Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH:4]([NH:12]C(OCC1C=CC=CC=1)=O)[CH2:5][C:6]1([CH3:11])[CH2:10][CH2:9][CH2:8][CH2:7]1.[C:24](#N)[CH3:25]>C([O-])(O)=O.[Na+]>[CH3:1][O:2][C:3](=[O:23])[C@@:4]([NH2:12])([C:3]([O:2][CH2:1][C:25]1[CH:24]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:23])[CH2:5][C:6]1([CH3:11])[CH2:7][CH2:8][CH2:9][CH2:10]1
Reactant: CC#N
Reactant: COC(=O)C(CC1(C)CCCC1)NC(=O)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Product: COC(=O)[C@](N)(CC1(C)CCCC1)C(=O)OCc1ccccc1
Reaction time: 8 h

Procedure:
2-Benzyloxycarbonylamino-3-(1-methylcyclopentyl)-propionic acid methyl ester (7.6 g, 23.8 mmol) was dissolved in a mixture of acetonitrile (82 mL) and 0.2 M aqueous NaHCO3 (158 mL) and Alcalase 2.4 L (1.1 mL) was added and the reaction mixture was stirred vigorously for 8 h. The reaction mixture was then evaporated at 30° C. to remove acetonitrile, and the aqueous residue was washed with ether. The ethereal layer was concentrated to yield (R)-2-benzyloxycarbonyl-amino-3-(1-methylcyclopentyl)propionic acid methyl ester (1.9 g). The aqueous phase was filtered with Celite®, the pH was adjusted to 3 with 6N HCl, and the solution was extracted with ethylacetate. The ethyl acetate layer was dried and evaporated to yield 2(8)-benzyloxycarbonylamino-3-(1-methylcyclopentyl)-propionic acid (1.4 g).
Reaction SMILES: O=C1CCC(=O)N1O[C:9](=[O:27])[C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17](=[O:26])[N:18]([CH3:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][CH:11]=1.[NH2:28][CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1>>[N:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[CH2:30][CH2:29][NH:28][C:9]([C:10]1[CH:11]=[CH:12][C:13]([O:16][C:17](=[O:26])[N:18]([CH3:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:14][CH:15]=1)=[O:27]
Reactant: CN(C(=O)Oc1ccc(C(=O)ON2C(=O)CCC2=O)cc1)c1ccccc1
Reactant: NCCc1ccccn1
Product: CN(C(=O)Oc1ccc(C(=O)NCCc2ccccn2)cc1)c1ccccc1

Procedure:
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and 2-aminoethylpyridine. The crude product was used without further purification (26%, oil). HPLC-MS: m/z=376.2 (M+1); Rt: 2.25 min.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:26])[CH2:9][N:10]2[C:14](=[O:15])[C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([CH2:16][CH2:17][CH3:18])[N:12]=[C:11]2[CH3:25])=[CH:4][CH:3]=1.[CH2:27]([CH:29]([CH2:33][CH3:34])[C:30](Cl)=[O:31])[CH3:28]>>[CH2:27]([CH:29]([CH2:33][CH3:34])[C:30]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:26])[CH2:9][N:10]2[C:14](=[O:15])[C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([CH2:16][CH2:17][CH3:18])[N:12]=[C:11]2[CH3:25])=[CH:6][CH:7]=1)=[O:31])[CH3:28]
Reactant: CCC(CC)C(=O)Cl
Reactant: CCCC1(c2ccccc2)N=C(C)N(CC(=O)c2ccc(N)cc2)C1=O
Product: CCCC1(c2ccccc2)N=C(C)N(CC(=O)c2ccc(NC(=O)C(CC)CC)cc2)C1=O

