Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]1[C:11](=[O:42])[CH:12]([CH:15]([OH:41])[C:16]3[N:17]=[CH:18][N:19]([C:22]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:20]=3[CH3:21])[CH2:13][CH2:14][C:6]1=[C:5]2[CH3:43].N1C=CC=CC=1.[C:50](OC(=O)C)(=[O:52])[CH3:51]>ClCCl>[C:50]([O:41][CH:15]([C:16]1[N:17]=[CH:18][N:19]([C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:20]=1[CH3:21])[CH:12]1[C:11](=[O:42])[N:7]2[C:8]3[C:4]([C:5]([CH3:43])=[C:6]2[CH2:14][CH2:13]1)=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)(=[O:52])[CH3:51]
Reactant: Cc1c2n(c3ccc(Cl)cc13)C(=O)C(C(O)c1ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c1C)CC2
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)OC(c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c1C)C1CCc2c(C)c3cc(Cl)ccc3n2C1=O

Procedure:
To a solution of 2-chloro-8,9-dihydro-7-[(hydroxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-10-methylpyrido[1,2-a]indol-6(7H)-one (1.64 g) in dichloromethane (32 ml) were added pyridine (0.83 ml) and acetic anhydride (0.53 ml). The solution was refluxed for 24 hours. After being cooled, the solution was washed with water twice and brine, dried over sodium sulfate, and evaporated, to give 7-[(acetoxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-2-chloro-8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (1.49 g).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:28]1[CH:36]=[C:35]2[C:31]([CH:32]=[CH:33][NH:34]2)=[CH:30][CH:29]=1.[H-].[Na+].[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([S:47](Cl)(=[O:49])=[O:48])=[CH:43][CH:42]=1.O>C(OCC)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:28]1[CH:36]=[C:35]2[C:31]([CH:32]=[CH:33][N:34]2[S:47]([C:44]2[CH:43]=[CH:42][C:41]([O:40][CH3:39])=[CH:46][CH:45]=2)(=[O:49])=[O:48])=[CH:30][CH:29]=1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3-c3ccc4cc[nH]c4c3)n(-c3ccccc3)c(=O)c12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: COc1ccc(S(=O)(=O)n2ccc3ccc(-c4c(N)ncnc4N[C@@H](C)c4nn5ccc(C)c5c(=O)n4-c4ccccc4)cc32)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 42 %

Procedure:
((S)-2-(1-((6-Amino-5-(1H-indol-6-yl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (126 mg, 0.26 mmol) was added to a suspension of sodium hydride (14 mg, 0.37 mmol, 60% dispersion in mineral oil) at 0° C. After 30 min., 4-methoxybenzene-1-sulfonyl chloride was added dropwise. After 10 min. the reaction was let to warm to room temperature. After 1 h the crude was poured over a mixture of ice and water. Ethyl acetate was added and the organic phase was washed with water and brine. After evaporation of the solvent, the residue was purified by flash chromatography using SP1® Purification System (50-100% hexane/Ethyl acetate) to give 75 mg (42% yield). Purity 97%.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:15][C:14](=[O:16])[O:13][C:12]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:11]=2[CH:29]=1.[CH:30]1([C:36]2[CH:41]=[CH:40][C:39]([SH:42])=[CH:38][CH:37]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH:30]1([C:36]2[CH:37]=[CH:38][C:39]([S:42][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]3[CH:8]=[CH:9][C:10]4[NH:15][C:14](=[O:16])[O:13][C:12]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)([CH:17]5[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]5)[C:11]=4[CH:29]=3)=[CH:40][CH:41]=2)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1
Reactant: Sc1ccc(C2CCCCC2)cc1
Reactant: O=C1Nc2ccc(OCCCCCl)cc2C(C2CCCCC2)(C2CCCCC2)O1
Product: O=C1Nc2ccc(OCCCCSc3ccc(C4CCCCC4)cc3)cc2C(C2CCCCC2)(C2CCCCC2)O1

