Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[CH2:17][CH2:16][C:15]2[C:14]3[CH:13]=[C:12]([CH3:18])[CH:11]=[CH:10][C:9]=3[NH:8][C:7]=2[CH2:6][CH2:5]1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2([CH3:29])[CH2:28][O:27]2)=[CH:22][CH:21]=1.C(O)(=O)C(O)=O>CN(C=O)C.C1COCC1.O>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([OH:27])([CH3:28])[CH2:29][N:8]2[C:9]3[CH:10]=[CH:11][C:12]([CH3:18])=[CH:13][C:14]=3[C:15]3[CH2:16][CH2:17][N:4]([CH3:3])[CH2:5][CH2:6][C:7]2=3)=[CH:24][CH:25]=1
Reactant: CC1(c2ccc(Cl)cc2)CO1
Reactant: Cc1ccc2[nH]c3c(c2c1)CCN(C)CC3
Agent: O=C(O)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc2c(c1)c1c(n2CC(C)(O)c2ccc(Cl)cc2)CCN(C)CC1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
The title compound was prepared by following general procedure 5. To a stirred suspension of sodium hydride (67 mg, 0.28 mmol) in 5 mL of DMF, 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.2 g, 0.934 mmol) was added and stirred at RT for 5 min. 2-(4-Chlorophenyl)-2-methyloxirane (235 mg, 1.4 mmol) was added slowly dropwise and stirred at RT for 14 h. The reaction was monitored by TLC and LCMS. After completion of the reaction, water was added, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, evaporated under reduced pressure and purified by column chromatography using 10% methanol-DCM. The freebase (30 mg, 0.078 mmol) was dissolved in THF (1.0 mL) and oxalic acid (9.8 mg, 0.078 mmol) in THF (1.0 mL) was added slowly, the mixture was stirred at RT for 20 min. and the formed solid was filtered, washed with ether and dried to afford product as oxalate salt.
Reaction SMILES: S(S([O-])=O)([O-])=O.[Na+].[Na+].[F:9][C:10]1[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=1[NH2:12].C(=O)([O-])O.[Na+].[Br:22][C:23]([F:32])([F:31])[C:24](Br)([F:29])[C:25]([F:28])([F:27])[F:26].C(=O)([O-])[O-].[Na+].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.COC(C)(C)C.O>[F:9][C:10]1[CH:16]=[C:15]([C:24]([F:29])([C:25]([F:28])([F:27])[F:26])[C:23]([Br:22])([F:32])[F:31])[CH:14]=[CH:13][C:11]=1[NH2:12]
Reactant: FC(F)(F)C(F)(Br)C(F)(F)Br
Reactant: Nc1ccccc1F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: O
Solvent: COC(C)(C)C
Product: Nc1ccc(C(F)(C(F)(F)F)C(F)(F)Br)cc1F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
First 195.86 g (1.12 mol) of sodium dithionite and then 50 g (0.45 mol) of 2-fluoroaniline were added at room temperature to a mixture of 450 ml of water, 225 ml of tert-butyl methyl ether, 94.50 (1.12 mol) of sodium hydrogencarbonate and 18.33 g of tetra-n-butylammonium hydrogensulphate. Subsequently, a solution of 348.54 g of 1,2-dibromo-1,1,2,3,3,3-hexafluoropropane in 200 ml of tert-butyl methyl ether was added dropwise at 35–40° C. and, on completion of addition, the mixture was stirred at RT overnight. Sodium carbonate was used to adjust to a pH of 5 and the organic phase was removed, dried and concentrated.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH2:3]1.Br[CH2:17][CH2:18][CH2:19][CH2:20]Br.C(=O)([O-])O.[K+]>CN(C=O)C.[Cl-].[Li+]>[N:1]1([C@H:2]2[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH2:4][CH2:3]2)[CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: BrCCCCBr
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](N)CC1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](N2CCCC2)CC1

