Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](C1NC=CN=1)(C1NC=CN=1)=S.[NH2:13][C:14]1[S:15][CH:16]=[CH:17][N:18]=1.[NH:19]([C:21](=[O:42])[C:22]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([C@H:31]2[CH2:36][CH2:35][C@H:34]([CH2:37][C:38]([O:40][CH3:41])=[O:39])[CH2:33][CH2:32]2)=[CH:27][CH:26]=1)=[O:23])[NH2:20].CCN=C=NCCCN(C)C>CC(N(C)C)=O.O>[S:15]1[CH:16]=[CH:17][N:18]=[C:14]1[NH:13][C:1]1[O:42][C:21]([C:22]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C@H:31]3[CH2:32][CH2:33][C@H:34]([CH2:37][C:38]([O:40][CH3:41])=[O:39])[CH2:35][CH2:36]3)=[CH:29][CH:30]=2)=[O:23])=[N:19][N:20]=1
Reactant: S=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: Nc1nccs1
Reactant: COC(=O)C[C@H]1CC[C@H](c2ccc(NC(=O)C(=O)NN)cc2)CC1
Agent: CCN=C=NCCCN(C)C
Solvent: O
Solvent: CC(=O)N(C)C
Product: COC(=O)C[C@H]1CC[C@H](c2ccc(NC(=O)c3nnc(Nc4nccs4)o3)cc2)CC1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
Thiocarbonyl diimidazole (179 mg, 1.00 mmol) was added in one portion to a solution of 2-aminothiazole (100 mg, 1.00 mmol) in DMA (5 mL) and the solution was stirred at room temperature for 6 h. Methyl [trans-4-(4-{[hydrazino(oxo)acetyl]amino}phenyl)cyclohexyl]-acetate (Intermediate 43, 267 mg, 0.80 mmol) was added in one portion and the reaction mixture was stirred at room temperature for 20 h and then heated at 80° C. for 10 minutes in the microwave. The solution was cooled to room temperature and EDCI (192 mg, 1.00 mmol) was added in one portion and the reaction mixture was heated to 90° C. for 15 minutes in the microwave. The reaction mixture was cooled to room temperature and poured into water (200 mL). The mixture was filtered and the resulting solid was recrystallised (CH3CN) to give the title compound (130 mg, 29%) as a solid; 1H NMR δ 1.09-1.18 (2H, m), 1.42-1.47 (2H, m), 1.79 (5H, m), 2.24-2.26 (2H, d), 2.45 (1H, t), 3.61 (3H, s), 6.99 (1H, d), 7.22 (2H, d), 7.38 (1H, d), 7.67-7.70 (2H, m), 10.78 (1H, s);
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])C(F)(F)F)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].[OH-:29].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:16])=[O:29])=[CH:7][N:8]2[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:4][CH:3]=1
Reactant: [OH-]
Reactant: CCCCCBr
Reactant: O=C(c1c[nH]c2cc(Cl)ccc12)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCn1cc(C(=O)O)c2ccc(Cl)cc21
Temperature: 60 °C
Yield: 98 %

Procedure:
A mixture of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (300 mg, 1.21 mmol), potassium carbonate (419 mg, 3.03 mmol), and 1-bromopentane (0.23 mL, 1.82 mmol) in N,N-dimethylformamide (4 mL) in a sealed reaction vessel was heated at 60° C. for 16 h. At this time, the reaction was cooled to 25° C. and partitioned between water (30 mL) and ethyl acetate (30 mL). This mixture was treated with a 1N aqueous hydrochloric acid solution (6 mL), shaken, and separated. The organic layer was concentrated in vacuo to afford a yellow solid. The resulting solid was treated with a 20% aqueous sodium hydroxide solution (7 mL) and was heated at 115° C. for 24 h. At this time, the reaction was cooled to 25° C. and was partitioned between water (75 mL) and ethyl acetate (75 mL). This solution was treated with a 1N aqueous hydrochloric acid solution (25 mL), shaken, and separated. The organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 6-chloro-1-pentyl-1H-indole-3-carboxylic acid (315 mg, 98%) as a yellow solid: mp 152-154° C.; EI-HRMS m/e calcd for C14H16ClNO2 (M+) 265.0870, found 265.0865.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1I.[CH2:10]([O:12][P:13]([O:17]CC)[O:14][CH2:15][CH3:16])[CH3:11]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[P:13](=[O:17])([O:14][CH2:15][CH3:16])[O:12][CH2:10][CH3:11]
Reactant: Fc1cccc(F)c1I
Reactant: CCOP(OCC)OCC
Product: CCOP(=O)(OCC)c1c(F)cccc1F
Reaction time: 20 h
Yield: 74 %

