benzothiopyran as light yellow powder.
Reaction SMILES: [ClH:1].[NH2:2][C@H:3]([C:9]([OH:11])=[O:10])[CH2:4][CH2:5][CH2:6][CH2:7][NH2:8].[OH-].[Na+].[CH2:14]([O:26][CH2:27][CH:28]1[O:30][CH2:29]1)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].Cl>O.C(O)(C)C>[ClH:1].[OH:30][CH:28]([CH2:27][O:26][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:29][NH:8][CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]([C:9]([OH:11])=[O:10])[NH2:2]
Reactant: CCCCCCCCCCCCOCC1CO1
Reactant: NCCCC[C@H](N)C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: CCCCCCCCCCCCOCC(O)CNCCCC[C@H](N)C(=O)O
Yield: 23.8 %

Procedure:
L-lysine hydrochloride (18.3 g, 0.1 mols) and 2.0 g (0.2 mols) of sodium hydroxide were dissolved in 100 ml of water in a three-necked round flask, and 100 ml of i-propanol were added thereto. Then, 24.2 g (0.1 mols) of dodecylglycidyl ether were added dropwise thereto over a period of 30 minutes while being heat-refluxed and stirred. Further, the mixture was stirred under reflux for 3 hours. It was identified through TLC and gas chromatography that dodecylglycidyl ether disappeared. Thereafter, the resulting mixture was neutralized with 10.1 g (0.1 mols) of 36% hydrochloric acid. The reaction solution was concentrated under reduced pressure, and the residue was purified through silica-gel column chromatography (Kieselgel 60, eluent=mixture of chloroform, methanol and acetic acid at a ratio of 3:1:0.5) to give 10.1 g of Nε-(2-hydroxy-3-dodecyloxypropyl)-L-lysine hydrochloride (yield 23.7%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2.C([O-])([O-])=O.[Cs+].[Cs+].[C:19]([O:27][CH2:28][CH3:29])(=[O:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].C(OCC)(=O)C>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[CH3:12][C:9]1[CH:8]=[CH:7][C:6]2[C:11](=[C:2]([CH:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:19]([O:27][CH2:28][CH3:29])=[O:26])[CH:3]=[CH:4][CH:5]=2)[N:10]=1
Reactant: Cc1ccc2cccc(Br)c2n1
Reactant: CCOC(=O)CC(=O)OCC
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C(=O)OCC)c1cccc2ccc(C)nc12
Temperature: 25 °C
Yield: 82.5 %

Procedure:
A solution of 8-bromo-2-methylquinoline (2.00 g, 9.01 mmol), Pd(PtBu3)2 (0.23 g, 0.45 mmol), Cs2CO3 (11.74 g, 36.02 mmol) and diethyl malonate (2.73 mL, 18.01 mmol) in dioxane (25 mL) was heated at 118° C. in a sealed tube for 1 hour. After cooling to ambient temperature, ethyl acetate (30 mL) and water (15 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (7:1 hexane/ethyl acetate) to give diethyl 2-(2-methylquinolin-8-yl)malonate (2.24 g, 82.54%) as an oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[S:25][C:19]3[N:20]=[CH:21][NH:22][C:23](=[O:24])[C:18]=3[C:17]=2[CH3:26])=[O:15])[CH2:10][CH2:9]1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:34][C:35]([NH:37][C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1[F:45])=[O:36]>CC#N>[F:45][C:39]1[CH:40]=[C:41]([F:44])[CH:42]=[CH:43][C:38]=1[NH:37][C:35](=[O:36])[CH2:34][N:22]1[C:23](=[O:24])[C:18]2[C:17]([CH3:26])=[C:16]([C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[CH2:13][CH2:12]3)=[O:15])[S:25][C:19]=2[N:20]=[CH:21]1
Reactant: O=C(CCl)Nc1ccc(F)cc1F
Reactant: Cc1c(C(=O)N2CCN(c3ccccc3F)CC2)sc2nc[nH]c(=O)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cc1c(C(=O)N2CCN(c3ccccc3F)CC2)sc2ncn(CC(=O)Nc3ccc(F)cc3F)c(=O)c12
Temperature: 130 °C
Yield: 34.6 %

