Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([C:18]2[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=2)[CH:7]2[CH:3]1[CH2:4][N:5]([C:8](=O)[CH2:9][CH2:10][C:11]1[S:12][CH:13]=[CH:14][C:15]=1[CH3:16])[CH2:6]2.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][C:2]1([C:18]2[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=2)[CH:7]2[CH:3]1[CH2:4][N:5]([CH2:8][CH2:9][CH2:10][C:11]1[S:12][CH:13]=[CH:14][C:15]=1[CH3:16])[CH2:6]2
Reactant: Cc1ccsc1CCC(=O)N1CC2C(C1)C2(C)c1cccc(NS(C)(=O)=O)c1
Agent: O=C([O-])O
Agent: [Al+3]
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccsc1CCCN1CC2C(C1)C2(C)c1cccc(NS(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.7 %

Procedure:
To a solution of N-(3-{6-methyl-3-[3-(3-methyl-2-thienyl)propanoyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide (Preparation 130, 150 mg, 0.358 mmol) in anhydrous tetrahydrofuran (10 ml) under a nitrogen atmosphere at 0° C. was added dropwise lithium aluminium hydride (1.0M solution in tetrahydrofuran, 0.72 ml, 0.72 mmol) and the reaction mixture was stirred at room temperature overnight. The rapidly stirred reaction mixture was treated sequentially with water (0.75 ml), sodium hydrogen carbonate (750 mg) and ethyl acetate (15 ml). After 15 min, the reaction mixture was filtered and concentrated in vacuo to afford 140 mg of a colourless oil. This was purified by chromatography using a Biotage Flash 12™ cartridge packed with silica gel (8 g) eluting with hexane:ethyl acetate (100:0 to 0:100 over 30 min) and then with ethyl acetate:methanol (100:0 to 0:100 over 5 min) to afford the title compound as a colourless oil (74 mg, 50%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:19][CH2:18][N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([C:16]#N)[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:20]=1.CC(C[AlH]CC(C)C)C.CC[O:32]C(C)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:19][CH2:18][N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([CH:16]=[O:32])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:20]=1
Reactant: N#Cc1cccc2c1cc1n2COc2ccc(Cl)nc2-1
Reactant: CCOC(C)=O
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Product: O=Cc1cccc2c1cc1n2COc2ccc(Cl)nc2-1
Temperature: -78 °C
Reaction time: 6 h
Yield: 40 %

Procedure:
To a solution of 2-chloro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-11-carbonitrile (500 mg, 1.77 mmol) in toluene (10 mL) was added DIBAL-H (505 mg, 3.55 mmol) in portion under nitrogen at −78° C. and then the mixture was stirred at −78° C. for 6 hours. The reaction mixture was quenched with ice water and extracted with EtOAc. Then the combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo to provide the 2-chloro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-11-carbaldehyde (200 mg, yield: 40%) through the column chromatography (petroleum ether:EtOAc=5:1˜2:1). 1H-NMR (CDCl3, 400 MHz) δ 10.29 (s, 1H), 8.03 (s, 1H), 7.69 (dd, J1=0.8 Hz, J2=7.2 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.44 (t, J=8.0 Hz, 1H), 7.38 (d, J=8.4 Hz, 1H), 7.22 (d, J=8.4 Hz, 1H), 6.05 (s, 2H). MS (M+H)+: 285/287.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([NH:14][C@H:15]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:16][O:17][CH2:18][CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[O:13])=[CH:9][CH:10]=2)[NH:5][CH:4]=1.[CH2:31]=O>>[Cl:2][C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([NH:14][C@H:15]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:16][O:17][CH2:18][CH:19]3[CH2:20][CH2:21][N:22]([CH3:31])[CH2:23][CH2:24]3)=[O:13])=[CH:9][CH:10]=2)[NH:5][CH:4]=1
Reactant: O=C(N[C@@H](COCC1CCNCC1)c1ccccc1)c1ccc2c(Cl)c[nH]c2c1
Reactant: C=O
Agent: Cl
Product: CN1CCC(COC[C@H](NC(=O)c2ccc3c(Cl)c[nH]c3c2)c2ccccc2)CC1

