Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[CH:2]([CH3:4])[O-:3].[Al+3].C[CH:7]([CH3:9])[O-:8].CC(C)[O-].C(O)(=O)CCCCCCCC.[C:25]([O-:44])(=[O:43])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]CCCCCCC.[K+]>>[C:2]1(=[O:3])[O:8][CH2:7][CH2:9][O:44][C:25](=[O:43])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:4]1
Reactant: CC(C)[O-]
Reactant: CCCCCCCCCCCCCCCCCC(=O)[O-]
Agent: CCCCCCCCC(=O)O
Agent: [Al+3]
Agent: [K+]
Product: O=C1CCCCCCCCCCCC(=O)OCCO1
Yield: 89.3 %

Procedure:
Aluminum tripelargonate, obtained by reacting 0.5 mole aluminum isopropoxide and 1.5 mole pelargonic acid at 120° C., was combined with an equimolar amount, based on aluminum, of potassium stearate and the resulting mixed metal catalyst (1.7 weight percent) charged to a reactor with 76 g poly(ethylene brassylate). The depolymerization was conducted in the usual manner. Ethylene brassylate was obtained at a rate of 42 mls/hr. and yield of 89.3%.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[C:4](I)[CH:3]=1.[Br:18][C:19]1[C:20]([NH2:26])=[N:21][CH:22]=[C:23]([CH3:25])[CH:24]=1>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:18][C:19]1[C:20]([NH:26][C:4]2[CH:3]=[C:2]([Cl:1])[CH:16]=[CH:15][C:5]=2[O:6][CH2:7][CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[N:21][CH:22]=[C:23]([CH3:25])[CH:24]=1
Reactant: Cc1cnc(N)c(Br)c1
Reactant: CN1CCC(COc2ccc(Cl)cc2I)CC1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCOC(C)=O
Product: Cc1cnc(Nc2cc(Cl)ccc2OCC2CCN(C)CC2)c(Br)c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 80 %

Procedure:
In a oven dried 50 mL round bottom flask were sequentially added Compound 173 (620 mg, 1.69 mmol), 3-bromo-5-methylpyridin-2-amine (381 mg, 2.03 mmol), Pd2(dba)3 (77 mg, 0.08 mmol), xantphos (59 mg, 0.10 mmol) and NatBuO (244 mg, 2.53 mmol) at room temperature. The solid materials were kept under vacuum for 5 min. and then refilled with nitrogen. This process was repeated thrice before adding dry, degassed dioxane (8 mL). The heterogeneous mixture was stirred at room temperature for 15 min. and then at 100° C. for 2 h. Finally upon completion of the reaction, it was diluted with EtOAc and filtered through a small pad of silica gel with several washings. All the washings and filtrate concentrated in vacuum and the crude residue was further purified by flash chromatography to provide pure Compound 174 (574 mg, 80%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[F:16][C:17]([F:38])([F:37])[C:18]1[CH:23]=[C:22]([C:24]2([C:29]([F:32])([F:31])[F:30])[CH2:28][CH2:27][NH:26][CH2:25]2)[CH:21]=[C:20]([C:33]([F:36])([F:35])[F:34])[N:19]=1.CC(C)([O-])C.[Na+].O>C1(C)C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[F:38][C:17]([F:16])([F:37])[C:18]1[CH:23]=[C:22]([C:24]2([C:29]([F:30])([F:31])[F:32])[CH2:28][CH2:27][N:26]([C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]4[CH2:15][CH2:14]4)=[O:12])[CH3:9])=[CH:4][CH:3]=3)[CH2:25]2)[CH:21]=[C:20]([C:33]([F:34])([F:35])[F:36])[N:19]=1
Reactant: C[C@H](NC(=O)C1CC1)c1ccc(Br)cc1
Reactant: FC(F)(F)c1cc(C2(C(F)(F)F)CCNC2)cc(C(F)(F)F)n1
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: C[C@H](NC(=O)C1CC1)c1ccc(N2CCC(c3cc(C(F)(F)F)nc(C(F)(F)F)c3)(C(F)(F)F)C2)cc1
Temperature: 25 °C
Yield: 100.9 %

