Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][S:10][C:11]2[NH:12][C:13]([CH3:30])=[C:14]([C:26]([O:28][CH3:29])=[O:27])[CH:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-:25])=[O:24])[CH:18]=3)[N:16]=2)=[CH:5][CH:4]=1.[C:31](Cl)(=[O:34])[CH2:32][CH3:33].N1C=CC=CC=1>ClCCl.CCOCC>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][S:10][C:11]2[N:16]([C:31](=[O:34])[CH2:32][CH3:33])[CH:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-:25])=[O:24])[CH:18]=3)[C:14]([C:26]([O:28][CH3:29])=[O:27])=[C:13]([CH3:30])[N:12]=2)=[CH:5][CH:4]=1
Reactant: CCC(=O)Cl
Reactant: COC(=O)C1=C(C)NC(SCc2ccc(OC)cc2)=NC1c1cccc([N+](=O)[O-])c1
Solvent: ClCCl
Solvent: CCOCC
Solvent: c1ccncc1
Product: CCC(=O)N1C(SCc2ccc(OC)cc2)=NC(C)=C(C(=O)OC)C1c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1,4-Dihydro-2-[[(4-methoxyphenyl)methyl]thio]-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, methyl ester (1.52 g., 3.5 mmole) in 15 ml of dichloromethane is cooled under argon to 0°-5° C. and treated with propionyl chloride (0.43 g., 4.7 mmole) and pyridine (0.55 g., 7.0 mmole). The mixture is then allowed to stir at room temperature for 3 hours, diluted with ether and the salt is filtered. The filtrate is washed with water, 1N hydrochloric acid, water, aqueous sodium bicarbonate, water and saturated brine. The aqueous fractions are back extracted with fresh ether. The combined organic solutions are dried (magnesium sulfate) and concentrated in vacuo to give 1.6 g. of a viscous oily product.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[C:3]=1[C:11](=[O:13])[CH3:12].[C:14](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[CH3:14][O:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[C:3]=1[C:11](=[O:13])[CH3:12]
Reactant: CC(=O)c1c(C)cc(C)c(C)c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: COc1c(C)c(C)cc(C)c1C(C)=O
Temperature: 25 °C
Yield: 88.4 %

Procedure:
In acetone (30 mL) was dissolved 2.00 g (11.2 mmol) of 1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone which can be produced by the method disclosed in Chemical Research in Toxicology, 1997, vol. 10, No. 3, pp. 335-343, 3.10 g (22.4 mmol) of potassium carbonate, then 1.40 mL (22.5 mmol) of methyl iodide were added to the solution, and the resulting mixture was refluxed for 5 hours. After cooling to room temperature, the reaction mixture was concentrated, and the residue was poured into water, and extracted with ethyl acetate. The organic layers were combined, washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Wako gel C-100, hexane:ethyl acetate gradient) to obtain 1.90 g (9.90 mmol, Yield: 88.4%) of 1-(2-methoxy-3,4,6-trimethylphenyl)ethanone.
Reaction SMILES: [CH2:1]([CH:19]1[CH2:24][C:23](=[O:25])[N:22]([C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-])=O)=[CH:28][C:27]=2[OH:35])[C:20]1=[O:21])[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].[H][H]>C(O)C.[Pd]>[CH2:1]([CH:19]1[CH2:24][C:23](=[O:25])[N:22]([C:26]2[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][C:27]=2[OH:35])[C:20]1=[O:21])[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]
Reactant: CCCCCCCCCCCCCCCCCCC1CC(=O)N(c2ccc([N+](=O)[O-])cc2O)C1=O
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCCC1CC(=O)N(c2ccc(N)cc2O)C1=O