Procedure:
2,6-difluoroiodobenzene (3.0 g, 12.5 mmol) was combined with triethylphosphite (10.7 mL, 62.5 mmol) in a pressure vessel which had been flushed with nitrogen. The vessel was sealed and rotated in the photoreactor (16 bulbs-350 nm) for 20 hours. The reaction mixture was put under hi-vacuum (0.08 Torr) at 50° C. for 5 hours. A column was run in hexanes and ethyl acetate (increasing polarity as run). The top spot, which was UV active, was separated. After removing solvent, a yellow-tinted liquid was left (2.30 g, 74% yield). 1H NMR (400.14 MHz, DMSO) δ 7.72 (m), 7.21 (m, 2H), 4.10 (m, 4H), 1.25 (t, J=7.04 Hz). 31P{1H} NMR (161.97 MHz, DMSO): δ 8.23. The phosphonate can be hydrolyzed as described above to provide the corresponding phosphonic acid.
Reaction SMILES: [ClH:1].[CH3:2][C:3]1[CH:11]=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1.[CH2:12]=O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[Cl:1][CH2:2][C:3]1[C:11]([CH3:12])=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1
Reactant: Cl
Reactant: Cc1ccc2c(c1)OCO2
Reactant: C=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: ClCCl
Product: Cc1cc2c(cc1CCl)OCO2
Reaction time: 8 h

Procedure:
To a mixture of methylene chloride (130 L), concentrated HCl (130 L), and tetrabutylammonium bromide (1.61 Kg) was added 5-methylbenzo[d][1,3]dioxole (10 Kg) followed by the slow addition of formaldehyde (14 L, 37 wt % in water). The mixture was stirred overnight. The organic layer was separated, dried with magnesium sulfate and concentrated to an oil. Hexane (180 L) was added and the mixture heated to boiling. The hot hexane solution was decanted from a heavy oily residue and evaporated to give almost pure 5-chloromethyl-6-methylbenzo[d][1,3]dioxole as a white solid. Recrystallization from hexane (50 L) gave 5-chloromethyl-6-methylbenzo[d][1,3]dioxole (80% recovery after recrystallization).
Reaction SMILES: [Cl:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][CH:18]4[CH2:20][O:19]4)[C:12](=[O:21])[N:11]([CH3:22])[C:10]=3[N:9]=[C:8]2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26](OC(F)(F)F)[CH:25]=2)=[CH:4][CH:3]=1.C(O)([C:39]([F:42])([F:41])[F:40])=O.[OH2:44]>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][CH:18]([OH:44])[CH2:20][OH:19])[C:12](=[O:21])[N:11]([CH3:22])[C:10]=3[N:9]=[C:8]2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:39]([F:42])([F:41])[F:40])[CH:25]=2)=[CH:35][CH:36]=1
Reactant: O
Reactant: Cn1c(=O)n(CC2CO2)c(=O)c2c1nc(Oc1cccc(OC(F)(F)F)c1)n2Cc1ccc(Cl)cc1
Reactant: O=C(O)C(F)(F)F
Solvent: C1COCCO1
Product: Cn1c(=O)n(CC(O)CO)c(=O)c2c1nc(Oc1cccc(C(F)(F)F)c1)n2Cc1ccc(Cl)cc1
Temperature: 80 °C
Reaction time: 2 h
Yield: 48.4 %

Procedure:
To a solution of 7-(4-chlorobenzyl)-3-methyl-1-(oxiran-2-ylmethyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (140 mg, 0.268 mmol) in 1,4-dioxane (10 mL) was added TFA (0.11 mL, 1.48 mmol) and water (2 mL); then the mixture was stirred at 80° C. for 2 h. The mixture was concentrated; then purified by silica gel chromatography eluting with DCM/methanol (50:1 to 20:1) to give 7-(4-chlorobenzyl)-1-(2,3-dihydroxypropyl)-3-methyl-8-(3-(trifluoromethyl)phenoxy)-1H-purine-2,6(3H,7H)-dione (70 mg, 48.4% yield) as white solid. 1H-NMR (DMSO-d6) δ 7.63-7.58(t, 1H), 7.48(s, 1H), 7.44-7.41(m, 5H), 7.34-7.31(d, 1H), 5.44(s, 2H), 4.68-4.67(d, 1H), 4.55-4.52(m, 1H), 4.01-3.98(m, 1H), 3.84-3.80(m, 2H), 3.33(s, 2H), 3.29(s, 3H). LCMS retention time 2.811 min; LCMS MH+ 541.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]=O)=[N:6][CH:7]=1.[Li+].C[Si]([N-:15][Si](C)(C)C)(C)C.CCCCC.[C:25]([Li])([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([NH2:15])[C:25]([CH3:28])([CH3:27])[CH3:26])=[N:6][CH:7]=1
Reactant: [Li]C(C)(C)C
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: O=Cc1ccc(F)cn1
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCCCC
Product: CC(C)(C)C(N)c1ccc(F)cn1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 84.5 %

