Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:11][C:12]1[N:17]2[N:18]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:20]=[C:16]2[N:15]=[C:14]([CH3:27])[C:13]=1[CH2:28][C:29]([O:31][CH3:32])=[O:30].C1(C2[O:41]N2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[Cl:11][C:12]1[N:17]2[N:18]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:20]=[C:16]2[N:15]=[C:14]([CH3:27])[C:13]=1[CH:28]([OH:41])[C:29]([O:31][CH3:32])=[O:30]
Reactant: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Reactant: COC(=O)Cc1c(C)nc2cc(-c3ccccc3)nn2c1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)C(O)c1c(C)nc2cc(-c3ccccc3)nn2c1Cl
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 50.9 %

Procedure:
To a stirred solution of KHMDS (0.5 M in toluene, 9.50 mL, 4.75 mmol) in THF (24 mL) at −78° C. was added a solution of methyl 2-(7-chloro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (1 g, 3.17 mmol) in THF (24 mL) dropwise over 40 min. The mixture was stirred at −78° C. for 30 min. A solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (1.241 g, 4.75 mmol) in THF (24 mL) was added over 20 min and the reaction mixture was stirred for additional 30 min at −78° C. The reaction mixture was quenched with saturated NH4Cl aqueous solution (4 mL). The reaction mixture was allowed to warm to room temperature and then diluted with ethyl acetate (100 mL). The organic phase was washed with water and brine and dried with sodium sulfate. The solvent was evaporated. Purification by silica gel chromatography provided the title compound (535 mg, 50.9%). 1H-NMR (500 MHz, CDCl3) δ ppm 2.62 (3H, s), 3.83 (3H, s), 5.29 (1H, s), 5.76 (1H, s), 6.94 (1H, s), 7.38-7.50 (3H, m), 8.00-8.02 (2H, m).
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:19])([C:7]3[CH:15]=[CH:14][C:13]([C:16]([OH:18])=[O:17])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:20].C(Cl)(=O)C(Cl)=O.[C:27]1(O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.N1C=CC=CC=1>CN(C)C=O.C1COCC1.C(OCC)(=O)C.C1C=CC=CC=1>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:19])([C:7]3[CH:15]=[CH:14][C:13]([C:16]([O:18][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[O:17])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:20]
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(C(=O)O)cc3CC[C@@H]12
Reactant: Oc1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: CN1C(=O)CC[C@]2(C)c3ccc(C(=O)Oc4ccccc4)cc3CC[C@@H]12
Temperature: 25 °C
Reaction time: 1.25 h
Yield: 11 %