Procedure:
To the solution of N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamide (0.134 g) and 2,6-bis(trifluoromethyl)-4-[3-(trifluoromethyl)pyrrolidin-3-yl]pyridine (0.195 g) in toluene was added sodium tert-butoxide (0.096 g), tris(dibenzylideneacetone)dipalladium chloroform complex (0.010 g) and xantphos (0.017 g) and the vessel was applied by Ar gas. The vessel was sealed and applied to microwave reactor at 120° C. for 10 min. The mixture was cooled to room temperature and then poured into water, which was then extracted twice with ethyl acetate. The organic layer was combined, which was then washed with water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield N-[(1S)-1-(4-{3-[2,6-bis(trifluoromethyl)pyridin-4-yl]-3-(trifluoromethyl)pyrrolidin-1-yl}phenyl)ethyl]cyclopropanecarboxamide (0.272 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH:8]=[CH2:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11](=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1COCC1.[N+](=[CH:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N-]>C1(C)C=CC=CC=1.[Cu]Cl>[C:11]([NH:10][C:3]1[CH:4]=[CH:5][C:6]([C@@H:8]2[CH2:9][C@H:26]2[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:7][C:2]=1[CH3:1])(=[O:18])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: C=Cc1ccc(NC(=O)c2ccccc2)c(C)c1
Reactant: CCOC(=O)C=[N+]=[N-]
Agent: Cl[Cu]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)[C@@H]1C[C@H]1c1ccc(NC(=O)c2ccccc2)c(C)c1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To a solution of N-(4-bromo-2-methylphenyl)benzamide(4.35 g) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (2.54 g) in THF (64.3 mL)/water (10.7 mL) were added 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (0.367 g) and triethylamine (4.18 mL). The reaction mixture was stirred at 60° C. overnight, and poured into saturated aqueous ammonium chloride solution. The reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give a mixture (4.42 g) containing N-(2-methyl-4-vinylphenyl)benzamide. To a solution of the mixture (4.42 g) and copper(I) chloride (0.233 g) in toluene (36 mL)/THF (5 mL) was added dropwise a solution of ethyl diazoacetate (9.79 mL) in toluene (25 mL) at 80° C. over 1 hr or longer. The mixture was stirred at 80° C. overnight, cooled to room temperature, and filtered through celite. The mother liquor was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.29 g).
Reaction SMILES: [C:1]1([C:14](O)=O)[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.OCC1C2CC3C(=CC=CC=3)C=2C=CC=1.P(Br)(Br)[Br:33].O>C1COCC1>[Br:33][CH2:14][C:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)c1cccc2c1Cc1ccccc1-2
Reactant: BrP(Br)Br
Agent: OCc1cccc2c1Cc1ccccc1-2
Solvent: C1CCOC1
Solvent: O
Product: BrCc1cccc2c1Cc1ccccc1-2
Temperature: -5 °C
Reaction time: 1.5 h

Procedure:
Fluorene-1-carboxylic acid was purchased from Aldrich. It was reduced as described in J. Am. Chem. Soc. 1961, 83, 417 via the methyl ester to 1-hydroxymethylfluorene 1H NMR (CDCl3): δ 4.84 ppm (CH2), 3.89 ppm (CH2). 4.1 g (21 mmol) 1-hydroxymethylfluorene dissolved in 60 ml THF was slowly added to 2.54 g PBr3 in 10 ml THF at −5° C. The orange solution was stirred for 1.5 hrs at −5° C. then stirred for 16 hrs at room temperature. This was then poured into iced water, allowed to settle and 5.1 g of 1-bromomethylfluorene was isolated on a frit as an off-white powder. 1H NMR (CDCl3): δ 4.65 ppm (CH2), 3.97 ppm (CH2).
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3]([NH2:5])=O.F[B-](F)(F)F.C([O+](CC)CC)C.N[C:20]1[C:21]([NH:29][C@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)=[C:22]2[S:28][CH:27]=[CH:26][C:23]2=[N:24][CH:25]=1>O1CCCC1.C(O)C>[OH:1][C@@H:2]([C:3]1[N:29]([C@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)[C:21]2=[C:22]3[S:28][CH:27]=[CH:26][C:23]3=[N:24][CH:25]=[C:20]2[N:5]=1)[CH3:6]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](Nc2c(N)cnc3ccsc23)C1
Reactant: C[C@@H](O)C(N)=O
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: CCO
Solvent: C1CCOC1
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CCCN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 1.25 h
Yield: 90 %

