Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:10][CH2:11][CH3:12])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[C:13](Cl)(=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(N(CC)CC)C>O1CCCC1>[C:13]([O:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[C:1]([O:10][CH2:11][CH3:12])=[O:9])(=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCOC(=O)c1ccccc1O
Reactant: CCCCCCCCCCCCCCCCCC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCCC(=O)Oc1ccccc1C(=O)OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.2 %

Procedure:
To a cold (+5° C.) solution of ethyl salicylate (0.136 moles) and stearoyl chloride (0.136 moles) in tetrahydrofuran (200 ml) was added triethylamine (0.136 moles) dropwise over 25 min. After refluxing for 20 hours, the solution was cooled to room temperature. Most of the tetrahydrofuran was removed with a N2 stream during the cooling process. The residue was poured into ice/water (1500 ml), stirred for 1 hour, and a white solid removed by filtration. Washing the solid with water, followed by air drying gave 56 g of the title product, m.p. 50.5°-53.5° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[C@H:7]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[NH2:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:25]1([C:31](Cl)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[C:1]([O:5][C:6](=[O:17])[C@H:7]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[NH:8][C:31]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)[C@@H](N)Cc1ccc(O)cc1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)[C@H](Cc1ccc(O)cc1)NC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
L-Tyrosine tert-butyl ester* was reacted at room temperature in DMF, in the presence of triethylamine, with an equimolar amount of triphenylmethylchloride. Through mixing of the DMF phase with the 4-fold amount of ice the raw product is precipitated and recrystallized from ethanol.
Reaction SMILES: [C:1]1(=O)[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[CH3:12][NH2:13]>O>[CH3:12][N:13]1[C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]2[C:1]1=[O:6]
Reactant: CN
Reactant: O=C1OC(=O)c2ccccc21
Solvent: O
Product: CN1C(=O)c2ccccc2C1=O
Temperature: 250 °C
Yield: 72 %

Procedure:
An addition funnel is charged with 46 parts of phthalic anhydride. After the anhydride is melted, it is added as a slow stream through an adaptor heated at 250° C containing a side arm. The adaptor is connected to a glass tube filled with glass beads. Through the side arm of the adaptor there is introduced methylamine gas. The mixture of the methylamine gas and the liquid phthalic anhydride is allowed to flow into the glass tube heated at 300° C which contains glass beads. At the bottom of the glass tube there is a receiver in the form of 100 ml flask fitted with a side arm. The methylamine gas is introduced at a rate of 1-2 parts per minute. The addition of the molten phthalic anhydride is completed in about 10-15 minutes while excess methylamine and water produced in the reaction being vented through the side arm. There is obtained a 72% yield of N-methylphthalimide as a white solid having a melting point of 129.5°-132° C. No unreacted phthalic anhydride and less than 1% by weight of bis-(N-methyl)amide of phthalic anhydride was detected in the final product based on liquid chromotography.
Reaction SMILES: [C:1]([N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].C1COCC1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1F>CN(C=O)C>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[O:12][CH:10]1[CH2:11][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CC(O)C1
Reactant: Fc1ccc(Br)c(F)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(Oc2cc(F)ccc2Br)C1
Reaction time: 1 h

Procedure:
To a solution of Boc-3-hydroxyazetidine (1.50 g, 8.67 mmol) in DMF (9.1 mL) was added 1 M potassium tert-butoxide in THF (9.96 mL, 9.96 mmol) followed by 1-bromo-2,4-difluorobenzene (2.50 g, 13.0 mmol). After a period of 1 h at 50° C., the reaction mixture was partitioned between ethyl acetate and saturated ammonium chloride. The organic phase was separated, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (15% ethyl acetate in hexane) to provide the title compound as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([OH:14])=[O:13].S(=O)(=O)(O)O.[C:20]([O-])(O)=O.[Na+]>CO>[CH3:20][O:13][C:12](=[O:14])[CH2:11][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)[NH:7][CH:6]=1
Reactant: O=C(O)Cc1c[nH]c2ccc(F)cc12
Reactant: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CO
Product: COC(=O)Cc1c[nH]c2ccc(F)cc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of (5-fluoro-1H-indol-3-yl)-acetic acid (1 g, 5.2 mmol) in MeOH (20 mL) is treated with sulfuric acid (20 μL) and stirred at rt for 1 h. This mixture is treated with 10% aqueous NaHCO3 (200 μL) and then concentrated in vacuo to afford (5-fluoro-1H-indol-3-yl)-acetic acid methyl ester, which is used in the next step without further purification. MS: 208 (M+H); 1H NMR (300 MHz, CD3OD): δ 3.68 (s, 3H), 3.72 (s, 2H), 6.86 (m, 1H), 7.16 (m, 1H), 7.21 (s, 1H), 7.28 (m, 1H).
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]1[C:9]([CH:10]2[C:20]3[C:15](=[CH:16][C:17]4[O:23][CH2:22][O:21][C:18]=4[CH:19]=3)[NH:14][C:12](=O)[CH2:11]2)=[CH:8][CH:7]=[CH:6][CH:5]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:33])=CC=1>C1(C)C=CC=CC=1>[CH2:2]([O:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=1[CH:10]1[C:20]2[CH:19]=[C:18]3[O:21][CH2:22][O:23][C:17]3=[CH:16][C:15]=2[NH:14][C:12](=[S:33])[CH2:11]1)[CH3:1]
Reactant: CCOc1ccccc1C1CC(=O)Nc2cc3c(cc21)OCO3
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CCOc1ccccc1C1CC(=S)Nc2cc3c(cc21)OCO3
Yield: 57.1 %