Procedure:
Synthesis in analogy to Example 8 starting from enantiomerically pure 3-[2-(4-amino-phenyl)-2-oxo-ethyl]-2-methyl-5-phenyl-5-propyl-3,5-dihydro-imidazol-4-one and 2-ethyl-butyryl chloride to yield (−)-2-ethyl-N-{4-[2-(2-methyl-5-oxo-4-phenyl-4-propyl-4,5-dihydro-imidazol-1-yl)-acetyl]-phenyl}-butyramide. LC/MS at 254 nm; [M+H] 448; Rt=3.313 min; optical rotation=−8.2°, c=1.0 in methanol.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([S:12](Cl)(=[O:14])=[O:13])=[C:7]([CH3:16])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]([F:31])([F:30])[C:19]1[CH:20]=[C:21]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[NH2:22]>N1C=CC=CC=1>[F:17][C:18]([F:30])([F:31])[C:19]1[CH:20]=[C:21]([NH:22][S:12]([C:8]2[C:9]([CH3:11])=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][C:7]=2[CH3:16])(=[O:14])=[O:13])[CH:23]=[C:24]([C:26]([F:27])([F:29])[F:28])[CH:25]=1
Reactant: Cc1cc(C(C)(C)C)cc(C)c1S(=O)(=O)Cl
Reactant: Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Solvent: c1ccncc1
Product: Cc1cc(C(C)(C)C)cc(C)c1S(=O)(=O)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 23 %

Procedure:
4-Tert-butyl-2,6-dimethyl-benzenesulfonyl chloride (0.100 g, 0.383 mmol) was added to a solution of 3,5-bis(trifluoromethyl)aniline (0.089 g, 0.387 mmol) in dry pyridine (1 mL). The reaction was capped and stirred at room temperature for 1 day then stirred at 30° C. for 1 day. The reaction was then concentrated under vacuum. To this was added diethyl ether (60 mL) and the mixture was washed with 0.1 N HCl (3×20 mL) followed by 0.1 N NaOH (2×20 mL) then saturated NaCl (2×20 mL). After drying the organic layer over MgSO4, the solution was filtered and concentrated under vacuum. The crude compound was triturated with hexanes (2×10 mL) to afford the title compound (0.040 g, 23% yield). LCMS (M+Na) 476.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[N:12]=[N:13][N:14]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]4=[O:28])=[CH:18][CH:17]=3)[CH:15]=2)=[O:8])=[CH:4][CH:3]=1.C=O.[BH3-][C:32]#N.[Na+]>C(O)(=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[N:12]=[N:13][N:14]([C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:27][CH2:26][N:25]([CH3:32])[CH2:24][C:23]4=[O:28])=[CH:20][CH:21]=3)[CH:15]=2)=[O:8])=[CH:4][CH:3]=1
Reactant: [BH3-]C#N
Reactant: O=C(NCc1cn(-c2ccc(N3CCNCC3=O)cc2)nn1)c1ccc(Cl)s1
Agent: C=O
Agent: [Na+]
Solvent: CC(=O)O
Product: CN1CCN(c2ccc(-n3cc(CNC(=O)c4ccc(Cl)s4)nn3)cc2)C(=O)C1
Reaction time: 0.17 h

Procedure:
5-Chloro-N-((1-(4-(2-oxopiperazin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide (24 mg, 0.06 mmol, prepared as shown in Example 60) was stirred in 2 mL acetic acid at RT. To it was added formaldehyde (37% in water, 22 μL, 0.3 mmol). The mixture was stirred for 10 min. NaBH3CN (30 mg, 0.48 mmol) was added. The reaction was allowed for 10 min, and directly subjected to reverse phase prep HPLC to isolate the title compound. MS found for C19H19ClN6O2S (M+H)+ 431.1, 433.1 (Cl pattern).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:7](I)=[CH:6][C:3]=1[C:4]#[N:5].[Cl-].[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][Zn+])=[CH:15][CH:14]=1.NC1C=CC(CC2C=CC=CC=2)=CC=1C#N>>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([CH2:17][C:16]2[CH:19]=[CH:20][C:13]([Cl:12])=[CH:14][CH:15]=2)=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: N#Cc1cc(I)ccc1N
Reactant: Clc1ccc(C[Zn+])cc1
Agent: N#Cc1cc(Cc2ccccc2)ccc1N
Agent: [Cl-]
Product: N#Cc1cc(Cc2ccc(Cl)cc2)ccc1N

