Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:23][O:24][CH2:25][CH2:26][N:27]1[C:31]([CH2:32][OH:33])=[N:30][C:29]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[N:28]1>C(Cl)Cl>[CH3:23][O:24][CH2:25][CH2:26][N:27]1[C:31]([CH:32]=[O:33])=[N:30][C:29]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[N:28]1
Reactant: COCCn1nc(-c2ccccc2)nc1CO
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: COCCn1nc(-c2ccccc2)nc1C=O

Procedure:
Dess-Martin periodinane (1530 mg, 3.60 mmol) was added to a stirred suspension of [2-(2-Methoxy-ethyl)-5-phenyl-2H-1,2,4-triazol-3-yl]-methanol (840 mg, 3.6 mmol) dissolved in Methylene chloride (36.0 mL) at rt under Ar. The solution was stirred ON. Some solid was filtered off and discarded. Sat NaHCO3 (35 ml) and more DCM (35 ml) were added to the DCM solution. The solvent was evaporated off and the crude product was purified by silica gel cromatography (Eluent: 50% EtOAc in heptane). Yield: 0.76 g of the title compound as an oil. H-NMR: (CDCl3) δ 10.04 (s, 1H), 8.13 (m, 2H), 7.45 (m, 3H), 4.82 (t, 2H), 3.83 (t, 2H), 3.32 (s, 3H).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:27]=[C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:29]=1[OH:30])[C:8]([NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18](=[O:26])OC1C=CC=CC=1)=[O:9])([CH3:4])([CH3:3])[CH3:2].[CH2:35]([NH:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C1C=CC=CC=1>[CH2:43]([N:42]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:18](=[O:26])[NH:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[NH:10][C:8](=[O:9])[C:7]1[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:29]([OH:30])=[C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
Reactant: CC(C)(C)c1cc(C(=O)Nc2ccccc2NC(=O)Oc2ccccc2)cc(C(C)(C)C)c1O
Reactant: c1ccc(CNCc2ccccc2)cc1
Solvent: c1ccccc1
Product: CC(C)(C)c1cc(C(=O)Nc2ccccc2NC(=O)N(Cc2ccccc2)Cc2ccccc2)cc(C(C)(C)C)c1O
Reaction time: 2 h
Yield: 24 %

Procedure:
Phenyl N-[2-(3,5-di-t-butyl-4-hydroxybenzoylamino)phenyl]carbamate (1.6 g) and dibenzylamine (0.7 g) were dissolved in benzene (10 ml) and stirred at 70°-80°0 C. for 2 hrs. The reaction solution was washed with 2N sodium hydroxide, saturated ammonium chloride solution, dried over anhydrous NaSO4 and the solvent was distilled off. Purification of the residue by a silica gel column chromatography followed by crystallization from ether afforded N-[2-(3,3-dibenzylureido )phenyl]-3,5-di-t-butyl-4-hydroxybenzamide (0.47 g, 23%).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[OH:25][CH2:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:3]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[O:10])=[N:4][C:5]([C:31]2[CH:30]=[CH:29][CH:28]=[C:27]([CH2:26][OH:25])[CH:32]=2)=[CH:6][N:7]=1
Reactant: OCc1cccc(B(O)O)c1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](NC(=O)c2nc(Br)cnc2N)C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC[C@H](NC(=O)c2nc(-c3cccc(CO)c3)cnc2N)C1
Temperature: 90 °C
Reaction time: 12 h
Yield: 93.7 %

Procedure:
1,1-dimethylethyl (3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate (765.0 mg, 1.91 mmol) was dissolved in DMF followed by addition of 3-hydroxymethyl phenylboronic acid (349.0 mg, 2.23 mmol), K2CO3 (660.0 mg, 4.77 mmol) and Pd(PPh3)4 (10 mol %, 220 mg). This mixture was stirred at 90° C. under nitrogen for 12 hours. The reaction mixture was poured into water (150 mL), and extracted with ethyl acetate (3×50 mL). The organic layers were washed with brine (50 mL) then dried over anhydrous sodium sulfate. Filteration, concentration and column chromatography on silica (50% ethylacetate/hexanes) gave a solid which was dried to affored 765.0 mg (92% yield) of 1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2yl}carbonyl)amino]piperidine-1-carboxylate: MS (EI) for C22H29N5O4: 428.23 (MH+).
Reaction SMILES: [SH:1][C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1.Cl[CH2:12][C:13]1[C:18]([CH3:19])=[C:17]([O:20][CH2:21][CH2:22][N:23]2[C:27](=[O:28])[CH2:26][CH2:25][C:24]2=[O:29])[CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[CH3:19][C:18]1[C:13]([CH2:12][S:1][C:2]2[NH:6][C:5]3[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=3[N:3]=2)=[N:14][CH:15]=[CH:16][C:17]=1[O:20][CH2:21][CH2:22][N:23]1[C:27](=[O:28])[CH2:26][CH2:25][C:24]1=[O:29]
Reactant: Cc1c(OCCN2C(=O)CCC2=O)ccnc1CCl
Reactant: Sc1nc2ccccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: Cc1c(OCCN2C(=O)CCC2=O)ccnc1CSc1nc2ccccc2[nH]1
Yield: 112.1 %