Procedure:
A stirred solution of tert-butyl trans-4-aminocyclohexylcarbamate (2.0 g, 9.33 mmol), 1,4-dibromobutane (1.33 mL, 11.2 mmol), and potassium hydrogen carbonate (4.67 g, 46.7 mmol) in DMF (90 mL) was stirred at room temperature overnight. After this time the reaction was diluted with aqueous lithium chloride and extracted with diethyl ether. The combined organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the desired product (399 mg, 16%) as an off-white solid: ESI MS m/z 269 [C15H28N2O2+H]+.
Reaction SMILES: C[C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([C:8](=[NH:20])[NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[N:3]=1.CS(O)(=O)=O.[NH:26]([C:28]1C=CC=CN=1)N>>[NH2:20][C:8]([NH:4][NH:3][C:2]1[CH:6]=[CH:5][CH:7]=[CH:28][N:26]=1)=[N:9][S:10]([C:13]1[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=1)(=[O:11])=[O:12]
Reactant: Cc1ccc(S(=O)(=O)NC(=N)n2nc(C)cc2C)cc1
Reactant: NNc1ccccn1
Agent: CS(=O)(=O)O
Product: Cc1ccc(S(=O)(=O)N=C(N)NNc2ccccn2)cc1

Procedure:
The compound of Example 9 was prepared according to the accompanying synthesis procedure from 0.5 ml of N-[(3,5-dimethylpyrazol-1-yl)-iminomethyl]-4-methylbenzene-sulfonamide solution (0.2 M, acetonitrile) with 19 mg of methanesulfonic acid and 0.5 ml of 2-hydrazinopyridine solution (1.0 M, acetonitrile) and filed in a substance databank. Calculated mol. wt. 305.36; found mol. wt. (M+H) 306.1; 621.6 (Dimer)
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:4]2[C:5]([NH:7][C:8](=[O:9])[C:3]=12)=[O:6].[I:29]I.O>C(O)C.S([O-])([O-])(=O)=O.[Ag+2]>[NH2:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]3[C:20]([C:21]=2[I:29])=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:4]2[C:5]([NH:7][C:8](=[O:9])[C:3]=12)=[O:6]
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(N)c3c2C(=O)NC3=O)cc2ccccc21
Reactant: II
Agent: [Ag+2]
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)n1c(-c2ccc(N)c3c2C(=O)NC3=O)c(I)c2ccccc21
Temperature: 25 °C
Reaction time: 1.3 h
Yield: 81.5 %

Procedure:
3-Amino-6-[1-(tert-butoxycarbonyl)indol-2-yl]phtalimide (300 mg, 0.795 mmol) was dissolved in ethanol (21 mL), and the solution was added with iodine (242 mg, 0.954 mmol) and silver sulfate (248 mg, 0.795 mmol), followed by stirring at room temperature for 1.3 hours. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by slurry using chloroform to obtain 3-amino-6-[1-(tert-butoxycarbonyl)-3-iodoindol-2-yl]phtalimide (326 mg, yield 82%).
Reaction SMILES: [Na].[OH:2][C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][CH:4]=1.Br[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1>C(O)C>[CH2:10]([O:9][C:7]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]2[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=2)=[CH:13][CH:12]=1)=[O:8])[CH3:11]
Reactant: Clc1ccc(OCCCCC#CCCCCCCCCBr)cc1
Reactant: CCOC(=O)c1ccc(O)cc1
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)c1ccc(OCCCCCCCCC#CCCCCOc2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 44.3 %