Procedure:
From 9 (488 mg, 2 mmol) and 4-chlorobenzylzinc chloride (0.5 M in THF, 10 mL, 5 mmol) by the same method as 10a; white powder (243 mg, 59%): mp 91.5-93° C.; 1H NMR (DMSO-d6) δ 3.79 (s, 2H, CH2), 5.87 (br s, 2H, NH2), 6.68 (d, J=8.0 Hz, 1H, H-3), 7.11 (d, J=8.0 Hz, H-4), 7.18 (d, J=8.4 Hz, 2H, H-2′ and H-6′), 7.20 (s, 1, H-6),7.29 (d, J=8.4 Hz, 2H, H-3′ and H-5′).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][CH:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[Na+].[CH3:39][S:40]([NH-:43])(=[O:42])=[O:41].[H-].[Na+].CS(N)(=O)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([NH:43][S:40]([CH3:39])(=[O:42])=[O:41])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1
Reactant: CS([NH-])(=O)=O
Reactant: CCC(C)Nc1cc(C(=O)OC)cc(Cl)n1
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CS(N)(=O)=O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC[C@H](C)Nc1cc(C(=O)OC)cc(NS(C)(=O)=O)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.1 %

Procedure:
Add 2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (500 mg, 2.07 mmol), toluene (10 mL), tris(dibenzylideneacetone)dipalladium(0) (95 mg, 0.104 mmol), 2-(di-tert-butylphosphino)biphenyl (62 mg, 0.207 mmol), and methanesulfonamide sodium salt (363 mg, 3.11 mmol) to a sealed flask flushed with nitrogen. (Prepare methanesulfonamide sodium salt by adding sodium hydride (2.0 g, 50.0 mmol, 60% dispersion in mineral oil) slowly to a solution of methanesulfonamide (5.0 g, 52.6 mmol) and THF (80 mL) at 0° C.) Stir the mixture at room temperature overnight. Concentrate and dry the residue under vacuum. Heat and stir the sealed flask at 100° C. for 18 h. Cool to room temperature, filter through a pad of filtering agent, wash with dichloromethane, concentrate the filtrate and purify (silica gel chromatography, eluting with 20:80 to 25:75 ethyl acetate:hexanes) to give the title compound (475 mg, 76%).
Reaction SMILES: C([NH:4][C:5]1[S:21][C:8]2[CH:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][N:11]([CH3:14])[CH2:12][CH2:13][C:7]=2[CH:6]=1)(=O)C.[ClH:22]>>[ClH:22].[ClH:22].[CH3:14][N:11]1[CH2:12][CH2:13][C:7]2[CH:6]=[C:5]([NH2:4])[S:21][C:8]=2[CH:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10]1
Reactant: CC(=O)Nc1cc2c(s1)C(c1ccccc1)CN(C)CC2
Agent: Cl
Product: CN1CCc2cc(N)sc2C(c2ccccc2)C1

Procedure:
A mixture of 2-acetamido-6-methyl-8-phenyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepine (10 mg) and 5M hydrochloric acid (2.0 ml) was heated to 90° for 30 minutes. The mixture was basified and extracted with dichloromethane (2×5 ml). The extracts were dried, filtered and evaporated to a yellow oil. This was immediately converted to the title product by dissolving in ethanolic hydrogen chloride and evaporating.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:13]([CH2:14][O:15][CH3:16])[CH2:12][N:11](C(OC(C)(C)C)=O)[CH:10](OC)[CH:9]2[C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)=[CH:4][CH:3]=1.[ClH:36].[CH3:37][OH:38]>C(Cl)Cl>[ClH:36].[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH:13]([CH2:14][O:15][CH3:16])[CH2:12][N:11]([O:38][CH3:37])[CH2:10][CH:9]2[C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)=[CH:6][CH:7]=1
Reactant: CO
Reactant: COCC1CN(C(=O)OC(C)(C)C)C(OC)C(c2ccc3ccccc3c2)C1c1ccc(Br)cc1
Agent: Cl
Solvent: ClCCl
Product: COCC1CN(OC)CC(c2ccc3ccccc3c2)C1c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 98 %