Procedure:
FQI-1 (200 mg, 1.0 equiv) was weighed into a dry reaction vial under an atmosphere of nitrogen. Dry toluene (4.3 mL) was added, followed by Lawesson's reagent (416 mg, 1.6 equiv). The vial was tightly sealed and the reaction was heated to reflux overnight. After cooling, the solvent was removed in vacuo and the residue was purified by flash column chromatography (gradient of 20% to 70% ethyl acetate in hexanes). Fractions which contained product were pooled to give 120 mg of an impure red oil which was recrystallized from dichloromethane/hexanes to give Compound X as white needles (40 mg, 19%). 1H NMR (400 MHz, CDCl3) δ=9.69 (br. s., 1 H), 7.20 (ddd, J=2.9, 6.0, 8.3 Hz, 1 H), 6.89-6.82 (m, 3 H), 6.46 (d, J=3.1 Hz, 2 H), 5.93 (d, J=1.2 Hz, 2 H), 4.54 (dd, J=6.4, 7.8 Hz, 1 H), 4.10-4.02 (m, 2 H), 3.42 (dd, J=7.8, 17.0 Hz, 1H), 3.23 (dd, J=6.4, 17.0 Hz, 1 H), 1.40 (t, J=7.0 Hz, 3 H). ESI-MS (M+H+) m/z=328.
Reaction SMILES: [NH:1]1[C:10]2[CH2:9][CH:8]3[CH2:11][CH2:12][CH2:13][CH2:14][CH:7]3[C:6](=[O:15])[C:5]=2[CH:4]=[CH:3][C:2]1=O.P(Cl)(Cl)([Cl:19])=O>>[Cl:19][CH:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:15])[CH:7]3[CH2:14][CH2:13][CH2:12][CH2:11][CH:8]3[CH2:9][C:10]=2[NH:1]1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=C1c2ccc(=O)[nH]c2CC2CCCCC12
Product: O=C1C2=C(CC3CCCCC13)NC(Cl)C=C2

Procedure:
In close analogy to (Shanazarov, A. K.; Kuzovkin, V. A.; Chistjakov, V. V.; Granik, V. G. Khim. Geterotsikl. Soedin. 1991, (1) 86-92) 6,7,8,9,9a,10-hexahydro-1H,5aH-benzo[g]quinoline-2,5-dione was treated with phosphoryl chloride (POCl3) to give after chromatographical separation the title compound as a colorless solid.
Reaction SMILES: [F-].[Cs+].[OH:3][C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([O:15][CH3:16])[C:13]=1[OH:14])[C:7]([O:9][CH3:10])=[O:8].Br[CH2:18]Br.CCOCC>CN(C=O)C>[CH2:16]1[O:14][C:13]2[C:4]([O:3][CH3:18])=[CH:5][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:11][C:12]=2[O:15]1
Reactant: COC(=O)c1cc(O)c(O)c(OC)c1
Reactant: BrCBr
Agent: [Cs+]
Agent: [F-]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COC(=O)c1cc(OC)c2c(c1)OCO2
Temperature: 110 °C
Reaction time: 1 h
Yield: 98.8 %