Procedure:
To an ice-cooled solution of 5-fluoropicolinaldehyde (0.10 g, 0.799 mmol) in THF (5 mL) was added a 1.0 M THF solution of LiHMDS (0.879 mL, 0.879 mmol). The violet solution was stirred at 0° C. for 20 min then cooled to −78° C. A 1.7 M pentane solution of tert-butyllithium (0.470 mL, 0.799 mmol) was added dropwise. Stirring was continued for 1.5 h at −78° C. The reaction was carefully quenched by addition of water (20 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organics were washed with brine, dried over anhydrous MgSO4, filtered, then concentrated to give the title compound (123 mg) as an orange oil. LCMS m/z=183.2 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[Cl:19][CH2:20][CH2:21][CH2:22][N:23]1[CH:28]=[C:27]([CH3:29])[C:26](=[O:30])[N:25]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:24]1=[O:38]>>[ClH:19].[CH2:31]([N:25]1[C:26](=[O:30])[C:27]([CH3:29])=[CH:28][N:23]([CH2:22][CH2:21][CH2:20][N:14]2[CH2:15][CH2:16][N:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][CH2:3][C:2]([F:1])([F:17])[F:18])[CH2:12][CH2:13]2)[C:24]1=[O:38])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: FC(F)(F)COc1ccccc1N1CCNCC1
Reactant: Cc1cn(CCCCl)c(=O)n(Cc2ccccc2)c1=O
Product: Cc1cn(CCCN2CCN(c3ccccc3OCC(F)(F)F)CC2)c(=O)n(Cc2ccccc2)c1=O
Product: Cl

Procedure:
substituting 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine and 1-(3-chloropropyl)-3-benzyl-5-methyl-2,4(1H,3H)-pyrimidinedione gave 3-benzyl-1-(3-{4-(2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl}propyl)-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 168°-169° C.; Anal.: Calcd. for C27H31F3N4O3.(HCl)1.9 : C, 55.01; H, 5.69; N, 9.50%; Found: C, 54.95; H, 5.59; N, 9.43%;
Reaction SMILES: C([Cl:4])(C)=O.[NH2:5][CH:6]1[CH:13]2[CH2:14][C:9]3([C:16]([OH:18])=[O:17])[CH2:10][CH:11]([CH2:15][CH:7]1[CH2:8]3)[CH2:12]2>CO>[ClH:4].[NH2:5][CH:6]1[CH:13]2[CH2:14][C:9]3([C:16]([OH:18])=[O:17])[CH2:10][CH:11]([CH2:15][CH:7]1[CH2:8]3)[CH2:12]2
Reactant: CC(=O)Cl
Agent: NC1C2CC3CC1CC(C(=O)O)(C3)C2
Solvent: CO
Product: Cl
Temperature: 45 °C
Reaction time: 12 h

Procedure:
At 0° C., in a 250-mL flask, MeOH (85 ml) was added with AcCl (16.08 g, 204.85 mmol), and then at room temperature, 4-amino-adamantane-1-carboxylic acid (8.0 g, 40.97 mmol) was added thereto. At 45° C., the mixture was stirred for 12 hours. After the reaction was completed, the solid was filtered by acetonitrile to obtain 4-amino-adamantane-1-carboxylate hydrochloride (8.17 g, 81%).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][CH2:3]1.[CH3:19][Si](C)(C)[N-][Si](C)(C)C.[Li+].IC>CN(C=O)C>[CH3:19][N:8]([CH:5]1[CH2:6][CH2:7][C:2](=[O:1])[CH2:3][CH2:4]1)[C:9](=[O:18])[O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C1CCC(NC(=O)OCc2ccccc2)CC1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CI
Solvent: CN(C)C=O
Product: CN(C(=O)OCc1ccccc1)C1CCC(=O)CC1
Reaction time: 0.5 h

