Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5](=[O:7])[C:4](=[CH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:16][C:17]4[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[CH:20][C:18]=4[N:19]=3)=[CH:11][CH:10]=2)[S:3]1.[Mg].O.Cl>CO>[O:1]=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:19][C:18]4[CH:20]=[C:21]([Cl:25])[C:22]([Cl:24])=[CH:23][C:17]=4[N:16]=3)=[CH:11][CH:10]=2)[S:3]1
Reactant: O=C1NC(=O)C(=Cc2ccc(-c3nc4cc(Cl)c(Cl)cc4[nH]3)cc2)S1
Agent: Cl
Agent: [Mg]
Solvent: O
Solvent: CO
Product: O=C1NC(=O)C(Cc2ccc(-c3nc4cc(Cl)c(Cl)cc4[nH]3)cc2)S1
Temperature: 25 °C
Reaction time: 40 h
Yield: 19.9 %

Procedure:
A suspension of 2-[4-[(2,4-dioxothiazolidin-5-ylidene)methyl]phenyl]-5,6-dichlorobenzimidazole (100 mg, 0.256 mmol) and magnesium turnings (125 mg, 5.1 mmol) in methanol (20 mL) was stirred for 40 h at room temperature. Water and hydrochloric acid (1 mol/L) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed washed with water and brine, dried on anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (10:1 chloroform/methanol) and triturated with ethanol to give 2-[4-[(2,4-dioxothiazolidin-5-yl)methyl]phenyl]-5,6-dichlorobenzimidazole (20 mg, 20%).
Reaction SMILES: [CH3:1][Mg]I.[C:4]([CH:6]([OH:21])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13](=O)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]=1)#[CH:5].S(=O)(=O)(O)O.S([O-])([O-])(=O)=S.[Na+].[Na+]>CCOCC.O1CCCC1>[C:4]([CH:6]([OH:21])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH2:1])[CH:8]=1)#[CH:5]
Reactant: C#CC(O)c1cccc(C(=O)c2ccccc2)c1
Reactant: C[Mg]I
Agent: O=S(=O)(O)O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: C#CC(O)c1cccc(C(=C)c2ccccc2)c1
Temperature: 20 °C
Reaction time: 0.17 h

Procedure:
To methyl magnesium iodide (1.4 g) in ether (25 cm3) was added a solution of α-ethynyl-3-benzoylbenzyl alcohol (0.5 g) in ether (10 cm3) with stirring during 10 minutes at 20° C., then the mixture refluxed for 5 minutes and poured onto a mixture of 40% sulphuric acid (40 cm3), sodium thiosulphate (3 g) and tetrahydrofuran (20 cm3). After 16 hours at 20° C., this mixture was extracted with ether (3×150 cm3), washed with sodium thiosulphate solution (2M), saturated sodium chloride, dried and finally evaporated to give the title product, yield 0.48 g (96%) nD20 1.5942.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH:10]([F:12])[F:11])[CH:5]=[CH:4][C:3]=1[C:13](=O)[CH3:14].[CH3:16][C:17]([S@:20]([NH2:22])=[O:21])([CH3:19])[CH3:18]>>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH:10]([F:12])[F:11])[CH:5]=[CH:4][C:3]=1[CH:13]([NH:22][S@@:20]([C:17]([CH3:19])([CH3:18])[CH3:16])=[O:21])[CH3:14]
Reactant: CC(C)(C)[S@](N)=O
Reactant: CC(=O)c1ccc(OCC(F)F)cc1Cl
Product: CC(N[S@](=O)C(C)(C)C)c1ccc(OCC(F)F)cc1Cl
Yield: 55 %