Procedure:
A solution of 60 mg (0.11 mg) of tert-butyl (3RS,4RS,5SR)-4-(4-bromo-phenyl)-5-methoxymethyl-3-naphthalen-2-yl-methoxy-piperidine-1-carboxylate in 5 ml of methylene chloride was treated with 2 ml of 2N hydrogen chloride in methanol and stirred at room temperature for 2 hours. For the working-up, the reaction solution was evaporated under reduced pressure. The residue was recrystallized from diethyl ether and gave 53 mg (98% of theory) of (3RS,4RS,5SR)-4-(4-bromo-phenyl)-5-methoxymethyl-3-naphthalen-2-yl-methoxy-piperidine hydrochloride as a colourless solid; MS: 442 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[S:3](Cl)(=[O:5])=[O:4].ClCCl.[CH2:11]1[CH:15]2[CH2:16][NH:17][CH2:18][CH:14]2[CH2:13][N:12]1[C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28]([F:31])([F:30])[F:29])=[N:26][N:27]=2)[N:24]=1>C1(C)C=CC=CC=1>[CH3:1][N:2]([CH3:7])[S:3]([N:17]1[CH2:16][CH:15]2[CH2:11][N:12]([C:19]3[CH:20]=[CH:21][C:22]4=[N:27][N:26]=[C:25]([C:28]([F:31])([F:29])[F:30])[N:23]4[N:24]=3)[CH2:13][CH:14]2[CH2:18]1)(=[O:5])=[O:4]
Reactant: CN(C)S(=O)(=O)Cl
Reactant: FC(F)(F)c1nnc2ccc(N3CC4CNCC4C3)nn12
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CN(C)S(=O)(=O)N1CC2CN(c3ccc4nnc(C(F)(F)F)n4n3)CC2C1
Reaction time: 1 h
Yield: 29.9 %

Procedure:
N,N-Dimethylsulfamoyl chloride (0.027 g, 0.19 mmol) and then dichloromethane were added sequentially to a mixture of diisopropylethylamineamine (0.044 g, 0.34 mmol) and 6-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (0.05 g, 0.17 mmol) in toluene (1.5 mL). The reaction mixture was stirred for 1 hour and evaporated to give an involatile residue. The residue was purified by preparative hplc using a Phenomenex Luna C18 100A column (10μ silica, 21 mm diameter, 150 mm length) eluted with decreasingly polar mixtures of water (containing 0.1% trifluoroacetic acid) and acetonitrile as eluents to give N,N-dimethyl-2-[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazin-6-yl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-sulfonamide (0.0206 g, 30%) as a white solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]2)=[CH:18][CH:17]=1.[C:29]1([C:35]#[CH:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(N(CC)CC)C.[Al]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:28][N:25]1[CH2:24][CH2:23][N:22]([C:19]2[CH:18]=[CH:17][C:16]([NH:15]/[CH:14]=[C:5]3\[C:6](=[O:13])[NH:7][C:8](=[O:12])[C:9]4[C:4]\3=[CH:3][C:2]([C:36]#[C:35][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:11][CH:10]=4)=[CH:21][CH:20]=2)[CH2:27][CH2:26]1
Reactant: C#Cc1ccccc1
Reactant: CN1CCN(c2ccc(N/C=C3\C(=O)NC(=O)c4ccc(Br)cc43)cc2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [Al]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN1CCN(c2ccc(N/C=C3\C(=O)NC(=O)c4ccc(C#Cc5ccccc5)cc43)cc2)CC1
Temperature: 70 °C
Yield: 53.6 %