Procedure:
To a solution of sodium (0.58 g.; 0.025 M.) in absolute ethanol (15 ml.) was added ethyl 4-hydroxybenzoate (4.15 g; 0.025 M.) in absolute ethanol (20 ml.) and the mixture was stirred at room temperature for 15 minutes. A solution of 1-bromo-14-(4-chlorophenoxy)-tetradec-9-yne (7.00 g.; 0.0175 M.) in absolute ethanol (20 ml). was added and the mixture was boiled under reflux with stirring for 6 hours. The reaction mixture was cooled to room temperature filtered and the solvent removed under reduced pressure. Dichloromethane (100 ml.) was added to the residual oil, the solution was washed with 5% sodium hydroxide solution (2×100 ml.), saturated sodium chloride solution (1×100 ml.), dried and evaporated. The oil thus produced was purified by chromatography on silica-gel (250 g.) in dichloromethane to give 1-(4-ethoxycarbonylphenoxy)-14-(4-chlorophenoxy)-tetradec-9-yne (3.76 g.; 44%) M.P. 52°-53° C.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:28]3[CH:29]=[C:30](/[CH:34]=[CH:35]/[C:36]([O:38]CCCC)=[O:37])[CH:31]=[CH:32][CH:33]=3)=[C:7]([CH2:13][C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])=[O:15])[C:8](=[O:12])[O:9]2)=[CH:4][C:3]=1[CH3:43].C(O)C.[OH-].[Na+].Cl>CC(C)=O>[CH3:5][C:10]([CH3:11])=[O:9].[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:28]3[CH:29]=[C:30](/[CH:34]=[CH:35]/[C:36]([OH:38])=[O:37])[CH:31]=[CH:32][CH:33]=3)=[C:7]([CH2:13][C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[C:24]([F:25])([F:27])[F:26])=[O:15])[C:8](=[O:12])[O:9]2)=[CH:4][C:3]=1[CH3:43]
Reactant: CCCCOC(=O)/C=C/c1cccc(-c2c(CC(=O)Nc3ccc(F)cc3C(F)(F)F)c(=O)oc3cc(Cl)c(C)cc23)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: CCO
Product: Cc1cc2c(-c3cccc(/C=C/C(=O)O)c3)c(CC(=O)Nc3ccc(F)cc3C(F)(F)F)c(=O)oc2cc1Cl
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 168.8 %

Procedure:
A mixture of butyl(2E)-3-{3-[7-chloro-3-(2-{[4-fluoro-2-(trifluoromethyl)phenyl]amino}-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl}acrylate (3.0 g), ethanol (9 ml) and 2N NaOH (9 ml) was stirred at 50° C. for 1.5 hours. After completion of the reaction, acetone (27 ml) was added to the reaction mixture at 50° C., and 6N HCl (3.5 ml) was added dropwise thereto to adjust pH to 0.6. The mixture was stirred at 50° C. for 30 minutes and then at 25° C. for 1 hour, and crystals were collected by filtration, and washed with acetone/water (2/1, 6 ml). To a mixture of the resulting crystals (2.79 g), acetone (2 ml) and water (6 ml) was added dropwise 5% aqueous ammonia (2.1 ml) with stirring at room temperature to adjust pH to 9.2 and dissolve the mixture. Toluene (4.5 ml) was added to the resulting solution and the mixture was stirred for 5 minutes and allowed to stand for 5 minutes to separate an aqueous layer. Acetone (12 ml) and activated charcoal (0.15 g) were added to the obtained aqueous layer and the mixture was stirred at room temperature for 15 minutes. The activated charcoal was removed by filtration, and washed with acetone (6 ml). The filtrate and washings were combined and warmed to 50° C., and 6N HCl (1.25 ml) was added dropwise thereto with keeping the temperature almost the same and stirring to adjust pH to 0.5 and precipitate crystals. The mixture was stirred at 50° C. for 30 minutes and then at about 25° C. for 1 hour, and the crystals were collected by filtration and washed with acetone/water (2/1, 6 ml) to obtain the title compound (2.54 g, yield 84.8%). This product contained 0.9 mol of acetone.
Reaction SMILES: [N:1]1([C:6]2[CH:41]=[CH:40][C:9]([C:10]([N:12]3[CH2:17][CH2:16][N:15]([S:18]([C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][C:25]([NH:31]C(OCC(Cl)(Cl)Cl)=O)=[CH:26][CH:27]=5)[CH:22]=4)(=[O:20])=[O:19])[CH2:14][CH2:13]3)=[O:11])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1>C(O)(=O)C.[Zn]>[NH2:31][C:25]1[CH:24]=[C:23]2[C:28]([CH:29]=[CH:30][C:21]([S:18]([N:15]3[CH2:14][CH2:13][N:12]([C:10](=[O:11])[C:9]4[CH:8]=[CH:7][C:6]([N:1]5[CH:5]=[CH:4][N:3]=[CH:2]5)=[CH:41][CH:40]=4)[CH2:17][CH2:16]3)(=[O:20])=[O:19])=[CH:22]2)=[CH:27][CH:26]=1
Reactant: O=C(Nc1ccc2ccc(S(=O)(=O)N3CCN(C(=O)c4ccc(-n5ccnc5)cc4)CC3)cc2c1)OCC(Cl)(Cl)Cl
Agent: [Zn]
Solvent: CC(=O)O
Product: Nc1ccc2ccc(S(=O)(=O)N3CCN(C(=O)c4ccc(-n5ccnc5)cc4)CC3)cc2c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 94.4 %