Procedure:
In 2 liters of ethanol were suspended 150 g of 2-octadecylsuccinimido-5-nitro-phenol and 7.5 g of palladium/carbon were added to the suspension, which was subjected to catalytic reduction with hydrogen gas at room temperature under normal pressure. After about 10 hours of reaction period of time, palladium/carbon was filtered off and ethanol was removed by distillation. The residue was recrystallized from benzene to give white powdery crystal melting at 85°-90° C. in the yield of 90 g.
Reaction SMILES: [C:1]([OH:12])(=O)[CH:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][OH:4].[NH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[OH:4][CH2:3][CH:2]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)[C:1]([N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:12]
Reactant: C1CCNC1
Reactant: O=C(O)C(CO)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: O
Solvent: CN(C)C=O
Product: O=C(C(CO)c1ccccc1)N1CCCC1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
To a solution of tropic acid (0.12 mmol) and pyrrolidine (0.12 mmol) in DMF (20 mL) are added HOAt (0.18 mmol) and EDCI-HCl (0.18 mmol). The reaction mixture is stirred at room temperature for 14 h. The reaction mixture is diluted with water, then extracted with AcOEt. The organic extracts are successively washed with water, sat. aq, NaHCO3, H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified by silica gel column chromatography to give 3-hydroxy-2-phenyl-1-pyrrolidin-1-yl propan-1-one.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:40]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])(=[O:43])[CH:41]=O>ClCCCl.CC(O)=O>[C:13]([O:12][C:11]([NH:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:1]([CH2:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=1)[CH2:41][C:40]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[O:17])([CH3:14])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OC(=O)C=O
Reactant: O=Cc1ccccn1
Reactant: CC(C)(C)OC(=O)NCCCCCCCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)CN(CCCCCCCCNC(=O)OC(C)(C)C)Cc1ccccn1
Temperature: 0 °C
Reaction time: 8 h
Yield: 57.7 %

Procedure:
A solution of tert-butyl 8-aminooctylcarbamate (1.61 g, 6.588 mmol), 2-pyridinecarboxaldehyde (0.63 mL, 6.588 mmol) and AcOH (0.10 mL) in DCE (30 mL) was heated at 75° C. for 30 min under nitrogen. The reaction mixture was cooled to 0° C., and treated sequentially with NaBH(OAc)3 (3.708 g, 17.5 mmol) and tert-butyl glyoxalate (1.53 g)1. The reaction mixture was stirred at room temperature overnight and quenched with water. The reaction mixture was then extracted with DCM and the organic layers was dried and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel to afford tert-butyl 2-((8-(tert-butoxycarbonylamino)octyl)(pyridin-2-ylmethyl)amino)acetate (1.71 g, 58%) as a yellow oil. 1H NMR (400 MHz, CD3Cl3) δ 8.52 (d, J=4.8 Hz, 1H), 7.65 (td, J=7.8, 1.6 Hz, 1H), 7.56 (d, J=7.6, 1H), 7.18-7.12 (m, 1H), 4.50 (s, 1H), 3.90 (s, 2H), 3.28 (s, 2H), 3.07 (q, J=6.3 Hz, 2H), 2.61 (t, J=7.6 Hz, 2H), 1.50-1.24 (m, 30H); ESMS m/z: 450.4 (M+H)+.
Reaction SMILES: Cl.[F:2][C:3]1[CH:8]=[C:7]([S:9]([CH3:12])(=[O:11])=[O:10])[CH:6]=[CH:5][C:4]=1[NH:13][C:14]1[C:15]2[O:22][CH:21]=[C:20]([CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[C:16]=2[N:17]=[CH:18][N:19]=1.Cl[C:30]1[N:35]=[CH:34][C:33]([Cl:36])=[CH:32][N:31]=1.C(N(CC)C(C)C)(C)C.O>CN(C)C=O>[Cl:36][C:33]1[CH:32]=[N:31][C:30]([N:26]2[CH2:27][CH2:28][CH:23]([C:20]3[C:16]4[N:17]=[CH:18][N:19]=[C:14]([NH:13][C:4]5[CH:5]=[CH:6][C:7]([S:9]([CH3:12])(=[O:10])=[O:11])=[CH:8][C:3]=5[F:2])[C:15]=4[O:22][CH:21]=3)[CH2:24][CH2:25]2)=[N:35][CH:34]=1
Reactant: CS(=O)(=O)c1ccc(Nc2ncnc3c(C4CCNCC4)coc23)c(F)c1
Reactant: Clc1cnc(Cl)nc1
Agent: Cl
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)c1ccc(Nc2ncnc3c(C4CCN(c5ncc(Cl)cn5)CC4)coc23)c(F)c1
Temperature: 80 °C
Reaction time: 2.5 h
Yield: 19 %

