Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][N:26]=[C:25](Cl)[N:24]=2)[CH:18]=1)[S:12]([CH3:15])(=[O:14])=[O:13])(C)(C)C.[NH2:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[CH:36][CH:35]=1>>[NH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:31][CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[CH:36][CH:35]=3)[N:24]=2)[CH:20]=[CH:21][CH:22]=1)[S:12]([CH3:15])(=[O:13])=[O:14]
Reactant: CC(=O)Nc1ccc(CCN)cc1
Reactant: CC(C)(C)OC(=O)NCCCN(Cc1cccc(-c2ccnc(Cl)n2)c1)S(C)(=O)=O
Product: CC(=O)Nc1ccc(CCNc2nccc(-c3cccc(CN(CCCN)S(C)(=O)=O)c3)n2)cc1

Procedure:
Intermediate 4 from above was coupled with N-[4-(2-Amino-ethyl)-phenyl]-acetamide by procedure F and the resulting product deprotected by procedure G to give 3. LC-MS showed the product had the expected M+H+ of 497. 1H NMR (Varian 300 MHz, CDCl3—CD3OD, shifts relative to the solvent peak at 7.24 ppm) δ 8.1 (m, 2H) 8.0 (m, 1H) 7.6 (m, 1H) 7.5 (m, 1H) 7.4 (m, 2H) 7.3 (m, 1H) 7.2 (d, 2H) 4.4 (s, 2H) 3.9 (m, 2H) 3.3 (m, 2H) 2.9 (m, 2H) 2.8 (s, 3H) 2.7 (m, 2H) 2.1 (s, 3H) 1.8 (m, 2H).
Reaction SMILES: [OH-:1].[Na+].[CH2:3]([SH:7])[C:4](O)=O.[CH3:8][O:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14]Cl)=[CH:12][C:11]=1[N+:18]([O-:20])=[O:19].Cl>CO>[CH3:8][O:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][CH2:4][C:3]([OH:1])=[S:7])=[CH:12][C:11]=1[N+:18]([O-:20])=[O:19]
Reactant: [OH-]
Reactant: O=C(O)CS
Reactant: COc1ccc(CCl)cc1[N+](=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COc1ccc(CCC(O)=S)cc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 95 %

Procedure:
To a cold solution of sodium hydroxide (9.75 g, 240 mmol) in methanol (200 mL), thioglycollic acid (11.25 g, 120 mmol) was added slowly over 30 minutes. Sodium thioglycollate precipitated was dissolved by stirring and warming up the solution. The solution was cooled to room temperature and 4-methoxy-3-nitrobenzyl chloride (30.0 g, 120 mmol) was added in portions to reduce the intensity of exothermic reaction. The reaction mixture was then refluxed for 4 hours, cooled and poured onto crushed ice (1 Kg) containing hydrochloric acid (50 mL). The precipitate formed was filtered, washed with ice cold water and dried under vacuum. (30.0 g, 95% yield) m.p. 130-132° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[C@@H:4]([C:5]#[C:6][C:7]([O:9][CH2:10][C:11]([Cl:14])([Cl:13])[Cl:12])=[O:8])[C@H:3]1[C:15]([OH:17])=[O:16].C(Cl)Cl.[C:22]([C@@H:24](O)[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:26]=1)#[N:23]>N1C=CC=CC=1>[CH3:1][C:2]1([CH3:18])[C@@H:4]([C:5]#[C:6][C:7]([O:9][CH2:10][C:11]([Cl:13])([Cl:14])[Cl:12])=[O:8])[C@H:3]1[C:15]([O:17][C@H:24]([C:22]#[N:23])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:26]=1)=[O:16]
Reactant: N#C[C@@H](O)c1cccc(Oc2ccccc2)c1
Reactant: CC1(C)[C@H](C(=O)O)[C@@H]1C#CC(=O)OCC(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC1(C)[C@H](C(=O)O[C@H](C#N)c2cccc(Oc3ccccc3)c2)[C@@H]1C#CC(=O)OCC(Cl)(Cl)Cl
Yield: 76.3 %