Procedure:
A mixture of (2R)-2-hydroxypropanamide (197 mg, 2.21 mmol) and triethyloxonium tetrafluoroborate (395 mg, 2.08 mmol) in tetrahydrofuran (4.0 mL) was stirred at room temperature for 75 min then concentrated. The residue was dissolved in ethanol (1.5 mL) and this solution was then added to a solution of tert-butyl (3S)-3-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]piperidine-1-carboxylate (0.24 g, 0.69 mmol) in ethanol (3.5 mL) in a vial. The resulting mixture was stirred at 80° C. for 2 h. The solvent was evaporated and the crude purified on silica gel, eluted with 0-10% MeOH in dichloromethane to give 250 mg (86%) of the desired product. LCMS calculated for C20H27N4O3S (M+H)+: m/z=403.2. Found: 403.1.
Reaction SMILES: [H-].[Na+].C([O:6][C:7]1[CH:31]=[CH:30][C:10]([C:11]([C:13]2[CH:14]=[C:15]([CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:16]3[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]3)=[O:12])=[CH:9][CH:8]=1)(=O)C>C(O)C.O1CCCC1>[OH:6][C:7]1[CH:8]=[CH:9][C:10]([C:11]([C:13]2[CH:14]=[C:15]([CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:16]3[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]3)=[O:12])=[CH:30][CH:31]=1
Reactant: CCOC(=O)CCCc1cc(C(=O)c2ccc(OC(C)=O)cc2)c2ccccn12
Agent: [H-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)CCCc1cc(C(=O)c2ccc(O)cc2)c2ccccn12
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 90.9 %

Procedure:
Sodium hydride (60% dispersion in mineral oil) (4.38 g) was added to an ice cold solution of ethyl 4-[1-(4-acetoxybenzoyl)indolizin-3-yl]butyrate (36.1 g) in a mixture of ethanol (200 ml) and tetrahydrofuran (200 ml). The mixture was stirred for 20 minutes at 0° C. and evaporated. The residual solution was poured into a mixture of diluted hydrochloric acid and ice, and extracted with a mixture of chloroform and methanol (10:1). The organic layer was washed with a sodium bicarbonate aqueous solution and brine, dried over magnesium sulfate and evaporated. The residue was washed with ethyl acetate and diethyl ether to give ethyl 4-[1-(4-hydroxybenzoyl)indolizin-3-yl]butyrate as yellow powder (29.3 g).
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([O:27][CH:28]=[CH2:29])[CH2:25][CH3:26])=[CH:4][CH:3]=1.[CH2:30]([Zn]CC)C.ICI>ClCCl>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([O:27][CH:28]2[CH2:30][CH2:29]2)[CH2:25][CH3:26])=[CH:4][CH:3]=1
Reactant: CC[Zn]CC
Reactant: C=COC(CC)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(OC)nc1C
Solvent: ClCCl
Solvent: ICI
Product: CCC(OC1CC1)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(OC)nc1C
Temperature: 0 °C
Reaction time: 5 h

Procedure:
To a solution of 9-chloro-6-[1-(ethenyloxy)propyl]-1-(6-methoxy-2-methylpyridin-3-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (65.0 mg, 0.157 mmol) in dichloromethane (1.5 mL) were added diethyl zinc (1.0 M solution in n-hexane, 0.787 mL, 0.787 mmol) and diiodomethane (0.13 mL, 1.57 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 5 hrs. The mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo, the residue was purified by silica gel column chromatography eluting with a 0-40% ethyl acetate/n-hexane gradient mixture to give the mixture contained title compound. To the solution of residue in ethyl acetate/MeOH (1.0 mL/0.5 mL) was added 4N hydrochloric acid/ethyl acetate (25 μL). The reaction mixture was stirred at room temperature for 3 hrs. After the mixture was concentrated. The residue was purified by silica gel column chromatography eluting with a 0-40% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless amorphous (7.0 mg, 0.0164 mmol, 10%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=O)=[CH:2]1.C(Cl)(=O)C(Cl)=O.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>ClCCl>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([N:23]2[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]2)=[O:12])=[CH:2]1
Reactant: O=C(O)c1c[nH]c2ccccc12
Reactant: CN1CCNCC1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: CN1CCN(C(=O)c2c[nH]c3ccccc23)CC1
Reaction time: 4 h