Procedure:
N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-(piperidin-4-yl)furo[3,2-d]pyrimidine-4-amine hydrochloride (9.8 mg, 0.023 mmol), 2,5-dichloropyrimidine (5.1 mg, 0.035 mmol) and N,N-diisopropylethylamine (9.0 mg, 0.069 mmol) were dissolved in N,N-dimethylformamide (0.5 mL) and stirred at 80° C. for 2.5 hours. Water was added to the reaction liquid, and the reaction liquid was extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated under a reduced pressure, and the obtained residue was purified by silica gel preparative thin layer chromatography (chloroform:methanol=25:1) to give the titled compound (2.2 mg, 19%) as a yellow solid.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([OH:16])=[O:15])=[N:10][N:11]=1.[OH:30][CH:31]1[O:37][C@H:36]([C@@H:38]([CH2:40][OH:41])[OH:39])[C@H:34](O)[C@H:32]1[OH:33]>N1C=CC=CC=1>[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([O:16][CH:34]2[CH:32]([OH:33])[CH:31]([OH:30])[O:37][CH:36]2[CH:38]([OH:39])[CH2:40][OH:41])=[O:15])=[N:10][N:11]=1
Reactant: O=C(O)CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12
Reactant: OC[C@@H](O)[C@H]1OC(O)[C@H](O)[C@H]1O
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: O=C(CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12)OC1C(O)C(O)OC1C(O)CO
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Phosphorus oxychloride (2.4 mmol) is added dropwise over 5 mins to a solution of 2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid (810 mg, 2.0 mmol) in pyridine (20 mL) at 0° C. The mixture is stirred at 0° C. for a further 1 hour and then a solution of 1,2:5,6-Di-O-isopropilydene-□-D-glucofuranose (320 mg, 2.0 mmol) in pyridine (5 mL) is added dropwise over 5 mins. The mixture is stirred at 0° C. for a further 1 hour and 1 hour at 20° C. and then is quenched by addition of water (1 mL). Volatile solvents are removed in vacuo and DCM (200 mL) added. The organic phase is washed with water (1×50 mL), saturated sodium carbonate solution (1×50 mL) and brine (1×50 mL), dried over Na2SO4 and concentrated to dryness. Ethanol and water are added to produce a solid which is collected by filtration. Additional product is recovered by extraction of the filtrate with DCM. Combined product is concentrated, dried and purified by column chromatography (acetone/DCM eluent). The combined solids are dissolved in acetic acid (25 mL) and water (5 mL) mixture, heated at 60° C. for 3 hours. Volatile solvents are removed in vacuo. Ethanol and water are added to produce a solid which is collected by filtration.
Reaction SMILES: O=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.[C:12]([CH2:14][C:15]([O:17][CH3:18])=[O:16])#[N:13]>N1CCCCC1.C(O)(=O)C.C(O)C>[C:12]([C:14](=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1)[C:15]([O:17][CH3:18])=[O:16])#[N:13]
Reactant: COC(=O)CC#N
Reactant: COc1cc(C=O)ccc1O
Solvent: CCO
Solvent: C1CCNCC1
Solvent: CC(=O)O
Product: COC(=O)C(C#N)=Cc1ccc(O)c(OC)c1