Procedure:
6.2 g of dicyclohexycarbodiimide were added to a solution of 9.5 g of the product of Step C, 30 ml of methylene chloride and 3 ml of pyridine and the reaction mixture was stirred for half an hour. 6.8 g of (S)α-cyano-3-phenoxy-benzyl alcohol were added thereto and the mixture was stirred for an hour and half and filtered. The filtrate was washed with N hydrochloric acid, then with water until neutral, dried, and evaporated to dryness. The 15.3 g of oil residue were chromatographed over silica gel and eluted with a 97-3 mixture of benzene-ethyl acetate to obtain 12 g of (S)α-cyano-3-phenoxy-benzyl(1R,cis)2,2-dimethyl-3-(2,2,2-trichloroethoxycarbonylethynyl)-cyclopropane-carboxylate melting at 101° C.
Reaction SMILES: [C:1]([CH:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:11]([CH3:16])([CH3:15])[CH2:10][CH2:9][C:8]([CH3:18])([CH3:17])[C:7]=2[CH:6]=1)[OH:4])#[CH:2].[CH3:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1I)[C:23]([O:25][CH3:26])=[O:24]>>[CH3:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[C:2]#[C:1][CH:3]([OH:4])[C:5]1[CH:14]=[CH:13][C:12]2[C:11]([CH3:16])([CH3:15])[CH2:10][CH2:9][C:8]([CH3:18])([CH3:17])[C:7]=2[CH:6]=1)[C:23]([O:25][CH3:26])=[O:24]
Reactant: COC(=O)c1ccc(I)c(C)c1
Reactant: C#CC(O)c1ccc2c(c1)C(C)(C)CCC2(C)C
Product: COC(=O)c1ccc(C#CC(O)c2ccc3c(c2)C(C)(C)CCC3(C)C)c(C)c1

Procedure:
Following the basic procedure of Example 11(d), by reacting 2.4 g (10 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 2.7 g (10 mmol) of methyl 3-methyl-4-iodobenzoate, 3.2 g (83%) of the expected ester, with a melting point of 130°-131° C., were obtained.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:31](/[CH:32]=[CH:33]/[C:34]4[CH:39]=[CH:38][C:37]([C:40]([N:42]5[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]5)=[O:41])=[CH:36][CH:35]=4)=[N:30][N:29](C4CCCCO4)[C:18]=3[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)[CH:21]=2)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(OCC)C>CO.O1CCOCC1>[OH:28][C:25]1[CH:26]=[CH:27][C:22]([C:20]2[N:19]=[C:18]3[NH:29][N:30]=[C:31](/[CH:32]=[CH:33]/[C:34]4[CH:35]=[CH:36][C:37]([C:40]([N:42]5[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]5)=[O:41])=[CH:38][CH:39]=4)[C:17]3=[C:16]([C:14]([N:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[O:15])[CH:21]=2)=[CH:23][CH:24]=1
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)c2cc(-c3ccc(O)cc3)nc3c2c(/C=C/c2ccc(C(=O)N4CCCCC4)cc2)nn3C2CCCCO2)CC1
Agent: Cl
Solvent: CO
Solvent: CCOCC
Solvent: C1COCCO1
Product: O=C(c1ccc(/C=C/c2n[nH]c3nc(-c4ccc(O)cc4)cc(C(=O)N4CCNCC4)c23)cc1)N1CCCCC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.2 %

Procedure:
To a solution of 4-[4-[6-(4-Hydroxy-phenyl)-3-{(E)-2-[4-(piperidine-1-carbonyl)phenyl]-vinyl}-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (0.25 g, 0.35 mmol) in methanol (5 ml) was added 4N HCl in dioxane (0.9 ml). The reaction mixture was stirred at room temperature for 18 hours, diethyl ether was then added, the resulting precipitated was filtered and washed once with diethyl ether to afford the hydrochloride salt of the title compound (0.175 g, 82%) as an orange solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[C:13]#[C:14][C:15]1([OH:25])[CH2:24][CH2:23][C:18]2([O:22][CH2:21][CH2:20][O:19]2)[CH2:17][CH2:16]1.[H][H]>C(O)C.O=[Pt]=O>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH2:13][CH2:14][C:15]1([OH:25])[CH2:16][CH2:17][C:18]2([O:22][CH2:21][CH2:20][O:19]2)[CH2:23][CH2:24]1
Reactant: COc1ccc2nccc(C#CC3(O)CCC4(CC3)OCCO4)c2n1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CCO
Product: COc1ccc2nccc(CCC3(O)CCC4(CC3)OCCO4)c2n1
Reaction time: 3 h

