Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][OH:12])[CH:5]=[CH:6][CH:7]=1.[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.C(N(CC)CC)C.[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][S:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:23])=[CH:14][CH:15]=2)(=[O:21])=[O:20])[CH:5]=[CH:6][CH:7]=1
Reactant: OCCCCc1cccc(Br)c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)OCCCCc2cccc(Br)c2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 133.2 %

Procedure:
A cold (0° C.) solution of 4-(3-bromophenyl)butan-1-ol (1.08 g, 4.7 mmol) and p-toluenesulfonyl chloride (1.2 g, 6.3 mmol) in THF was treated slowly with triethyl amine (1.8 mL, 12.3 mmol), stirred at room temperature for 4 hours, poured into cold saturated aqueous NH4Cl and extracted with ether. The organic extracts were combined, washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the resultant residue on silica gel (ISCO) using (hexanes/EtOAC 9.5/0.5) as the eluting solvent afforded toluene-4-sulfonic acid 4-(3-bromophenyl)-butyl ester as a colorless oil (2.4 g, 76% yield). m/e (M+NH4)+ 400.1 1H NMR (400 MHz, DMSO-d6) δ ppm, 1.4-1.6 (m, 4H), 2.4 (s, 3H), 2.4-2.5 (m, 2H), 4.0 (t, J=6.0 Hz, 2H), 7.2 (t, J=7.8 Hz, 1H), 7.3-7.3 (m, 1H), 7.3-7.3 (m, J=8.0, 1.0 Hz, 1H), 7.4-7.5 (m, J=8.6 Hz, 2H), 7.7-7.8 (m, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([O:19][CH:20]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[CH2:21][C:22](O)=[O:23])=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:40]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.N.Cl>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([O:19][CH:20]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[CH2:21][C:22]([NH2:40])=[O:23])=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: On1nnc2ccccc21
Reactant: CC(C)CCCCCCCCCCCC(CC(=O)O)OC(=O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: N
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)CCCCCCCCCCCC(CC(N)=O)OC(=O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 3-(N-tertiarybutoxycarbonyl-L-phenylalanyl)oxy-15-methylhexadecanoic acid (2.30 g) in tetrahydrofuran (30 ml) was added 1-hydroxybenzotriazole (0.58 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.82 g). The mixture was stirred at room temperature for 30 minutes. 28% Ammonia solution (0.5 ml) was added to the mixture and then the mixture was stirred at room temperature for 2 hours. The mixture was poured into a mixture of ethyl acetate and diluted hydrochloric acid. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column eluting with chloroform to give 3-(N-tertiarybutoxycarbonyl-L-phenylalanyl)oxy-15-methylhexadecanamide as white wax (1.41 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:13]([CH2:14][CH2:15][CH:16]=2)=[N:12][N:11]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH:10]=3)=[CH:4][CH:3]=1.C(O)C.[H][H]>[Pt](=O)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:16][CH2:15][CH2:14][C:13]3[C:9]2=[CH:10][N:11]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[N:12]=3)=[CH:4][CH:3]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc3c(n2)CCC=C3c2ccc(Cl)cc2)cc1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)n2cc3c(n2)CCCC3c2ccc(Cl)cc2)cc1
Yield: 68.8 %

Procedure:
4-(4-Chlorophenyl)-2-(p-tolylsulfonyl)-6,7-dihydroindazole (0.62 g, 1.89 mmol) is added to ethanol (20.0 mL) and ethyl acetate (10 mL). Platinum (IV) oxide (0.22 g) is added and the reaction is stirred under 40 psi of hydrogen at room temperature for 6.0 h. The mixture is filtered through a plug of diatomaceous earth and evaporated under reduced pressure to give the title compound (0.503 g, 80%). LC/MS m/z 389 (M+H), Tr=2.704 min.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[C:23]([F:27])([F:26])[CH:24]=[CH2:25].O>CN(C)C=O>[F:26][C:23]([F:27])=[CH:24][CH2:25][O:14][C:13]([CH:10]1[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)=[O:15]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)C1
Reactant: C=CC(F)(F)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(C(=O)OCC=C(F)F)C1
Temperature: 60 °C
Reaction time: 6 h