Procedure:
Cesium fluoride (26.5 g, 174 mmol) was added quickly to a stirred solution of diol 4 (7.7 g, 39 mmol) in DMF (80 ml) at rt under Ar. After stirring for 1 h, dibromomethane (5.4 ml, 78 mmol) was added dropwise at rt and the mixture heated to 110° C. for 12 h. Upon cooling to rt, ether (300 ml) was added and the mixture washed with cold water (3×50 ml). The combined aqueous phase was then extracted with ether (2×100 ml), dried and concentrated in vacuo. The resultant crude residue was absorbed onto silica gel (gravity) and purified via silica gel chromatography (gravity, 1:5; EtOAc in n-hexane), affording methylenedioxy derivative 5 (8.1 g, 99%) as a colorless powder; m.p. 89–91° C. (mp 89–91° C., Pettit and Singh, 1987); 1H-NMR (300 MHz):3.89 (3H, s, —OCH3), 3.94 (3H, s, —OCH3), 6.05 (2H, s, —OCH2O—), 7.21 (1H, d,J=1.8 Hz, ArH), 7.33 (I H, d, J=1.8 Hz, ArH).
Reaction SMILES: C(N(CC)CC)C.Cl.[Cl:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]2[CH2:19][CH2:20][NH2:21].Cl[C:23](=[O:29])[C:24]([O:26]CC)=[O:25].[OH-].[Na+].Cl>ClCCl>[Cl:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]2[CH2:19][CH2:20][NH:21][C:23](=[O:29])[C:24]([OH:26])=[O:25]
Reactant: CCOC(=O)C(=O)Cl
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(O)C(=O)NCCc1c[nH]c2ccc(Cl)cc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78.6 %

Procedure:
Triethylamine (2.28 mL; 16.22 mmol) was added to the mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (1.53 g; 6.49 mmol) and ethyl 2-chloro-2-oxoacetate (0.815 mL; 7.14 mmol) in dichloromethane (50 mL) at 0° C. After addition, the mixture was stirred at room temperature for 30 minutes and washed with an aqueous solution of sodium carbonate, dried over magnesium sulfate, and concentrated under reduced pressure. Ethanol (2 mL) and water (7.5 mL) were added to the resulting residue, followed by a 2M solution of sodium hydroxide (9.5 mL, 19 mmol). The mixture was stirred at room temperature for 20 minutes and the pH of the solution was adjusted to 1 by addition of a 6N hydrochloric acid. The precipitate was collected, and was dissolved in ethyl acetate. The ethyl acetate layer was dried over magnesium sulfate and was evaporated to dryness to give 1.36 g (81%) of 2-(2-(5-chloro-1H-indol-3-yl)ethylamino)-2-oxoacetic acid as a yellowish solid.
Reaction SMILES: [CH3:1][NH:2]C(C1N(CC2N3C=C(C)C=CC3=NC=2C2C=CC(C)=CC=2)N=CN=1)=O.[F:28][C:29]1[CH:30]=[CH:31][C:32]2[N:33]([C:35]([CH2:45][N:46]3[C:50]([C:51]([O:53]C)=O)=[N:49][CH:48]=[N:47]3)=[C:36]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[N:37]=2)[CH:34]=1.CN>>[F:28][C:29]1[CH:30]=[CH:31][C:32]2[N:33]([C:35]([CH2:45][N:46]3[C:50]([C:51]([NH:2][CH3:1])=[O:53])=[N:49][CH:48]=[N:47]3)=[C:36]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[N:37]=2)[CH:34]=1
Reactant: CNC(=O)c1ncnn1Cc1c(-c2ccc(C)cc2)nc2ccc(C)cn12
Reactant: COC(=O)c1ncnn1Cc1c(-c2ccc(F)cc2)nc2ccc(F)cn12
Agent: CN
Product: CNC(=O)c1ncnn1Cc1c(-c2ccc(F)cc2)nc2ccc(F)cn12

Procedure:
The title compound was prepared according to the procedure described for compound 68 from methyl 1-((6-fluoro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)-1H-1,2,4-triazole-5-carboxylate and methylamine. m/e+ 368 for C18H15F2N6O (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][CH:3]=1.C([O:13][CH:14](O)[C:15]([F:18])([F:17])[F:16])C.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1>[OH:13][CH:14]([NH:8][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:15]([F:18])([F:17])[F:16]
Reactant: NC(=O)c1ccc(Cl)cc1
Reactant: CCOC(O)C(F)(F)F
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: O=C(NC(O)C(F)(F)F)c1ccc(Cl)cc1