Procedure:
To a suspension of 6-(4-(2-fluorophenyl)piperazine-1-carbonyl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one, (0.06 g, 0.16 mmol) in CH3CN (0.5 mL) was added K2CO3 (22 mg, 0.16 mmol), KI (29 mg, 0.17 mmol), and 2-chloro-N-(2,4-difluorophenyl)acetamide, (36 mg, 0.16 mmol). The reaction mixture was heated at 130° C. for 25 min in a microwave reactor. The reaction was quenched with H2O (25 mL) and the aqueous layer was extracted with EtOAc (25 mL). The organic layer was washed with brine (25 mL), dried over Na2SO4 and concentrated. The crude material was purified by flash chromatography (Et2O:DCM, 1:1) providing 30 mg of pure N-(2,4-difluorophenyl)-2-(6-(4-(2-fluorophenyl)piperazine-1-carbonyl)-5-methyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetamide, (yield: 35%).
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][C:18]=3[Cl:32])=[O:16])[CH2:6][C:5]=12.FC(F)(F)S(O[C:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]=1)(=O)=O>C(OCC)C>[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]=4)=[CH:19][C:18]=3[Cl:32])=[O:16])[CH2:6][C:5]=12
Reactant: O=S(=O)(OC1=CCCCC1)C(F)(F)F
Reactant: CC1(C)OB(c2ccc(C(=O)N3Cc4cccn4Cc4ccccc43)c(Cl)c2)OC1(C)C
Solvent: CCOCC
Product: O=C(c1ccc(C2=CCCCC2)cc1Cl)N1Cc2cccn2Cc2ccccc21
Yield: 92.9 %

Procedure:
(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone of Step B (0.300 g, 0.668 mmol) and cyclohexen-1-yl trifluoromethanesulfonate (0.169 g, 0.735 mmol) were reacted by the procedure described in Example 1, Step F. The crude product was purified by flash column chromatography on silica gel, eluting with 30% ethyl acetate/hexane to afford a clear oil. The oil was dissolved in diethyl ether and precipitated with petroleum ether to afford 0.250 g of a white solid.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[C:19]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:24]=[CH:23][CH:22]=[C:21]([C:25]2[O:29][C:28]([CH3:30])=[N:27][C:26]=2[C:31](O)=[O:32])[CH:20]=1>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[CH:16][C:15]([NH:18][C:31]([C:26]3[N:27]=[C:28]([CH3:30])[O:29][C:25]=3[C:21]3[CH:20]=[C:19]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH:24]=[CH:23][CH:22]=3)=[O:32])=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2ccc(Cn3ccc(N)n3)o2)OCCO1
Reactant: Cc1nc(C(=O)O)c(-c2cccc(-c3ccccc3)c2)o1
Product: CC(=O)c1ccc(Cn2ccc(NC(=O)c3nc(C)oc3-c3cccc(-c4ccccc4)c3)n2)o1

Procedure:
Following general procedure B followed by T, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-3-ylamine and 5-biphenyl-3-yl-2-methyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=1.11 min; [M+H]+=467.31.
Reaction SMILES: C1C2C3C=CC(C2C=C1)C3.C(C1CCC=CC1)=C.C(C1CCCCC=1)=C.C1CC=CC=1.[CH2:32]1[CH:36]2[CH:37]3[CH:41]4[CH:42]5[CH:46]=[CH:45][CH:44]([CH:40]4[CH:39]([CH:35]2C=[CH:33]1)[CH2:38]3)C5>C1CCCCC1>[CH:41]1([CH:37]2[CH2:38][CH:39]3[CH2:35][CH:36]2[CH:32]=[CH:33]3)[CH2:40][CH2:44][CH:45]=[CH:46][CH2:42]1
Reactant: C1=CC2C(C1)C1CC2C2C3C=CC(C3)C12
Agent: C1=CCC=C1
Agent: C=CC1=CCCCC1
Agent: C=CC1CC=CCC1
Solvent: C1=CC2C3C=CC(C3)C2C1
Solvent: C1CCCCC1
Product: C1=CCC(C2CC3C=CC2C3)CC1