Procedure:
A solution of 8-(6-methoxy-[1,5]naphthyridin-4-ylethynyl)-1,4-dioxa-spiro[4.5]decan-8-ol (965 mg, 2.8 mmol) in ethanol (100 ml) was hydrogenated for 6 hours over PtO2 (200 mg) at 1 bar of hydrogen. The catalyst was filtered off and replaced by fresh catalyst and the hydrogenation was continued for a further 3 hours. The catalyst was filtered off and the solvent was concentrated. The crude product was purified by chromatography on silica gel (EtOAc).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]2[C:22]([CH:23]=[O:24])=[C:21]([Cl:25])[N:20]=[C:19]2[CH2:26][CH2:27][CH2:28][CH3:29])=[CH:13][CH:12]=1)([O:3][CH3:4])=[O:2].[Br:30]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]2[C:22]([CH:23]=[O:24])=[C:21]([Cl:25])[N:20]=[C:19]2[CH:26]([Br:30])[CH2:27][CH2:28][CH3:29])=[CH:13][CH:12]=1)([O:3][CH3:4])=[O:2]
Reactant: CCCCc1nc(Cl)c(C=O)n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: CCCC(Br)c1nc(Cl)c(C=O)n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
Yield: 40.4 %

Procedure:
A mixture of 1.12 g of 1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-2-butyl-4-chloroimidazole-5-carboxaldehyde and 0.49 g of N-bromosuccinimide in 40 mL of CCl4 was irradiated (UV-lamp, pyrex filter) for 0.5 hours. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. Column chromatography (elution: ethyl acetate/benzene) afforded 0.54 g of 1-[(2'-carbomethoxybiphenyl-4-yl)-methyl]-2-(1-bromobutyl)-4-chloroimidazole-5-carboxaldehyde. NMR (200 MHz, CDCl3) δ9.87 (s, 1H); 7.86 (d, 1H); 7.54 (t, 1H); 7.46 (t, 1H); 7.30 (m, 3H); 7.11 (d, 2H); 6.16 (d, 1H); 5.32 (d, 1H); 4.79 (t, 1H); 3.65 (s, 3H); 2.32 (m, 2H); 1.34 (sext., 2H); 0.83 (t, 3H).
Reaction SMILES: CCCC[Sn]([O:14][Sn:15]([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:16][CH2:17][CH2:18][CH3:19])(CCCC)CCCC.[CH3:28][N:29]([CH3:34])[CH2:30][CH:31](O)[CH3:32].O>C1C=CC=CC=1>[CH2:24]([Sn:15]([O:14][CH:31]([CH3:32])[CH2:30][N:29]([CH3:34])[CH3:28])([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:25][CH2:26][CH3:27]
Reactant: CC(O)CN(C)C
Reactant: CCCC[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)CCCC
Solvent: c1ccccc1
Solvent: O
Product: CCCC[Sn](CCCC)(CCCC)OC(C)CN(C)C