Procedure:
Using alkylation method B, 3-chloro-N-[(R)-1-phenyl-2-(piperidin-4-ylmethoxy)ethyl]-1H-indole-6-carboxamide hydrochloride (200 mg, 0.44 mmol) and paraformaldehyde (134 mg, 4.4 mmol) afforded, after purification (SiO2: 2.5% isopropylamine in 10:2:2:DCM:EtOAc:hexane), 80 mg (42%) of the title compound.
Reaction SMILES: [CH:1]1([SiH:7]([Cl:9])[Cl:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:10]=[CH:11][CH2:12][CH2:13][CH2:14][CH3:15]>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH2:10]([Si:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)([Cl:9])[Cl:8])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: C=CCCCC
Reactant: Cl[SiH](Cl)C1CCCCC1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Product: CCCCCC[Si](Cl)(Cl)C1CCCCC1
Temperature: 60 °C

Procedure:
This cyclohexyldichlorosilane in an amount of 139.3 g (0.761 mol), 95.1 g of 1-hexene (1.16 mol) and 0.05 mol % of chloroplatinic acid (relative to cyclohexyldichlorosilane) were reacted by heating in an oil bath at 60° C. for 3 hours with stirring. Thereafter 183.5 g (0.69 mol) of hexylcyclohexyldichlorosilane was obtained by vacuum distillation. The yield relative to cyclohexyldichlorosilane was 90.7% and that relative to dichlorosilane was 83.2%. This hexylcyclohexyldichlorosilane had a boiling point of 92°~95° C./1.5 mmHg and a refractive index nD20 of 1.4744. The results of elemental analysis were as follows: measured value, C, 54.28%; H, 9.15%; Cl, 25.6%, theoretical value, C, 53.92%; H2, 9.05%; Cl, 26.83%. Further infrared spectrum is shown in FIG. 3 and NMR spectrum is shown in FIG. 7 and from the above-mentioned result, it was confirmed that the product had a formula (cyclohexyl)(n--C6H13)SiCl2.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:8](O)[CH3:9].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH2:8]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:9]
Reactant: Nc1ccccc1
Reactant: CCO
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Solvent: O
Product: CCNc1ccccc1
Yield: 83 %

Procedure:
200 parts of aniline, 50 parts of ethyl alcohol and 10 parts of triphenyl phosphite are heated for 10 hours at 250° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, excess aniline and unconverted alcohol are distilled off under reduced pressure. 110 parts of N-ethylaniline, corresponding to a yield of 83% of theory, distil at a boiling point of 205° C/760 mm Hg.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:18]=[CH:17][C:7]2[NH:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[O:11][CH2:12][C:6]=2[CH:5]=1.Cl[C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:30][CH:29]=2)[CH2:21]1.C(=O)([O-])O.[Na+]>CCCCCC.CS(C)=O.C(OCC)(=O)C>[F:3][C:4]1[CH:18]=[CH:17][C:7]2[N:8]([CH2:24][C@H:23]3[CH2:25][CH2:20][CH2:21][N:22]3[CH2:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([N:34]4[CH2:35][CH2:36][CH2:37][CH2:38]4)=[CH:32][CH:33]=3)[C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[O:11][CH2:12][C:6]=2[CH:5]=1
Reactant: Fc1ccc2c(c1)COc1ccccc1N2
Reactant: Cl[C@@H]1CCCN(CCc2ccc(N3CCCC3)cc2)C1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Fc1ccc2c(c1)COc1ccccc1N2C[C@H]1CCCN1CCc1ccc(N2CCCC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
60% sodium hydride (348 mg, 8.7 mmol) was washed with hexane in argon stream and then suspended in dimethyl sulfoxide (50 ml), and the obtained suspension was stirred at room temperature for 30 minutes. 2-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepine (1.70 g, 7.90 mmol) was added to the suspension, and they were.stirred at room temperature for 30 minutes and then at 50° C. for additional 30 minutes. A solution of (R)-3-chloro-1-(4-pyrrolidinophenethyl)piperidine (2.64 g, 9.02 mmol) in dimethyl sulfoxide (25 ml) was added dropwise to the obtained solution, and they were stirred at 50° C. for 3 hours. The reaction mixture was distributed into saturated aqueous sodium hydrogencarbonate solution and ethyl acetate. The organic layer was dried and the solvent was evaporated under reduced pressure. The residue was subjected to the silica gel column chromatography. After the elution with hexane and ethyl acetate (6:1) and then with hexane and ethyl acetate (1:1) as the eluent, suitable fractions were collected and the solvent was evaporated under reduced pressure to obtain (R)-2-fluoro-5,11-dihydro-5-[1-(4-pyrrolidinophenethyl)pyrrolidin-2-ylmethyl]dibenzo[b,e][1,4]oxazepine in the form of a light yellow oily substance (2.29 g, 68%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C:9](=[O:15])[CH2:8][CH2:7][CH2:6][C:5]2=1.CN(C)C=O.[Cl-].[K+].[CH2:23]1[O:25][CH2:24]1>O>[CH3:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:23][CH2:24][OH:25])[C:10]1[C:9](=[O:15])[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: C1CO1
Reactant: Cc1ccc2[nH]c3c(c2c1)CCCC3=O
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)c1c(n2CCO)C(=O)CCC1
Temperature: 50 °C
Reaction time: 20 h