Procedure:
Prepared analogously to Example 1 from 6-(4-chlorobutoxy)-4,4-dicyclohexyl-4H-3,1-benzoxazin-2-one and 4-cyclohexyl-thiophenol.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[C:5](=[O:19])[CH2:6][C:7]([C:10]1[C:18]2[O:17][CH2:16][O:15][C:14]=2[CH:13]=[CH:12][CH:11]=1)([CH3:9])[CH3:8])[CH3:2].[F:21][C:22]([Si](C)(C)C)([F:24])[F:23].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C.CCCCCC>[CH2:1]([O:3][C:4](=[O:20])[C:5]([OH:19])([C:22]([F:24])([F:23])[F:21])[CH2:6][C:7]([C:10]1[C:18]2[O:17][CH2:16][O:15][C:14]=2[CH:13]=[CH:12][CH:11]=1)([CH3:9])[CH3:8])[CH3:2]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: CCOC(=O)C(=O)CC(C)(C)c1cccc2c1OCO2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)C(O)(CC(C)(C)c1cccc2c1OCO2)C(F)(F)F
Yield: 215.6 %

Procedure:
6.1 g (21.91 mmol) of 4-(1,3-benzodioxol-4-yl)-4-methyl-2-oxopentanoic acid ethyl ester, dissolved in 130 ml of tetrahydrofuran, is reacted with 9.5 ml (65.7 mmol) of (trifluoromethyl)trimethylsilane and 4.42 ml of a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran. Carrying out and working up the reaction are carried out as described in Example 3. The crude product that is obtained is purified together with one batch of a similar order of magnitude [9.19 g (33.02 mmol) of 4-(1,3-benzodioxol-4-yl)-4-methyl-2-oxopentanoic acid ethyl ester as a starting material] by chromatography on silica gel (mobile solvent ethyl acetate/hexane). 16.45 g (86%) of the desired product is isolated from the two batches.
Reaction SMILES: I[C:2]1[C:7]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)=[CH:6][CH:5]=[C:4]([CH3:23])[N:3]=1.[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[C:7]([O:8][C:9]3[C:18]4[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=4)[N:12]=[CH:11][CH:10]=3)=[CH:6][CH:5]=[C:4]([CH3:23])[N:3]=2)=[CH:27][CH:26]=1
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: COc1cc2nccc(Oc3ccc(C)nc3I)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(C)nc3-c3ccc(Cl)cc3)c2cc1OC
Temperature: 80 °C
Reaction time: 3 h
Yield: 91.4 %