Procedure:
1-Dimethylamino-2-Propyl Tributylstannyl Ether is prepared from 89.4 gm (0.15 mole) bis(tributyltin) oxide and 30.9 gm (0.3 mole) 1-dimethylamino-2-propanol in 200 ml benzene. This is stirred and heated to reflux in a system that contains a Dean-Starke tube. After refluxing 23 hours a total of 2.6 ml of water (theory 2.7 ml) had collected in the Dean-Starke tube. The solvent is stripped off on a rotating evaporator to provide 111.0 gm of yellow liquid. This is fractionated at reduced pressure with collection at 167°-175° C. at 0.5 mm of 63.4 gm of straw colored liquid. (Percent yield - 54). Infrared spectral analysis shows this liquid to be the desired ether.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13](CO)=[C:14]([CH3:17])[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.B(F)(F)F.O(CC)[CH2:25]C.[CH3:29][O:30][C:31]([O:35][Si](C)(C)C)=[C:32]([CH3:34])[CH3:33]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH2:33][C:32]([CH3:25])([CH3:34])[C:31]([O:30][CH3:29])=[O:35])=[C:14]([CH3:17])[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1
Reactant: COC(O[Si](C)(C)C)=C(C)C
Reactant: Cc1cc2c(cnn2-c2ccc(F)cc2)cc1CO
Reactant: CCOCC
Agent: FB(F)F
Solvent: ClCCl
Product: COC(=O)C(C)(C)Cc1cc2cnn(-c3ccc(F)cc3)c2cc1C
Reaction time: 0.5 h
Yield: 69.7 %

Procedure:
(1-(4-Fluorophenyl)-6-methyl-1H-indazol-5-yl)methanol (178 mg, 0.51 mmol) was dissolved in 5 mL of dry DCM and BF3—OEt2 (0.09 mL, 0.7 mmol) was added portionwise and then stirred 30 min. Then the reaction was treated with 1-methoxy-2-methyl-1-(trimethylsiloxy)propene (0.43 mL, 2.1 mmol). The reaction was quenched with aqueous sodium bicarbonate and extracted 2×EtOAc, the organic layers dried over MgSO4, filtered, and concentrate. The residue was purified on SiO2 by MPLC using a 5:95 to 1:9 gradient to give 121 mg (51% yield) of methyl 3-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)-2,2-dimethylpropanoate. MS found: (M+H)+=341.
Reaction SMILES: [CH:1]1([CH:4]=[CH:5][C:6]2[S:10][C:9]([CH2:11]O)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:32]1(=[O:42])[NH:36][C:35](=[O:37])[C:34]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:33]12.COC(N=NC(OC)=O)=O>O1CCCC1.O>[CH:1]1([CH:4]=[CH:5][C:6]2[S:10][C:9]([CH2:11][N:36]3[C:32](=[O:42])[C:33]4[C:34](=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:35]3=[O:37])=[CH:8][CH:7]=2)[CH2:2][CH2:3]1
Reactant: OCc1ccc(C=CC2CC2)s1
Reactant: O=C1NC(=O)c2ccccc21
Agent: COC(=O)N=NC(=O)OC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1Cc1ccc(C=CC2CC2)s1
Temperature: 25 °C
Yield: 20.6 %

Procedure:
(5-(2-Cyclopropylvinyl)thiophen-2-yl)methanol described in Preparation Example 149 (930 mg, 5.19 mmol), triphenylphosphine (2040 mg, 7.78 mmol) and phthalimide (1140 mg, 7.78 mmol) were dissolved in tetrahydrofuran (50 mL), azodicarboxylic acid dimethyl ester (1140 mg, 7.78 mmol) was added under stirring at room temperature, and the solution was stirred for 1 hour. Water (50 mL) was added to the reaction solution, which was then extracted with ethyl acetate (50 mL). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=9:1), and the title compound (330 mg, 1.07 mmol, 20.6%) was obtained as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O[CH2:12][CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)OC>>[C:15]1([CH:14]([C:2]2([NH2:1])[CH:7]=[CH:6][CH:5]=[CH:4][CH2:3]2)[CH:13]=[CH2:12])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)OCC=Cc1ccccc1
Reactant: Nc1ccccc1
Product: C=CC(c1ccccc1)C1(N)C=CC=CC1
Reaction time: 24 h