Procedure:
199 g. (1 mole) of 6-methyl-1,2,3,4-tetrahydrocarbazol-1-one dissolved in 2000 ml. of dimethylformamide are taken initially and 5.6 g. (0.1 mole) of potassium chloride dissolved in 200 ml. of water are added. Thereafter 66.1 g.=74.2 ml. (1.5 mole) of ethyleneoxide are added at room temperature and heated up to 50° C. within 30 minutes, a maximum pressure of 0.2 to 0.5 bar being generated. Stirring is done for 20 hours at 50° C., the solvent is distilled off in a vacuum, the residue stirred with a mixture of 800 ml. water and 10 ml. of glacial acetic acid, the product which took a crystalline form is filtered with suction, washed with 500 ml. water and dried at 40° C. in vacuo.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH2:13][C:14]([O:16]C)=O)[N:9]=2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH2:22][N:23]1[CH2:28][CH2:27][O:26][C@@H:25]([CH2:29][NH2:30])[CH2:24]1>CN1CCCC1=O.CO>[Cl:18][C:19]1[CH:20]=[C:21]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH2:22][N:23]1[CH2:28][CH2:27][O:26][C@@H:25]([CH2:29][NH:30][C:14](=[O:16])[CH2:13][C:10]2[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[O:12][N:11]=2)[CH2:24]1
Reactant: COC(=O)Cc1noc(-c2ccc(F)cc2)n1
Reactant: NC[C@H]1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Solvent: CO
Solvent: CN1CCCC1=O
Product: O=C(Cc1noc(-c2ccc(F)cc2)n1)NC[C@H]1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Yield: 57.4 %

Procedure:
A mixture of Intermediate 38 (0.024 g), Intermediate 9 (0.025 g), and 1-methyl-2-pyrrolidinone (1 drop) was subjected was subjected to irradiation in a 600 W microwave oven on full power for 4 mins. The reaction mixture was dissolved in methanol and applied to an ion exchange cartridge (2 g Isolute SCX, pre-conditioned with methanol). Elution with methanol (3 column volumes) followed 10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the first basic fraction in vacuo gave the crude product. Purification by Biotage flash column chromatography on silica gel (8 g cartridge), eluting with 100:8:1 dichloromethane/ethanol/0.880 ammonia, gave the title compound as a white solid (0.025 g). LCMS (System A) Rf 2.85 min Mass Spectrum m/z 479, 481 [MH+]
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:9]([OH:13])(=[O:12])[CH:10]=[CH2:11]>C(#N)C>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][CH2:11][CH2:10][C:9]([OH:13])=[O:12]
Reactant: Nc1ccccc1F
Reactant: C=CC(=O)O
Solvent: CC#N
Product: O=C(O)CCNc1ccccc1F