Procedure:
A mixture comprising 0.03 g (0.18 mmol) of 2-mercapto-1H-benzimidazole, 0.06 g (0.21 mmol) of 2-chloromethyl-3-methyl-4-(2-succinimidoethoxy)pyridine, 0.03 g (0.21 mmol) of potassium carbonate and 10 ml of methyl ethyl ketone was heated under reflux in a nitrogen atmosphere for 3 hours, cooled and filtered. The filtrate was concentrated and dried in a vacuum, followed by the addition of water. The obtained mixture was extracted with 50 ml of chloroform thrice. The extract was dried over magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to obtain 0.08 g of 2-[{3-methyl-4-(2-succinimidoethoxy)pyridine-2-yl}methylthio]-1H-benzimidazole as a white crystal.
Reaction SMILES: [CH:1]([C:4]1[N:8]2[CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:20][OH:21])[CH:11]=[CH:12][C:7]2=[N:6][N:5]=1)([CH3:3])[CH3:2].[CH2:22]([N:24]=[C:25]=[O:26])[CH3:23]>>[CH:1]([C:4]1[N:8]2[CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:20][O:21][C:25](=[O:26])[NH:24][CH2:22][CH3:23])[CH:11]=[CH:12][C:7]2=[N:6][N:5]=1)([CH3:3])[CH3:2]
Reactant: CCN=C=O
Reactant: CC(C)c1nnc2ccc(Oc3ccccc3CO)cn12
Product: CCNC(=O)OCc1ccccc1Oc1ccc2nnc(C(C)C)n2c1
Temperature: 60 °C
Yield: 48 %

Procedure:
A suspension of [2-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-phenyl]-methanol (28 mg, 0.1 mmol) and ethyl isocyanate (14 μL, 0.2 mmol) was heated at 60° C. for 18 hours. The reaction was then cooled and concentrated in vacuo to an oil. The crude was purified by flash chromatography (eluting with 2% methanol/ethyl acetate), followed by suspension in 7:3 hexane:ethyl acetate. The solid was filtered to give the title compound as a white solid (17 mg, 48%) LCMS (m/z) 355.4 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6](Cl)[C:5]([Cl:12])=[CH:4][N:3]=1.[N:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[Cl:12][C:5]1[C:6]([N:23]2[CH2:24][CH2:25][N:20]([CH2:19][C:16]3[CH:15]=[CH:14][N:13]=[CH:18][CH:17]=3)[CH2:21][CH2:22]2)=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([NH2:1])=[N:3][CH:4]=1
Reactant: c1cc(CN2CCNCC2)ccn1
Reactant: Nc1ncc(Cl)c(Cl)c1[N+](=O)[O-]
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1ncc(Cl)c(N2CCN(Cc3ccncc3)CC2)c1[N+](=O)[O-]
Temperature: 45 °C