Procedure:
Benzyl (4-oxocyclohexyl)carbamate (500 mg, 2.0 mmol) in DMF was treated with lithium hexamethyldisilazid (2.0 mmol) at room temperature. This solution was stirred for 30 min and was then treated with iodomethane (0.25 mL, 4.0 mmol) and stirred for 18 h. DMF was removed under vacuum and the residue was purified by silica column chromatography to give the title compound.
Reaction SMILES: CC1[N:3]([C:8]2[C:9]([C:20]([OH:22])=[O:21])=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)C(C)=CC=1.Cl.NO>CCO.O.CCOC(C)=O>[NH2:3][C:8]1[C:9]([C:20]([OH:22])=[O:21])=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:13]=1
Reactant: COc1nc(C(=O)O)c(-n2c(C)ccc2C)cc1C(F)(F)F
Agent: Cl
Agent: NO
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCO
Product: COc1nc(C(=O)O)c(N)cc1C(F)(F)F
Temperature: 25 °C

Procedure:
3-(2,5-Dimethyl-pyrrol-1-yl)-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (2.1 g, 6.68 mmol) was dissolved in EtOH (40 ml) and water (20 ml). To this mixture was added TEA (2.79 ml, 20.05 mmol) followed by hydroxylamine hydrochloride (4.64 g, 66.8 mmol). The resulting mixture was heated at reflux for 5 hours. After cooling to RT, the mixture was diluted with EtOAc (100 ml) and washed with aqueous HCl (1M, 100 ml). The aqueous phase was back extracted with EtOAc (100 ml) and the combined organic phases washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo to afford the product as an orange solid. The material can be used crude or recrystallised from isohexane-EtOAc (10:1) LC-MS Rt=1.0 min[M+H]+ 237 (Method 2minLC_v003)
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH2:12]([NH2:16])[CH2:13][CH2:14][CH3:15].C(N(C(C)C)CC)(C)C>C(#N)C.CCOC(C)=O>[CH2:12]([NH:16][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)[CH2:13][CH2:14][CH3:15]
Reactant: Clc1ccc2ccccc2n1
Reactant: CCCCN
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCCCNc1ccc2ccccc2n1
Yield: 30.7 %

Procedure:
2-Chloroquinoline (500 mg, 3.06 mmol), butylamine (0.90 nrL, 9.16 mmol), and diisopropylethylamine (0.82 mL, 4.58 mmol) were dissolved in acetonitrile (5 mL), and solution refluxed 2 days. Reaction cooled and diluted with EtOAc. Reaction washed with water and brine. Organic layer dried with Na2SO4, filtered, and concentrated in vacuo. Residue purified by flash chromatography on silica gel eluting with 15% EtOAc/Hexanes to afford the desired product as a pale yellow oil (188 mg, 31% ). m/e (DCI) 201 (MH+)
Reaction SMILES: [CH3:1][NH:2][NH2:3].O=[C:5]([CH2:12][C:13](=O)[CH2:14][CH2:15]C)[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].O>C(O)C>[CH3:1][N:2]1[C:12]([CH2:13][CH2:14][CH3:15])=[CH:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N:3]1
Reactant: CCCC(=O)CC(=O)CC(=O)OCC
Reactant: CNN
Solvent: CCO
Solvent: O
Product: CCCc1cc(C(=O)OCC)nn1C
Yield: 7.9 %

Procedure:
10.4 g of methylhydrazine were initially charged in 50 ml of ethanol and, with stirring and external cooling, admixed with a solution of 42.9 g of ethyl 2,4-diketoheptanecarboxylate in 50 ml of ethanol, during which the internal temperature was kept at 5 to 10° C. (time for the dropwise addition: 10 minutes). The solution was stirred at 5 to 10° C. for another 30 minutes, the solvent and the water which had been formed were distilled off and the residue was fractionated under reduced pressure. The desired ethyl 1-methyl-3-n-propyl-pyrazole-5-carboxylate passed over at 125 to 128° C. (13 mm). The yield was 78.3% of theory. By further distillation (166 to 168° C./13 mm), the undesired isomer (=ethyl 1-methyl-5-n-propyl-pyrazole-3-carboxylate) was obtained in a yield of 7.9% of theory. Thus, the isomer ratio was approximately 10:1 in favor of the desired isomer.
Reaction SMILES: C(O[C:4]([C:6]1[N:7]=[C:8]([C:26]#[N:27])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])C.Cl.[OH2:29]>C[O-].[Na+].CO>[Cl:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[O:17][C:11]1[CH:10]=[C:9]2[C:14]([C:15]([OH:16])=[C:6]([C:4]([NH:27][CH2:26][CH2:8][CH2:9][CH2:10][C:11]([OH:17])=[O:29])=[O:5])[N:7]=[C:8]2[C:26]#[N:27])=[CH:13][CH:12]=1
Reactant: O
Reactant: CCOC(=O)c1nc(C#N)c2cc(Oc3ccc(F)cc3Cl)ccc2c1O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: N#Cc1nc(C(=O)NCCCCC(=O)O)c(O)c2ccc(Oc3ccc(F)cc3Cl)cc12
Yield: 45 %