Procedure:
To a solution of 2-fluoroaniline (2.0 g) in acetonitrile (20 ml), acrylic acid (1.4 ml) was added and heated under reflux for 21 hours. After the reaction mixture was concentrated, the residue was diluted with 10% aqueous sodium hydroxide and washed with chloroform. The aqueous layer was adjusted to pH 3.3 by addition of 12M aqueous hydrochloric acid, and the precipitated crystal was collected by filtration and dried to give N-(2-fluorophenyl)-β-alanine (1.35 g) as a light-yellow solid. N-(2-Fluorophenyl)-(3-alanine thus obtained (1.30 g) was added to polyphosphoric acid (20g) heated at 130° C., followed by stirring for 2.5 hours. After addition of ice-cold water, the reaction mixture was adjusted to pH 5 with 8M aqueous sodium hydroxide. The precipitated crystal was collected by filtration to give 8-fluoro-2,3-dihydroquinolin-4(1H)-one (770 mg) as a yellow solid. To a solution of 8-fluoro-2,3-dihydroquinolin-4(1H)-one thus obtained (700 mg) in trifluoroacetic acid (20 ml), triethylsilane (4.1 ml) was added and stirred at room temperature for 2 hours. Triethylsilane (2.1 ml) was further added and stirred overnight at room temperature. After the reaction mixture was concentrated, the residue was diluted with 1M aqueous sodium hydroxide and extracted with diethyl ether. To the organic layer, 6M aqueous hydrochloric acid was added and stirred to separate the aqueous layer. The aqueous layer was alkalized with 8M aqueous sodium hydroxide and extracted with chloroform. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=20:1) to give the titled compound, i.e., 8-fluoro-1,2,3,4-tetrahydroquinoline (427 mg) as a light-yellow oil.
Reaction SMILES: [CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.[CH2:9]([C:13]1[C:17]([CH2:18][CH2:19][C:20]2[S:21][C:22]([C:26](O)=[O:27])=[C:23]([CH3:25])[N:24]=2)=[C:16]([CH3:29])[O:15][N:14]=1)[CH2:10][CH2:11][CH3:12]>O1CCOCC1.C1(C)C=CC=CC=1>[CH:1]([NH:4][C:26]([C:22]1[S:21][C:20]([CH2:19][CH2:18][C:17]2[C:13]([CH2:9][CH2:10][CH2:11][CH3:12])=[N:14][O:15][C:16]=2[CH3:29])=[N:24][C:23]=1[CH3:25])=[O:27])([CH3:3])[CH3:2]
Reactant: CCCCc1noc(C)c1CCc1nc(C)c(C(=O)O)s1
Reactant: CC(C)N
Agent: C[Al](C)C
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: CCCCc1noc(C)c1CCc1nc(C)c(C(=O)NC(C)C)s1
Temperature: 90 °C
Reaction time: 1 h
Yield: 44.7 %

Procedure:
To a stirred solution of isopropylamine (77 mg, 1.3 mmol) in dioxane (3 mL) under argon and at room temperature was added trimethylaluminium (0.65 mL of a 2M solution in toluene, 1.3 mmol). After 1 h, a solution of 2-[2-(3-butyl-5-methyl-isoxazol-4-yl)-ethyl]-4-methyl-thiazole-5-carboxylic acid (100 mg, 0.32 mmol) in dioxane (4 mL) was added and the reaction mixture heated at 90° C. overnight. The reaction mixture was then cooled, quenched with ice water and extracted with dichloromethane. The combined extracts were washed with Seignette's salt solution then dried, filtered, and concentrated. Purification by chromatography (silica, 0 to 5% methanol in dichloromethane) gave the title compound (50 mg, 44%) as a light yellow oil. MS: m/e=350.5 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:11]C(=O)C)[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=O.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1.CN(C)C1C=CC=CC=1>CC(C)=O>[OH:11][C:4]1[CH:3]=[C:2]([CH3:1])[CH:10]=[CH:9][C:5]=1[C:6]([NH:23][C:20]1[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=1)=[O:8]
Reactant: COc1ccc(N)cc1
Reactant: CC(=O)Oc1cc(C)ccc1C(=O)O
Solvent: CC(C)=O
Solvent: CN(C)c1ccccc1
Product: COc1ccc(NC(=O)c2ccc(C)cc2O)cc1
Yield: 80 %

Procedure:
4-Methyl-acetylsalicylic acid (5 g.) was converted to its acid chloride by a conventional method and dissolved in acetone (200 ml.). Then p-anisidine (3.2 g.) and dimethylaniline (3.1 g.) were dissolved in acetone (100 ml.) and the above acid chloride solution was added by drops while cooling and mixing; agitation was maintained for 1 to 2 hours. Then the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate and treated as in the similar method of Example 5 to give 2-hydroxy-4-methyl-4'-methoxybenzanilide (5.3 g.). Yield: 80%, melting point: 185°-186° C.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:9](Cl)=[N:10][C:11]([Cl:14])=[N:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][CH2:17][CH2:18][CH2:19][NH:20][S:21]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-:32])=[O:31])[CH:25]=1)(=[O:23])=[O:22].C(N(CC)CC)C>C1COCC1>[C:1]([NH:5][C:6]([C:8]1[C:9]([NH:16][CH2:17][CH2:18][CH2:19][NH:20][S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-:32])=[O:31])[CH:25]=2)(=[O:22])=[O:23])=[N:10][C:11]([Cl:14])=[N:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: NCCCNS(=O)(=O)c1cccc([N+](=O)[O-])c1
Reactant: CC(C)(C)NC(=O)c1cnc(Cl)nc1Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)NC(=O)c1cnc(Cl)nc1NCCCNS(=O)(=O)c1cccc([N+](=O)[O-])c1
Reaction time: 19 h