Procedure:
A 50 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-carboxy-10b-methyl-1,2,3,4,4a,-5,6,10b-octahydrobenzo[f]quinolin-3-one (300 mg, 1.10 mmol) and 6 mL of benzene. Oxalyl chloride (3.3 mmol) was added dropwise via syringe to the stirred mixture, followed by a catalytic amount of dimethylformamide (two drops). It was allowed to stir at room temperature for 75 min. and then the volatiles were removed in vacuo. Four mL of THF was added, followed by a solution of phenol and pyridine (4 eq) in 2 mL of THF at 0°. It was allowed to warm to room temperature, diluted with 50 mL of ethyl acetate, and washed with 0.1N hydrochloric acid (2×25 mL), 10% sodium bicarbonate (2×25 mL), water, (2×25 mL), and brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated and chromatographed on silica (0-2% methanol/dichloromethane gradient eluent), followed by additional chromatography (80% ethyl acetate/hexanes eluent) to give 43 mg (11%) of the title compound as a yellow solid. mp 194°-196°. FDMS: m/e=349. α[D]589 =+78.53 (c=1.00, chloroform).
Reaction SMILES: Cl[C:2]1[C:11]([Cl:12])=[N:10][C:9]2[C:4](=[CH:5][C:6]([CH3:17])=[C:7]([C:13]([O:15][CH3:16])=[O:14])[CH:8]=2)[N:3]=1.N1C=CC=CC=1.O.[NH2:25][NH2:26]>CO>[Cl:12][C:11]1[C:2]([NH:25][NH2:26])=[N:3][C:4]2[C:9]([N:10]=1)=[CH:8][C:7]([C:13]([O:15][CH3:16])=[O:14])=[C:6]([CH3:17])[CH:5]=2
Reactant: NN
Reactant: COC(=O)c1cc2nc(Cl)c(Cl)nc2cc1C
Solvent: O
Solvent: CO
Solvent: c1ccncc1
Product: COC(=O)c1cc2nc(Cl)c(NN)nc2cc1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 3.57 g of methyl 2,3-dichloro-7-methylquinoxaline-6-carboxylate in 214 mL of methanol were added 7.0 mL of pyridine and 2.34 mL of hydrazine monohydrate at 0° C., and then the mixture was stirred at room temperature overnight. The mixture was concentrated until its total amount reached about 100 mL, and water was added thereto, followed by stirring at room temperature for 1 hour. The precipitate was collected by filtration, washed with water and ethanol, and dried under reduced pressure to obtain 2.94 g of methyl 3-chloro-2-hydrazino-7-methylquinoxaline-6-carboxylate.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]3[CH2:11][CH2:12][C:13]4([CH2:18][C:9]=3[S:8][C:4]=2[N:5]=[CH:6][N:7]=1)[O:17][CH2:16][CH2:15][O:14]4.[Cl:19][C:20]1[CH:21]=[C:22]([NH2:34])[CH:23]=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1.Cl>C(O)C>[ClH:1].[Cl:19][C:20]1[CH:21]=[C:22]([NH:34][C:2]2[C:3]3[C:10]4[CH2:11][CH2:12][C:13]5([CH2:18][C:9]=4[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[O:17][CH2:16][CH2:15][O:14]5)[CH:23]=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1
Reactant: Clc1ncnc2sc3c(c12)CCC1(C3)OCCO1
Reactant: Nc1ccc(OCc2ccccn2)c(Cl)c1
Agent: Cl
Solvent: CCO
Product: Clc1cc(Nc2ncnc3sc4c(c23)CCC2(C4)OCCO2)ccc1OCc1ccccn1
Temperature: 80 °C
Reaction time: 12 h

Procedure:
To ethanol (60 mL) were sequentially added 4-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2′-[1,3]dioxolane] (5.70 g, 20.2 mmol), 3-Chloro-4-(pyridin-2-ylmethoxyl)-phenylamine (4.78 g, 20.37 mmol), and HCl in ethanol (1N, 4 mL). The suspension was stirred with heating to 80° C., upon which time the contents turn brown and homogeneous. After 12 h, the dark orange-yellow heterogeneous mixture was removed from heating, and allowed to cool to rt. The contents were concentrated down to about 30 mL in volume and the precipitate was collected by filtration as a light-brown solid (10.1 g, 92%). 1H-NMR (DMSO-d6) δ 8.71 (d, 1H), 8.40 (s, 1H), 8.33 (s, 1H), 8.10 (td, 1H), 7.80 (d, 1H), 7.75 (d, 1H), 7.56 (m, 2H), 7.25 (d, 1H), 5.48 (br, 1H), 5.38 (s, 2H), 3.99 (s, 4H), 3.28 (t, 2H), 3.03 (s, 2H), 1.97 (t, 2H); LCMS RT=2.73 min; [M+H]+=481.1.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[C:13]([CH:20]=O)=[CH:14][NH:15]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O>CS(C)=O.[Cl-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1>[CH2:3]([O:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[C:13](/[CH:20]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH:14][NH:15]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=Cc1c[nH]c2cccc(OCc3ccccc3)c12
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: C(=C/c1c[nH]c2cccc(OCc3ccccc3)c12)\c1ccccc1
Temperature: 65 °C
Reaction time: 1 h
Yield: 197.7 %