Procedure:
To a solution of 1-[4-(1-imidazolyl)benzoyl]-4-[7-(2,2,2-trichloroethoxycarbonylamino)naphthalene-2-sulfonyl]piperazine (475 mg) in acetic acid (5 ml) was added zinc powder (1 g), and the mixture was stirred at room temperature for 1 day. The reaction solution was filtered, and the filtrate was concentrated. The residue was dissolved in 0.5 N hydrochloric acid, washed with ethyl acetate and made alkaline with 1 N sodium hydroxide aqueous solution. The precipitate was collected by filtration, and the filtrate was washed with water and dried to give a colorless solid of the title compound (325 mg).
Reaction SMILES: [C:1]([C:4]1[CH:27]=[CH:26][C:7]([C:8]([NH:10][CH2:11][C:12]([C:14]2[CH:25]=[CH:24][C:17]([O:18][CH2:19][C:20]([O:22]C)=[O:21])=[CH:16][CH:15]=2)=[O:13])=[O:9])=[CH:6][CH:5]=1)(=[NH:3])[NH2:2].C(=O)([O-])[O-].[K+].[K+].C(O)C.Cl>O>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:10][CH2:11][C:12]([C:14]2[CH:25]=[CH:24][C:17]([O:18][CH2:19][C:20]([OH:22])=[O:21])=[CH:16][CH:15]=2)=[O:13])=[O:9])=[CH:26][CH:27]=1)(=[NH:2])[NH2:3]
Reactant: COC(=O)COc1ccc(C(=O)CNC(=O)c2ccc(C(=N)N)cc2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: N=C(N)c1ccc(C(=O)NCC(=O)c2ccc(OCC(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 67.6 %

Procedure:
A mixture of 80 mg of methyl p-(p-amidinobenzamidoacetyl)phenoxyacetate (Example 25), 40 mg of potassium carbonate, 10 ml of ethanol and 4 ml of water was stirred at room temperature under argon for 4 hours. 10 ml of water were then added to the mixture, which was neutralized to pH 6 with 1N HCl. It was concentrated to 10 ml in vacuo and left to stand in a refrigerator overnight. The precipitate which had separated out was filtered off with suction and dried over KOH in vacuo at 50° C. 52 mg of amorphous p-(p-amidinobenzamidoacetyl)phenoxyacetic acid were obtained, IR bands (KBr) at 3354, 3286, 3042, 1647, 1598, 1542, 1485, 1422, 1360, 1232, 1177, 994 and 710 cm-1.
Reaction SMILES: [F:1][C:2]1[CH:30]=[C:29]([I:31])[CH:28]=[CH:27][C:3]=1[NH:4][C:5]1[C:6]([C:13]([O:15]C2C(F)=C(F)C(F)=C(F)C=2F)=O)=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1.[CH2:32]([NH2:36])[CH2:33][CH2:34][NH2:35]>C1COCC1>[NH2:35][CH2:34][CH2:33][CH2:32][NH:36][C:13]([C:6]1[C:5]([NH:4][C:3]2[CH:27]=[CH:28][C:29]([I:31])=[CH:30][C:2]=2[F:1])=[CH:10][C:9](=[O:11])[N:8]([CH3:12])[CH:7]=1)=[O:15]
Reactant: NCCCN
Reactant: Cn1cc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)c(Nc2ccc(I)cc2F)cc1=O
Solvent: C1CCOC1
Product: Cn1cc(C(=O)NCCCN)c(Nc2ccc(I)cc2F)cc1=O
Temperature: 25 °C
Reaction time: 15 h

