Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7]([C:10]2[C:11]([S:27][CH3:28])=[N:12][N:13]3[C:18](O)=[C:17]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:16]([CH3:26])=[N:15][C:14]=23)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=P(Cl)(Cl)[Cl:31]>>[C:1]1([S:7]([C:10]2[C:11]([S:27][CH3:28])=[N:12][N:13]3[C:18]([Cl:31])=[C:17]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:16]([CH3:26])=[N:15][C:14]=23)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)Cc1c(C)nc2c(S(=O)(=O)c3ccccc3)c(SC)nn2c1O
Reactant: O=P(Cl)(Cl)Cl
Product: CCOC(=O)Cc1c(C)nc2c(S(=O)(=O)c3ccccc3)c(SC)nn2c1Cl
Temperature: 25 °C
Yield: 94 %

Procedure:
A suspension of 1.5 g (3.56 mmol) of ethyl 2-(3-benzenesulphonyl-7-hydroxy-5-methyl -2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-6-yl)-acetate in 30 ml of POCl3 was heated at reflux for 4 hrs. The reaction solution was cooled to RT and evaporated. The residue was treated with 100 ml of ice-water and the pH value of the solution was adjusted to 8 with sat. NaHCO3 solution. The aqueous phase was extracted three times with 70 ml of CH2Cl2, and the organic phases were dried (MgSO4), filtered and evaporated.Chroma-tography (SiO2, CH2Cl220:1) of the residue yielded 1.0 g (94%) of ethyl 2-(3-benzenesulphonyl-7-chloro-5-methyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-6-yl)-aceate as a pale yellow solid.
Reaction SMILES: I[C:2]1[C:12]([CH3:13])=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].C([Sn](CCCC)(CCCC)[C:19]1[O:20][CH:21]=[CH:22][N:23]=1)CCC>COCCOC.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][C:12]1[C:2]([C:19]2[O:20][CH:21]=[CH:22][N:23]=2)=[C:3]([CH:9]=[CH:10][CH:11]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ncco1
Reactant: CCOC(=O)c1cccc(C)c1I
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Product: CCOC(=O)c1cccc(C)c1-c1ncco1
Temperature: 150 °C
Yield: 2057.2 %

Procedure:
In a microwave vial was dissolved ethyl 2-iodo-3-methylbenzoate (627 mg, 2.16 mmol) and 2-(tributylstannyl)oxazole (0.54 mL, 0.07 mmol) in DME (2.59 mL). The solution was degassed with N2 for 5 minutes then CuI (21 mg, 0.11 mmol) and Pd(PPh3)4 (125 mg, 0.11 mmol) were added. The reaction was purged with N2 and heated at 150° C. for 1 h. The reaction was cooled to room temperature, filtered through a pad of Celite and purified via silica gel chromatography (0-40% EtOAc in hexanes) to give the title compound of step A (333 mg, 67%). MS (ESI) mass calcd. for C13H13NO3, 231.1. m/z found 232.1 [M+H]+. 1H NMR (500 MHz, Chloroform-d) δ 7.89-7.82 (m, 1H), 7.79 (d, J=0.8 Hz, 1H), 7.48-7.43 (m, 2H), 7.30 (d, J=0.9 Hz, 1H), 4.17 (q, J=7.1 Hz, 2H), 2.27 (s, 3H), 1.18 (t, J=7.1 Hz, 3H).
Reaction SMILES: C([N:9]1[CH2:14][CH2:13][C:12]2([CH2:23][C:22]3[C:17](=[CH:18][C:19]([O:24][CH3:25])=[CH:20][CH:21]=3)[C:16](=[O:26])[CH2:15]2)[CH2:11][CH2:10]1)(=O)C1C=CC=CC=1.[ClH:27]>C(O)C.O>[ClH:27].[CH3:25][O:24][C:19]1[CH:18]=[C:17]2[C:22]([CH2:23][C:12]3([CH2:15][C:16]2=[O:26])[CH2:11][CH2:10][NH:9][CH2:14][CH2:13]3)=[CH:21][CH:20]=1
Reactant: COc1ccc2c(c1)C(=O)CC1(CCN(C(=O)c3ccccc3)CC1)C2
Agent: Cl
Solvent: O
Solvent: CCO
Product: COc1ccc2c(c1)C(=O)CC1(CCNCC1)C2
Temperature: 90 °C