Procedure:
4-[(2-Iodo-6-methyl-3-pyridyl)oxy]-6,7-dimethoxyquinoline (compound 116) (84 mg), 4-chlorophenylboronic acid (156 mg), and tetrakistriphenylphosphine palladium (12 mg) were dissolved in toluene (1 ml) to prepare a solution. A saturated aqueous sodium hydrogencarbonate solution (1 ml) was added to the solution, and the mixture was stirred at 80° C. for 3 hr. The reaction solution was filtered, the solvent was then removed by distillation under the reduced pressure, and the residue was purified by column chromatography using methanol-chloroform to give the title compound (74 mg, yield 91%).
Reaction SMILES: [C:1](S)(=S)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)O.C1(C)C=CC=CC=1.CC1C=CC2[S:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22](=[O:33])C=2C=1.CC1C=CC2C(=O)C3C(SC=2C=1)=CC=CC=3>S(=O)(=O)(O)O.O>[CH3:1][C:2]1[C:3]2[C:22](=[O:33])[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[S:29][C:5]=2[CH:6]=[CH:7][CH:8]=1
Reactant: Cc1ccc2sc3ccccc3c(=O)c2c1
Reactant: Oc1ccccc1C(=S)S
Agent: Cc1ccc2c(=O)c3ccccc3sc2c1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1cccc2sc3ccccc3c(=O)c12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Dithiosalicylic acid [product of Wako Pure Chemical Industries, Ltd.] (10 parts) was dissolved in sulfuric acid (139 parts), and the solution was stirred at room temperature (about 25° C.) for one hour and then cooled in an ice bath. Toluene (25 parts) was added dropwise in small portions to the cooled solution, while the temperature of the cooled solution was controlled to 20° C. or lower. Thereafter, the temperature was recovered to room temperature (about 25° C.), and the solution was further stirred for two hours. The resulting reaction mixture was added in small portions to water (815 parts), and precipitated yellow solids were filtered. The yellow solids were dissolved in dichloromethane (260 parts). To the resulting solution, water (150 parts) was added, and then 24% KOH aqueous solution (6.7 parts) was added to alkalinize the aqueous phase. After stirring the resulting mixture for one hour, the aqueous phase was removed by a separation operation, and the organic phase was washed with water (130 parts) three times. Then, the organic phase was dried over anhydrous sodium sulfate, and the organic solvent was evaporated under reduced pressure. As a result, 8.7 parts of an intermediate (C122-2-1) was obtained (as yellow solids). The intermediate (C122-2-1) was a mixture of 2-methylthioxanthone and 3-methylthioxanthone.
Reaction SMILES: [C:1]([NH:5][S:6]([C:9]1[S:10][CH:11]=[CH:12][N:13]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.C1(S([Cl:28])(=O)=O)C=CC=CC=1>C(OCC)C.CCOC(C)=O>[C:1]([NH:5][S:6]([C:9]1[S:10][C:11]([Cl:28])=[CH:12][N:13]=1)(=[O:7])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NS(=O)(=O)c1nccs1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: CC(C)(C)NS(=O)(=O)c1ncc(Cl)s1
Temperature: -78 °C
Reaction time: 1 h
Yield: 32.5 %

Procedure:
To a solution of (tert-butyl)(1,3-thiazol-2-ylsulfonyl)amine (0.15 g, 0.7 mmol) in ethyl ether (3 mL) at −78° C. was added a 1.6M solution of n-butyllithium (0.875 mL, 1.4 mmol) in hexanes via syringe under argon. The reaction mixture was stirred at −78° C. for 1 hr, then neat benzenesulfonyl chloride (90 μL, 0.7 mmol) was added. The resulting suspension was stirred at room temp for 2 hr. The reaction was diluted with EtOAc, washed with water and brine, dried, concentrated in vacuo and chromatographed (15% EtOAc/hexane) to give pure desired compound (58 mg, 33%). ES-MS (M+Na)+=277, 279 (Cl), (M−tBu+H)+=199, 201 (Cl).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH:17]([CH3:18])[CH2:16][C:15]3[C:10](=[CH:11][C:12]([C:19]4[CH:20]=[CH:21][C:22]([C:25](O)=[O:26])=[N:23][CH:24]=4)=[CH:13][CH:14]=3)[CH2:9]2)[CH:5]=[C:4]([N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)[N:3]=1.Cl.[NH:36]1[CH2:39][CH2:38][CH2:37]1>>[N:36]1([C:25]([C:22]2[N:23]=[CH:24][C:19]([C:12]3[CH:11]=[C:10]4[C:15]([CH2:16][CH:17]([CH3:18])[N:8]([C:6]5[CH:5]=[C:4]([N:28]6[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]6)[N:3]=[C:2]([NH2:1])[N:7]=5)[CH2:9]4)=[CH:14][CH:13]=3)=[CH:20][CH:21]=2)=[O:26])[CH2:39][CH2:38][CH2:37]1
Reactant: C1CNC1
Reactant: CC1Cc2ccc(-c3ccc(C(=O)O)nc3)cc2CN1c1cc(N2CCN(C)CC2)nc(N)n1
Agent: Cl
Product: CC1Cc2ccc(-c3ccc(C(=O)N4CCC4)nc3)cc2CN1c1cc(N2CCN(C)CC2)nc(N)n1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 50A starting from 5-{2-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl}pyridine-2-carboxylic acid (Example 50A, Step 1) and azetidine hydrochloride (Aldrich, Cat. No. 414336). LCMS (M+H)+: m/z=499.2.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[N:7][CH:6]=[CH:5][N:4]=1.[Na].Cl.[NH2:11][CH2:12][CH2:13][SH:14].Cl>C(O)C>[ClH:1].[NH2:11][CH2:12][CH2:13][S:14][CH2:2][C:3]1[CH:8]=[N:7][CH:6]=[CH:5][N:4]=1
Reactant: NCCS
Reactant: ClCc1cnccn1
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: NCCSCc1cnccn1
Reaction time: 2 h