Procedure:
Dicyclopentadiene and 4-vinylcyclohexene in equimolar mixture were heated in an autoclave at 240° C. for 4-4.5 hours. The reaction product was diluted with cyclohexane and passed through a packed bed of alumina to remove the t-butylcatechol inhibitor introduced with the reactants. The resulting product mixture was distilled in a wiped film evaporator at 3 mm Hg pressure at 90° C. to produce a light fraction containing unreacted vinylcyclohexene and dicyclopentadiene and the mono-adducts of 4-vinylcyclohexene and cyclopentadiene. A 150 g sample of this distillate was vacuum distilled using a 10-tray Oldershaw column to give four fractions. The fourth fraction, 65 g, was shown by gas chromatographic analysis to consist of 0.15% dicyclopentadiene, 88.3% endo-5-(3-cyclohexen-1-yl)-2-norbornene, 6.1% exo-5-(3-cyclohexen-1-yl)-2-norbornene and two additional components present in the amount of 1.9% and 2.4% which are believed to be isomeric adducts of the formula ##STR5## several additional components totalling about 0.4%, 0.4% tricyclopentadiene and about 0.4% unidentified components. Analysis of the fraction by nuclear magnetic resonance indicated about 87 mole percent of the endo adduct, about 9 mole percent of the exo adduct and about 5% of the isomeric adducts.
Reaction SMILES: Br.[CH2:2]([O:9][C:10]1[CH:11]=[C:12]([C:16]2[N:17]=[C:18]([NH2:21])[S:19][CH:20]=2)[CH:13]=[CH:14][CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.Cl>N1C=CC=CC=1>[CH2:2]([O:9][C:10]1[CH:11]=[C:12]([C:16]2[N:17]=[C:18]([NH:21][S:28]([C:25]3[CH:26]=[CH:27][C:22]([CH3:32])=[CH:23][CH:24]=3)(=[O:30])=[O:29])[S:19][CH:20]=2)[CH:13]=[CH:14][CH:15]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1nc(-c2cccc(OCc3ccccc3)c2)cs1
Agent: Br
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2nc(-c3cccc(OCc4ccccc4)c3)cs2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61 %

Procedure:
A mixture of 3.0 g of 4-(3-benzyloxy-phenyl)-thiazol-2-ylamine hydrobromide with 1.8 g of p-toluenesulfonyl chloride was stirred for 2 hours with 12 ml of pyridine. The resulting, red colored suspension was poured into 100 ml of 2N hydrochloric acid and the mixture was extracted with ethyl acetate. The organic phase was dried with magnesium sulphate and concentrated. The residue was dissolved in a mixture of 120 ml of ethanol and 120 ml of 2N sodium hydroxide solution. After the addition of 2.4 g of active charcoal the mixture was stirred at room temperature for 30 minutes and subsequently the active charcoal was filtered off. After neutralization with concentrated hydrochloric acid the mixture was concentrated and the aqueous residue was extracted twice with ethyl acetate. The organic phases were combined, dried with magnesium sulphate and freed from solvent. The residue was chromatographed on 300 g of Kieselgel 60 with ethyl acetate/hexane (1:2) as the eluent. The product-containing fractions were concentrated and yielded 2.2 g of N-[4-(3-benzyloxy-phenyl)-thiazol-2-yl]-4-methyl-benzenesulfonamide as a colorless, amorphous solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([C@H:8]([NH:13][C@H:14]([C:19]([OH:21])=O)[CH2:15][CH:16]([CH3:18])[CH3:17])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.Cl.[NH2:23][C:24]1([C:27]#[N:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C@H:8]([NH:13][C@H:14]([C:19]([NH:23][C:24]2([C:27]#[N:28])[CH2:26][CH2:25]2)=[O:21])[CH2:15][CH:16]([CH3:17])[CH3:18])[C:9]([F:10])([F:11])[F:12])=[CH:4][CH:3]=1
Reactant: CC(C)C[C@H](N[C@@H](c1ccc(Cl)nc1)C(F)(F)F)C(=O)O
Reactant: N#CC1(N)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)C[C@H](N[C@@H](c1ccc(Cl)nc1)C(F)(F)F)C(=O)NC1(C#N)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a solution of the crude acid (0.73 g, 2.25 mmol) from Step 2 in DMF (12 mL) was added 1-aminocyclopropanecarbonitrile hydrochloride (0.4 g, 3.37 mmol.) and HATU (0.86 g, 2.25 mmol). Diisopropylethylamine (1.96 mL, 11.24 mmol) was added, the mixture was stirred at rt for 20 h. EtOAc and water were added. The mixture was separated after agitation and the organic extract was washed with water and brine and dried over anhyd. MgSO4. Concentration of the organic extract followed by chromatography (30-50% EtOAc/hexane) gave the title compound.
Reaction SMILES: [C:1]1([C:7]2[NH:11][C:10]([C:12]3[CH:13]=[CH:14][C:15]([N:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)=[N:16][CH:17]=3)=[N:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[C:32]1[N:37]=[CH:36][CH:35]=[CH:34][N:33]=1.[OH-].[NH4+]>C(O)C>[C:1]1([C:7]2[N:11]=[C:10]([C:12]3[CH:13]=[CH:14][C:15]([N:18]4[CH2:23][CH2:22][N:21]([C:32]5[N:37]=[CH:36][CH:35]=[CH:34][N:33]=5)[CH2:20][CH2:19]4)=[N:16][CH:17]=3)[NH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Clc1ncccn1
Reactant: c1ccc(-c2cnc(-c3ccc(N4CCNCC4)nc3)[nH]2)cc1
Agent: [NH4+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: CCO
Product: c1ccc(-c2c[nH]c(-c3ccc(N4CCN(c5ncccn5)CC4)nc3)n2)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 75.2 %