Procedure:
The title compound is prepared in 55% yield (990 mg, clear colorless oil) from 1-(2-chloro-4-(2,2-difluoroethoxy)phenyl)ethanone (1.2 g, 5.2 mmol, Step-4) and (R)-2-methylpropane-2-sulfinamide by the similar manner in Step-4 of Amine-1.
Reaction SMILES: I[C:2]1[N:3]=[CH:4][N:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:9](=[O:16])[N:8]3[CH2:17][CH2:18][CH2:19][C@H:7]3[C:6]=12.[CH3:20][C:21]([OH:25])([C:23]#[CH:24])[CH3:22]>C(NCC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:25][C:21]([CH3:22])([CH3:20])[C:23]#[C:24][C:2]1[N:3]=[CH:4][N:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:9](=[O:16])[N:8]3[CH2:17][CH2:18][CH2:19][C@H:7]3[C:6]=12
Reactant: C#CC(C)(C)O
Reactant: O=C1c2ccccc2-n2cnc(I)c2[C@@H]2CCCN12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCNCC
Product: CC(C)(O)C#Cc1ncn2c1[C@@H]1CCCN1C(=O)c1ccccc1-2

Procedure:
3.65 g (10 mmol) of (S)-11,12,13,13a-tetrahydro-1-iodo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one was heated to boiling under reflux for 1.5 hours with 1.26 g (15 mmol) of 2-methyl-3-butyn-2-ol, 70 mg of bis-(triphenylphosphine)-palladium(II) dichloride and 20 mg of copper(I) iodide in 30 ml of diethylamine. The reaction mixture was evaporated and the residue was chromatographed on silica gel while eluting with ethyl acetate. By recrystallization of the crude product from methanol and water there was obtained (S)-11,12,13,13a-tetrahydro-1-(3-hydroxy-3-methyl-1-butynyl)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 128°.
Reaction SMILES: [CH:1]#[N:2].[CH:3](=[N:10][C:11]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:13][CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C(O)C>[C:1]([CH:3]([NH:10][C:11]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:13]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)#[N:2]
Reactant: C#N
Reactant: CCOC(=O)C1(N=Cc2ccccc2)CC1
Solvent: CCO
Product: CCOC(=O)C1(NC(C#N)c2ccccc2)CC1
Temperature: 25 °C
Yield: 100 %

Procedure:
Liquid HCN (2.4 ml; 0.062 M) was added to a solution of ethyl N-benzylidene-1-aminocyclopropane carboxylate (5.61 g, obtained as described in Example 1) in ethanol (25 ml) at room temperature. The solution was stirred at room temperature for forty eight hours; subsequently the excess ethanol was evaporated. The desired product was obtained in a yield of 100% (6.3 g).
Reaction SMILES: [NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3].CC(C)([O-])C.[K+].Br[CH2:19][CH2:20][CH2:21][Cl:22].Cl>CN(C)C=O.C(OCC)(=O)C>[Cl:22][CH2:21][CH2:20][CH2:19][N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3]
Reactant: O=C1Nc2ccccc2C1=O
Reactant: ClCCCBr
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C1C(=O)N(CCCCl)c2ccccc21
Temperature: 5 °C
Reaction time: 0.17 h
Yield: 88.1 %

Procedure:
To a solution of isatin (14.7 g) in N,N-dimethylformamide (150 ml) was added potassium tert-butoxide (13.95 g) under cooling at 5° C., and the mixture was stirred vigorously for about 10 minutes. To the mixture was added dropwise a solution of 1-bromo-3-chloropropane (17.35 g) in N,N-dimethylformamide (50 ml) over a period of about 30 minutes at ambient temperature, and the mixture was stirred for 5 hours at the same temperature. The reaction mixture was poured into a mixture of ethyl acetate (300 ml) and ice-water (500 ml) containing 50 ml of 10% hydrochloric acid. After separation of the ethyl acetate layer, the aqueous layer was further extracted with ethyl acetate. The ethyl acetate layers were combined, washed with water, dried over anhydrous magnesium sulfate and then evaporated. The residue was subjected to column chromatography on silica gel (100 g) using chloroform as an eluent. The fractions containing the object compound were collected, and concentrated to give crystals of 1-(3-chloropropyl)isatin (19.68 g), mp. 72°-76.5° C.
Reaction SMILES: [CH2:1]([CH:9]1[CH2:14][CH2:13][CH:12]([NH2:15])[CH2:11][CH2:10]1)[CH:2]1[CH2:7][CH2:6][CH:5]([NH2:8])[CH2:4][CH2:3]1.[C:16]([OH:21])(=O)[CH:17]([CH3:19])[OH:18]>O>[CH2:1]([CH:2]1[CH2:3][CH2:4][CH:5]([NH:8][C:16](=[O:21])[CH:17]([OH:18])[CH3:19])[CH2:6][CH2:7]1)[CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:16](=[O:21])[CH:17]([OH:18])[CH3:19])[CH2:11][CH2:10]1
Reactant: CC(O)C(=O)O
Reactant: NC1CCC(CC2CCC(N)CC2)CC1
Solvent: O
Product: CC(O)C(=O)NC1CCC(CC2CCC(NC(=O)C(C)O)CC2)CC1
Reaction time: 4 h