Procedure:
1H-Indole-3-carboxylic acid (1.61 g, 0.01 moles) was stirred with oxalyl chloride (0.99 g, 0.011 moles) in 20 mL dichloromethane at 0 to 25° C. for 3-4 hours. After completion of the reaction (TLC), volatile substances were distilled off under the reduced pressure. The residue was taken in 20 mL dichloroethane and to this stirred solution, was added N-methylpiperazine (1.1 g, 0.011 moles). The reaction mixture was further stirred for next 3-5 hours, till the reaction completes (TLC). Reaction mixture was diluted with dichloromethane 20 mL), washed with water, brine and saturated solution of sodium bicarbonate. The organic layer was dried over sodium sulfate and the organic solvents were evaporated under vacuo. The product was purified using column chromatography on silica gel G stationary phase and suitable combinations of ethyl acetate and methanol in increasing gradient, as the mobile phase.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.N1C=CC=CC=1.[CH2:19]([S:22](Cl)(=[O:24])=[O:23])[CH2:20][CH3:21]>C(Cl)Cl>[CH2:19]([S:22]([NH:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1)(=[O:24])=[O:23])[CH2:20][CH3:21]
Reactant: CCOC(=O)Cc1csc(N)n1
Reactant: CCCS(=O)(=O)Cl
Agent: CCOC(=O)Cc1csc(=N)[nH]1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCS(=O)(=O)Nc1nc(CC(=O)OCC)cs1
Temperature: 40 °C

Procedure:
A mixture of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate, which can be represented as ethyl 2-(2-imino-2,3-dihydro-1,3-thiazol-4-yl)acetate, (40 g.) and pyridine (200 ml.) was stirred in a stream of nitrogen gas at 40° C., and to the mixture was dropwise added a mixture of propanesulfonyl chloride (61.3 g.) and methylene chloride (100 ml.) over 2 hours, and then the mixture was stirred for 2 hours at the same temperature. After the reaction, pyridine and methylene chloride were distilled off from the reaction mixture. The residue was dissolved in ethyl acetate, and the solution was washed with water, 1/2 N hydrochloric acid and water in turn and then dried. The ethyl acetate was distilled off from the solution, and the residue was washed with a mixture of ethyl acetate and diethyl ether and then dried to give ethyl 2-(2-propanesulfonylamino-1,3-thiazol-4-yl)acetate, which can be represented as ethyl 2-(2-propanesulfonylimino-2,3-dihydro-1,3-thiazol-4-yl)acetate, (16.4 g.), mp 140° to 142° C.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][O:6][C@@H:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][C@@H:3]1[OH:21].[NH:22]1[C:30]2[C:25](=[CH:26][C:27]([CH:31]=O)=[CH:28][CH:29]=2)[CH:24]=[CH:23]1.C(O)(=O)C.C([C@@H]1CC=CCO1)(C1C=CC=CC=1)C1C=CC=CC=1>CC(C)=O>[CH:8]([C@H:5]1[CH2:4][C@H:3]([OH:21])[C@@H:2]([NH:1][CH2:31][C:27]2[CH:26]=[C:25]3[C:30](=[CH:29][CH:28]=2)[NH:22][CH:23]=[CH:24]3)[CH2:7][O:6]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: N[C@H]1CO[C@@H](C(c2ccccc2)c2ccccc2)C[C@@H]1O
Reactant: O=Cc1ccc2[nH]ccc2c1
Agent: C1=CC[C@@H](C(c2ccccc2)c2ccccc2)OC1
Solvent: CC(=O)O
Solvent: CC(C)=O
Product: O[C@H]1C[C@H](C(c2ccccc2)c2ccccc2)OC[C@@H]1NCc1ccc2[nH]ccc2c1