Procedure:
2-Chloromethylpyrazine (6.4 g.) was added over 20 minutes to a solution freshly prepared from sodium (0.23 g.) in ethanol (50 ml.) to which cysteamine hydrochloride (5.7 g.) had been added gradually at 0° and stirred at this temperature for 2 hours. The suspension finally obtained was stirred at room temperature overnight, acidified with hydrochloric acid (pH 5) and concentrated under reduced pressure. The dry residue was extracted with ethanol and the extracts filtered and concentrated to give the crude product. Extraction with isopropyl alcohol, with the removal of some polymeric material and the addition of ether gave a cream coloured solid (3.5 g.), which was recrystallised from ethanol-ether to furnish 2-[(2-aminoethyl)thiomethyl]pyrazine hydrochloride m.p. 144°-146°.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br/[CH:19]=[CH:20]/[C:21]([F:24])([F:23])[F:22].C(=O)([O-])[O-].[Cs+].[Cs+]>O.CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](/[CH:19]=[CH:20]/[C:21]([F:24])([F:23])[F:22])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: FC(F)(F)/C=C/Br
Reactant: OB(O)c1ccc(OCc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: FC(F)(F)/C=C/c1ccc(OCc2ccccc2)cc1
Temperature: 90 °C
Yield: 74.3 %

Procedure:
A mixture of 4-(benzyloxy)phenylboronic acid (1026 mg, 4.50 mmol, Alfa Aesar), (E)-1-bromo-3,3,3-trifluoroprop-1-ene (262 mg, 1.5 mmol, SynQuest), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (122 mg, 0.15, Combiphos Catalysts, Inc.) and cesium carbonate (2444 mg, 7.50 mmol, Aldrich) in Water (0.5 mL) and DMF (3.0 mL) was heated under microwave conditions (90° C., 20 min). The reaction mixture was diluted with EtOAc and filtered. The filtrate was washed with water and brine, dried (Na2SO4) and concentrated in vacuo. The residual was purified by flash chromatography on silica gel (0 to 100% EtOAc/hexanes) to yield the title compound (310 mg, 74%) as a pale yellow solid.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.Cl[C:12]1[N:20]=[C:19]2[C:15]([N:16]=[C:17]([CH2:22][N:23]3[CH:28]4[CH2:29][CH2:30][CH:24]3[CH2:25][O:26][CH2:27]4)[N:18]2[CH3:21])=[C:14]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[N:13]=1>>[CH3:21][N:18]1[C:17]([CH2:22][N:23]2[CH:24]3[CH2:30][CH2:29][CH:28]2[CH2:27][O:26][CH2:25]3)=[N:16][C:15]2[C:19]1=[N:20][C:12]([N:3]1[C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=[C:2]1[CH3:1])=[N:13][C:14]=2[N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1
Reactant: Cn1c(CN2C3CCC2COC3)nc2c(N3CCOCC3)nc(Cl)nc21
Reactant: Cc1nc2ccccc2[nH]1
Product: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3C4CCC3COC4)n(C)c2n1