Procedure:
By the procedure with [(COD)IrCl]2 (6.7 mg, 0.010 mmol) and L1 (Sa,Sc,Sc) (10.8 mg, 0.020 mmol) the reaction of aniline (130 mg, 1.40 mmol) and methyl cinnamyl carbonate (188 mg, 0.980 mmol) was conducted at room temperature for 24 h. 1H NMR and GC analysis of the crude reaction mixture showed that the conversion of the reaction was less than 1%.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[N:11]([C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:25])[N:12]=[N:13][C:14]=2[CH:15]([CH3:17])[CH3:16])[CH:5]=[CH:4][C:3]=1[C:26]1[CH:31]=[CH:30][C:29]([C:32](Cl)=[O:33])=[CH:28][CH:27]=1.[CH:35]([NH2:39])([CH2:37][CH3:38])C.Cl[CH2:41]Cl>>[CH2:35]([NH:39][C:32]([C:29]1[CH:30]=[CH:31][C:26]([C:3]2[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]3[N:11]([C:18]4[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=4[Cl:25])[N:12]=[N:13][C:14]=3[CH:15]([CH3:16])[CH3:17])=[CH:7][C:2]=2[Br:1])=[CH:27][CH:28]=1)=[O:33])[CH:37]([CH3:41])[CH3:38]
Reactant: CC(C)c1nnn(-c2c(Cl)cccc2Cl)c1COc1ccc(-c2ccc(C(=O)Cl)cc2)c(Br)c1
Reactant: ClCCl
Reactant: CCC(C)N
Product: CC(C)CNC(=O)c1ccc(-c2ccc(OCc3c(C(C)C)nnn3-c3c(Cl)cccc3Cl)cc2Br)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 2′-bromo-4′-[3-(2,6-dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-biphenyl-4-carbonyl chloride (0.043 mmol) in dichloromethane (2 mL) is added s-butyl amine (0.05 mL, 0.5 mmol). The reaction is stirred at room temperature for 1 h and concentrated under reduced pressure. The residue is slurried in 1 N hydrochloric acid, and the solid is filtered to give the title compound (0.011 g). ES/MS m/e 617.0 (M+1).
Reaction SMILES: Br[C:2]1[C:11]2[O:10]C[N:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][C:6]=2[CH:5]=[C:4]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:3]=1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:23]=[N:24][CH:25]=[C:26](B(O)O)[CH:27]=1>>[C:16]([C:4]1[CH:3]=[C:2]([C:26]2[CH:25]=[N:24][CH:23]=[C:22]([C:21]([F:32])([F:31])[F:20])[CH:27]=2)[C:11]([OH:10])=[C:6]([CH2:7][NH:8][C:12]([CH3:13])([CH3:14])[CH3:15])[CH:5]=1)([CH3:17])([CH3:18])[CH3:19]
Reactant: CC(C)(C)c1cc(Br)c2c(c1)CN(C(C)(C)C)CO2
Reactant: OB(O)c1cncc(C(F)(F)F)c1
Product: CC(C)(C)NCc1cc(C(C)(C)C)cc(-c2cncc(C(F)(F)F)c2)c1O

Procedure:
The title compound was prepared as a white solid using the procedure described in Example 1 from 8-bromo-3,6-di-tert-butyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (Intermediate 1) and 3-(trifluoromethyl)pyridine-5-boronic acid [Intermediate 2].
Reaction SMILES: O1CCCCC1[O:7][C:8]([CH3:29])([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])/[CH:9]=[CH:10]/[CH:11]1[CH2:13][C:12]1([C:19]([O:21]CC)=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15].[CH:30](C(OCC)=O)([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38]>>[C:42]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]1([C:37]([O:39][CH2:40][CH3:41])=[O:38])[C@@H:11]([CH:10]=[CH:9][C:8]([OH:7])([CH3:29])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH2:13][C@H:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:19]1=[O:21])([O:44][CH2:45][CH3:46])=[O:43]
Reactant: CCCCCC(C)(/C=C/C1CC1(C(=O)OCC)C(=O)OCC)OC1CCCCO1
Reactant: CCOC(=O)CCCCCCC(C(=O)OCC)C(=O)OCC
Product: CCCCCC(C)(O)C=C[C@H]1C[C@H](C(=O)OCC)C(=O)C1(CCCCCCC(=O)OCC)C(=O)OCC