Procedure:
To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.052 g, 0.25 mmol) and isopropanol (4.5 ml) was added 1-[(4-pyridyl)-methyl]-piperazine (0.049 g, 0.28 mmol) followed by diisopropylethylamine (0.05 ml, 0.28 mmol). The reaction mixture was heated at 45° C. for 24 h, then allowed to cool to room temperature, and diluted with isopropanol (3 ml). The precipitate was collected by filtration and washed with isopropanol and diethyl ether. The title compound was thus obtained as yellow solid (0.035 g). The filtrate was concentrated in vacuo, and purification of the residue on a isolute silica column using 0 to 5% methanol in ethyl acetate/dichloromethane (v/v; 1:1) as eluant gave an additional 0.036 g of the product (total yield: 81%); 1H-NMR (500 MHz, DMSO-d6) 3.09 (br s, 4H, piperazine N(CH2)2), 3.57 (s, 2H, NCH2), 6.96 (s, 2H, NH2), 7.34 (d, J=5.81 Hz, 2H), and 8.51 (d, J=5.88 Hz, 2H) (pyrid-4-yl protons), 8.06 (s, 1H, 6-H);
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=O)[C:5]([NH2:11])=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[N:20]=[C:21]=[O:22].S(=O)(=O)(O)O>C(OCC)(=O)C>[Cl:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[N:20]1[C:7](=[O:9])[C:6]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=2)[NH:11][C:21]1=[O:22]
Reactant: Nc1ccc(F)cc1C(=O)O
Reactant: O=C=Nc1ccc(Cl)cc1Cl
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Product: O=c1[nH]c2ccc(F)cc2c(=O)n1-c1ccc(Cl)cc1Cl
Temperature: 65 °C
Reaction time: 2 h
Yield: 90.8 %

Procedure:
In a four-necked flask equipped with stirrer, reflux cooler, thermometer and dropping funnel, 31 g of 5-fluoroanthranilic acid were dissolved in 280 ml of ethyl acetate at 50° C. To this were added dropwise in the course of 20 minutes 37.6 g of molten 2,4-dichlorophenyl isocyanate from a heatable dropping funnel. The internal temperature increased to 65° C., at which the reaction mixture thickened, but still remained stirrable. It was further stirred for 2 hours under reflux, then cooled to 70° C. and 39.5 g of concentrated sulphuric acid were added dropwise in the course of 10 minutes. The internal temperature again increased to reflux temperature. At this temperature the mixture was further stirred for 4.5 hours, a readily stirrable suspension resulting. The mixture was then cooled to room temperature, the product filtered off by suction and washed twice on the filter each time using 75 ml of ethyl acetate. After drying, 59 g of 3-(2,4-dichlorophenyl)-6-fluoroquinazoline-2,4-dione were obtained having a melting point above 250° C., in a purity of 99% and in a yield of 89.8% of theory.
Reaction SMILES: [OH:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([C:8]2[CH:28]=[CH:27][C:11]([CH2:12][S:13][C:14]3[N:23]([CH3:24])[C:22](=[O:25])[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][C:20]=4[CH3:26])[N:15]=3)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.Cl.[Cl:32][CH2:33][CH2:34][N:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[ClH:32].[CH3:24][N:23]1[C:22](=[O:25])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][C:20]=2[CH3:26])[N:15]=[C:14]1[S:13][CH2:12][C:11]1[CH:27]=[CH:28][C:8]([C:6](=[O:7])[C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:33][CH2:34][N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)=[CH:30][CH:29]=2)=[CH:9][CH:10]=1
Reactant: Cc1cccc2nc(SCc3ccc(C(=O)c4ccc(O)cc4)cc3)n(C)c(=O)c12
Reactant: ClCCN1CCCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cccc2nc(SCc3ccc(C(=O)c4ccc(OCCN5CCCC5)cc4)cc3)n(C)c(=O)c12
Yield: 44.8 %

Procedure:
A solution of 2-[4-(4-hydroxybenzoyl)benzylthio]-3,5-dimethyl-4(3H)-quinazolinone (384 mg), 1-(2-chloroethyl)pyrrolidine hydrochloride (181 mg) and potassium carbonate (414 mg) in DMF (5 ml) was stirred at 60° C. for 62 hours. This reaction mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water, and dried. Then, hydrogen chloride/ethyl acetate was added and the precipitated hydrochloride was collected by filtration to provide the title compound as colorless solid (227 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9](=O)[C:10]#[C:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:20][NH2:21]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[NH:21][N:20]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: NN
Reactant: CC(C)(C)OC(=O)C#CC(=O)c1ccc(Cl)c(Cl)c1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)c1cc(-c2ccc(Cl)c(Cl)c2)n[nH]1

Procedure:
To a solution of the intermediate from step B (4.74 g, 15.84 mmol) in DMF (30 mL) was added hydrazine (1.58 mL, 35% by wt., 17.43 mmol). After stirring the reaction at room temperature for 18 hours, it was concentrated in vacuo. The residue was suspended in ethyl acetate and washed with water (2×) and saturated NaCl solution (2×). The organic layer was dried over anhydrous MgSO4 filtered and concentrated in vacuo. 1H NMR (CDCl3, 500 MHz): 8.02 (s, 1H), 7.69 (d, J=8.2 Hz, 1H), 7.52 (d, J=8.2 Hz, 1H), 7.07 (s, 1H), 1.66 (s, 9H). LC-MS=2.52 min; (M+H−56)=257.1.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN([CH:10]=[O:11])C>>[NH2:1][C@@H:6]([CH:5]1[CH2:6][C:5]2[C:3](=[CH:2][CH:2]=[CH:3][CH:4]=2)[CH2:4]1)[CH2:10][OH:11]
Reactant: C1CCNCC1
Reactant: CN(C)C=O
Product: N[C@H](CO)C1Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 19 h