Procedure:
To a suspension of sodium hydride (60%, 48 mg) in dimethyl sulfoxide (3 mL) was added benzyltriphenylphosphonium chloride (0.47 g), and the mixture was stirred at 65° C. for 1 hour. The reaction mixture was cooled in ice. To the mixture was added 4-benzyloxy-3-formylindole (0.25 g), and the mixture was stirred at 85° C. for 3 hours. The reaction mixture was cooled to room temperature. To the mixture was added water, and the mixture was extracted with ethyl acetate (three times). The extract was washed with water twice, a saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: n-hexane/ethyl acetate=3/1) to give the title compound (0.32 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([CH3:12])=[CH:5]2.[N+:13]([O-])([O-:15])=[O:14].[K+].N>OS(O)(=O)=O>[Cl:1][C:2]1[C:3]([N+:13]([O-:15])=[O:14])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([CH3:12])=[CH:5]2
Reactant: Cc1cnc2ccc(Cl)cc2c1
Reactant: O=[N+]([O-])[O-]
Agent: N
Agent: O=S(=O)(O)O
Agent: [K+]
Product: Cc1cnc2ccc(Cl)c([N+](=O)[O-])c2c1
Temperature: 0 °C
Reaction time: 12 h
Yield: 89.6 %

Procedure:
To a solution of 6-chloro-3-methylquinoline (6.3 g, 35.6 mmol) in concentrated H2SO4 (22 mL) was added dropwise a solution of KNO3 (3.77 g, 37.2 mmol) in concentrated H2SO4 (22 mL) at 0° C. Care was taken that the temperature of the reaction mixture did not rise above 10° C. The reaction mixture was stirred for 1 h at 0° C. and 12 h at room temperature. It was then poured onto ice (150 g) and rendered basic (pH=10) with a 33% aqueous ammonia solution. A dark yellow precipitate was formed, which was filtered off, thoroughly rinsed with water and dried in vacuo to afford the title compound as a brown solid (7.1 g, 31.9 mmol, 90%). 1H NMR (400 MHz, CDCl3, 298 K): δ=8.89 (s, 1H), 8.20 (d, J=9.0 Hz, 1H), 7.82 (s, 1H), 7.72 (s, 1H), 2.59 (s, 3H). MS (ES+): 223 (M(C10H735ClN2O2)+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C@H:10]([C:12]([OH:14])=O)[CH3:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:15][C@H:16]1[CH2:23][CH2:22][CH2:21][NH:20][C:18](=[O:19])[CH2:17]1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([C:12]([NH:15][CH:16]2[CH2:23][CH2:22][CH2:21][NH:20][C:18](=[O:19])[CH2:17]2)=[O:14])[CH3:11])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: N[C@H]1CCCNC(=O)C1
Reactant: C[C@H](Nc1ccc(Cl)c(Cl)c1)C(=O)O
Product: CC(Nc1ccc(Cl)c(Cl)c1)C(=O)NC1CCCNC(=O)C1

Procedure:
Following General Procedure A above using N-(3,4-dichlorophenyl)-D,L-alanine (Example Q) and 3-(S)-amino-ε-caprolactam (Sigma), the title compound was prepared as a solid having a melting point of 199° C. The reaction was monitored by tlc on silica gel (Rf=0.4 in 50% ethyl acetate/hexanes) and purification was by preparative thin layer chromatography using 50% ethyl acetate/hexanes as the eluant.
Reaction SMILES: C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH:30]=[CH:31][C:32]=1[O:33][CH2:34][C:35]1[N:36]=[C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[O:38][CH:39]=1)[CH:23]=[CH:24][C:25](OCC)=[O:26].Cl>O1CCCC1.CO>[CH3:18][O:19][C:20]1[CH:21]=[C:22](/[CH:23]=[CH:24]/[CH2:25][OH:26])[CH:30]=[CH:31][C:32]=1[O:33][CH2:34][C:35]1[N:36]=[C:37]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[O:38][CH:39]=1
Reactant: CCOC(=O)C=Cc1ccc(OCc2coc(-c3ccccc3)n2)c(OC)c1
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: C1CCOC1
Solvent: CO
Solvent: Cc1ccccc1
Product: COc1cc(/C=C/CO)ccc1OCc1coc(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 98.7 %