Procedure:
A solution of N-Benzoyl-3,4-dihydro-7-methoxyspiro-[naphthalene-3,4'-piperidine]-1-one (3.4 g, 7.8 mmole) in ethanol (100 mL) is treated with 6 N HCl (100 mL) and heated to reflux for 5 hours. The reaction is cooled to 90 ° C. and heated at this temperature for 16 hours. The reaction is cooled to room temperature, diluted with 300 mL water and extracted with two 75 mL portions of ethyl acetate. The aqueous phase is then diluted with ethanol (1 L) and concentrated at reduced pressure to dryness. The residue is crystallized from ethanol (100 mL) to give the product as the hydrochloride.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][N:5]([CH2:12][CH:13]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])[C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-])=O)[C:6](=[O:11])[C:7]([F:10])([F:9])[F:8]>C(OC(=O)C)C.[Pd]>[CH3:1][O:2][C:3](=[O:31])[CH2:4][N:5]([CH2:12][CH:13]([C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[NH2:21])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])[C:6](=[O:11])[C:7]([F:10])([F:9])[F:8]
Reactant: COC(=O)CN(CC(c1ccccc1Cl)c1cc(Cl)ccc1[N+](=O)[O-])C(=O)C(F)(F)F
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COC(=O)CN(CC(c1cc(Cl)ccc1N)c1ccccc1Cl)C(=O)C(F)(F)F
Yield: 41.6 %

Procedure:
To a solution of N-[2-(2-chlorophenyl)-2-(2-nitro-5-chlorophenyl)ethyl]-N-(trifluoroacetyl)glycine methyl ester (1 g) in acetic acid ethyl ester (20 ml) was added 10% Pd/C catalyst (100 mg). The mixture was subjected to catalytic reduction at ambient temperature under atmospheric pressure. After the reaction, the catalyst was removed and the solvent was distilled off. The residue was purified by means of a silica-gel column chromatography (hexane:acetic acid ethyl ester=4:1 v/v as an eluent) to give 0.39 g of an oily compound.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][C@H:15]([N:18](C)[C:19](=O)OCC1C=CC=CC=1)[CH2:16][OH:17].[H][H]>CO.[Pd]>[OH:17][CH2:16][C@@H:15]([NH:18][CH3:19])[CH2:14][CH2:13][CH2:12][N:3]1[C:4](=[O:11])[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]1=[O:1]
Reactant: [H][H]
Reactant: CN(C(=O)OCc1ccccc1)[C@H](CO)CCCN1C(=O)c2ccccc2C1=O
Agent: [Pd]
Solvent: CO
Product: CN[C@H](CO)CCCN1C(=O)c2ccccc2C1=O
Reaction time: 8 h
Yield: 96.4 %

Procedure:
To a solution of (S)-benzyl 5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl(methyl)carbamate (5.01 g, 12.65 mmol) in MeOH (100 mL) was added Pd/C (1.0 g). The mixture was transferred to an autoclave reactor, charged with 50 psi of hydrogen, and stirred overnight. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give (S)-2-(5-hydroxy-4-(methylamino)pentyl)isoindoline-1,3-dione (3.2 g, 97%). LRMS (M+H+) m/z 263.1
Reaction SMILES: [Cl:1][C:2]([O:4]C(Cl)(Cl)Cl)=O.[CH3:9][N:10]([CH3:22])[S:11]([C:14]1[S:18][C:17]([NH:19][CH3:20])=[N:16][C:15]=1[CH3:21])(=[O:13])=[O:12]>O1CCOCC1>[CH3:9][N:10]([CH3:22])[S:11]([C:14]1[S:18][C:17]([N:19]([CH3:20])[C:2]([Cl:1])=[O:4])=[N:16][C:15]=1[CH3:21])(=[O:12])=[O:13]
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: CNc1nc(C)c(S(=O)(=O)N(C)C)s1
Solvent: C1COCCO1
Product: Cc1nc(N(C)C(=O)Cl)sc1S(=O)(=O)N(C)C
Yield: 124.9 %