Procedure:
For example, the use of the compound of formula 4, diethyl trans-2-{3-[(tetrahydropyran-2-yl)oxy]-3-methyl-1-octenyl}cyclopropane-1,1-dicarboxylate, described in Example 41, and the compound of formula 5, triethyl heptane-1,1,7-tricarboxylate, described in Example 42, in the procedure of Example 45 gives diethyl trans-3-(6-carboethoxyhexanyl)-4-(3-hydroxy-3-methyl-1-octenyl)-2-oxo-1,3-cyclopentanedicarboxylate, γmaxfilm 3500, 1725 cm-1, nmr (CDCl3) δ 0.88 (t, 3H), 4.17 (m, 6H), 5.64 (m, 2H), via the intermediate diethyl trans-3-(6-carboethoxyhexanyl)-4-{3-[(tetrahydropyran-2-yl)oxy]-3-methyl-1-octenyl}-2-oxo-1,3-cyclopentanedicarboxylate, γmaxfilm 1730 cm-1.
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[S:3].[CH:5]([O:18][C:19]([C:21]1[N:22]2[CH:25]([S:26][CH2:27][C:28]=1[CH:29](Br)[CH:30]=O)[CH:24]([NH:33][C:34](=[O:45])[CH2:35][S:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=1)[C:23]2=[O:46])=[O:20])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>O.O1CCCC1>[NH2:1][C:2]1[S:3][C:29]([C:28]2[CH2:27][S:26][CH:25]3[N:22]([C:23](=[O:46])[CH:24]3[NH:33][C:34](=[O:45])[CH2:35][S:36][C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=3)[C:21]=2[C:19]([O:18][CH:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:20])=[CH:30][N:4]=1
Reactant: O=CC(Br)C1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)CSc3ccc(Cl)c(Cl)c3)C2SC1
Reactant: NC(N)=S
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Nc1ncc(C2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)C(NC(=O)CSc4ccc(Cl)c(Cl)c4)C3SC2)s1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
A solution of thiourea (0.054 g) in distilled water (1 cc) is added to a solution of 2-benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-(3,4-dichlorophenylthio)acetamido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (mixture of the diastereoisomers at the substituent in the 3-position) (0.5 g) in tetrahydrofuran (10 cc), and the reaction mixture is then stirred for 17 hours at 25° C. before being poured into a mixture of distilled water (250 cc), a saturated solution of sodium bicarbonate (60 cc) and ethyl acetate (60 cc). The organic phase is washed with distilled water (3×30 cc) and then with a saturated solution of sodium chloride (30 cc) and dried over magnesium sulphate. The residue obtained after concentration of the solvent to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. is chromatographed on a column (height: 28 cm, diameter: 2 cm) of silica gel (0.04-0.063 mm), elution being carried out under a pressure of 0.5 bar (50 kPa) with a 30/70 by volume mixture of cyclohexane and ethyl acetate, and 15 cc fractions being collected. Fractions 7 to 10, containing the pure product, are combined and concentrated under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give 3-(2-aminothiazol-5-yl)-2-benzhydryloxycarbonyl-7-(3,4-dichlorophenylthio)acetamido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.29 g) in the form of a hard, pale yellow foam.
Reaction SMILES: [C:1]([OH:11])(=[O:10])[CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[OH:3].O.[NH3:13]>>[C:1]([O-:11])(=[O:10])[CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[OH:3].[NH4+:13]
Reactant: N
Reactant: O=C(O)C(O)c1ccccc1
Solvent: O
Product: O=C([O-])C(O)c1ccccc1
Product: [NH4+]

Procedure:
Each resulting crystal and, for reference, standard mandelic acid was dissolved in 6N aqueous ammonia and messed up with distilled water to form ammonium mandelate at a concentration of 1.0 w/v%. Optical rotation of the thus formed ammonium mandelate was determined.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[CH:12][N:13]2[CH2:16][CH2:17][NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:9][CH:8]=1)=[O:6]>CO.C1COCC1>[C:22]([O:21][C:19]([NH:18][CH2:17][CH2:16][N:13]1[C:14]2[C:10](=[CH:9][CH:8]=[C:7]([C:5]([OH:6])=[O:4])[CH:15]=2)[CH:11]=[CH:12]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]
Reactant: COC(=O)c1ccc2ccn(CCNC(=O)OC(C)(C)C)c2c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)NCCn1ccc2ccc(C(=O)O)cc21
Temperature: 25 °C
Reaction time: 68 h