Procedure:
(2R,4S,5S)-5-amino-2-benzhydryl-tetrahydropyran-4-ol 31b (0.05 g, 0.18 mmol) was reacted with 1H-indol-5-carbaldehyde (0.03 g, 0.18 mmol), glacial acetic acid (0.01 g, 0.18 mmol) and NaCNBH3 (0.02 g, 0.35 mmol) (Procedure C) to give (2R,4S,5S)-2-benzhydryl-5-[(1H-indol-5-ylmethyl)-amino]-tetrahydropyran-4-ol, (+)32b, 0.05 g (69%, [α]D=(+)70.9, c=1, Acetone).
Reaction SMILES: [NH2:1][CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[NH:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@@H:14]([C:16](O)=[O:17])[CH3:15].C1C2C3C(=O)N(O)C(=O)C3C1C=C2.C1CCC(N=C=NC2CCCCC2)CC1>C(#N)C>[NH:13]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[C@@H:14]([C:16]([NH:1][CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4])=[O:17])[CH3:15]
Reactant: C[C@@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: NCC(=O)OCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1C2C3C=CC(C3)C2C(=O)N1O
Solvent: CC#N
Product: C[C@@H](NC(=O)OC(C)(C)C)C(=O)NCC(=O)OCc1ccccc1

Procedure:
To 7.4 g H-Gly-OBzl.p-Tos-OH, 100 ml acetonitrile was added, and this was followed by cooling with ice, then 3.1 ml TEA, 3.78 g Boc-D-Ala-OH, 3.96 g HONB and 4.54 g DCC were added, and this was followed by agitation for one night. The resulting DCU was filtered, and the filtrate was concentrated, then the resulting residue was dissolved in 300 ml AcOEt. The resulting solution was washed with 4% aqueous NaHCO3 and 10% aqueous citrate, after which it was dried with Na2SO4. The dried product, after concentration, was crystallized with petroleum benzine and collected by filtration.
Reaction SMILES: CC1C=C(C2OC3C=CC=CC=3C=2)C=C(C)C=1.C1(C2OC3C=CC=CC=3C=2)C=CC=CC=1.[CH3:33][C:34]1[CH:35]=[C:36]([C:41]2[O:42][C:43]3[CH:59]=[CH:58][CH:57]=[CH:56][C:44]=3[C:45]=2[C:46](=[O:55])[C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[CH:37]=[C:38]([CH3:40])[CH:39]=1.[CH2:60]([N:62]([CH2:67][CH3:68])[CH2:63][CH2:64]CCl)[CH3:61]>>[CH2:60]([N:62]([CH2:67][CH3:68])[CH2:63][CH2:64][CH2:54][O:53][C:50]1[CH:49]=[CH:48][C:47]([C:46]([C:45]2[C:44]3[CH:56]=[CH:57][CH:58]=[CH:59][C:43]=3[O:42][C:41]=2[C:36]2[CH:35]=[C:34]([CH3:33])[CH:39]=[C:38]([CH3:40])[CH:37]=2)=[O:55])=[CH:52][CH:51]=1)[CH3:61]
Reactant: COc1ccc(C(=O)c2c(-c3cc(C)cc(C)c3)oc3ccccc23)cc1
Reactant: CCN(CC)CCCCl
Agent: Cc1cc(C)cc(-c2cc3ccccc3o2)c1
Agent: c1ccc(-c2cc3ccccc3o2)cc1
Product: CCN(CC)CCCOc1ccc(C(=O)c2c(-c3cc(C)cc(C)c3)oc3ccccc23)cc1

Procedure:
Substitution of an equivalent amount of 2-(3,5-dimethylphenyl)benzofuran in the procedure of Example 2 for 2-phenylbenzofuran followed by demethylation of the 2-(3,5-dimethylphenyl)-3-(4-methoxybenzoyl)benzofuran thus formed and reaction of the resulting product with 3-diethylaminopropyl chloride as described therein gives the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11][S:12][CH3:13])[CH:10]=1)[NH:7][CH:6]=[CH:5]2.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)O)=[CH:17][CH:16]=1.FC1C=CC(C(C2C=CC(F)=CC=2)C2C3C(=C(CSC)C=CC=3)NC=2)=CC=1>>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([CH:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[C:5]2[C:4]3[C:8](=[C:9]([CH2:11][S:12][CH3:13])[CH:10]=[C:2]([F:1])[CH:3]=3)[NH:7][CH:6]=2)=[CH:19][CH:20]=1
Reactant: CSCc1cc(F)cc2cc[nH]c12
Reactant: OC(c1ccc(F)cc1)c1ccc(Cl)cc1
Agent: CSCc1cccc2c(C(c3ccc(F)cc3)c3ccc(F)cc3)c[nH]c12
Product: CSCc1cc(F)cc2c(C(c3ccc(F)cc3)c3ccc(Cl)cc3)c[nH]c12
Temperature: 80 °C
Reaction time: 4 h