Procedure:
A solution of 0.95 g (3.83 mmol) of 2,4-dichloro-pyrimidine-5-carboxylic acid-tert-butylamide in 6 ml of THF is mixed at room temperature while being stirred with a suspension that consists of 1.00 g (3.86 mmol) of N-(3-amino-propyl)-3-nitro-benzenesulfonamide in 9 ml of THF/0.55 ml of triethylamine. After 19 hours, the precipitate that is formed is suctioned off and washed with ethyl acetate. The filtrate is spun in, and the residue that is formed is purified by chromatography (hexane/ethyl acetate 2:1, Flashmaster II). 0.79 g (1.67 mmol, corresponding to 44% of theory) of the product is obtained.
Reaction SMILES: [Cl:1][C:2]1[C:23]2[O:22][C:9]3[C:10](=[O:21])[N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14](O)=[O:15])[CH2:12][C:8]=3[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:24][C:25]1[S:26][CH:27]=[CH:28][N:29]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[S:26]1[CH:27]=[CH:28][N:29]=[C:25]1[NH:24][C:14](=[O:15])[C@@H:13]([N:11]1[CH2:12][C:8]2[CH2:7][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[C:23]=3[O:22][C:9]=2[C:10]1=[O:21])[CH2:17][CH:18]([CH3:19])[CH3:20]
Reactant: Nc1nccs1
Reactant: CC(C)C[C@@H](C(=O)O)N1CC2=C(Oc3c(Cl)cccc3C2)C1=O
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: CC(C)C[C@@H](C(=O)Nc1nccs1)N1CC2=C(Oc3c(Cl)cccc3C2)C1=O
Yield: 99.1 %

Procedure:
A solution of (S)-2-(5-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (130 mg, 0.35 mmol) (Example 22, Step 1c), commercially available 2-aminothiazole (47 mg, 0.36 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (82 mg, 0.43 mmol), and N-hydroxybenzotriazole (HOBt) (57 mg, 0.43 mmol) in methylene chloride (15 mL) was stirred for 16 hours at 25° C. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradient elution, afforded (S)-2-(5-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamide (145 mg, 58.2%), as a white solid. 1H NMR (DMSO-d6) δ: 12.57 (s, 1H), 7.50 (d, J=3.4 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.20-7.29 (m, 2H), 7.08-7.16 (m, 1H), 5.05 (dd, J=10.8, 4.4 Hz, 1H), 4.39 (d, J=19.1 Hz, 1H), 4.09 (d, J=19.1 Hz, 1H), 3.75-3.91 (m, 2H), 1.80-1.93 (m, 1H), 1.62-1.75 (m, 1H), 1.46 (br. s., 1H), 0.94 (t, J=6.6 Hz, 6H).
Reaction SMILES: [C:1]1([N:7]2[CH:11]=[CH:10][CH:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Br:13][C:14]1[CH:25]=[CH:24][C:17]([CH:18]=[N+:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:16][CH:15]=1.BrC1C=CC(C=O)=CC=1.N1CCCC1>>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([CH:18]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:8]2[N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:11]=[CH:10][CH:9]=2)=[CH:24][CH:25]=1
Reactant: c1ccc(-n2cccc2)cc1
Reactant: Brc1ccc(C=[N+]2CCCC2)cc1
Agent: O=Cc1ccc(Br)cc1
Agent: [Cl-]
Solvent: C1CCNC1
Product: Brc1ccc(C(c2cccn2-c2ccccc2)N2CCCC2)cc1

Procedure:
The preparation was carried out in accordance with general synthesis instructions 4 from 1-phenyl-1H-pyrrole and 1-(4-bromo-benzylidene)-pyrrolidinium chloride, which had been prepared in accordance with example 4 from 4-bromobenzaldehyde and pyrrolidine.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=3)[C:12](Br)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)#[N:24].C(N1C2C(=CC=C([N+]([O-])=O)C=2)C(C2C=CC(C#N)=CC=2)=C1)(C)C>>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=3)[C:12]([C:28]3[CH:29]=[CH:30][C:25]([C:23]#[N:24])=[CH:26][CH:27]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: O=[N+]([O-])c1ccc2c(Br)cn(S(=O)(=O)c3ccccc3)c2c1
Agent: CC(C)n1cc(-c2ccc(C#N)cc2)c2ccc([N+](=O)[O-])cc21
Product: N#Cc1ccc(-c2cn(S(=O)(=O)c3ccccc3)c3cc([N+](=O)[O-])ccc23)cc1