Procedure:
Sodium hydroxide (1N, 6.0 mL, 6.00 mmol) was added to a solution of 1-(2-tert-Butoxycarbonylamino-ethyl)-1H-indole-6-carboxylic acid methyl ester (0.501 g, 1.57 mmol) in methanol (12 mL) and THF (4.0 mL). The reaction was stirred at room temperature for 68 hr. The reaction was concentrated in vacuo. The aqueous residue was acidified to pH˜1 with 1N HCl and extracted with ethyl acetate (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was carried forward without purification. ESI-MS m/z 327 (M+Na).
Reaction SMILES: N1C=CC(C2[CH:11]=[N:10][NH:9]C=2C2C=CC(CCC3C=CC4C(=CC=CC=4)N=3)=CC=2)=CC=1.[CH3:30]NN.[Cl:33][C:34]1[CH:35]=[C:36]([C:52](=O)[CH2:53][C:54]2[CH:59]=[CH:58][N:57]=[CH:56][CH:55]=2)[CH:37]=[CH:38][C:39]=1[O:40][CH2:41][C:42]1[CH:51]=[CH:50][C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:43]=1>>[Cl:33][C:34]1[CH:35]=[C:36]([C:52]2[C:53]([C:54]3[CH:59]=[CH:58][N:57]=[CH:56][CH:55]=3)=[CH:30][N:10]([CH3:11])[N:9]=2)[CH:37]=[CH:38][C:39]=1[O:40][CH2:41][C:42]1[CH:51]=[CH:50][C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:43]=1
Reactant: CNN
Reactant: c1ccc2nc(CCc3ccc(-c4[nH]ncc4-c4ccncc4)cc3)ccc2c1
Reactant: O=C(Cc1ccncc1)c1ccc(OCc2ccc3ccccc3n2)c(Cl)c1
Product: Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ccccc4n3)c(Cl)c2)n1

Procedure:
Following the procedure for the preparation of 2-{2-[4-(4-Pyridin-4-yl-2H-pyrazol-3-yl)-phenyl]-ethyl}-quinoline but substituting methyl hydrazine and 1-[3-Chloro-4-(quinolin-2-ylmethoxy)-phenyl]-2-pyridin-4-yl-ethanone provided the title compound. 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=6.2 Hz, 2 H), 8.21 (d, J=8.3 Hz, 1 H), 8.04 (d, J=7.5 Hz, 1H), 7.83 (d, J=8.3 Hz, 1 H), 7.78 (d, J=8.7 Hz, 1 H), 7.72 (m, 1H), 7.56 (m, 3 H), 7.21 (m, 1H), 7.14 (d, J=6.2 Hz, 2 H), 6.97 (d, J=8.7 Hz, 1 H), 5.46 (s, 2H), 3.95 (s, 3H); MS: (M+H m/z=427.1).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH2:9])=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:19](Cl)([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:20]>C1C=CC=CC=1>[C:19]([O:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH2:9])=[CH:6][CH:5]=1)([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:20]
Reactant: C=Cc1ccc(CCO)cc1
Reactant: CCOC(=O)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: C=Cc1ccc(CCOC(=O)C(=O)OCC)cc1
Temperature: 10 °C
Reaction time: 2 h

Procedure:
A 200 ml flask equipped with a stirrer, a thermometer and a dropping funnel was charged with 14.8 g (0.1 mol) of p-hydroxyethylstyrene, 150 ml of benzene and 10.1 g (0.1 mol) of triethylamine and cooled to 10° C. To the mixture was added dropwise with stirring 13.7 g (0.1 mol) of ethoxalyl chloride for one hour at 10° C. to precipitate a hydrochloride of triethylamine (white solid). After mixting at room temperature for 2 hours, 80 g of hexane was added to complete precipitation of the hydrochloride. The hydrochloride is removed by filteration and the resultant filtrate was condensed to obtain the aimed compound. The compound was identified by 1H NMR (360 Mz) and IR. ##STR7##