Procedure:
The title compound was prepared starting from 500 mg (2.56 mmol) of the compound from Example 11A and 667 mg (2.56 mmol) of the compound from Example 81A in analogy to the synthesis of the compound from Example 278. A difference was that stirring at 80° C. was for only 4 h. 535 mg (50% of theory) of the target compound were obtained.
Reaction SMILES: [NH2:1][C:2]1[C:7](=[O:8])[C:6]2[CH:9]=[C:10]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][C:5]=2[O:4][CH:3]=1.CO[CH:27]1[CH2:31][CH2:30][CH:29](OC)O1.O>C(O)(=O)C>[CH3:17][S:14]([NH:13][C:11]1[C:10]([O:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:9][C:6]2[C:7](=[O:8])[C:2]([N:1]3[CH:27]=[CH:31][CH:30]=[CH:29]3)=[CH:3][O:4][C:5]=2[CH:12]=1)(=[O:15])=[O:16]
Reactant: COC1CCC(OC)O1
Reactant: CS(=O)(=O)Nc1cc2occ(N)c(=O)c2cc1Oc1ccccc1
Solvent: CC(=O)O
Solvent: O
Product: CS(=O)(=O)Nc1cc2occ(-n3cccc3)c(=O)c2cc1Oc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 43.7 %

Procedure:
In 5 ml of acetic acid were dissolved 500 mg of 3-amino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one and 250 mg of 2,5-dimethoxytetrahydrofuran. The mixture was stirred for 30 minutes at 70°-80° C. and then cooled to room temperature. 50 ml of water was added thereto. The resulting crystal was collected by filtration and recrystallized from ethyl acetate-diisopropyl ether to obtain 250 mg (yield: 43.7%) of 7-methylsulfonylamino-6-phenoxy-3-(1-pyrrolyl)-4H-1-benzopyran-4-one having a melting point of 238.5°-240° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH3:11][C:12]1[S:16][C:15]([C:17](Cl)=[O:18])=[CH:14][CH:13]=1>N1C=CC=CC=1>[S:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[NH:1][C:17]([C:15]1[S:16][C:12]([CH3:11])=[CH:13][CH:14]=1)=[O:18]
Reactant: Nc1nc2ccccc2s1
Reactant: Cc1ccc(C(=O)Cl)s1
Solvent: c1ccncc1
Product: Cc1ccc(C(=O)Nc2nc3ccccc3s2)s1

Procedure:
Using 2-amino-benzothiazole and 5-methyl-thiophene-2-carboxylic acid chloride in pyridine the title compound was obtained as a yellow solid (87% yield), MS: m/e=275.1 (M+H+).
Reaction SMILES: [I:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[CH3:19][Mg]Br.[Cl-].[NH4+].O>O1CCCC1>[I:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH:15]([OH:16])[CH3:19])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1
Reactant: O=Cc1ccc(-c2cn3cc(I)ccc3n2)cc1
Reactant: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Product: CC(O)c1ccc(-c2cn3cc(I)ccc3n2)cc1
Reaction time: 5 h

Procedure:
4-(6-Iodoimidazo[1,2-a]pyridin-2-yl)benzaldehyde (820 mg) was dissolved in tetrahydrofuran (25 mL), and the solution was stirred under ice cooling. Methyl magnesium bromide (787 mL) was added dropwise to the reaction mixture, followed by stirring for 15 minutes under ice cooling and then for 5 hours at room temperature. Aqueous saturated ammonium chloride solution (25 mL) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with dichloromethane-methanol. Subsequently, the solvent was evaporated, and the residue was purified through silica gel column chromatography (dichloromethane:methanol=97:3), followed by concentration under reduced pressure, to thereby yield the title compound (579 mg).