Procedure:
A mixture of 1-cyano-4-hydroxy-7-(4-fluoro-2-chloro-phenoxy)-isoquinoline-3-carboxylic acid ethyl ester (50 mg, 0.13 mmol) and 5-amino-petanoic acid (45 mg, 0.39 mmol) in 0.5 M NaOMe/MeOH solution was microwaved at 130° C. for 1 h. Reaction mixture was diluted with water (60 mL) and acidified by 1 N HCl to pH=3-4. Precipitate was collected and dried. Crude product was then purified by silica gel chromatography, eluting with 5-70% EtOAc/hexanes to provide the title compound 27 mg (0.06 mmol) in 45% yield. LC-MS ESI−: 455.89 (M−1)−.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:45]([O:46]C(=O)C)[C@@H:44]([O:50]C(=O)C)[C@@H:43]([CH2:54][N:55]2C(=O)C3=CC=CC=C3C2=O)[O:42][C@H:6]1[S:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C@H:15]1[CH2:39][CH2:38][C@@:37]2([CH3:40])[C:17](=[CH:18][CH2:19][C@@H:20]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:41])[C@H:21]3[CH2:22][CH2:23][C@@H:24]2[C@H:25]([CH3:32])[CH2:26][CH2:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:16]1)(=O)C.C(Cl)(Cl)Cl.[NH4+].[OH-]>CO.C(N)CCC>[NH2:55][CH2:54][C@H:43]1[O:42][C@@H:6]([S:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C@H:15]2[CH2:39][CH2:38][C@@:37]3([CH3:40])[C:17](=[CH:18][CH2:19][C@@H:20]4[C@@H:36]3[CH2:35][CH2:34][C@@:33]3([CH3:41])[C@H:21]4[CH2:22][CH2:23][C@@H:24]3[C@H:25]([CH3:32])[CH2:26][CH2:27][CH2:28][CH:29]([CH3:30])[CH3:31])[CH2:16]2)[C@H:5]([OH:4])[C@@H:45]([OH:46])[C@H:44]1[OH:50]
Reactant: CC(=O)O[C@H]1[C@@H](OC(C)=O)[C@@H](CN2C(=O)c3ccccc3C2=O)O[C@@H](SCCCCCCO[C@H]2CC[C@@]3(C)C(=CC[C@H]4[C@@H]5CC[C@H]([C@H](C)CCCC(C)C)[C@@]5(C)CC[C@@H]43)C2)[C@@H]1OC(C)=O
Agent: [NH4+]
Agent: [OH-]
Solvent: CCCCN
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OCCCCCCS[C@@H]5O[C@H](CN)[C@H](O)[C@H](O)[C@H]5O)CC[C@]4(C)[C@H]3CC[C@]12C