Procedure:
A mixture of vanillin (7.60 g, 0.05 mol), methyl cyanoacetate (4.95 g, 0.05 mol), ethanol (50 mL), piperidine (12 drops) and acetic acid (6 drops) is heated at reflux for 3 hours with stirring and then cooled. The pale yellow product crystallizes and additional ethanol (25 mL) is added to promote stirring and 5% HCl (10 mL) is added to neutralize any phenol salt present. The product, methyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate, is collected by filtration, washed with ethanol and dried in air. A yield of 9.4 g (80.6%) is obtained. The identity of the product is supported by mass spectroscopy analysis and is shown below as compound I. ##STR16##
Reaction SMILES: OCCN1CCN(CC(NC2C(SC)=NC(C)=CC=2SC)=O)CC1.O[CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]([NH:37][C:38]2[C:39]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[N:40][C:41]([CH3:50])=[CH:42][C:43]=2[N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)=[O:36])[CH2:30][CH2:29]1.SC1NC2C=CC=CC=2N=1.[SH:67][C:68]1[O:69][C:70]2[CH:76]=[CH:75][CH:74]=[CH:73][C:71]=2[N:72]=1>>[O:69]1[C:70]2[CH:76]=[CH:75][CH:74]=[CH:73][C:71]=2[N:72]=[C:68]1[S:67][CH2:26][CH2:27][N:28]1[CH2:29][CH2:30][N:31]([CH2:34][C:35]([NH:37][C:38]2[C:39]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[N:40][C:41]([CH3:50])=[CH:42][C:43]=2[N:44]2[CH2:45][CH2:46][O:47][CH2:48][CH2:49]2)=[O:36])[CH2:32][CH2:33]1
Reactant: Cc1cc(N2CCOCC2)c(NC(=O)CN2CCN(CCO)CC2)c(N2CCOCC2)n1
Reactant: Sc1nc2ccccc2o1
Agent: CSc1cc(C)nc(SC)c1NC(=O)CN1CCN(CCO)CC1
Agent: Sc1nc2ccccc2[nH]1
Product: Cc1cc(N2CCOCC2)c(NC(=O)CN2CCN(CCSc3nc4ccccc4o3)CC2)c(N2CCOCC2)n1

Procedure:
The reaction and treatments of Example 12 were repeated, except that 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide was replaced by 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4 bis(morpholino)-6-methylpyridin-3-yl]acetamide, and 2-mercaptobenzimidazole was replaced by 2-mercaptobenzoxazole, to thereby yield the title compound as a colorless foamed substance.
Reaction SMILES: [Cl:1]/[C:2](/[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)=[CH:3]\[C@H:4]1[C@H:6]([C:7](Cl)=[O:8])[C:5]1([CH3:11])[CH3:10].[C-:19]#[N:20].[Na+].O.[CH:23]([C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:26]=1)=[O:24]>CCCCCC.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Cl:1]/[C:2](/[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)=[CH:3]\[C@H:4]1[C@H:6]([C:7]([O:24][CH:23]([C:19]#[N:20])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:26]=2)=[O:8])[C:5]1([CH3:11])[CH3:10]
Reactant: CC1(C)[C@@H](/C=C(\Cl)c2ccc(Cl)cc2)[C@@H]1C(=O)Cl
Reactant: O=Cc1cccc(Oc2ccccc2)n1
Reactant: [C-]#N
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCCCCC
Product: CC1(C)[C@@H](/C=C(\Cl)c2ccc(Cl)cc2)[C@@H]1C(=O)OC(C#N)c1cccc(Oc2ccccc2)n1
Yield: 64.9 %

Procedure:
6.7 g (0.02 mol) of (±)-trans-Z-3-(2-chloro-2-(4-chloro-phenyl)-vinyl)-2,2-dimethyl-1-cyclopropanecarboxylic acid-chloride, dissolved in 10 ml of n-hexane, were added dropwise to a mixture of 40 ml of n-hexane, 1.5 g of sodium cyanide, 2 ml of water, 3.98 g (0.02 mol) of 2-formyl-6-phenoxy-pyridine and 0.5 g of tetrabutylammonium bromide at 20° to 25° C., while stirring, and the mixture was then stirred for 4 hours at 20° to 25° C. 100 ml of toluene were then added to the reaction mixture, and the latter was extracted by shaking twice with 60 ml of water. The organic phase was separated off and dried over magnesium sulphate, and the solvent was distilled off in a water jet vacuum. The last solvent residues were removed by incipient distillation for a short time at a bath temperature of 60° C./1 mm Hg. 6.4 g (77 % of theory) of cyano-(6-phenoxy-2-pyridinyl)-methyl (±)-trans-Z-3-(2-chloro-2-(4-chloro-phenyl)-vinyl)-2,2-dimethyl-cyclopropanecarboxylate were obtained as a viscous yellow oil. The structure was established by the 1H-NMR spectrum.
Reaction SMILES: [F:1][C:2]1([F:13])[O:6][C:5]2[CH:7]=[CH:8][C:9]([CH2:11]O)=[CH:10][C:4]=2[O:3]1.S(Cl)([Cl:16])=O>>[Cl:16][CH2:11][C:9]1[CH:8]=[CH:7][C:5]2[O:6][C:2]([F:13])([F:1])[O:3][C:4]=2[CH:10]=1
Reactant: O=S(Cl)Cl
Reactant: OCc1ccc2c(c1)OC(F)(F)O2
Product: FC1(F)Oc2ccc(CCl)cc2O1
Yield: 89 %