Procedure:
To a solution of pyrrolidine-1,3-dicarboxylic acid-1-tert-butyl ester (3.40 g) in N,N-dimethylformamide (34 ml) were added potassium carbonate (4.37 g) and 3-bromo-3,3-difluoropropene (1.93 ml), and the mixture was stirred at 60° C. for 6 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=5/1) to give the titled compound (3.73 g).
Reaction SMILES: [O-]S(C(F)(F)F)(=O)=O.[C:9]([O:13][C:14](=[O:42])[C@H:15]([CH2:34][C:35]1[CH:40]=[CH:39][C:38](O)=[CH:37][CH:36]=1)[NH:16][C:17](=[O:33])[C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[S:23]([C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)(=[O:25])=[O:24])([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[K+].[K+].[C:49]1(B(O)O)[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:9]([O:13][C:14](=[O:42])[C@H:15]([CH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[CH:39][CH:40]=1)[NH:16][C:17](=[O:33])[C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[S:23]([C:26]1[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=1)(=[O:25])=[O:24])([CH3:10])([CH3:12])[CH3:11]
Reactant: OB(O)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)OC(C)(C)C)cc1
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(-c3ccccc3)cc2)C(=O)OC(C)(C)C)cc1

Procedure:
The title compound was prepared from the corresponding triflate (which was prepared from (N-(Toluene-4-sulfonyl)-L-prolyl-L-tyrosine tert-butyl ester as taught by Tilley and coworkers, J. Org. Chem., 55, 906, 1990). The dipeptide (505 mg, 0.8 mmol.), a catalytic amount of tetrakis(triphenylhosphine)palladium(0), potassium carbonate (201 mg, 1.5 eq.), phenylboronic acid (199 mg, 2.0 eq.), and 15 mL of toluene were refluxed for 10 hours with stirring. Ethyl acetate was added and the organic layer was washed with water, 1N NaOH, brine and dried over magnesium sulfate. Upon filtration, the solvent was evaporated under reduced pressure. The crude material was purified on a preparative plate (1:1 ethyl acetate:hexanes). The silica gel was washed several times with acetonitrile and ethyl acetate. The combined fractions were evaporated and the residue was dried under reduced pressure.
Reaction SMILES: [CH3:1][CH2:2][C@H:3]1[O:20][C:18](=[O:19])[CH2:17][C@@H:16]([OH:21])[C@H:15]([CH3:22])[C@@H:14]([O:23][C@@H:24]2[O:29][C@H:28]([CH3:30])[C@@H:27]([OH:31])[C@H:26]([N:32]([CH3:34])[CH3:33])[C@H:25]2[OH:35])[C@@H:13]([CH2:36]C=O)[CH2:12][C@@H:11]([CH3:39])[C:9](=[O:10])[CH:8]=[CH:7][C:6]([CH3:40])=[CH:5][C@@H:4]1[CH2:41][O:42][C@@H:43]1[O:48][C@H:47]([CH3:49])[C@@H:46]([OH:50])[C@@H:45]([O:51][CH3:52])[C@H:44]1[O:53][CH3:54]>C1C=CC=CC=1.C(OCC)(=O)C>[CH3:1][CH2:2][CH:3]1[O:20][C:18](=[O:19])[CH2:17][CH:16]([OH:21])[CH:15]([CH3:22])[CH:14]([O:23][CH:24]2[O:29][CH:28]([CH3:30])[CH:27]([OH:31])[CH:26]([N:32]([CH3:33])[CH3:34])[CH:25]2[OH:35])[CH:13]([CH3:36])[CH2:12][CH:11]([CH3:39])[C:9](=[O:10])[CH:8]=[CH:7][C:6]([CH3:40])=[CH:5][CH:4]1[CH2:41][O:42][CH:43]1[O:48][CH:47]([CH3:49])[CH:46]([OH:50])[CH:45]([O:51][CH3:52])[CH:44]1[O:53][CH3:54]
Reactant: CC[C@H]1OC(=O)C[C@@H](O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]2O)[C@@H](CC=O)C[C@@H](C)C(=O)C=CC(C)=C[C@@H]1CO[C@@H]1O[C@H](C)[C@@H](O)[C@@H](OC)[C@H]1OC
Agent: CCC1OC(=O)CC(O)C(C)C(OC2OC(C)C(O)C(N(C)C)C2O)C(C)CC(C)C(=O)/C=C/C(C)=C\C1COC1OC(C)C(O)C(OC)C1OC
Agent: CC[C@H]1OC(=O)C[C@@H](O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]2O)[C@@H](CC=O)C[C@@H](C)C(=O)/C=C/C(C)=C/[C@@H]1CO[C@@H]1O[C@H](C)[C@@H](O)[C@@H](OC)[C@H]1OC
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: CCC1OC(=O)CC(O)C(C)C(OC2OC(C)C(O)C(N(C)C)C2O)C(C)CC(C)C(=O)C=CC(C)=CC1COC1OC(C)C(O)C(OC)C1OC
Temperature: 90 °C