Procedure:
A toluene solution of diisobutylaluminum hydride (1.5M, 72.2 ml) was added dropwise, at 0° C., to a solution of ethyl 3-methoxy-4-(2-phenyl-4-oxazolylmethoxy)cinnamate (16.4 g) in tetrahydrofuran (THF) (240 ml). The mixture was stirred for 2 hours at room temperature, to which was added, under ice-cooling, methanol (7 ml). The reaction mixture was poured into 2N HCl (600 ml), which was subjected to extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and concentrated to yield (E)-3-[3-methoxy-4-(2-phenyl-4-oxazolylmethoxy)phenyl]-2-propen-1-ol (14.4 g, 98%), which was recrystallized from ethyl acetate-hexane to give colorless needles, m.p.113-114° C.
Reaction SMILES: [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[C:6](#[N:9])[CH:7]=[CH2:8]>>[N:1]1([CH2:8][CH2:7][CH2:6][NH2:9])[CH:5]=[N:4][CH:3]=[N:2]1
Reactant: C=CC#N
Reactant: c1nc[nH]n1
Product: NCCCn1cncn1

Procedure:
A mixture of about 20.7 of 1H-1,2,4-triazole and about 37.5 ml of acrylonitrile was heated on a steam bath for about 3 hours and then concentrated to an oil. This oil was added to about 200 ml of methanol and about 100 ml of concentrated ammonium hydroxide containing Raney nickel catalyst in a Paar apparatus and hydrogenated for about 81/4 hours with an uptake of about 46 psi of hydrogen. The catalyst was removed by filtration and ethanol was added to the filtrate. The mixture was filtered, the filtrate was concentrated, then reconcentrated from toluene, giving about 36.6 g of the desired intermediate as an oil.
Reaction SMILES: [C@@H:1]1([N:9]2[C:13]3[N:14]=[C:15]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[NH:16][C:17](=[O:18])[C:12]=3[C:11]([I:25])=[CH:10]2)[O:6][C@H:5]([CH2:7][OH:8])[C@@H:3]([OH:4])[CH2:2]1.[CH3:26][O:27][C:28]1[CH:49]=[CH:48][C:31]([C:32](Cl)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[CH:30][CH:29]=1.CO.C([O-])(O)=O.[Na+]>N1C=CC=CC=1>[CH3:40][O:39][C:36]1[CH:35]=[CH:34][C:33]([C:32]([O:8][CH2:7][C@H:5]2[O:6][C@@H:1]([N:9]3[C:13]4[N:14]=[C:15]([NH:19][C:20](=[O:24])[CH:21]([CH3:22])[CH3:23])[NH:16][C:17](=[O:18])[C:12]=4[C:11]([I:25])=[CH:10]3)[CH2:2][C@@H:3]2[OH:4])([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:31]2[CH:48]=[CH:49][C:28]([O:27][CH3:26])=[CH:29][CH:30]=2)=[CH:38][CH:37]=1
Reactant: CC(C)C(=O)Nc1nc2c(c(I)cn2[C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: c1ccncc1
Product: COc1ccc(C(OC[C@H]2O[C@@H](n3cc(I)c4c(=O)[nH]c(NC(=O)C(C)C)nc43)C[C@@H]2O)(c2ccccc2)c2ccc(OC)cc2)cc1
Reaction time: 8 h