Procedure:
20% Piperidine in DMF (15 mL) was added to a solution of 9 H-fluoren-9-ylmethyl-(1S)-1-(2,3-dihydro-1H-inden-2-yl)-2-hydroxyethylcarbamate (1.05 g, 2.63 mmol) in DMF (5 mL). The reaction was stirred at 25° C. for 19 h. After solvent evaporation, the crude product was dissolved in ethyl acetate (50 mL) and dried over MgSO4, filtered and concentrated to obtain a crude yellow oil (1.05 g). Mass Spectrum (+ESI): 179 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[C:12]([CH3:13])=[CH:11][C:8]([CH:9]=O)=[CH:7][C:6]=1[CH3:14].[NH2:15][C:16]1[CH:31]=[CH:30][CH:29]=[CH:28][C:17]=1[C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:19].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C.O>[F:27][C:24]1[CH:25]=[CH:26][C:21]([N:20]2[C:18](=[O:19])[C:17]3[C:16](=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:15]=[C:9]2[C:8]2[CH:11]=[C:12]([CH3:13])[C:5]([O:4][CH2:3][CH2:2][OH:1])=[C:6]([CH3:14])[CH:7]=2)=[CH:22][CH:23]=1
Reactant: Nc1ccccc1C(=O)Nc1ccc(F)cc1
Reactant: Cc1cc(C=O)cc(C)c1OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: Cc1cc(-c2nc3ccccc3c(=O)n2-c2ccc(F)cc2)cc(C)c1OCCO
Temperature: 155 °C

Procedure:
To a mixture of 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (0.420 g, 2.17 mmol) and 2-amino-N-(4-fluoro-phenyl)-benzamide (0.500 g, 2.17 mmol) in N,N-dimethylacetamide (5 mL) was added sodium hydrogen sulfite (0.350 g, 3.26 mmol) and p-toluenesulfonic acid (0.21 g, 0.11 mmol). The reaction mixture was heated at 155° C. for 14 hours. The reaction mixture was cooled to room temperature and diluted with cold water (20 mL) to produce the precipitate. The yellow solid was filtered, washed with cold water (2×20 mL), methanol, and dried under vacuum to provide crude product, which was purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent) to give the title compound as white solid. Yield: 0.10 g (11%). MP 95-97° C. 1H-NMR (400 MHz, CDCl3): δ 8.35 (d, 1H), 7.81-7.78 (d, 2H), 7.58-7.40 (m, 1H), 7.20-7.15 (m, 2H), 7.15-7.01 (m, 4H), 3.98-3.80 (m, 4H), 2.21 (s, 6H), 2.01 (t, 1H). MS (ES+) m/z: 405.01 (M+1).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[CH:16]=[C:15]([CH3:17])[C:14]([O:18][CH3:19])=[C:13]([CH3:20])[CH:12]=3)[O:10][C:3]=12.[CH3:21][C:22]1[C:30]([NH2:31])=[CH:29][CH:28]=[C:27]2[C:23]=1[CH:24]=[CH:25][NH:26]2>>[CH3:19][O:18][C:14]1[C:15]([CH3:17])=[CH:16][C:11]([C:9]2[O:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[NH:31][C:30]3[C:22]([CH3:21])=[C:23]4[C:27](=[CH:28][CH:29]=3)[NH:26][CH:25]=[CH:24]4)[CH:8]=2)=[CH:12][C:13]=1[CH3:20]
Reactant: COc1c(C)cc(-c2cc3nccc(Cl)c3o2)cc1C
Reactant: Cc1c(N)ccc2[nH]ccc12
Product: COc1c(C)cc(-c2cc3nccc(Nc4ccc5[nH]ccc5c4C)c3o2)cc1C