Procedure:
Desmycosin (Merck Index, Tenth Edition p. 1405) (18.9 o) was dissolved in degassed benzene (580 mL) and tris(triphenYlphospbine)rhodium chloride (29.5 g.) was added. The mixture was heated under dry nitrogen at 90° C. for 16 h. The mixture was diluted with ethyl acetate and extracted twice with 0.2N hydrochloric acid. The aqueous acid layer was adjusted to pH 10 and extracted with dichloromethane. The latter was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on a silica gel column (60×5 cm.) using 5% methanol in chloroform (v/v) as the eluant to give 19deformyldesmycosin (13.2 g., 73%) as a colorless amorphous solid (Anal.: found: C, 57.05; H, 7.99; N, 1.62%. C38H65NO13. 0.5 CHCl3 requires C, 56.79; H, 8.15; N, 1.74%); MS: m/z 744 (MH+); Rotation: [α]D26 0° (CHCl3); UV: λmax (CH3OH) 282 nm (ε20,676); IR: νmax (CDCl3) 3540, 3450, 1705, 1670, 1590, 1185, 1163, 1055 cm-1 ; 1H-NMR: δH (CDCl3) 0.92 (3H,tJ16,17-CH3 7 Hz, 17-CH3), 1.02 (3H,d,J 7 Hz, CH3), 1.03 (3 H,d,J 7 Hz, CH3), 1.18 (3H,d,J 7 Hz, CH3), 1.26 (3H,d,J 7 Hz, CH3), 1.30 (3H,d,J 7 Hz, CH3), 1.78 (3H,d,J12 -CH3,13 1 Hz, 12-CH3), 2.53 (6H,s,3'-N(CH3)2), 3.48 (3H,s,2"-OCH3), 3.60 (3H,s,3"-OCH3), 4.28 (1H,d,J1'ax,2'ax 8 Hz, H1'ax), 4.55 (1H,d,J1"ax,2"ax 8 Hz, H1"ax), 4.97 (1H,m,H15), 5.82 (1H,dc,J12-CH3,13 1 Hz, J13,14 10 Hz, H13), 6.24 (1H,d,J10,11 16 Hz, H10), and 7.24 (1H,d,J10,11 16 Hz, H11)
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:18]=[CH:17][C:16]2[S:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3B3OC(C)(C)C(C)(C)O3)[S:8][C:7]=2[CH:6]=1)=[O:4].Cl[C:29]1[O:30][C:31]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:32][C:33](=[O:35])[CH:34]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[CH:18]=[CH:17][C:16]2[S:15][C:10]3[C:9](=[CH:14][CH:13]=[CH:12][C:11]=3[C:29]3[O:30][C:31]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)=[CH:32][C:33](=[O:35])[CH:34]=3)[S:8][C:7]=2[CH:6]=1)=[O:4]
Reactant: O=c1cc(Cl)oc(N2CCOCC2)c1
Reactant: COC(=O)c1ccc2c(c1)Sc1cccc(B3OC(C)(C)C(C)(C)O3)c1S2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: COC(=O)c1ccc2c(c1)Sc1cccc(-c3cc(=O)cc(N4CCOCC4)o3)c1S2
Temperature: 90 °C