Procedure:
Compound (59) is repeatedly dried by evaporating off anhydrous pyridine. 400 mg (0.87 mmol) of compound (59) which has been dried in this way are dissolved in 5 ml of anhydrous pyridine. After adding 4,4'-dimethoxytrityl chloride (328 mg, 0.95 mmol) at room temperature, the reaction mixture is stirred overnight. MeOH (3 ml) and 5% aq. NaHCO3 (30 ml) are then added. The aqueous phase is extracted 3 times with CH2Cl2. The organic phase is dried (Na2SO4) and evaporated, and the residue is subjected to flash chromatography (column: 10×5 cm, solvent CH2Cl2 /acetone, 9:1). Isolating the material from the main zone affords the colorless, amorphous title compound (61). (600 mg, 91%). 1H-NMR ([D6 ] DMSO: δ=1.13 (m, 4 CH3), 2.24 (m, H--C(2')), 2.77 (m, CH), 3.12 (m, H--C(5')), 3.75 (s, 2 CH3O), 3.93 (m, H--C(4')), 4.35 (m, H--C(3')), 5.30 (d, 3'-OH), 6.39 (dd, H--C(1')), 6.86-7.39 (m, aromatic H +H--C(6)), 11.54, 11.82 (2s, 2 NH). Anal. calculated for C36H37JN4O7 (764.6): C 56.55, H 4.88, N 7.33: found C 56.42, H 4.82, N 7.30.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][C:9]2[CH:17]=[CH:16][C:12]3=[N:13][O:14][N:15]=[C:11]3[CH:10]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[O:18]1[CH2:20][CH:19]1[C:21]1[CH:30]=[CH:29][C:24]2[C:25](=[O:28])[O:26][CH2:27][C:23]=2[CH:22]=1>>[N:13]1[O:14][N:15]=[C:11]2[CH:10]=[C:9]([CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][N:4]([CH2:20][CH:19]([C:21]4[CH:30]=[CH:29][C:24]5[C:25](=[O:28])[O:26][CH2:27][C:23]=5[CH:22]=4)[OH:18])[CH2:3][CH2:2]3)[CH:17]=[CH:16][C:12]=12
Reactant: O=C1OCc2cc(C3CO3)ccc21
Reactant: c1cc2nonc2cc1CCN1CCNCC1
Product: O=C1OCc2cc(C(O)CN3CCN(CCc4ccc5nonc5c4)CC3)ccc21

Procedure:
5-(2-{4-[2-(2,1,3-benzoxadiazol-5-yl)ethyl]piperazin-1-yl}-1-hydroxyethyl)-2-benzofuran-1(3H)-one was prepared in a similar fashion as to the synthesis described in EXAMPLE 12 starting from 5-[2-(piperazin-1-yl)ethyl]-2,1,3-benzoxadiazole and 5-oxiran-2-yl-2-benzofuran-1(3H)-one. LC/MS: [(M+1)]+=409.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8](Cl)(=[O:12])[C:9]([CH3:11])=[CH2:10].[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[C:9]([CH3:11])=[CH2:10])=[CH:4][CH:3]=1
Reactant: Brc1ccccc1
Reactant: C=C(C)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: C=C(C)C(=O)c1ccc(Br)cc1