Procedure:
A mixture of (4Z)-6-bromo-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (0.10 g, 0.23 mmol), 0.03 mL (0.27 mmol) of phenylacetylene, 0.04 g (0.046 mmol) of dichlorobis(triphenylphosphine)-palladium(II), 0.0043 g (0.023 mmol) of CuI, and 0.12 mL (1.14 mmol) of triethylamine in 2 mL of N,N′-dimethylformamide is added to a 10 mL round bottom flask, sealed with a rubber septum, de-aired and backfilled with nitrogen gas 3 times, and wrapped around with aluminum foil. The reaction mixture is stirred vigorously at 70° C. in an oil bath under nitrogen. Mass spectroscopy suggested the completion of reaction after 45 min. The reaction mixture is filtered through celite, and subsequently evaporated under high-pressure vacuum to brown solid. The solid is dissolved in warm chloroform and ran through a pad of florisil, which is rinsed with 200 mL of warm chloroform. The collected organic portion is evaporated under vacuum to give 0.057 g (54.3% yield) of brown solid: mp 169-170° C.; MS (ESI) m/z 463.1 (M+H)+1
Reaction SMILES: [CH2:1]1[C:6]2[NH:7][C:8]3[C:13]([C:5]=2[CH2:4][CH2:3][NH:2]1)=[CH:12][CH:11]=[CH:10][CH:9]=3.[C:14]([C:16]1[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=1)#[N:15].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[C:14]([C:16]1[CH:24]=[CH:23][C:19]([C:20]([N:2]2[CH2:3][CH2:4][C:5]3[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[NH:7][C:6]=3[CH2:1]2)=[O:21])=[CH:18][CH:17]=1)#[N:15]
Reactant: N#Cc1ccc(C(=O)O)cc1
Reactant: c1ccc2c3c([nH]c2c1)CNCC3
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: N#Cc1ccc(C(=O)N2CCc3c([nH]c4ccccc34)C2)cc1
Temperature: 25 °C
Yield: 80 %

Procedure:
A mixture of 175 mg of 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole, 5 ml of dimethylformamide, 0.2 g of 4-cyano-benzoic acid, 0.35 g of diphenylphosphoryl azide and 0.4 ml of diisopropylethylamine was stirred at room temperature over night. The solvent was removed under reduced pressure and the residue was partitioned between methylene chloride and 10% aqueous sodium carbonate solution. The organic phase was washed with 1 N hydrochloric acid, dried over magnesium sulfate and evaporated. Crystallization of the residue from methylene chloride/ether yielded 245 mg of 2-(4-cyano-benzoyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole with m.p. 228-232° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([CH3:22])=[C:12]([C:17](=[O:21])[CH2:18][CH2:19][CH3:20])[CH:13]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].[CH2:23](I)[CH3:24]>CN(C)C=O.[H-].[Na+]>[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([CH3:22])=[C:12]([C:17](=[O:21])[CH2:18][CH2:19][CH3:20])[CH:13]=2)[N:8]([CH2:23][CH3:24])[CH:7]=1)=[O:5])[CH3:2]
Reactant: CCI
Reactant: CCCC(=O)c1cc2c(=O)c(C(=O)OCC)c[nH]c2cc1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCC(=O)c1cc2c(=O)c(C(=O)OCC)cn(CC)c2cc1C
Reaction time: 1 h