Procedure:
Molten 4,4'-methylenebis(cyclohexylamine) (224.0 g, 1.065 moles) was placed in a 1 liter round bottom flask and 85% lactic acid (225.5 g, 2.13 moles) added slowly through an addition funnel with stirring and cooling. The resultant liquid was then heated in an oil bath to 190° C. whereupon distillation of water occurred. Heating was continued at 190° C. for 4 hours after which time distillation of water subsided and the liquid was poured into a Pyrex baking dish. Upon cooling the product solidified into a clear, amber colored glass. The solid was broken up and recrystallized twice from tetrahydrofuran containing 10% methanol to give lustrous, white flakes; m.p. 195°-199° C.; infrared (Nujol), 1640 cm-1, 3300 cm-1 ; proton nuclear magnetic resonance (DMSO-d6 /TMS, 100 MHz), δ0.6-1.5 (complex multiplet with doublet superimposed at δ1.15, 18 protons), δ1.5-1.8 (doublet, 8 protons), δ3.50 (broad singlet, 2 protons), δ3.7-4.1 (multiplet, 2 protons), δ5.35 (doublet, 2 protons), δ7.30 (doublet, 2 protons).
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][O:6][C@@H:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:4][CH2:3]1.[H-].[Na+].[Na].[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Cl>>[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][O:1][C@H:2]1[CH2:3][O:4][C@@H:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:6][CH2:7]1
Reactant: O[C@H]1CO[C@@H](c2ccccc2)OC1
Reactant: Fc1ccccc1CCl
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Product: Fc1ccccc1CO[C@H]1CO[C@@H](c2ccccc2)OC1

Procedure:
Using the method of Example 8, cis-5-hydroxy-2-phenyl-1,3-dioxane (8.4 g, 0.047 mole) was reacted with sodium hydride (2.0 g of 61%, 0.047 mole). The reactant sodium salt was reacted with 2-fluorobenzyl chloride (7.2 g, 0.05 mole) to give, after recrystallization from benzene-ligroin, 2.8 g of white solid, m.p. 65°-67° C, and on further recrystallization, a solid, m.p. 70°-71° C. Analysis by VPC indicated the product to be 90% cis-5-(2-fluorobenzyloxy)-2-phenyl-1,3-dioxane.
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[OH-].[K+].[CH3:13]I>CC(C)=O.C(OCC)(=O)C>[CH3:13][N:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[NH2:1]
Reactant: CI
Reactant: Nc1nc2ccccc2[nH]1
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: Cn1c(N)nc2ccccc21
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of 2-aminobenzimidazole (3.0 g, 0.0225 mol) in acetone (30 ml) was added KOH (6.32 g, 0.112 mol) followed by methyl iodide (3.51 g, 0.025 mol) and stirred at room temperature for 10 min. The reaction mixture was diluted with ethyl acetate and the organic layer washed with water, brine and dried over anhydrous Na2SO4 to afford crude residue which was column purified to yield the desired product: 1H NMR (300 MHz, DMSO-d6) δ 3.47 (s, 3H), 6.34 (br s, 2H), 6.82-6.92 (m, 2H), 7.06-7.09 (m, 2H); ESI-MS (m/z) 148.49 (M+H)+.
Reaction SMILES: [CH:1]([N:5]1[CH:10]=[C:9]([Cl:11])[N:8]=[C:7](Cl)[C:6]1=[O:13])([CH2:3][CH3:4])[CH3:2].Cl.[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([CH3:26])[CH:25]=1)[NH:22][CH2:21][CH2:20]2>>[Cl:11][C:9]1[N:8]=[C:7]([N:22]2[C:23]3[C:19](=[CH:18][C:17]([O:16][CH3:15])=[CH:25][C:24]=3[CH3:26])[CH2:20][CH2:21]2)[C:6](=[O:13])[N:5]([CH:1]([CH3:2])[CH2:3][CH3:4])[CH:10]=1
Reactant: CCC(C)n1cc(Cl)nc(Cl)c1=O
Reactant: COc1cc(C)c2c(c1)CCN2
Agent: Cl
Product: CCC(C)n1cc(Cl)nc(N2CCc3cc(OC)cc(C)c32)c1=O