Procedure:
The title compound was prepared by procedure E using 7-chloro-2-(4-methoxy-3,5-dimethylphenyl)furo[3,2-b]pyridine (28.90 mg; 0.10 mmol; 1.00 eq.) instead of 7-chloro-2-(3,4,5-trimethoxyphenyl)furo[3,2-b]pyridine, and 4-methyl-1H-indol-5-ylamine (15.42 mg; 0.11 mmol; 1.05 eq.) instead of 6-amino-2,2-difluoro-4H-benzo[1,4]oxazin-3-one, and was obtained as a white solid (22 mg, 56%). (HPLC (method F): 99%, RT: 4.37 min); 1H NMR (500 MHz, DMSO-d6) δ [ppm] 11.15 (s, 1H), 8.51 (s, 1H), 7.94 (d, J=5.5, 1H), 7.54 (s, 2H), 7.38 (t, J=2.7, 1H), 7.30 (d, J=8.3, 1H), 7.25 (s, 1H), 7.00 (d, J=8.4, 1H), 6.52 (s, 1H), 6.14 (d, J=5.5, 1H), 3.69 (s, 3H), 2.35 (s, 3H), 2.25 (s, 6H); MS (m/z) 398 [M+H]+, RT: 4.2 min.
Reaction SMILES: [CH3:1][N:2]([C@@H:12]([C:24](=[O:39])[N:25]([CH3:38])[C@@H:26]([C:34](=[O:37])[NH:35][CH3:36])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:3](=[O:11])/[CH:4]=[CH:5]/[CH2:6][C:7]([NH2:10])([CH3:9])[CH3:8].C(O)(=O)C.[Si:44]([O:51][C@H:52]([CH3:55])[CH:53]=O)([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45].C([BH3-])#N.[Na+]>CO>[Si:44]([O:51][C@H:52]([CH3:55])[CH2:53][NH:10][C:7]([CH3:8])([CH3:9])[CH2:6]/[CH:5]=[CH:4]/[C:3]([N:2]([C@H:12]([CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:24]([N:25]([C@H:26]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:34]([NH:35][CH3:36])=[O:37])[CH3:38])=[O:39])[CH3:1])=[O:11])([C:47]([CH3:48])([CH3:49])[CH3:50])([CH3:46])[CH3:45]
Reactant: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)/C=C/CC(C)(C)N
Reactant: C[C@H](C=O)O[Si](C)(C)C(C)(C)C
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)/C=C/CC(C)(C)NC[C@@H](C)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 23.5 %

Procedure:
(2E)-5-Amino-5-methylhex-2-enoic acid N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)amide (318 mg, 0.60 mmol) was dissolved in methanol (20 ml) and glacial acetic acid (0.48 ml, 8.4 mmol). 3 Å mol sieves (9 g) and a solution of (2R)-2-(tert-butyldimethylsilyloxy)propanal (1.33 9, 7.06 mmol) in methanol (10 ml) were added successively. Sodium cyanoborohydride (220 mg, 3.53 mmol) was added as a solid. The reaction mixture was stirred at room temperature for 45 min, before a second batch of sodium cyanoborohydride (220 mg, 3.53 mmol) was added. The reaction mixture was stirred for 16 h at room temperature. The mol sieves was filtered off through a plug of celite. The celite was washed with methanol (200 ml). The solvents of the combined filtrates were removed in vacuo. The residue was dissolved in 1 N sodium hydroxide solution (50 ml) and tert-butyl methyl ether (50 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×50 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (35 g), using ethyl acetate/heptane/triethylamine (20:10:1) as eluent, to give 99 mg of (2R)-2-(N-((2R)-2-(N-((2E)-5-((2R)-2-(tert-butyldimethylsilyloxy)propylamino)-5-methylhex-2-enoyl)-N-methylamino)-3-(2-naphthyl)propionyl)-N-methylamino)-N-methyl-3-phenylpropionamide.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH3:15])[CH:12]=2)[C:7](=O)[CH2:6]1.Cl.[NH2:19][OH:20].C([O-])(=O)C.[Na+].CO>O>[CH3:1][O:2][C:3](=[O:17])[CH2:4][CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH3:15])[CH:12]=2)[C:7](=[N:19][OH:20])[CH2:6]1
Reactant: NO
Reactant: COC(=O)CC1CC(=O)c2ccc(OC)cc21
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)CC1CC(=NO)c2ccc(OC)cc21
Temperature: 25 °C