Procedure:
6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-thianthrene-2-carboxylic acid methyl ester (1.1 g, 2.83 mmol), 2-chloro-6-morpholin-4-yl-pyran-4-one (3) (0.73 g, 3.4 mmol) and K2CO3 (0.8 g, 5.66 mmol) were dissolved in dry 1,4-dioxane (7 ml). The mixture was degassed for 15 mins and Pd(PPh3)4 (0.16 g, 5 mol %) was then added The dark brown mixture was heated to 90° C. under an atmosphere of N2 for 24 hour. The reaction mixture was concentrated in vacuo and water (100 ml) was added. The brown solid was filtered and washed with water (1.23 g, 96%). m/z (LC-MS, ESP), RT=4.49 min, (M++1)=454.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](Cl)=[O:28])=[CH:22][CH:21]=1>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:27](=[O:28])[CH2:26][C:23]1[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Reactant: O=C(Cl)Cc1ccc(F)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=C(Cc1ccc(F)cc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 8089 %

Procedure:
To a cooled (−78° C.) solution of (S)-4-benzyloxazolidin-2-one (10 g, 58 mmol, 1.0 equiv) in 100 mL THF was added dropwise n-BuLi (40 mL, 1.6 M in hexanes, 64 mmol, 1.1 equiv). After stirring for 30 minutes, 4-fluorophenylacetyl chloride (10 g, 0.58 mmol, 1.0 equiv) was added dropwise. After stirring for an additional 30 minutes, the reaction mixture was allowed to warm to room temperature. The reaction was quenched with saturated aq. NH4Cl, extracted with dichloromethane, and washed with brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel (10-20% EtOAc/hexanes) provided the title compound as a thick oil (14.7 g, 81%).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH:12]=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[CH3:15][NH2+]C.C=O>>[CH2:1]([O:8][CH2:9][CH2:10][C:11](=[CH2:15])[CH:12]=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[NH2+]C
Reactant: O=CCCCOCc1ccccc1
Agent: C=O
Agent: [Cl-]
Product: C=C(C=O)CCOCc1ccccc1
Reaction time: 1 h

Procedure:
8.0 g (44.9 mmol) of 4-benzyloxybutanal, 4.12 g (50.6 mmol) of dimethylammonium chloride and 3.95 ml (52.6 mmol) of 37% formaldehyde solution are kept at a bath temperature of 110° for one hour with stirring. The mixture is allowed to cool and is extracted three times with ether. The organic phases are washed with saturated sodium chloride solution, combined, dried over MgSO4, filtered and concentrated by evaporation. 4-benzyloxy-2-methylenebutanal is obtained in the form of a yellowish oil which can be reacted further without further purification.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)(=[O:18])=[O:17])=[N:11][CH:12]=[CH:13][N:14]=2)=[CH:5][CH:4]=1.[CH3:26][NH:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=1>>[CH3:25][C:22]1[CH:21]=[CH:20][C:19]([S:16]([NH:15][C:10]2[C:9]([C:6]3[CH:5]=[CH:4][C:3]([CH2:2][N:27]([CH3:26])[C:28]4[CH:33]=[CH:32][C:31]([O:34][C:35]([F:36])([F:37])[F:38])=[CH:30][CH:29]=4)=[CH:8][CH:7]=3)=[N:14][CH:13]=[CH:12][N:11]=2)(=[O:17])=[O:18])=[CH:24][CH:23]=1
Reactant: Cc1ccc(S(=O)(=O)Nc2nccnc2-c2ccc(CCl)cc2)cc1
Reactant: CNc1ccc(OC(F)(F)F)cc1
Product: Cc1ccc(S(=O)(=O)Nc2nccnc2-c2ccc(CN(C)c3ccc(OC(F)(F)F)cc3)cc2)cc1
Yield: 69 %