Procedure:
2,3,4,5,6-pentafluorophenyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate (0.20 g, 0.4 mmol) in THF (5 ml) was added to 1,3-propanediamine (0.35 ml, >10 eq) in THF (5 ml) and stirred at RT for 15 h. The solution was then concentrated under reduced pressure and the residue dissolved in 5% MeOH/EtOAc. The organic phase was washed with water, brine, dried (Na2SO4) and concentrated to give crude N-(3-aminopropyl)-4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide which was then recrystallised (MeOH/Hexane/EtOAc) (0.04 g, 22%); m.p. 201-206° C. 1H NMR [400 MHz, (CD3)2SO] δ 8.42 (br s, 1H), 8.25 (s, 1H), 7.74 (dd, J=10.2, 1.9 Hz, 1H), 7.57 (dt, J=8.5, 0.9 Hz, 1H), 7.29 (t, J=8.5 Hz, 1H), 5.60 (d, J=0.9 Hz, 1H), 3.38 (s, 3 H, obscured), 3.3-3.25 (m, 2 H, obscured), 2.81 (t, J=7.4 Hz, 2H), 1.75 (p, J=7.4 Hz, 2H). HPLC 94.4% (254 nm). HRMS (FAB+) calcd for C16H19FIN4O2 445.0537 (M+), found 445.0543.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[NH:10][S:9]1(=[O:18])=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:25][S:26]([O:29][CH2:30][C:31]#[C:32][CH2:33]OS(C)(=O)=O)(=[O:28])=[O:27]>>[CH3:25][S:26]([O:29][CH2:30][C:31]#[C:32][CH2:33][N:10]1[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[S:9]1(=[O:18])=[O:17])(=[O:28])=[O:27]
Reactant: O=S1(=O)Nc2ccccc2N1c1ccccc1F
Reactant: CS(=O)(=O)OCC#CCOS(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CS(=O)(=O)OCC#CCN1c2ccccc2N(c2ccccc2F)S1(=O)=O

Procedure:
In an analogous manner to general procedure IV, 1-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (prepared in an analogous manner as described in general procedure I, 0.79 g, 3.0 mmol) was treated with cesium carbonate (1.46 g, 4.5 mmol) and but-2-yne-1,4-diyl dimethane-sulfonate (3.63 g, 15.0 mmol) to give 0.55 g of 4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]but-2-yn-1-yl methanesulfonate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])=[CH:4][CH:3]=1.CO[CH:19](OC)[N:20]([CH3:22])[CH3:21]>CN(C=O)C>[CH3:19][N:20]([CH3:22])[CH:21]=[C:10]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)=[O:9]
Reactant: O=C(Cc1ccccc1)c1ccc(Cl)cc1
Reactant: COC(OC)N(C)C
Solvent: CN(C)C=O
Product: CN(C)C=C(C(=O)c1ccc(Cl)cc1)c1ccccc1
Yield: 100 %

Procedure:
A solution of benzyl 4-chlorophenyl ketone (10.0 g, 43.3 mmol) and dimethylformamide dimethylacetal (23 mL, 173 mmol) in DMF (125 mL) was heated at 75° C. for 20 h. The volatiles were removed in vacuo to provide 3-dimethylamino-1-(4-chlorophenyl)-2-(phenyl)prop-2-en-1-one (43.3 mmol assumed) which was used directly in the next step. 1HNMR (CDCl3): δ 2.76 (s, 6H), 7.15 (m, 2H), 7.16-7.3 (m, 5H), 7.36 (m, 2H), 7.41 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:27](=[O:28])[N:26]([CH3:29])[C:12]2[N:13]([CH3:25])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][C:17]([C:20]1[CH:24]=[CH:23][NH:22][N:21]=1)=[CH:16][CH:15]=3.[C:30](Cl)(=[O:32])[CH3:31]>>[C:30]([N:22]1[CH:23]=[CH:24][C:20]([C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:25])[C:12]2[N:26]([CH3:29])[C:27](=[O:28])[C:9]([C:3]4[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=4[Cl:1])=[CH:10][C:11]3=2)=[N:21]1)(=[O:32])[CH3:31]
Reactant: Cn1c(=O)c(-c2ccc(Cl)cc2Cl)cc2c3cc(-c4cc[nH]n4)ccc3n(C)c21
Reactant: CC(=O)Cl
Product: CC(=O)n1ccc(-c2ccc3c(c2)c2cc(-c4ccc(Cl)cc4Cl)c(=O)n(C)c2n3C)n1