Procedure:
Following General Procedure I for Buchwald coupling, 2-methylbenzimidazole and 8-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-3-oxa-8-aza-bicyclo[3.2.1]octane were reacted to give 380. LCMS m/z: 475.2 (MH+)
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[S:6][C@@H:5]2[C@H:7]([NH:10]C(CC3C=CC=CC=3)=O)[C:8](=[O:9])[N:4]2[C@H:3]1[C:20]([O-:22])=[O:21].[K+].CC1(C)S[C@@H]2[C@H](NC(COC3C=CC=CC=3)=O)C(=O)N2[C@H:27]1[C:45]([OH:47])=[O:46].CC1(C)S[C@@H]2[C@H](NC(CC3C=CC=CC=3)=O)C(=O)N2[C@H]1C(O)=O.CC(OCC1CS[C@@H]2[C@H](NC(CCC[C@@H](N)C(O)=O)=O)C(=O)N2C=1C(O)=O)=O.O(CC(NC1C(=O)N2C(C(O)=O)=C(C)CS[C@H]12)=O)C1C=CC=CC=1.ClCC(NC1C(=O)N2C(C(O)=O)=C(C)CS[C@H]12)=O.C1(CC(NC2C(=O)N3C(C(O)=O)=C(C)CS[C@H]23)=O)C=CC=CC=1.C(NC1C(=O)N2C(C(O)=O)=C(C)CS[C@H]12)C1C=CC=CC=1>>[CH3:27][C:45]([O:47][CH2:23][C:2]1[CH2:1][S:6][C@@H:5]2[C@H:7]([NH2:10])[C:8](=[O:9])[N:4]2[C:3]=1[C:20]([OH:22])=[O:21])=[O:46]
Reactant: CC1(C)S[C@@H]2[C@H](NC(=O)COc3ccccc3)C(=O)N2[C@H]1C(=O)O
Reactant: CC1(C)S[C@@H]2[C@H](NC(=O)Cc3ccccc3)C(=O)N2[C@H]1C(=O)[O-]
Agent: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(=O)O)[C@H]2SC1
Agent: CC1(C)S[C@@H]2[C@H](NC(=O)Cc3ccccc3)C(=O)N2[C@H]1C(=O)O
Agent: CC1=C(C(=O)O)N2C(=O)C(NC(=O)CCl)[C@H]2SC1
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1

Procedure:
In an iminohalide/iminoether reaction for converting amido groups to amino groups present on a penicillin or cephalosporin selected from the group consisting of penicillin V, penicillin G, cephalosporin C, 6-chloracetamidopenicillanic acid, N-[2,2-diethoxycarbonylvinyl(1)]cephalosporin C, N-[2-nitro-2-carbethoxyvinyl(1)]cephalosporin C, 7-[N-(2,2-diethoxycarbonyl)vinyl]adipinoylamino-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, 7-[N-(2,2-diethoxycarbonyl)vinyl]adipinamido-3-[(2,5-dihydro-6-hydroxy-5-oxo-2-methyl-1,2,4-triazin-3-yl)thiomethyl]ceph-3-em-4-carboxylic acid, 7-[N-(2,2-diethoxycarbonyl)vinyl]adipinamido-3-[(4,5-dihydro-6-hydroxy-5-oxo-4-methyl-1,2,4-triazin-3-yl)thiomethyl]ceph-3-em-4-carboxylic acid, 3-desacetoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)thiocephalosporin C, 3-desacetoxy-3-(2,5-dihydro-6-hydroxy-5-oxo-2-methyl-1,2,4-triazin-3-yl)thiocephalosporin C, 3-desacetoxy-3-(4,5-dihydro-6-hydroxy-5-oxo-4-methyl-1,2,4-triazin-3-yl)thiocephalosporin C, 7-phenoxyacetamido-3-methylceph-3-em-4-carboxylic acid, 7-chloracetamido-3-methylceph-3-em-4-carboxylic acid, 7-phenylacetamido-3-methylceph-3-em-4-carboxylic acid, N-ethoxycarbonylcephalosporin C, N-methoxycarbonylcephalosporin C, N-isobutoxycarbonylcephalosporin C, N-iso-propyloxycarbonylcephalosporin C, N-(N'-butylcarbamoyl)cephalosporin C, N-(N'-phenylcarbamoyl)cephalosporin C, N-chloracetylcephalosporin C, or 7-benzylamino-3-methylceph-3-em-4-carboxylic acid; to prepare an amino-compound of formula I, ##STR11## in which X is a group of formula II or IIa, ##STR12## in which R1 is methyl, methoxy, halogen, acetoxymethyl or --CH2 --S-heterocyclic, and esters and salts thereof,
Reaction SMILES: [CH3:1][C@H:2]1[C:6]([CH3:8])([CH3:7])[O:5][C:4](=[O:9])[NH:3]1.C([Li])CCC.[C:15](Cl)(=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17]>O1CCCC1>[CH3:17][C:16]([CH3:19])([CH3:18])[C:15]([N:3]1[C@@H:2]([CH3:1])[C:6]([CH3:8])([CH3:7])[O:5][C:4]1=[O:9])=[O:20]
Reactant: CC(C)(C)C(=O)Cl
Reactant: C[C@@H]1NC(=O)OC1(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[C@@H]1N(C(=O)C(C)(C)C)C(=O)OC1(C)C
Yield: 92.4 %