Procedure:
A solution of 4-chlorobenzamide (22.0 g, 0.141 mol) and trifluoroacetaldehyde ethyl hemiacetal (25.0 g as is, 22.5 g real, 0.156 mol) in dioxane (200 mL) is treated with anhydrous sodium sulfate (10 g, to dry the 10% water in the hemiacetal) and refluxed for 60 hours. The solids are filtered and the filtrate is evaporated to a solid. The solids are dissolved in about 200 mL of 15% ethyl acetate in heptane. Unreacted starting material (5.6 g) crystallizes out and is filtered. The title product is obtained from the mother liquors as a white crystalline solid (22.1 g, 82.9% based on recovery of starting material): mp 139.5-140.5° C.; characterized by 1H and 19F NMR and Mass spectra. 1H NMR (DMSO-d6) δ9.45 (d, J=8.7 Hz, NH), 7.93, 7.54 (AB with fine splitting, J=8.4 Hz, ArH), 7.54 (broad s, OH), 5.90 (m, J=8.7, 2.9, 5.8 Hz, CH); 19F NMR δ−80.3 (d, J=5 Hz).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])=[CH:5]2.[Li]CCCC.[C:26](=[O:28])=[O:27]>C1COCC1>[Si:14]([O:13][CH2:12][C:6]1[N:7]([CH3:11])[C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([C:26]([OH:28])=[O:27])=[CH:10][CH:9]=2)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: Cn1c(CO[Si](C)(C)C(C)(C)C)cc2cc(Br)ccc21
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cn1c(CO[Si](C)(C)C(C)(C)C)cc2cc(C(=O)O)ccc21

Procedure:
To a stirred solution of 5-bromo-2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-1H-indole (5.32 g, 15.0 mmol), prepared according to procedure described in Example 39, Step 3, in THF (30 mL) was added n-BuLi (2.5 M solution in hexanes, 7.30 mL, 18.25 mmol, 1.2 eq) at −78° C. dropwise. The mixture was stirred for 30 min at −78° C. before dry CO2 (g) was bubbled into reaction for 10 min. The reaction was quenched with saturated aqueous NH4Cl then extracted by CH2Cl2 (3×50 mL). The combined organic layers were dried over Na2SO4 then concentrated under reduced pressure to give the title compound (4.80 g, ca. 15.0 mmol) in quantitative yield. The acid was carried over to next step without further purification.
Reaction SMILES: [CH:1]([NH2:3])=[O:2].C(OC(=O)[CH2:8][C:9]1[C:10]([Cl:23])=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH2:19][N:20]([CH3:22])[CH3:21])[CH:15]=[CH:14]2)C.C[O-].[Na+]>CN(C)C=O.O>[Cl:23][C:10]1[C:9]([CH2:8][C:1]([NH2:3])=[O:2])=[C:18]2[C:13]([CH:14]=[CH:15][C:16]([CH2:19][N:20]([CH3:21])[CH3:22])=[N:17]2)=[CH:12][CH:11]=1
Reactant: NC=O
Reactant: CCOC(=O)Cc1c(Cl)ccc2ccc(CN(C)C)nc12
Agent: C[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)Cc1ccc2ccc(Cl)c(CC(N)=O)c2n1
Temperature: 105 °C
Reaction time: 1 h
Yield: 74.3 %

Procedure:
Formamide (118 mg, 2.62 mmol, 3.35 equiv) was added to a solution of (7-chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetic acid ethyl ester (240 mg, 0.78 mmol) in N,N-dimethylformamide (1.0 ml). The solution was heated to 105° C., and then sodium methoxide (5.4 M in MeOH, 0.14 ml, 0.78 mmol, 1.0 equiv) was added dropwise over 20 minutes. After 1 hour, the reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc and CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue via flash chromatrography (gradient of CH2Cl2/MeOH 96:4 to 60:40) afforded the title compound (161 mg, 74%) as a white solid. 1H NMR (400 MHz, d6-DMSO): δ=8.35 (d, J=8.9 Hz, 1H), 7.89 (d, J=9.2 Hz, 1H), 7.63 (d, J=9.2 Hz, 1H), 7.60 (d, J=8.9 Hz, 1H), 7.41 (br s, 1H), 6.88 (br s, 1H), 4.26 (s, 2H), 3.69 (s, 2H), 2.21 (s, 6H). MS (ES+): 278.3 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17](I)=[CH:16][CH:15]=2)[N:13]=1.[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=[CH2:27])=[CH:24][CH:23]=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([CH:27]=[CH:26][C:25]3[CH:28]=[CH:29][C:22]([F:21])=[CH:23][CH:24]=3)=[CH:16][CH:15]=2)[N:13]=1
Reactant: Fc1cccc(F)c1C1=NC(c2ccc(I)cc2)CO1
Reactant: C=Cc1ccc(F)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CN(C)C=O
Product: Fc1ccc(C=Cc2ccc(C3COC(c4c(F)cccc4F)=N3)cc2)cc1
Reaction time: 3 h
Yield: 41 %