Procedure:
Prepared in a similar fashion as described for Example 413 using 1-sec-butyl-3,5-dichloro-2(1H)-pyrazinone and 5-methoxy-7-methylindoline hydrochloride as the starting materials. mp 176-178° C.; 1H NMR (300 MHz, CDCl3): δ 6.70 (s, 1H), 6.66 (d, J=2.2 Hz, 1H), 6.57 (d, J=2.2 Hz, 1 3H), 4.98-4.91 (m, 1 H), 4.38 (t, J=7.7 Hz, 2 H), 3.77 (s, 3 H), 3.02 (t, J=7.7 Hz, 2 H), 2.04 (s, 3 H), 1.74-1.64 (m, 2 H), 1.33 (d, J=6.9 Hz, 3 H), 0.90 (t, J=7.5 Hz, 3 H); HRMS (ESI) calcd for C18H23N3O2Cl (M+H)+: 348.1479; found m/z 348.1490.
Reaction SMILES: Cl.[NH2:2][OH:3].O=[C:5]([C:11]1[N:12]=[CH:13][S:14][CH:15]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7]>C(O)C>[OH:3][N:2]=[C:5]([C:11]1[N:12]=[CH:13][S:14][CH:15]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: CCOC(=O)C(=O)c1cscn1
Reactant: NO
Agent: Cl
Solvent: CCO
Product: CCOC(=O)C(=NO)c1cscn1
Reaction time: 3 h

Procedure:
Hydroxylamine hydrochloride (1.37 g) was added to a stirred solution of ethyl 2-oxo-2-(4-thiazolyl)acetate (2.54 g) in ethanol (50 ml). The mixture was stirred for 3 h, the solvent was evaporated and the residue partitioned between ethyl acetate and sodium bicarbonate solution. The organic phase was washed with brine, dried over magnesium sulphate and evaporated. The residue was recrystallised from ethyl acetate to give the title oxime as a single isomer (1.315 g), m.p. 171-175° C.
Reaction SMILES: [C:1]([O:5][C:6]([CH2:8][NH:9][C:10]1[CH:11]=[C:12]([C:16]2[N:21]=[CH:20][C:19]([CH:22]=[C:23]([O:29][CH2:30][CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:18][CH:17]=2)[CH:13]=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>O1CCCC1.[Pd]>[C:1]([O:5][C:6]([CH2:8][NH:9][C:10]1[CH:11]=[C:12]([C:16]2[N:21]=[CH:20][C:19]([CH2:22][CH:23]([O:29][CH2:30][CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:18][CH:17]=2)[CH:13]=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: [H][H]
Reactant: CCOC(=O)C(=Cc1ccc(-c2cccc(NCC(=O)OC(C)(C)C)c2)nc1)OCC
Agent: [Pd]
Solvent: C1CCOC1
Product: CCOC(=O)C(Cc1ccc(-c2cccc(NCC(=O)OC(C)(C)C)c2)nc1)OCC
Yield: 51.3 %