Procedure:
A solution of (2,2-difluorobenzo[d][1,3]dioxol-5-yl)methanol (120 g, 0.64 mol) in neat thionyl chloride (500 mL) was stirred for 2 h at 25° C. The excess thionyl chloride was distilled off in vacuo. The residue was partitioned between saturated NaHCO3 (400 mL) and dichloromethane (200 mL). The separated aqueous layer was extracted with dichloromethane (300 mL×3). The combined organic layers were dried, filtered and concentrated in vacuo to give 5-(chloromethyl)-2,2-difluorobenzo[d][1,3]dioxol (117.6 g, 89%), which was directly used in the next step.
Reaction SMILES: [Br:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6]4=[C:7]([C:16](=[O:26])[C:17]([CH2:19][C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)=[CH:18][N:5]4[C:4]=2[CH:3]=1)[CH:8]=[C:9]([OH:15])[CH:10]=3.C(=O)([O-])[O-].[K+].[K+].Br[CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>CS(C)=O>[Br:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6]4=[C:7]([C:16](=[O:26])[C:17]([CH2:19][C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)=[CH:18][N:5]4[C:4]=2[CH:3]=1)[CH:8]=[C:9]([O:15][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:10]=3
Reactant: O=c1c(Cc2cccnc2)cn2c3cc(Br)ccc3c3cc(O)cc1c32
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)COc1cc2c(=O)c(Cc3cccnc3)cn3c4cc(Br)ccc4c(c1)c23
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 56 %

Procedure:
9-bromo-2-hydroxy-5-(3-pyridylmethyl)-4H-pyrido[3,2,1-jk]carbazole-4-one (200 mg) produced in Example 102 was suspended in dimethyl sulfoxide (8 ml). After adding potassium carbonate (136 mg), the mixture was stirred at room temperature for 30 minutes, and t-butyl bromoacetate (0.09 ml) was added. After stirring at room temperature for 2 hours, the reaction mixture was poured into ice water (20 ml) and the crystals precipitated were recovered by filtration. The thus obtained crude crystals were washed with water, ethanol and ether in succession and recovered by filtration to obtain the title compound (144 mg, 56%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:15]([O:17][C:18]([C:20]1([CH2:35]I)[CH2:24][CH2:23][N:22]([C:25](=[O:34])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[O:32][CH3:33])[CH2:21]1)=[O:19])[CH3:16]>>[CH2:15]([O:17][C:18]([C:20]1([CH2:35][O:14][C:11]2[CH:12]=[N:13][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:9][CH:10]=2)[CH2:24][CH2:23][N:22]([C:25](=[O:34])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[O:32][CH3:33])[CH2:21]1)=[O:19])[CH3:16]
Reactant: CCOC(=O)C1(CI)CCN(C(=O)c2ccccc2OC)C1
Reactant: Oc1ccc(-c2ccc(F)cc2)nc1
Product: CCOC(=O)C1(COc2ccc(-c3ccc(F)cc3)nc2)CCN(C(=O)c2ccccc2OC)C1

Procedure:
The title compound was prepared according to the method described for Preparation 29 using 6-(4-fluoro-phenyl)-pyridin-3-ol (Preparation 21) and 3-iodomethyl-1-(2-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (Preparation 15) to afford the racemate as a white solid (127 mg, 73.7%)
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH:15]1N=CN(C(N2C=NC=C2)=O)C=1.CO>C1COCC1>[CH3:15][O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:9]=[CH:10][C:2]=1[I:1]
Reactant: CS(=O)(=O)c1ccc(I)c(C(=O)O)c1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)c1cc(S(C)(=O)=O)ccc1I
Temperature: 70 °C
Yield: 86 %