Procedure:
Reaction of the auxiliary (5) (0.180 g, 1.40 mmol) in solution in tetrahydrofuran (3 ml) at -78° C. with butyllithium (1.4M, 1 ml, 1.41 mmol) and pivaloyl chloride (0.190 ml, 1.55 mmol) for 30 minutes and then at room temperature for 1 hour with work-up and recrystallisation at ca -10° C. from 60-80 petroleum ether furnished the title compound (16) as a solid (0.276 g, 93%); νmax (CH2Cl2) 1683 and 1775 cm-1 ; [α]D24 (c 1 in CHCl3)=+51.3; (Found: C, 62.25; H, 9.09; N, 6.45. C11H19NO3 requires C, 61.95; H, 8.98; N, 6.57%); δH (CDCl3 ; 300 MHz) 1.20 (3H, d, J=6.5, CH3CH), 1.31 (9H, s, C(CH3)3), 1.33 (3H, s, C(CH3)2), 1.37 (3H, s, C(CH3)2), 4.11 (1H, q, J=6.5, CHCH3) ; δC (125 MHz; CDCl3) 14.33 (CH3), 21.41 (CH3), 26.31 (CH3), 27.22 (CH3), 41.60 (CH3), 60.92 (CH), 81.01 (C), 151.75 (CO), 179.08 (CO); m/z (CI+, NH3) 214 (M+ +1).
Reaction SMILES: [Na].Cl[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1.[O-2].[Ca+2]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN1CCCC1=O>[C:7]([C:6]1[CH:9]=[CH:10][C:3]([C:3]2[CH:10]=[CH:9][C:6]([CH3:7])=[CH:5][CH:4]=2)=[CH:4][CH:5]=1)#[N:8]
Reactant: N#Cc1ccc(Cl)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: [Ca+2]
Solvent: CN1CCCC1=O
Product: Cc1ccc(-c2ccc(C#N)cc2)cc1
Yield: 49 %