Procedure:
A solution of 0.2 g (0.5 mmol) of ethyl 3-{6-[3-(tert-butoxycarbonylmethylamino)phenyl]pyrid-3-yl}-2-ethoxyacrylate in 10 ml of tetrahydrofuran is degassed and 0.02 g (10% by mass) of 10% Pd/C is added. After reaction for 5 hours under an atmospheric pressure of hydrogen, the reaction medium is stirred under 3 atm of hydrogen for 24 hours. After filtration through Celite and evaporation of the filtrate, 0.11 g (55%) of ethyl 3-{6-[3-(tert-butoxycarbonylmethylamino)phenyl]pyrid-3-yl}-2-ethoxypropanoate is obtained.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:25]=[CH:24][C:9]2[N:10]=[C:11]([NH:14][C@H:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)[O:12][CH2:13][C:8]=2[CH:7]=1)=[O:4].[NH:26]1[CH2:31][CH2:30][S:29](=[O:33])(=[O:32])[CH2:28][CH2:27]1>C(#N)C>[O:32]=[S:29]1(=[O:33])[CH2:30][CH2:31][N:26]([CH2:2][C:3]([NH:5][C:6]2[CH:25]=[CH:24][C:9]3[N:10]=[C:11]([NH:14][C@H:15]4[C:23]5[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=5)[CH2:17][CH2:16]4)[O:12][CH2:13][C:8]=3[CH:7]=2)=[O:4])[CH2:27][CH2:28]1
Reactant: O=C(CCl)Nc1ccc2c(c1)COC(N[C@@H]1CCc3ccccc31)=N2
Reactant: O=S1(=O)CCNCC1
Solvent: CC#N
Product: O=C(CN1CCS(=O)(=O)CC1)Nc1ccc2c(c1)COC(N[C@@H]1CCc3ccccc31)=N2
Yield: 11.7 %

Procedure:
Prepared from 2-chloro-N-[2-((R)-indan-1-ylamino)-4H-benzo[d][1,3]oxazin-6-yl]-acetamide (Example 3 step A) (100 mg, 0.281 mmol) and thiomorpholine 1,1 dioxide (190 mg, 1.405 mmol) in acetonitrile (1 ml) according to the procedure described for Example 3 step B. Obtained the title compound as a white solid (15 mg, 12%), MS (ISP) m/e=455.3 [(M+H)+].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(N(CC)CC)C.[CH:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[S:40][CH:41]([C:45](O)=[O:46])[C:42](O)=[O:43])([CH3:33])[CH3:32]>C(Cl)Cl>[OH:46][C:45]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[O:11][C:42](=[O:43])[C:41]=1[S:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[CH:31]([CH3:33])[CH3:32]
Reactant: CC(C)c1ccccc1SC(C(=O)O)C(=O)O
Reactant: COc1ccc(C(C)=O)cc1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(-c2cc(O)c(Sc3ccccc3C(C)C)c(=O)o2)cc1

Procedure:
The title compound was prepared by Method A using 4'-methoxyacetophenone (2.26 g, 15.1 mmol), trimethylsilyl triflate (3.5 mL, 18.1 mmol), triethylamine (4.26 mL, 30.6 mmol), methylene chloride (30 mL), and diethyl ester of [(2-isopropylphenyl)thio]propanedioic acid (3.11 g, 10.0 mmol) m.p. 221°-223° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.25 (d, 6H), 3.40 (m, 1H), 3.85 (s, 3H), 6.78 (s, 1H), 6.92 (m, 1H), 7.10 (m, 4H), 7.27 (m, 1H), 7.81 (d, 2H), 12.38 (brs, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:10]3[CH:19]=[C:20]([S:23][CH3:24])[CH:21]=[CH:22][C:9]=3[S:8][C:7]=2[CH:25]=1.Cl[CH2:27][C:28]#[C:29][CH2:30][OH:31]>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH:11]([N:13]3[CH2:14][CH2:15][N:16]([CH2:27][C:28]#[C:29][CH2:30][OH:31])[CH2:17][CH2:18]3)[C:10]3[CH:19]=[C:20]([S:23][CH3:24])[CH:21]=[CH:22][C:9]=3[S:8][C:7]=2[CH:25]=1
Reactant: COc1ccc2c(c1)Sc1ccc(SC)cc1C(N1CCNCC1)C2
Reactant: OCC#CCCl
Product: COc1ccc2c(c1)Sc1ccc(SC)cc1C(N1CCN(CC#CCO)CC1)C2