Procedure:
Following the general method as outlined in Example 1 (Method B), starting from N-{3-[4-(chloromethyl)phenyl]pyrazin-2-yl}-4-methylbenzenesulfonamide, and N-methyl-4-(trifluoromethoxy)aniline, the title compound was isolated as a yellow solid in 69% yield (94% purity by HPLC).
Reaction SMILES: C(C1C=CC2SCCC(=O)C=2C=1)C.N(OCCC(C)C)=O.[K].[CH2:23]([C:25]1[CH:26]=[CH:27][C:28]2[S:33][CH2:32][C:31](=[N:34]O)[C:30](=[O:36])[C:29]=2[CH:37]=1)[CH3:24].Cl.NC1C(=O)C2C=C(CC)C=CC=2SC=1Cl>>[NH2:34][C:31]1[C:30](=[O:36])[C:29]2[CH:37]=[C:25]([CH2:23][CH3:24])[CH:26]=[CH:27][C:28]=2[S:33][CH:32]=1
Reactant: CCc1ccc2c(c1)C(=O)C(=NO)CS2
Agent: CC(C)CCON=O
Agent: CCc1ccc2c(c1)C(=O)CCS2
Agent: CCc1ccc2sc(Cl)c(N)c(=O)c2c1
Product: CCc1ccc2scc(N)c(=O)c2c1

Procedure:
In a manner analogous to that described in Example 1, starting from 4-ethylthiophenol there is obtained 3-(4-ethylphenylthio)-propionic acid, melting point 59°-60°, which is converted into 6-ethyl-2,3-dihydro-4H-1-benzothiopyran-4-one (red oil). This is converted into an oxime with isopentyl nitrite, and the resulting crude potassium salt of 6-ethyl-3-hydroxyimino-2,3-dihydro-4H-1-benzothiopyran-4-one is converted with concentrated hydrochloric acid into 3-amino-2-chloro-6-ethyl-4H-1-benzothiopyran-4-one, melting point 79°-81°. After hydrogenation there is obtained 3-amino-6-ethyl-4H-1-benzothiopyran-4-one having a melting point of 106°-107°.
Reaction SMILES: [ClH:1].[CH:2]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[O:15][CH2:16][CH2:17][NH:18][CH2:19][CH:20]([C:22]1[CH:23]=[CH:24][C:25]([O:35]CC2C=CC=CC=2)=[C:26]([NH:28][S:29]([CH:32]([CH3:34])[CH3:33])(=[O:31])=[O:30])[CH:27]=1)[OH:21].CO.C(OCC)(=O)C>CO.[Pd]>[ClH:1].[CH:2]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[O:15][CH2:16][CH2:17][NH:18][CH2:19][CH:20]([C:22]1[CH:23]=[CH:24][C:25]([OH:35])=[C:26]([NH:28][S:29]([CH:32]([CH3:33])[CH3:34])(=[O:31])=[O:30])[CH:27]=1)[OH:21]
Reactant: CC(C)S(=O)(=O)Nc1cc(C(O)CNCCOc2ccc3c(c2)[nH]c2ccccc23)ccc1OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)S(=O)(=O)Nc1cc(C(O)CNCCOc2ccc3c(c2)[nH]c2ccccc23)ccc1O

Procedure:
According to the procedures described in Example 2, the compound of Example 53 (369 mg) was dissolved in 39.9 ml of methanol and subjected to a hydrogenolysis using 10% Pd-C (190 mg). The catalyst was filtered on celite at room temperature and washed with hot methanol. After the filtrate and the washed liquor were brought together, the solvent was distilled off under a reduced pressure, whereby the above-identified compound (267 mg) was obtained. Rf=0.27(methanol/ethyl acetate of 1/3).
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].[O:11]1[C:21]2[C:16](=[CH:17][C:18]([CH:22]=O)=[CH:19][CH:20]=2)[CH:15]=[CH:14][C:12]1=[O:13]>>[O:13]=[C:12]1[CH:14]=[CH:15][C:16]2[C:21](=[CH:20][CH:19]=[C:18]([CH2:22][NH:4][C:3]3[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=3[C:1]([OH:10])=[O:9])[CH:17]=2)[O:11]1
Reactant: O=Cc1ccc2oc(=O)ccc2c1
Reactant: Nc1ccccc1C(=O)O
Product: O=C(O)c1ccccc1NCc1ccc2oc(=O)ccc2c1