Procedure:
The compound of Example 2 (0.7 g, 1.8 mmol), 4-fluorostyrene (1 g, 2.6 mmol), palladium acetate (0.03 g, 0.013 mmol) and tri-o-tolyphosphine (0.03 g, 0.01 mmol) were heated to 100°-120° C. in dimethylformamide (20 mL). After 3 h, palladium acetate (0.03 g, 0.013 mmol) was added and heating was continued for 2 h. The cooled reaction mixture was extracted with diethylether (50 mL) and water (100 mL). The diethylether solution was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using hexanes/ethyl acetate (6:1) as eluent. The product was isolated as a solid (0.28 g): m.p.: 154°-156° C. 1H NMR (CDCl3, 200 MHz) δ 7.5-7.0 (m, 13H), 5.5 (m, 1H), 4.8 (m, 1H), 4.3 (m, 1H).
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[N+:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])([O-:8])=[O:7]>>[CH3:15][C:10]1[CH:11]=[CH:12][C:13]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:14][C:9]=1[N+:6]([O-:8])=[O:7]
Reactant: Cc1ccccc1[N+](=O)[O-]
Reactant: O=S(=O)(O)Cl
Product: Cc1ccc(S(=O)(=O)Cl)cc1[N+](=O)[O-]
Temperature: 85 °C

Procedure:
Placed chlorosulfonic acid (128 mL, 1.91 mmol) in a 500 mL four necked round bottomed flask. Then added 2-nitro toluene (65 mL, 0.547 mmol) drop wise, under stirring in 25 minutes at 25° C. The reaction mass was heated at 85° C. for 3 hours. Quenched the reaction mass into ice cold water and extracted with ethylacetate (4×250 mL), the combined organic layer was washed with brine solution (1×100 mL), dried over anhydrous sodium sulfate and solvent was removed under reduced pressure to obtain syrupy product. Yield: 109.5 grams.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:3]=1.N1C=CN=C1.[CH3:24][C:25]([Si:28](Cl)([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CN(C=O)C.O>[C:15]([C:4]1[CH:3]=[C:2]([NH2:1])[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][O:14][Si:28]([C:25]([CH3:27])([CH3:26])[CH3:24])([CH3:30])[CH3:29])=[CH:9][CH:8]=2)[N:5]=1)([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(C)(C)c1cc(N)n(-c2ccc(CO)cc2)n1
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)c1cc(N)n(-c2ccc(CO[Si](C)(C)C(C)(C)C)cc2)n1
Yield: 93.2 %

Procedure:
To a stirred solution of the benzyl alcohol (66) (640 mg, 2.61 mmol) and imidazole (266 mg, 3.91 mmol) in DMF (5.0 mL) at RT was added TBDMS-Cl (590 mg, 3.91 mmol). After 3 hr the reaction mixture was diluted with water and extracted with Et2O. The organic layer was washed with brine, dried (MgSO4) and then evaporated in vacuo to afford the title compound (Intermediate N) (875 mg, 89%): m/z 360 (M+H)+ (ES+)
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH2:17][C:18]1[CH:27]=[CH:26][C:25]2[NH:24][C:23](=[O:28])[C:22]3[NH:29][CH:30]=[CH:31][C:21]=3[C:20]=2[CH:19]=1.[CH2:32]([C:34]([O-:36])=[O:35])[CH3:33]>CN(C)C=O>[C:8]([NH:17][C:18]1[CH:27]=[CH:26][C:25]2[NH:24][C:23](=[O:28])[C:22]3[NH:29][CH:30]=[CH:31][C:21]=3[C:20]=2[CH:19]=1)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH2:32]([C:34]([O-:36])=[O:35])[CH3:33]
Reactant: Nc1ccc2[nH]c(=O)c3[nH]ccc3c2c1
Reactant: O=C(Cl)c1ccccc1
Agent: CCC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(Nc1ccc2[nH]c(=O)c3[nH]ccc3c2c1)c1ccccc1
Temperature: 40 °C
Reaction time: 2.5 h
Yield: 53.1 %