Procedure:
Bromobenzene (0.5 mL), methacryloyl chloride (110 mg), and aluminium chloride (150 mg) were reacted in dichloromethane (1.5 mL) at from −20° C. to room temperature for 4 hours. The resultant was treated in the same manner as described in Example 1 to obtain the title compound (1207 mg).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[N:13]=2)=[CH:4][CH:3]=1.[OH:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1>C1(C)C=CC=CC=1>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][CH:17]([O:16][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:9]=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[N:13]=3)=[CH:6][N:7]=2)[CH2:18][CH2:19]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]
Reactant: Cn1nc(-c2ccc(Cl)nc2)ccc1=O
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Solvent: Cc1ccccc1
Product: Cn1nc(-c2ccc(OC3CCN(C(=O)OC(C)(C)C)CC3)nc2)ccc1=O
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To 6-(6-chloro-pyridin-3-yl)-2-methyl-2H-pyridazin-3-one (3 g, 13.6 mmol) in toluene (50 mL) was added 4-hydroxy-boc-piperidine (2.7 g, 13.6 mmol) and 1M KtOBu (16.3 mL, 16.3 mmol). After overnight stirring at 80° C., the reaction was concentrated, partitioned between dichloromethane/1N sodium carbonate, washed with water/brine, dried over sodium sulfate, and concentrated. The product was purified by column chromatography (99:1 dichloromethane:methanol) to obtain 2.7 g (51%); MS m/z 387 (M+H).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([N:14]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:15][C:16]([C:18]1[CH:26]=[C:22]([C:23]([NH2:25])=[O:24])[C:21]([OH:27])=[CH:20][CH:19]=1)=[O:17])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.I[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]>CC(=O)CC>[CH2:28]([N:14]([CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:15][C:16]([C:18]1[CH:19]=[CH:20][C:21]([O:27][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[C:22]([CH:26]=1)[C:23]([NH2:25])=[O:24])=[O:17])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: CCCCCCCI
Reactant: NC(=O)c1cc(C(=O)CN(Cc2ccccc2)Cc2ccccc2)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCCCCCOc1ccc(C(=O)CN(Cc2ccccc2)Cc2ccccc2)cc1C(N)=O
Yield: 99.8 %

Procedure:
A mixture of potassium carbonate (3.73 g), 5-(N,N-dibenzylglycyl) salicylamide (10 g) and 1-iodo heptane (7.5 g) in butanone (200 ml) was stirred and heated under reflux for 24 hours. The solid was filtered off and the filtrate was evaporated. The residue was partitioned between ethyl acetate and water. The dried (MgSO4) ethyl acetate solution was evaporated to give a yellow oil (12.6 g) which crystallised twice from isopropanol to yield the ether (6.3 g) m.p. 97.5°-98°.
Reaction SMILES: [CH2:1]([CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[CH2:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([NH2:25])(=[O:24])[CH2:22][CH3:23].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[CH2:11][CH2:10][C:9]=1[NH:25][C:21](=[O:24])[CH2:22][CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCC(N)=O
Reactant: COc1ccc2c(c1)C(Cc1ccccc1)C(=O)CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCC(=O)NC1=C(Cc2ccccc2)c2cc(OC)ccc2CC1
Temperature: 25 °C
Yield: 64.5 %

Procedure:
In a three-necked flask equipped with a Dean-Stark apparatus, heating mantle and magnetic stirrer were charged 1-benzyl-7-methoxy-3,4-dihydronaphthalen-2(1H)-one (120 g, 451 mmol), propionamide (82 g, 1126 mmol) and p-toluenesulfonic acid monohydrate (17.14 g, 90 mmol) followed by toluene (1.8 I). The resulting solution was heated to reflux for 5 days and monitored by HPLC (about 16% of starting material remained). The reaction mixture was cooled to r.t. and washed with 8% aqueous sodium bicarbonate solution (250 ml) and water (250 ml). The layers were separated. The organic layer was concentrated to near dryness and chase distilled with IPA (100 ml). The crude product was transferred to a flask equipped with a mechanical stirrer, heating mantle and nitrogen inlet. IPA (500 ml) was added to the flask and suspension was heated to 62° C. and all the solids were dissolved. The suspension was allowed to cool over 2 hrs to 30° C. then cooled to 5° C. Solids were filtered and washed with mixture of heptane/IPA (4:1, 100 ml). Solids were dried under vacuum to give 93.5 g (yield: 65%) product as a white solid.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([OH:21])=O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1.Cl.[OH:25][C:26]1[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[C:32]2[C:27]=1[CH2:28][CH2:29][NH:30][CH2:31]2>>[F:22][C:2]([F:23])([F:1])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:18]=[C:17]([C:19]([N:30]3[CH2:29][CH2:28][C:27]4[C:32](=[CH:33][CH:34]=[C:35]([O:36][CH3:37])[C:26]=4[OH:25])[CH2:31]3)=[O:21])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc2c(c1O)CCNC2
Reactant: O=C(O)c1nc(-c2ccc(C(F)(F)F)cc2)nc2ccccc12
Agent: Cl
Product: COc1ccc2c(c1O)CCN(C(=O)c1nc(-c3ccc(C(F)(F)F)cc3)nc3ccccc13)C2
Yield: 15 %