Procedure:
The process is carried out as in Example 99 above, with the compound from Example 39, 3-(2,4-dichlorophenyl)-1,9-dimethyl-6-(1H-pyrazol-3-yl)-1,9-dihydropyrido[2,3-b]indol-2-one and acetyl chloride.
Reaction SMILES: C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:27])[N:14]([CH2:19][O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[CH:15]=[N:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1>C(O)(C(F)(F)F)=O>[OH:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:27])[N:14]([CH2:19][O:20][C:21](=[O:26])[C:22]([CH3:23])([CH3:24])[CH3:25])[CH:15]=[N:16]2)=[CH:11][CH:10]=1
Reactant: CC(C)(C)C(=O)OCn1cnc2cc(OCc3ccccc3)ccc2c1=O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)C(=O)OCn1cnc2cc(O)ccc2c1=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 89.2 %

Procedure:
7-benzyloxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (8.0 g, 22 mmol) was dissolved in TFA (40ml) and the mixture heated at reflux for 3 hours then allowed to cool to ambient temperature and stirred for 18 hours. The TFA was removed by evaporation and the residue resuspended in a mixture of ether and aqueous sodium hydrogen carbonate solution. The solid was collected by filtration, washed with water and ether and dried at 40° C. for 3 hours under high vacuum to give 7-hydroxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (5.42 g, 90%).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][NH2:15])(=[O:3])[CH3:2].[C:16]1(=O)[O:21][C:19](=[O:20])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.C([O-])(=O)C.[Na+]>C(O)(=O)C>[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][N:15]1[C:19](=[O:20])[C:18]2[C:17](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:16]1=[O:21])(=[O:3])[CH3:2]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: CC(=O)c1ccc2[nH]cc(CCN)c2c1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(=O)c1ccc2[nH]cc(CCN3C(=O)c4ccccc4C3=O)c2c1