Procedure:
A suspension of 6-(5-cholesten-3β-yloxy)hexyl 2,3,4-tri-O-acetyl-6-deoxy-6-phthalimido-1-thio-β-D-galactopyranoside (710 mg.) in methanol (10 ml.) and n-butylamine (10 ml.) is heated under reflux for 16 hours. The solution is evaporated to a crystalline mass. Chloroform is added and the solid is filtered and washed with chloroform. The combined filtrates are evaporated to a syrup which is put on a column of silica gel and eluted with chloroform-methanol-ammonium hydroxide (80:20:2). The desired fractions are combined and evaporated to a syrup which is triturated with ethyl ether to give crystals (390 mg. 76%); Rf 0.28 (CHCl3 --MeOH--NH4OH, 80:20:2), [α]D27 -29.5° C. (C 1.05, chloroform), m.s.: m/e 665 (M+ +1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:35][O:36][C:37]1[CH:38]=[C:39]([CH:41]=[C:42]([O:44][CH3:45])[CH:43]=1)[NH2:40].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH3:45][O:44][C:42]1[CH:41]=[C:39]([NH:40][C:24]([NH:22][C:19]2[CH:18]=[CH:17][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][CH:7]=3)=[CH:21][CH:20]=2)=[O:26])[CH:38]=[C:37]([O:36][CH3:35])[CH:43]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc(N)cc(OC)c1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc(NC(=O)Nc2ccc(Oc3ccnc4cc(OC)c(OC)cc34)cc2)cc(OC)c1
Yield: 99.9 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (53 mg) was dissolved in toluene (5 ml) with heat, after the addition of triethylamine (1 ml), triphosgene (101 mg) was added, and the admixture was ref luxed with heat for 4 minutes. 3,5-Dimethoxyaniline (62 mg) was added to the reaction mixture, and the admixture was refluxed with heat for 13 minutes. After the addition of aqueous sodium hydrogen carbonate, the reaction mixture was extracted 2 times with ethyl acetate, and the organic layer was then washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by reduced-pressure distillation, and the resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 85 mg of the title compound (yield: 100%)).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][C:11](=[O:17])[NH:12]3)=[CH:4][CH:3]=1.[CH3:18][C:19]1[C:23]([C:24]([N:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[O:25])=[C:22]([CH3:33])[NH:21][C:20]=1[CH:34]=O>C(O)C.N1CCCCC1>[CH3:18][C:19]1[C:23]([C:24]([N:26]2[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]2)=[O:25])=[C:22]([CH3:33])[NH:21][C:20]=1[CH:34]=[C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[CH:16][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[NH:12][C:11]1=[O:17]
Reactant: O=C1Cc2c(cccc2-c2ccc(F)cc2)N1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)N1CCN(C)CC1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1[nH]c(C=C2C(=O)Nc3cccc(-c4ccc(F)cc4)c32)c(C)c1C(=O)N1CCN(C)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 55.7 %

Procedure:
To a solution of 4-(4-fluoro-phenyl)-1,3-dihydro-indol-2-one (56.8 mg, 0.25 mmol) and 3,5-dimethyl-4-(4-methyl-piperazine-1-carbonyl)-1H-pyrrole-2-carbaldehyde (64.8 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide 3-[3,5-Dimethyl-4-(4-methyl-piperazine-1-carbonyl)-1H-pyrrol-2-ylmethylene]-4-(4-fluoro-phenyl)-1,3-dihydro-indol-2-one as a yellow solid (63.9 mg, 56%)
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([CH3:19])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH2:18])=O)[C:6]=2[CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>O1CCOCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([CH3:19])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]#[N:18])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CN1Cc2c(C(N)=O)ncn2-c2cccc(Cl)c2C1=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: C1COCCO1
Product: CN1Cc2c(C#N)ncn2-c2cccc(Cl)c2C1=O

Procedure:
19.0 g 7-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepene-3-carboxamide (VI) were suspended under stirring and argon atmosphere in 95 ml 1,4-dioxane and 6.58 phosphorous oxychloride were added in one portion. The reaction mixture was heated to reflux for one hour giving a yellow solution, which was concentrated at 50° C. under reduced pressure. The residue was digested in 100 ml deionized water for two hours at r.t. The precipitate (7-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carbonitrile (VII)) was filtered off, washed three times with 30 ml deionized water and dried under vacuum at 80° C. for 18 hours. Crude product: 17.3 g as a light yellow powder. m.p. 238.5-239.5° C.
Reaction SMILES: [CH2:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH:3]([C:14]([OH:16])=[O:15])[NH:2]1.[OH-].[Na+].CS(C)=O.[CH:23]1(Br)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.[C:30](=[S:32])=[S:31]>O>[CH:23]1([S:32][C:30]([N:2]2[CH:3]([C:14]([OH:16])=[O:15])[CH2:4][C:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[NH:12][C:13]=3[CH2:1]2)=[S:31])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: O=C(O)C1Cc2c([nH]c3ccccc23)CN1
Reactant: S=C=S
Reactant: BrC1CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: O=C(O)C1Cc2c([nH]c3ccccc23)CN1C(=S)SC1CCCCC1
Yield: 61 %

Procedure:
In the same manner as described in Example 6, (3RS)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (4.32 g), NaOH (1.8 g), dimethylsulfoxide (25 ml), water (2 ml), carbon disulfide (1.45 ml) and cyclohexyl bromide (3.9 g) are reacted and treated. The product is crystallized from chloroform-n-hexane to give the title compound (4.5 g, 61%), m.p. 150.5°-151° C.