Procedure:
In a manner analogous to that described in Example 5, from 1-[10,11-dihydro-3-methoxy-8-methylthio-dibenzo[b,f]thiepin-10-yl]-piperazine and 4-chloro-2-butyn-1-ol there is obtained 4-{4-[10,11-dihydro-3-methoxy-8-methylthio-dibenzo-[b,f]thiepin-10-yl]-1-piperazinyl}-2-butyn-1-ol, the dihydrochloride of which melts at 208°-210° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C:11]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][CH:34]=1>>[CH3:31][O:32][C:33]1[CH:34]=[CH:35][C:36]([S:39]([NH:1][C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([O:21][CH2:22][CH2:23][O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)[C:11]=2[O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[C:5]([O:7][CH3:8])=[O:6])(=[O:41])=[O:40])=[CH:37][CH:38]=1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: COC(=O)c1cc(N)c(Oc2cccc(OC)c2)c(OCCOC2CCCCO2)c1
Product: COC(=O)c1cc(NS(=O)(=O)c2ccc(OC)cc2)c(Oc2cccc(OC)c2)c(OCCOC2CCCCO2)c1

Procedure:
Analogously to Example 86, by condensing methyl 3-amino-4-(3-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate with 4-methoxybenzenesulphonyl chloride there was obtained methyl 3-(4-methoxy-benzenesulphonyl-amino)-4-(3-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate and therefrom by treatment with 5.5M HCl there was obtained methyl 3-(2-hydroxy-ethoxy)-5-(4-methoxy-benzenesulphonylamino)-4-(3-methoxy-phenoxy)-benzoate.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:21][C:22](=[O:27])[CH2:23][C:24](=O)[CH3:25])[CH:5]=[CH:6][C:7]=1[N:8]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[NH3:28]>CO>[NH2:28]/[C:24](/[CH3:25])=[CH:23]\[C:22]([NH:21][C:4]1[CH:5]=[CH:6][C:7]([N:8]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[C:2]([Br:1])[CH:3]=1)=[O:27]
Reactant: N
Reactant: CCCCCCN(CCCCCC)c1ccc(NC(=O)CC(C)=O)cc1Br
Solvent: CO
Product: CCCCCCN(CCCCCC)c1ccc(NC(=O)/C=C(/C)N)cc1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
A mixture of N-(3-bromo-4-(dihexylamino)phenyl)-3-oxobutanamide (5.10 g, 11.6 mmol), MeOH (60 mL) and ammonia (60 mL) was stirred at rt overnight. The mixture was then concentrated in vacuo to give the title compound as black oil (5.10 g, 100%).
Reaction SMILES: [O:1]1CCO[CH:2]1[C:6]1[S:7][C:8]([C:11]([OH:18])([CH3:17])[CH:12]([O:15][CH3:16])[O:13][CH3:14])=[CH:9][N:10]=1.Cl.C(=O)([O-])O.[Na+]>CC(C)=O>[OH:18][C:11]([C:8]1[S:7][C:6]([CH:2]=[O:1])=[N:10][CH:9]=1)([CH3:17])[CH:12]([O:13][CH3:14])[O:15][CH3:16]
Reactant: COC(OC)C(C)(O)c1cnc(C2OCCO2)s1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Product: COC(OC)C(C)(O)c1cnc(C=O)s1
Temperature: 60 °C
Reaction time: 8 h
Yield: 70.8 %