Procedure:
(Reference: J. Am. Chem. Soc. 1954, 1484) A solution of 1-[5-(5-phenyl-1H-imidazol-2-yl)-pyridin-2-yl]-piperazine (0.16 g, 0.52 mmol), triethylamine (0.22 ml, 0.16 g, 1.58 mmol, 3.0 equiv) and 2-chloro-pyrimidine (0.90 mg, 0.79 mmol, 1.5 equiv) in absolute ethanol (5 ml) under nitrogen atmosphere was heated at reflux for 1 hour, after which additional triethylamine (0.22 ml, 0.16 g, 1.58 mmol, 3.0 equiv) and 2-chloro-pyrimidine (0.90 mg, 0.79 mmol, 1.5 equiv) were added. The reaction was heated at reflux for an additional 1.5 hour, then stirred at room temperature for two days. The mixture was basified to pH 10 with concentrated ammonium hydroxide, and then concentrated in vacuo. The residue was partitioned between water (20 ml) and ethyl acetate (50 ml). The organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to a solid, which was triturated with ether to give the desired product (0.15 g, 74%). MS m/z 446 (M++1).
Reaction SMILES: OS(O)(=O)=O.[O:6]=[C:7]1[C:16]2[C:15]([C:17]([O:19][CH3:20])=[O:18])=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:10][CH2:9][CH2:8]1.[N-:21]=[N+]=[N-].[Na+].C(=O)([O-])[O-].[K+].[K+].[OH-].[K+]>C(Cl)(Cl)Cl.O>[O:6]=[C:7]1[NH:21][C:16]2[C:15]([C:17]([O:19][CH3:20])=[O:18])=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:10][CH2:9][CH2:8]1
Reactant: COC(=O)c1cccc2c1C(=O)CCC2
Reactant: [N-]=[N+]=[N-]
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: O
Product: COC(=O)c1cccc2c1NC(=O)CCC2
Temperature: 10 °C
Reaction time: 2.5 h

Procedure:
Conc. H2SO4 is added dropwise at 0° C. to a solution of 3.040 g of methyl 8-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylate in 550 ml of chloroform, in the course of which the temperature is kept at 0-3° C. On completion of addition, the reaction solution is warmed to 10° C. and 21.80 g of sodium azide are added in portions over the course of 45 minutes. The reaction mixture is subsequently stirred at 50° C. over 2.5 hours. The reaction mixture is cooled to room temperature and subsequently poured onto a mixture of 200 g of potassium carbonate, 1000 ml of water and 400 g of ice. The mixture is made basic with 44 ml of 50% KOH and extracted with 2×500 ml of dichloromethane. The combined organic phases are washed with 1000 ml of water and concentrated. The title compound is obtained as a reddish solid from the residue by means of flash chromatography (SiO2 60F). Rf=0.25 (1:1 EtOAc-heptane); Rt=3.38.