Procedure:
A suspension of 5-acetyl-1H-indole-3-ethanamine (1.0 g), phthalic anhydride (0.83 g) and sodium acetate (1.0 g) in acetic acid (15 ml) was heated at reflux for 3 h. On cooling the title compound was deposited as an off-white crystalline solid (1.5 g) m.p. 234°-5°.
Reaction SMILES: Cl.C(O[CH:5]=[CH:6][C:7]1[N:8]([C:18]2[N:19]=[CH:20][N:21]=[C:22]([NH2:25])[C:23]=2[N:24]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11])C.C([O-])([O-])=[O:27].[K+].[K+].CO>C1COCC1.C(Cl)Cl>[C:6]([C:7]1[N:8]([C:18]2[N:19]=[CH:20][N:21]=[C:22]([NH2:25])[C:23]=2[N:24]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11])(=[O:27])[CH3:5]
Reactant: O=C([O-])[O-]
Reactant: CCOC=Cc1nc2c(N)ncnc2n1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Agent: Cl
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(=O)c1nc2c(N)ncnc2n1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
1 M HCl (10 ml) was added to a solution of 8-ethoxyvinyladenosine (17k) (1.48 g, 4.37 mmol) in THF (40 ml) and the solution stirred at room temperature for 20 h. Aqueous K2CO3 was added to neutral pH and the mixture applied directly onto a flash chromatography silica gel column which was developed with 15% MeOH in CH2Cl2; yield 1.17 g (87%). 1H NMR: (300 MHz, DMSO-d6); δ 2.72 (3H, s, COCH3), 3.52-3.71 (2H, m, H-5′), 3.94-3.96 (1H, m, H-4′ el. H-3′), 4.10-4.23 (1H, m, H-3′ or H-4′), 4.94 (1H, m, H-2′), 5.11 (1H, d, J 4.4 Hz, 3′-OH), 5.24 (1H, d, J 6.1 Hz, 2′-OH), 5.56-5.59 (1H, m, 5′-OH), 6.76 (1H, d, J 6.5 Hz, H-1′), 7.87 (2H, s, NH2), 8.21 (1H, s, H-2). 13C NMR: (75 MHz, DMSO-d6); δ 27.9 (CH3), 62.3 (C-5′), 70.9/72.0 (C-2′, C-3′), 86.3/89.3 (C-4′, C-1′), 118.7 (C-5), 143.7/150.5/154.7/157.7 (C-6, C-8, C-2, C-4), 191.7 (CO).
Reaction SMILES: C(O[C:9]([N:11]([CH:13]([CH:31]([CH3:33])[CH3:32])[C:14]([NH:16][CH:17]([CH3:30])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:20]=1)=[O:15])C)=O)C1C=CC=CC=1.[H][H]>[OH-].[OH-].[Pd+2].CO>[C:26]([C:21]1[CH:20]=[C:19]([CH2:18][CH:17]([NH:16][C:14](=[O:15])[CH:13]([NH:11][CH3:9])[CH:31]([CH3:32])[CH3:33])[CH3:30])[CH:24]=[CH:23][C:22]=1[OH:25])([CH3:27])([CH3:29])[CH3:28]
Reactant: CC(Cc1ccc(O)c(C(C)(C)C)c1)NC(=O)C(C(C)C)N(C)C(=O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CNC(C(=O)NC(C)Cc1ccc(O)c(C(C)(C)C)c1)C(C)C

Procedure:
A suspension of 0.54 g (1.19 mmol) of 2-[N-(benzyloxycarbonyl)-N-methylamino]-N-[2-(3-tert-butyl-4-hydroxyphenyl)-1-methylethyl]-3-methylbutanamide and 0.10 g of a 20% palladium hydroxide on carbon catalyst in methanol (8 ml) was stirred in a hydrogen atmosphere for 2 hours. After filtering off the catalyst, the solvent was distilled off under reduced pressure to give N-[2-(3-tert-butyl-4-hydroxyphenyl)-1-methylethyl]-3-methyl-2-(methylamino)butanamide in the amount of 0.36 g (95%).
Reaction SMILES: Cl[SiH:2]1[N:6]([C:7]([CH3:10])([CH3:9])[CH3:8])[CH:5]=[CH:4][N:3]1[C:11]([CH3:14])([CH3:13])[CH3:12].[S-:15][C:16]#[N:17].[Na+]>O1CCCC1>[C:11]([N:3]1[CH:4]=[CH:5][N:6]([C:7]([CH3:10])([CH3:9])[CH3:8])[SiH:2]1[N:17]=[C:16]=[S:15])([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)N1C=CN(C(C)(C)C)[SiH]1Cl
Reactant: N#C[S-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)N1C=CN(C(C)(C)C)[SiH]1N=C=S
Temperature: 25 °C
Reaction time: 14 h
Yield: 90 %

Procedure:
In an argon atmosphere, 6.10 g (26.2 mmol) of Si(tBuNCHCHNtBu)(H)Cl was dissolved in 20 mL of tetrahydrofuran and after adding 2.15 g (purity: 99%, 26.3 mmol) of sodium thiocyanate, the mixture was stirred at room temperature for 14 hours. Insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 108° C./3.3×102 Pa) to obtain 1,3-di-tert-butyl-2-thioisocyanato-1,3-diaza-2-silacyclopent-4-ene (Si(tBuNCHCHNtBu)(H)NCS) as a pale yellow liquid (yielded amount: 6.05 g, yield: 90%).