Procedure:
30 g of 6-butyryl-7-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester are dissolved in 1000 ml of dimethylformamide and, in the course of one hour, 4.8 g of a 50% strength sodium hydride dispersion in mineral oil are added in portions. Stirring is carried out for 1 hour at room temperature and then 31.2 g of ethyl iodide are added, and the mixture is then stirred at room temperature for 1 hour, concentrated under reduced pressure, cooled with ice-water and filtered with suction. The product obtained by filtering with suction is dissolved in ethyl acetate, washed with water, dried over sodium sulphate, concentrated and cooled in an ice bath. The precipitated crystallisate is filtered with suction and recrystallised from ethyl acetate. 1-Ethyl-6-butyryl-7-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester having a melting point of 145°-146° is obtained.
Reaction SMILES: [Cl-].C1([C:8]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2C=CC=CC=2)N2C=C(CCC)N=C2)C=CC=CC=1.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:36]2[CH:40]=[C:39]([CH2:41][CH2:42][CH2:43][OH:44])[N:38]=[CH:37]2)C=CC=CC=1.S(Cl)(Cl)=O.C1(CC[O-])C=CC=CC=1.[Na+]>>[C:23]1([CH2:8][CH2:17][O:44][CH2:43][CH2:42][CH2:41][C:39]2[N:38]=[CH:37][NH:36][CH:40]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: OCCCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: CCCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: [Cl-]
Agent: [Na+]
Agent: [O-]CCc1ccccc1
Solvent: O=S(Cl)Cl
Product: c1ccc(CCOCCCc2c[nH]cn2)cc1

Procedure:
5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propane chloride, prepared from 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol with thionyl chloride, and 15 mmol of sodium 2-phenylethanolate are treated as described in Example 5.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:18]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][NH:15][C:16]=4[CH:17]=3)[O:9][CH2:8]2)[CH2:4][CH2:3]1.[CH3:19][C:20]1[CH:25]=[C:24]([C:26]2[O:30][N:29]=[C:28]([CH3:31])[CH:27]=2)[CH:23]=[CH:22][C:21]=1[C:32]1[CH:37]=[CH:36][C:35]([C:38](O)=[O:39])=[CH:34][CH:33]=1>>[CH3:1][N:2]1[CH2:3][CH2:4][C:5]2([C:18]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][N:15]([C:38]([C:35]5[CH:36]=[CH:37][C:32]([C:21]6[CH:22]=[CH:23][C:24]([C:26]7[O:30][N:29]=[C:28]([CH3:31])[CH:27]=7)=[CH:25][C:20]=6[CH3:19])=[CH:33][CH:34]=5)=[O:39])[C:16]=4[CH:17]=3)[O:9][CH2:8]2)[CH2:6][CH2:7]1
Reactant: CN1CCC2(CC1)COc1cc3c(cc12)NCC3
Reactant: Cc1cc(-c2ccc(-c3ccc(C(=O)O)cc3)c(C)c2)on1
Product: Cc1cc(-c2ccc(-c3ccc(C(=O)N4CCc5cc6c(cc54)C4(CCN(C)CC4)CO6)cc3)c(C)c2)on1

Procedure:
The title compound was prepared from 1'-methyl-2,3,6,7-tetrahydrospiro [furo[2,3-f]indole-3,4'-piperidine] (D8) and 2'-methyl-4'-(3-methylisoxazol-5-yl)biphenyl-4-carboxylic acid (D79) using a procedure similar to that of Example 1 (58%) m.p. 224-5° C.
Reaction SMILES: [F:1][C:2](I)([F:4])[F:3].[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[SH:13].C(N(CC)CC)C>CN(C)C=O.O>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13][C:2]([F:4])([F:3])[F:1]
Reactant: Fc1ccccc1S
Reactant: FC(F)(F)I
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Fc1ccccc1SC(F)(F)F
Reaction time: 24 h

Procedure:
Methyl viologen hydrochloride (1.17 g) in N,N-dimethylformamide (80 mL) at 25° C. was saturated with trifluoromethyl iodide, treated with 2-fluorobenzenethiol (9.7 mL) and triethylamine (20 mL), stirred for 24 hours, diluted with water (240 mL) and extracted with diethyl ether. The extract was washed with 1M aqueous NaOH, saturated ammonium chloride and brine and concentrated.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH:5]1[C:19](=[O:20])[C:9]2[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:11][O:12][C:8]=2[CH2:7][CH2:6]1.[CH3:21][C:22]1[NH:23][CH:24]=[CH:25][N:26]=1.C(N(C(C)C)CC)(C)C.[I-].[Na+]>CN(C)C=O>[CH3:21][C:22]1[N:23]([CH2:2][CH2:3][CH2:4][CH:5]2[C:19](=[O:20])[C:9]3[C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[N:11][O:12][C:8]=3[CH2:7][CH2:6]2)[CH:24]=[CH:25][N:26]=1
Reactant: Cc1ncc[nH]1
Reactant: O=C1c2c(-c3ccccc3)noc2CCC1CCCCl
Agent: [I-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1nccn1CCCC1CCc2onc(-c3ccccc3)c2C1=O
Temperature: 76 °C
Yield: 40.2 %