Procedure:
3.56 g (20 mmol) of sodium p-tolunesulfinate, 2.75 g (20 mmol) of p-chlorobenzonitrile, 0.0225 g (0.1 mmol) of palladium acetate, 0.0478 g (0.12 mmol) of 1,2-bis(diphenylphosphino) ethane, 11.2 g (200 mmol) of calcium oxide and 60 ml of N-methyl-2-pyrrolidone were placed in a 100 ml round bottom flask and reacted at 150° C. in a nitrogen gas stream for 6 hours. After the completion of the reaction, the reaction mixture solution was analyzed by means of high performance liquid chromatography. The analysis showed that 4.9 mmol (yield 25%) of 4'-cyano-4-methyl-biphenyl was formed in the reaction mixture solution.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[N:19]([S:20]([CH3:23])(=[O:22])=[O:21])[CH2:18][CH2:17][C:16]([C:24](O)=[O:25])=[CH:15][C:14]=3[CH:27]=2)=[CH:6][CH:5]=1)[CH3:2].S(Cl)(Cl)=O.[CH3:32][N:33]([CH:35]=O)[CH3:34]>>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[N:19]([S:20]([CH3:23])(=[O:21])=[O:22])[CH2:18][CH2:17][C:16]([C:24]([NH:19][C:13]4[CH:14]=[CH:27][C:10]([CH2:35][N:33]([CH3:32])[CH:34]5[CH2:5][CH2:4][O:3][CH2:1][CH2:2]5)=[CH:11][CH:12]=4)=[O:25])=[CH:15][C:14]=3[CH:27]=2)=[CH:8][CH:9]=1)[CH3:2]
Reactant: CN(C)C=O
Reactant: CCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3S(C)(=O)=O)cc1
Solvent: O=S(Cl)Cl
Product: CCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3S(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In DMF (12 ml) was suspended 7-(4-ethoxyphenyl)-1-methanesulfonyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.13 g). To the suspension was added, under ice-cooling, thionyl chloride (0.04 ml) and DMF (catalytic amount), and the mixture was stirred at room temperature for 2 hours. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in THF (15 ml). The solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.08 g) and triethylamine (0.14 ml) in THF (5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature overnight. Under reduced pressure, the solvent was evaporated. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated to give crude crystals, which were recrystallized from ethyl acetate/hexane to give 7-(4-ethoxyphenyl)-1-methanesulfonyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl]amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (0.16 g) as colorless crystals.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:9][SiH:10]([Cl:12])[Cl:11]>[Pt].C1(C)C=CC=CC=1>[CH2:1]([Si:10]([Cl:12])([Cl:11])[Cl:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: Cl[SiH](Cl)Cl
Agent: [Pt]
Solvent: Cc1ccccc1
Product: Cl[Si](Cl)(Cl)CCc1ccccc1
Yield: 39 %

Procedure:
Reaction between styrene and trichlorosilane with platinum catalyst (no substance acting as auxiliary catalyst). 518 mg Styrene and 694 mg trichlorosilane were introduced into a glass tube, and 2.5 mg of a toluene solution of a 0-valent platinum complex of divinylsiloxane (0.04 wt % platinum content) were added. The tube was sealed with Teflon tape and a rubber septum and then placed in a 50° C. oil bath where it was heated for 30 minutes. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of 93% and a phenethyltrichlorosilane yield of 39%. The ratio between the phenethyltrichlorosilane and the (α-methylbenzyl)trichlorosilane was 5.5:1.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:8][N:7]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]4[C:31](=[CH:32][CH:33]=3)[O:30][C:21]3=[N:22][C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=5[CH:29]=[C:20]3[C:19]4=[O:34])=[CH:12][CH:11]=2)[CH2:6]1)=[O:4].COC(C1CN(CC2C=CC(OCC3C4C=C(Cl)C=CC=4OC=3)=CC=2)C1)=O>>[O:34]=[C:19]1[C:20]2[C:21](=[N:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=3[CH:29]=2)[O:30][C:31]2[C:18]1=[CH:17][C:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][N:7]3[CH2:8][CH:5]([C:3]([OH:4])=[O:2])[CH2:6]3)=[CH:11][CH:12]=1)=[CH:33][CH:32]=2
Reactant: COC(=O)C1CN(Cc2ccc(-c3ccc4oc5nc6ccccc6cc5c(=O)c4c3)cc2)C1
Agent: COC(=O)C1CN(Cc2ccc(OCc3coc4ccc(Cl)cc34)cc2)C1
Product: O=C(O)C1CN(Cc2ccc(-c3ccc4oc5nc6ccccc6cc5c(=O)c4c3)cc2)C1
Yield: 50 %

Procedure:
When the product of Step D was substituted for methyl-1-(4-((5-chlorobenzofuran-3-yl)methoxy)benzyl)azetidine-3-carboxylate in Example 25, Step E, the similar procedure afforded the title compound in 50% yield, as yellow solid. 1H-NMR (CDCl+CD3OD) 9.25 (broad s, 1H); 8.44 (m, 2H); 7.76-7.54 (m, 5H); 4.31-4.07 (m, 4H); 4.27-3.95 (m, 2H).