Procedure:
Prepared by a similar procedure as described for preparation 1A, starting from anthranilic acid and coumarin-6-carboxaldehyde (Matrix). 13C-NMR (DMSO-d6) δ 169.9, 159.9, 152.5, 150.4, 144.1, 135.8, 134.3, 131.7, 130.7, 126.4, 118.6, 116.4, 116.3, 114.6, 111.6, 110.5, 45.0.
Reaction SMILES: [CH3:1][N:2]([CH3:16])[CH:3]([C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][CH:15]=1)[O:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH3:4].[CH2:17]1[C@@H:21]([CH2:22][CH2:23][CH2:24][CH2:25][C:26](O)=[O:27])[S:20][S:19][CH2:18]1>>[CH3:16][N:2]([CH3:1])[CH:3]([C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][CH:15]=1)[O:8][CH2:9][CH2:10][CH2:11][NH:12][C:26](=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[CH2:17][CH2:18][S:19][S:20]1)[CH3:4]
Reactant: O=C(O)CCCC[C@@H]1CCSS1
Reactant: CC(c1cccc(OCCCN)c1)N(C)C
Product: CC(c1cccc(OCCCNC(=O)CCCCC2CCSS2)c1)N(C)C

Procedure:
5-[1,2]dithiolan-3-yl-pentanoic acid {3-[3-(1-dimethylamino-ethyl)-phenoxy]-propyl}-amide (19) was synthesized from 19c (150 mg, 0.67 mmol) and lipoic acid (210 mg, 1.02 mmol) following the procedure described for 17, and purified by gravity column. Elution with petroleum ether/toluene/CH2Cl2/MeOH/aqueous 30% ammonia solution (6:1:1.5:1.5:0.01) afforded 19 as a waxy solid; 30% yield, 1H NMR (200 MHz, CDCl3) δ 7.27 (t, J=8.2 Hz, 1H); 6.78-6.98 (m, 3H), 5.99 (br t, 1H); 4.09 (t, J=6.0 Hz, 2H); 3.21-3.62 (m, 5H), 3.05-3.19 (m, 3H), 2.40-2.53 (m, 1H), 2.32 (s, 6H), 2.22 (t, J=7.2 Hz, 2H); 1.81-2.0 (m, 3H), 1.65-1.73 (m, 4H), 1.47 (d, J=6.6 Hz, 3H); MS (ESI+) m/z 411 (M+H)+. Anal. Calculated for C21H34N2O2S2: C, 61.42; H, 8.35; N, 6.82. Found: C, 61.62; H, 8.36, N, 6.80.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[N:8]([C:9]([C:11]2[N:12]=[C:13]([CH3:23])[S:14][C:15]=2[C:16]2[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=2)=[O:10])[CH2:7][C@H:6]2[C@@H:4]1[CH2:5]2.[O:24]1[C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([C:34](O)=[O:35])[C:28]=2[CH:27]=[CH:26][CH2:25]1>>[CH3:23][C:13]1[S:14][C:15]([C:16]2[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=2)=[C:11]([C:9]([N:8]2[CH2:7][C@H:6]3[C@H:4]([CH2:5]3)[C@H:3]2[CH2:2][NH:1][C:34]([C:29]2[C:28]3[CH:27]=[CH:26][CH2:25][O:24][C:33]=3[CH:32]=[CH:31][CH:30]=2)=[O:35])=[O:10])[N:12]=1
Reactant: Cc1cccc(-c2sc(C)nc2C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CN)c1
Reactant: O=C(O)c1cccc2c1C=CCO2
Product: Cc1cccc(-c2sc(C)nc2C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CNC(=O)c2cccc3c2C=CCO3)c1