Procedure:
A mixture of 2-[2-(1,3-dioxolan-2-yl)-1,3-thiazol-5-yl]-1,1-dimethoxypropan-2-ol (1.58 g), 1M hydrochloric acid (5 ml) and acetone (15 mL) was stirred overnight at 60° C. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography, and the title compound (0.94 g, yield 71%) was obtained as colorless crystals from a fraction eluted with ethyl acetate-hexane (4:1, volume ratio). melting point 98-99° C.
Reaction SMILES: O[CH:2]([CH:7]1[CH2:11][CH2:10][CH2:9][C:8]1=[O:12])[CH2:3][CH2:4][CH2:5][CH3:6].II.C1(C)C(C)=CC=CC=1>O>[CH2:2]([C:7]1[C:8](=[O:12])[CH2:9][CH2:10][CH:11]=1)[CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCC(O)C1CCCC1=O
Agent: II
Solvent: Cc1ccccc1C
Solvent: O
Product: CCCCCC1=CCCC1=O
Yield: 97.3 %

Procedure:
In a 100 ml four-neck flask fitted with a thermometer, a reflux condenser and a stirrer were placed 2-(1-hydroxypentyl)cyclopentanone (20 g) synthesized in Reference Example 1, iodine (0.01 g) and xylene (10 ml), and water was removed under refluxing, followed by 2 hours of the reaction at 170° C. The reaction mixture was washed with water and the layers were separated from each other. Further, the resulting organic layer was washed with saturated brine and separated. The organic layer was evaporated on a rotary evaporator under reduced pressure to recover xylene, whereby a crude product (19.8 g) was obtained. The product was distilled using a Claisen distillation apparatus to obtain 17.4 g of 2-pentyl-2-cyclopentenone (boiling point: 105° C./933 Pa; GC purity: 98.2%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=1)[C:6]1[C:22](=[O:27])[O:23][C:24](=[O:26])[CH2:25][C:5]2=1.[NH2:28][CH2:29][C:30]([NH2:32])=[O:31]>>[C:30]([CH2:29][NH:28][C:24]([CH2:25][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)[N:7]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[C:6]=1[C:22]([OH:23])=[O:27])=[O:26])(=[O:31])[NH2:32]
Reactant: NCC(N)=O
Reactant: O=C1Cc2c(n(Cc3cccc4ccccc34)c3ccc(F)cc23)C(=O)O1
Product: NC(=O)CNC(=O)Cc1c(C(=O)O)n(Cc2cccc3ccccc23)c2ccc(F)cc12

Procedure:
6-Fluoro-9-naphthalen-1-ylmethyl-4,9-dihydro-pyrano[3,4-b]indole-1,3-dione (from example 34.1.) was ring opened with glycinamide at 22° C. to give the title compound as a colorless gum. MS: 432.3 ([M−H]−).
Reaction SMILES: C(N(CC)CC)C.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][N:10]=1.[C:19]([O:22][CH2:23][C:24](Cl)=[O:25])(=[O:21])[CH3:20]>C(Cl)Cl>[C:19]([O:22][CH2:23][C:24](=[O:25])[NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:16])([F:18])[F:17])=[CH:11][N:10]=1)(=[O:21])[CH3:20]
Reactant: CC(=O)OCC(=O)Cl
Reactant: Nc1ccc(C(F)(F)F)cn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OCC(=O)Nc1ccc(C(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 40.9 %

Procedure:
Triethylamine (9.30 g, 91.9 mmol) was added at 0° C. to a stirred solution of 2-amino-5-trifluoromethylpyridine (5.0 g, 30.8 mmol) in DCM, and stirring was continued for 15 min. 2-Chloro-2-oxoethyl acetate (5.03 g, 36.8 mmol) was added at 0° C., and the temperature was raised to room temperature and the mixture was stirred for 4 hrs. The reaction mixture was diluted with DCM and washed with ice-water, aq. NaHCO3 solution and saturated brine solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford the crude compound. This was purified by column chromatography (100-200 silica gel), eluting with 0-20% EtOAc/pet ether to give the title compound (3.30 g) as a pale brown solid.