Procedure:
To a solution consisting of 5-(3-chloropropyl)-6,7-dihydro-3-phenyl-1,2-benzisoxazol-4(5H)-one (5.80 g) and dimethylformamide (57.0 ml) was added 2-methylimidazole (3.30 g), diisopropylethyl amine (10.5 ml) and sodium iodide (9.04 g) at room temperature with stirring. The reaction was flushed with nitrogen and warmed at 76° C. for 1 hour. Upon cooling to room temperature, dilute aqueous sodium bicarbonate and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous layer extracted twice with ethyl acetate and once with ether. The combined organic layers were washed with brine and concentrated to give the crude product. Drying was accomplished by azeotroping with benzene. Purification via flash column chromatography (silica gel, 2% triethylamine/0-20% methanol/ether) afforded 2.70 g (40%) of 6,7-dihydro-5-[3-(2-methyl-1H-imidazol-1-yl)-propyl]-3-phenyl -1,2-benzisoxazol-4(5H)-one. Recrystallization from dichloromethane/ether/pentane gave the product, m.p. 97°-99° C.
Reaction SMILES: [CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([NH2:17])[CH:11]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>CN(C)C=O>[CH2:24]([O:16][C:13]1[CH:14]=[CH:15][C:10]([C@H:7]2[CH2:8][CH2:9][C@H:4]([CH2:1][CH2:2][CH3:3])[CH2:5][CH2:6]2)=[CH:11][C:12]=1[NH2:17])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CCC[C@H]1CC[C@H](c2ccc(O)c(N)c2)CC1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC[C@H]1CC[C@H](c2ccc(OCc3ccccc3)c(N)c2)CC1

Procedure:
116.5 g of 4-(trans-4-n-propylcyclohexyl)-2-amino-phenol, 80 g of potassium carbonate and 110 g of benzyl bromide are heated to 100° for 10 seconds in 500 ml of N,N-dimethyl-formamide. Subsequently, the reaction mixture is poured into 1 l of water. From the mixture obtained, the 4-(trans-4-n-propylcyclohexyl)-2-aminophenyl benzyl ether formed is extracted with dichloromethane and, after distilling off of the extraction agent, is recrystallized from isopropanol; yield 120 g.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][N:10]([C:13]3[N:14]=[C:15](O)[C:16]4[S:21][CH2:20][CH2:19][C:17]=4[N:18]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)([Cl:25])=O>>[Cl:25][C:15]1[C:16]2[S:21][CH2:20][CH2:19][C:17]=2[N:18]=[C:13]([N:10]2[CH2:11][CH2:12][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]2)[N:14]=1
Reactant: Oc1nc(N2CCN(c3ccccc3)CC2)nc2c1SCC2
Reactant: O=P(Cl)(Cl)Cl
Product: Clc1nc(N2CCN(c3ccccc3)CC2)nc2c1SCC2
Temperature: 120 °C
Reaction time: 5 h
Yield: 100 %

Procedure:
4.3 g (13.7 mmol) of 2-(4-phenylpiperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-ol (IV) and 25 mL of phosphorus oxychloride are combined and stirred for 5 hours at 120° C. Excess phosphorus oxychloride is concentrated by evaporation, the residue is combined with ice water and dichloromethane. The organic phase is separated off and evaporated to dryness. The residue is triturated with water, suction filtered, and dried. 5.6 g of the product (100%) is obtained as a powder.