Procedure:
52 μL (0.37 mmol) of triethylamine and then 24 μL (0.20 mmol) of benzoyl chloride are added to 50 mg (0.18 mmol) of 8-amino-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate (synthesis 64) suspended in anhydrous dimethylformamide (1 mL). The solution is stirred for 2.5 h at 40° C. The solvent is evaporated and the residue obtained is purified by recrystallization from methanol to give 36 mg (52%) of 8-benzoylamino-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in the form of a white solid.
Reaction SMILES: [H-].[Na+].[CH:3]1[C:13]2[CH2:12][O:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.Cl[C@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)[CH2:20]1>CS(C)=O>[C:33]([C:30]1[CH:29]=[CH:28][C:27]([CH2:26][CH2:25][N:21]2[CH2:22][CH2:23][CH2:24][C@@H:20]2[CH2:19][N:8]2[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=3[CH2:12][O:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]2=3)=[CH:32][CH:31]=1)#[N:34]
Reactant: N#Cc1ccc(CCN2CCC[C@H](Cl)C2)cc1
Reactant: c1ccc2c(c1)COc1ccccc1N2
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: N#Cc1ccc(CCN2CCC[C@@H]2CN2c3ccccc3COc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 14.4 %

Procedure:
Three-hundred milligrams (7.5 mmols) of 60% sodium hydride were washed with petroleum ether, and then suspended in 30 ml of dimethyl sulfoxide. To the suspension were added 1.4 g (7.1 mmols) of 5,11-dihydrodibenzo[b,e][1,4]oxazepine. The mixture was stirred in a nitrogen atmosphere at room temperature for 40 minutes. To this reaction solution was added dropwise a solution of 1.7 g (6.8 mmols) of (S)-(+)-3-chloro-1-(4-cyanophenethyl)piperidine [[α]D25=+16.7° (c=0.5, ethanol)] in 10 ml of dimethyl sulfoxide, and the mixed solution was stirred at room temperature for 17 hours and at 40° C. for 6 hours. The reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with water and with a saturated aqueous solution of sodium chloride in this order, and dried. Subsequently, the solvent was distilled off under reduced pressure. The resulting residue was subjected to column chromatography, and eluted with a mixed solvent of ethyl acetate and hexane at a ratio of 1:2. This mixed solvent was distilled off under reduced pressure to give 0.4 g of (R)-(+)-5,11-dihydro-5-[1-(4-cyanophenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine as a pale yellow oil in a yield of 14%.
Reaction SMILES: [CH:1](=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[N+:20]([CH3:23])([O-:22])=[O:21]>CCOCC>[N+:20]([CH2:23][CH:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])([O-:22])=[O:21]
Reactant: C[N+](=O)[O-]
Reactant: CCCCCCCCCCCCCCCCCC=O
Solvent: CCOCC
Product: CCCCCCCCCCCCCCCCCC(O)C[N+](=O)[O-]
Yield: 88.3 %

Procedure:
To a solution of octadecanal (9a) (2.22 g, 8.28 mmol) and nitromethane (1.52 g, 24.90 mmol) in anhyd Et2O (10 mL), Amberlyst A-21 (1.2 g) was added at r.t. The mixture was stirred and heated at reflux for 48 h. After removal of the Amberlyst A-21 by filtration, the filtrate was concentrated under reduced pressure. Flash column chromatography of the residue (EtOAc/petroleum spirit, 5/95) gave 1-nitrononadecan-2-ol (10a) (2.41 g, 89%) as a white solid; mp 55-56° C.
Reaction SMILES: [CH3:1][C:2]([CH3:6])=[CH:3][CH2:4]O.[C:7]([O-:13])([O-])([O:9][CH2:10][CH3:11])[CH3:8]>B(O)(O)O.C(O)C>[CH3:1][C:2]([CH3:6])([CH:3]=[CH2:4])[CH2:8][C:7]([O:9][CH2:10][CH3:11])=[O:13]
Reactant: CCOC(C)([O-])[O-]
Reactant: CC(C)=CCO
Agent: OB(O)O
Solvent: CCO
Product: C=CC(C)(C)CC(=O)OCC
Yield: 80.1 %

Procedure:
A mixture of 4.3 g of 3-methyl-2-buten-1-ol, 16.2 g of ethyl orthoacetate and 86 mg of boric acid was heated for 2 hours at 120° with stirring, during which ethanol was evolved and removed. The temperature was then increased to 145°-150° where it was maintained for an additional 8 hours. When ethanol evolution ceased, the mixture was distilled to separate unreacted ethyl orthoacetate from 6.25 g (80% yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 78°-80°/51 mm.