Procedure:
Prepare this compound from 1-benzenesulfonyl-3-bromo-6-nitro-1H-indole, 7, and 4-cyanophenylboronic acid using Method C described above for 4-(1-isopropyl-6-nitro-1H-indol-3-yl)-benzonitrile 5. Purify by precipitation from EtOAc/hexanes. 1H NMR (DMSO-d6) δ 8.78 (d, 1H, J=1.8 Hz), 8.73 (s, 1H), 8.17 (dd, 1H, J=2.2, 8.8 Hz), 8.14-8.11 (m, 2H), 8.07 (d, 1H, J=8.8 Hz), 7.97-7.92 (m, 4H), 7.72 (tt, 1H, J=1.3, 7.5 Hz), 7.63-7.59 (m, 2H).
Reaction SMILES: [C:1]1([C:7]2[CH:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10](=[S:18])[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:20][CH2:21][O:22][CH2:23][CH3:24].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:21]([O:22][CH2:23][CH2:24][S:18][C:10]1[NH:9][N:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]=1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH3:20]
Reactant: CCOCCBr
Reactant: S=C1NN=C(c2ccccc2)C1c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOCCSc1[nH]nc(-c2ccccc2)c1-c1ccccc1
Reaction time: 4 h
Yield: 70 %

Procedure:
To a solution of 3,4-diphenyl-1H-pyrazole-5(4H)-thione (0.5 g, 1.981 mmol) in DMF (5 mL), were added 1-bromo-2-ethoxyethane (0.303 g, 1.981 mmol) and K2CO3 (0.274 g, 1.981 mmol) at room temperature. After stirring for 4 h, the reaction was poured into water and extracted with ethyl acetate, which was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography to give the title compound (0.45 g). LCMS m/z=343.5 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20 (t, J=7.1 Hz, 3H), 3.25 (m, 2H), 3.45 (m, 2H), 4.25 (q, J=7.1 Hz, 2H), 7.25-7.56 (m, 10H), 13.0 (s, 1H).
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH2:2][SH:3].[H-].[Na+].Br[C:9]1[N:10]([C:22]2[N:23]=[CH:24][N:25]=[C:26]([NH2:29])[C:27]=2[N:28]=1)[C@@H:11]1[O:21][C@H:16]([CH2:17][N:18]=[N+:19]=[N-:20])[C@@H:14]([OH:15])[C@H:12]1[OH:13].C([O-])(=O)CS>CN(C=O)C>[C:1]([CH2:2][S:3][C:9]1[N:10]([C:22]2[N:23]=[CH:24][N:25]=[C:26]([NH2:29])[C:27]=2[N:28]=1)[C@@H:11]1[O:21][C@H:16]([CH2:17][N:18]=[N+:19]=[N-:20])[C@@H:14]([OH:15])[C@H:12]1[OH:13])([OH:5])=[O:4]
Reactant: O=C(O)CS
Reactant: [N-]=[N+]=NC[C@H]1O[C@@H](n2c(Br)nc3c(N)ncnc32)[C@H](O)[C@@H]1O
Agent: O=C([O-])CS
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NC[C@H]1O[C@@H](n2c(SCC(=O)O)nc3c(N)ncnc32)[C@H](O)[C@@H]1O
Reaction time: 8 h
Yield: 56.3 %

Procedure:
A solution of thioglycolic acid (0.2 mmol) and NaH (0.4 mmol, 60% in oil) in anhydrous DMF (2 mL) was stirred for 10 min, then 8-bromo-5′-azido-5′-deoxyadenosine (8) (50 mg, 0.13 mmol) in DMF (1 mL) was added at 0° C. After 8 h at room temperature, more thioglycolate (0.2 mmol) in DMF was added. After stirring overnight, the reaction mixture was concentrated to dryness and the residue purified by reverse phase HPLC (10-30% ACN in TEAA over 20 min) to give 10 (28 mg, 56%); UV λmax 279 nm; HRMS (ESI-TOF) m/z calcd for C12H14N8O5S (M+H) 383.0886; found 383.0890.