Procedure:
Reaction of 2-(4-(trifluoromethyl)phenyl)quinazoline-4-carboxylic acid with 5-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride gave compound 37 (15% yield) as off-white oil. 1H NMR (300 MHz, DMSO-d6) δ 2.62 and 2.91 (2t, 2H), 3.50 and 4.04 (2t, 2H), 3.74 and 3.80 (2s, 3H), 4.40 and 4.93 (2s, 2H), 6.31 and 6.77 (2d, 1H), 6.71 and 6.91 (2d, 1H), 7.26-7.84 (m, 1H), 7.90-8.02 (m, 3H), 8.11-8.24 (m, 2H), 8.68-8.76 (m, 3H); MS (ESI) m/z 480 ([M+H]+).
Reaction SMILES: [C:1]([O:5][CH2:6][C:7]#[CH:8])(=[O:4])[CH:2]=[CH2:3].[C:9]1([N:15]=[N+:16]=[N-:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CN(C=O)C.O>[C:9]1([N:15]2[CH:8]=[C:7]([CH2:6][O:5][C:1](=[O:4])[CH:2]=[CH2:3])[N:17]=[N:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: [N-]=[N+]=Nc1ccccc1
Reactant: C#CCOC(=O)C=C
Solvent: CN(C)C=O
Solvent: O
Product: C=CC(=O)OCc1cn(-c2ccccc2)nn1
Temperature: 25 °C
Reaction time: 24 h
Yield: 89 %

Procedure:
Propargyl acrylate (13.5 g, moles), phenyl azide (12.5 g, moles) and tetrakis(acetonitrile)copper (I) hexafluorophosphate (0.84 g, 2.3 mmoles) are dissolved in DMF (100 ml) and stirred at room temperature under nitrogen for 24 hours. The reaction mixture is poured in water and the product is extracted with ethyl acetate. The solvent is distilled under reduced pressure, and mixed with diethyl ether wherefrom the product crystallized as an off-white, crystalline solid (23 g; yield 89%; mp 55-56° C.). 1H NMR (CDCl3, δ ppm) 8.08 (s, 1H), 7.72 (d, 2H), 7.51 (t, 2H), 7.44 (q, qH), 6.48 (d, 1H), 6.17 (q, 1H), 5.88 (d, 1H), 5.50 (s, 2H). 13C NMR (CDCl3, δ ppm) 165.9, 143.4, 136.8, 131.5, 129.7, 128.8, 127.8, 122.1, 120.5, 57.5.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[NH:12][CH:13]=[C:14]([C:15]([OH:17])=O)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[NH:3]1.[NH2:18][CH2:19][CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1>C(OCC)C>[NH:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:21]([CH2:20][CH2:19][NH:18][C:15]([C:14]2[C:10]3[C:9]4[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=4[NH:3][C:2](=[O:1])[C:11]=3[NH:12][CH:13]=2)=[O:17])=[CH:22]1
Reactant: O=C(O)c1c[nH]c2c(=O)[nH]c3ccccc3c12
Reactant: NCCc1c[nH]c2ccccc12
Solvent: CCOCC
Product: O=C(NCCc1c[nH]c2ccccc12)c1c[nH]c2c(=O)[nH]c3ccccc3c12
Yield: 39.3 %

Procedure:
This compound is prepared according to synthesis 79 from 75 mg (0.33 mmol) of 4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid (synthesis 75) and 58 mg (0.36 mmol) of tryptamine. After trituration in diethyl ether, 48 mg (40%) of N-[2-(1H-indol-3-yl)-ethyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxamide is obtained in the form of a light brown solid.