Procedure:
(6-Methoxy-3-oxo-indan-1-yl)-acetic acid methyl ester (12.0 g), hydroxylamine hydrochloride (4.6 g), and sodium acetate (5.5 g) dissolved in water (40 mL) and methanol (50 mL) are stirred at reflux temperature for 3 h. After cooling to room temperature, water (100 mL) is added and the solution is extracted with ethyl acetate. The combined organic extracts are washed with water and brine and dried (MgSO4). The solvent is evaporated to give the product as a brown oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.Cl[Sn](Cl)(Cl)Cl.[CH2:14]=[O:15].Cl>C1(C)C=CC=CC=1.O>[OH:8][C:4]1[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][C:5]=1[CH:14]=[O:15]
Reactant: C=O
Reactant: Cc1cccc(O)c1
Agent: Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1ccc(C=O)c(O)c1
Temperature: 100 °C
Reaction time: 0.33 h
Yield: 25.5 %

Procedure:
To a stirred solution of 3-methyl-phenol (1 g, 9.2 mmol) in toluene (5 ml) at room temperature under nitrogen was added SnCl4 (241 mg, 0.92 mmol) and tri-nbutylamine (0.6 ml, 2.77 mmol). After 20 min, paraformaldehyde (611 mg, 20.3 mmol) was added and the whole stirred at 100° C. for 16 h. The reaction mixture was diluted with water (20 ml) and acidified with 2N HCl to pH2. The solution was extracted with ether (25 ml), washed with brine (20 ml), dried (MgSO4) filtered and evaporated to a brown oil. This oil was purified by column chromatography using 5% EtOAc in pentane as eluant to provide the title product (319 mg, 25%); 1HNMR (400 MHz, CDCl3) δ: 2.3 (s, 3H), 6.75 (m, 2H), 7.35 (d, 1H), 9.75 (s, 1H), 11.00 (s, 1H).
Reaction SMILES: C1(S(O[CH2:11][CH2:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH3:24])[CH:21]=3)[CH:16]=[CH:15][CH:14]=2)(=O)=O)C=CC=CC=1.[C:25]1(=[O:35])[NH:29][C:28](=[O:30])[C:27]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]12.[K].O>CN(C)C=O>[CH3:24][O:23][C:20]1[CH:21]=[C:22]2[C:17]([CH:16]=[CH:15][CH:14]=[C:13]2[CH2:12][CH2:11][N:29]2[C:28](=[O:30])[C:27]3=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]3[C:25]2=[O:35])=[CH:18][CH:19]=1
Reactant: COc1ccc2cccc(CCOS(=O)(=O)c3ccccc3)c2c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc2cccc(CCN3C(=O)c4ccccc4C3=O)c2c1
Temperature: 25 °C
Yield: 79.5 %

Procedure:
The compound IV (14 g, 0.041 mol) produced as described above and potassium phthalimide (8.3 g, 0.045 mol) were added into a flask containing dimethylformamide (180 ml) as a solvent, heated and refluxed for 2 hours. After cooling the content to room temperature, 200 ml of water was added. The mixture was stirred and filtered. The filter cake formed was washed with water and dried, to produce 10.8 g of N-[2-(7-methoxy-1-naphthyl)ethyl]phthalimide (II). The yield was 80%. The melting point was 159-160° C.
Reaction SMILES: N1C=CC=CC=1.[CH3:7][N:8]([CH2:10][CH2:11][OH:12])[CH3:9].[C:13](Cl)(=[O:23])[CH:14]=[CH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>O1CCCC1>[C:13]([O:12][CH2:11][CH2:10][N:8]([CH3:9])[CH3:7])(=[O:23])/[CH:14]=[CH:15]/[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CN(C)CCO
Reactant: CCCCCCCC=CC(=O)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CCCCCCC/C=C/C(=O)OCCN(C)C

Procedure:
Thionyl chloride (8 ml) was added to trans-2-decenoic acid (3.4 g, 0.02 mol) followed by refluxing on a hot water bath for 2 hours. An excessive thionyl chloride was evaporated in vacuo to give 2-decenoic acid chloride. Pyridine (1 ml) was added to a solution of N,N-dimethylaminoethanol (2.0 g, 0.022 mol) in tetrahydrofuran (30 ml) followed by dropping into a solution of 2-decenoic acid chloride in tetrahydrofuran (20 ml). The reaction solution was heated to reflux on a hot water bath for 3 hours, tetrahydrofuran was evaporated in vacuo, water and ethyl acetate were added to the residue to partition and an ethyl acetate layer was collected therefrom. The ethyl acetate layer was washed with water and evaporated followed by purifying by silica gel column chromatography (developer: chloroform) to give the aimed compound as a light brown oily product.