Procedure:
To 30.7 mmol 2-Iodo-5-methanesulfonyl-benzoic acid in 250 ml THF was added 33.7 mmol CDI and the mixture was heated at 70° C. for 1 h. Methanol (12.4 ml) was then added and the mixture was heated at 70° C. for a further 1 h. The mixture was then cooled to room temperature and concentrated in vacuo. The residue was chromatographed over SiO2 (ethyl acetate/dichloromethane 4:1) to afford the title compound (86%) as a white crystalline solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14](OS(C3C=CC(C)=CC=3)(=O)=O)=[N:13][C:12]=12.C(N(CC)CC)C.[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40]>CN(C)C=O.O>[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][N:49]([C:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:11]3[N:10]=[N:9][C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])=[C:12]3[N:13]=2)[CH2:48][CH2:47]1)=[O:45])([CH3:42])([CH3:40])[CH3:41]
Reactant: Cc1ccc(S(=O)(=O)Oc2nc3c(-c4ccccc4F)nnn3c3ccccc23)cc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(c2nc3c(-c4ccccc4F)nnn3c3ccccc23)CC1
Yield: 87.9 %

Procedure:
A solution of 3-(2-fluorophenyl)-5-(4-methylbenzenesulfonyloxy)-[1,2,3]triazolo[1,5-α]quinazoline (0.33 g, 0.71 mmol), triethylamine (0.3 ml, 2.1 mmol) and piperazine-1-carboxylic acid tert-butyl ester (0.26 g, 1.4 mmol) in dry N,N-dimethylformamide (6 ml) was stirred at 50° C. under nitrogen for 18 h. The mixture was cooled, then diluted with water (30 ml) and extracted with EtOAc (2×75 ml). The combined organic extracts were washed with brine, dried over MgSO4 and evaporated to give a brown oil. Purification by flash column chromatography eluting with CH2Cl2:MeOH (93:7) gave 4-[3-(2-fluorophenyl)-[1,2,3]triazolo[1,5-α]quinazolin-5-yl]piperazine-1-carboxylic acid tert-butyl ester as a white solid (0.28 g, 88%). δH (400 MHz; CDCl3) 1.50 (9H, s), 3.59-3.62 (4H, m), 3.69-3.72 (4H, m), 7.19-7.30 (2H, m), 7.32-7.37 (1H, m), 7.63 (1H, ddd, J=8, 8 and 1), 7.91 (1H, ddd, J=8, 8 and 1), 8.02 (1H, d, J=8), 8.11 (1H, ddd, J=7, 7 and 2), 8.70 (1H, dd, J=8 and 1).
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:21])[C@H:10]([NH:13]C(=O)OC(C)(C)C)[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].S(OC)(O[CH3:28])(=O)=O.O>ClCCl>[NH2:13][C@H:10]([CH2:11][O:12][CH3:28])[C:9]([NH:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:21]
Reactant: COS(=O)(=O)OC
Reactant: CC(C)(C)OC(=O)N[C@H](CO)C(=O)NCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: COC[C@@H](N)C(=O)NCc1ccccc1
Temperature: -10 °C
Reaction time: 4 h

Procedure:
Accordingly to a solution of the compound tert-butyl [(R)-2-(benzylamino)-1-(hydroxymethyl)-2-oxoethyl]carbamate of Formula-XXI in dichloromethane, charged the phase transfer catalyst and cooled the reaction mass to −10° C. and charged dilute solution of sodium hydroxide. Maintaining the temperature at −10° C.-0° C. charged dimethyl sulfate and maintained the reaction under stirring for 3-5 hours. Charged water at the end of the reaction, stirred, separated the organic layer and extracted the aqueous layer with the dichloromethane. Combined the organic layer and acidified with concentrated hydrochloric acid. Charged water to the clear solution and stirred. Separated the aqueous layer and extracted the organic layer further with water. Combined the entire aqueous layer and adjusted the pH to 12 with aqueous sodium hydroxide solution. Extracted the aqueous layer with dichloromethane and separated the organic layer. Extracted the aqueous layer further with dichloromethane to ensure the complete extraction of the desired product. The organic layer is washed and concentrated to isolate the compound (2R)-2-amino-N-benzyl-3-methoxypropanamide of Formula-VIII.