Procedure:
prepared by reaction of ((1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone with 2H-Chromene-5-carboxylic acid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:20])[CH2:9][CH:10]([CH2:16][CH2:17][O:18][CH3:19])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1.[N+:21]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)([O-:23])=[O:22].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1>[CH3:19][O:18][CH2:17][CH2:16][CH:10]([CH2:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([C:27]2[CH:28]=[CH:29][C:24]([N+:21]([O-:23])=[O:22])=[CH:25][CH:26]=2)=[CH:3][CH:4]=1)=[O:20])[C:11]([O:13][CH2:14][CH3:15])=[O:12]
Reactant: O=[N+]([O-])c1ccc(B(O)O)cc1
Reactant: CCOC(=O)C(CCOC)CC(=O)c1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: CCOC(=O)C(CCOC)CC(=O)c1ccc(-c2ccc([N+](=O)[O-])cc2)cc1
Temperature: 85 °C
Reaction time: 0.25 h
Yield: 87.3 %

Procedure:
To a 150 mL 3-neck flask fitted with a reflux condenser was added ethyl 4-(4-bromophenyl)-2-(2-methoxyethyl)-4-oxobutanoate (1.06 g, 3.09 mmol) and 4-nitro-phenyl boronic acid (0.62 g, 3.70 mmol) dissolved in toluene (30 mL) and dioxane (8.50 mL), followed by addition of saturated aqueous sodium carbonate solution (8.50 mL). A thin-gauge needle was inserted into the bi-phasic mixture and degassed with argon over 30 minutes, at which point 1,2-bis[(diphenylphosphino)ferrocene]dichloropalladium(II) (0.13 g, 0.15 mmol) was added, followed by an additional 15 minutes of degassing. The reaction mixture was heated at 85° C. for 16 h, and then the resulting dark-colored reaction mixture was allowed to cool, and was diluted with ethyl acetate (75 mL) and saturated aqueous sodium chloride solution (75 mL). The layers were separated, the aqueous layer was extracted twice with ethyl acetate (50 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution (75 mL), dried over anhydrous magnesium sulfate, and filtered in vacuo through 2 cm Celite®/2 cm silica. The filtrate was concentrated in vacuo, leaving a dark red-brown oil, that was purified by flash chromatography (4:1 hexane/ethyl acetate, then 3:1 hexane/ethyl acetate, then 2:1 hexane/ethyl acetate) to afford ethyl 2-(2-methoxyethyl)-4-(4′-nitro-1,1′-biphenyl-4-yl)-4-oxobutanoate (1.04 g, 88%). LC-MS ret. time 3.38 min, m/z 385.9 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.27 (t, 3H), 1.80-1.95 (m, 1H), 1.95-2.10 (m, 1H), 3.10-3.25 (m, 2H), 3.40-3.58 (m, 3H), 4.17 (q, 2H), 7.67-7.82 (2d, 4H), 8.10 (d, 2H), 8.33 (d, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:12])[O:5][C:6]2=[O:11].[H-].[Na+].[CH3:15]I>CN(C)C=O>[CH3:15][O:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:12])[O:5][C:6]2=[O:11]
Reactant: O=C1OC(=O)c2c(O)cccc21
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cccc2c1C(=O)OC2=O
Reaction time: 0.25 h
Yield: 46.8 %

Procedure:
To a solution of 4-hydroxy-isobenzofuran-1,3-dione (195 mg, 1.2 mmol) in anhydrous N,N-dimethylformamide (4 ml) under nitrogen was added sodium hydride (61 mg, 1.56 mmol). The solution was stirred for 15 minutes and then methyl iodide (0.37 ml, 6.0 mmol) was added. The reaction was stirred for 48 hours and then quenched with saturated ammonium chloride. The mixture was concentrated in vacuo, diluted in ethyl acetate (20 ml) and the organic phase washed with 1N hydrochloric acid (5 ml) and brine (3×5 ml). The organic layer was dried (MgSO4) and concentrated in vacuo. To the crude solid was added methanol causing a precipitate to form. The flask was cooled in an ice bath for 2 hours and the solid filtered off, washed with methanol and dried in vacuo which afforded 0.1 g (47%) of 4-methoxy-isobenzofuran-1,3-dione as a solid.