Procedure:
15.4 g (78 mmol) of trichloromethyl chloroformate (“diphosgene”) were added at room temperature to a solution of 22.9 g (97 mmol) of N,N,4-trimethyl-2-(methyl-amino)-1,3-thiazole-5-sulphonamide in 360 ml of dioxane, and the mixture was heated to reflux until a homogeneous solution was obtained, and TLC showed that no starting material remained. After removal of the solvent in vacuo, 29.0 g of the product were obtained in the form of an oil. (Yield 100%, NMR (CDCl3): 3.89 (3H), 2.81 (6H), 2.62 (3H) ppm).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([O-:3])=[O:2].[C:11]([C:13]([C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=1)[C:19](Cl)=[O:20])([CH3:15])[CH3:14])#[N:12]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:11]([C:13]([C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=1)[C:19]([NH:7][C:6]1[CH:8]=[CH:9][CH:10]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[O:20])([CH3:15])[CH3:14])#[N:12]
Reactant: Nc1cccc([N+](=O)[O-])c1
Reactant: CC(C)(C#N)c1cccc(C(=O)Cl)c1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CC(C)(C#N)c1cccc(C(=O)Nc2cccc([N+](=O)[O-])c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89 %

Procedure:
To a solution of 3-(1-cyano-1-methylethyl)benzoic acid (7.85 g, 41.5 mmol) in tetrahydrofuran (80 mL) were added N,N-dimethylformamide (50 μL) and oxalyl chloride (4.33 mL, 49.8 mmol), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was concentrated under reduced pressure to give 3-(cyano-1-methylethyl)benzoyl chloride as a pale-brown oil. To a solution of 3-nitroaniline (5.73 g, 41.5 mmol) and N,N-dimethylpyridine-4-amine (253 mg, 2.07 mmol) in pyridine (50 mL) was added dropwise a suspension of 3-(cyano-1-methylethyl)benzoyl chloride in pyridine (30 mL), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and to the residue was added saturated aqueous sodium hydrogen carbonate solution (150 mL), and the mixture was extracted with ethyl acetate (200 mL, 50 mL). The combined organic layer was washed with saturated brine (30 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was washed with ethyl acetate/hexane mixture to give the title compound (11.46 g, 89%) as a pale-yellow solid.
Reaction SMILES: [NH2:1][CH:2]([C:5]1[CH:6]=[N:7][CH:8]=[N:9][CH:10]=1)[C:3]#[N:4].Cl.C(=O)([O-])[O-:13].[Na+].[Na+]>>[NH2:1][CH:2]([C:5]1[CH:6]=[N:7][CH:8]=[N:9][CH:10]=1)[C:3]([NH2:4])=[O:13]
Reactant: O=C([O-])[O-]
Reactant: N#CC(N)c1cncnc1
Agent: Cl
Agent: [Na+]
Product: NC(=O)C(N)c1cncnc1
Yield: 81 %

Procedure:
Amino (pyrimidin-5-yl)acetonitrile (1.1 g, 8.2 mmol) is hydrolyzed by refluxing in a small volume of dilute HCl for 1 hour. The pH is raised to 10 by addition of saturated sodium carbonate and the mixture then extracted with chloroform. Evaporation of the chloroform and chromatography (silica, chloroform/methanol) gives product as a yellow solid 950 mg (81%) ms m/z=142.
Reaction SMILES: Cl[C:2]1[C:11]([O:12][CH3:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([F:14])[CH:8]=2)[N:3]=1.[CH3:15][O:16][C:17]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].O>CS(C)=O>[CH3:15][O:16][C:17]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:18]=1[CH2:19][NH:20][C:2]1[C:11]([O:12][CH3:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([F:14])[CH:8]=2)[N:3]=1
Reactant: COc1nc2cc(F)ccc2nc1Cl
Reactant: COc1ccc(CN)c(OC)c1
Solvent: O
Solvent: CS(C)=O
Product: COc1ccc(CNc2nc3ccc(F)cc3nc2OC)c(OC)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 68.9 %

Procedure:
To 2-chloro-6-fluoro-3-methoxyquinoxaline (4.00 g, 18.8 mmol) dissolved in dimethylsulfoxide (40 ml), 2,4-dimethoxybenzylamine (7.86 g, 47.0 mmol) was added at room temperature. The mixture was stirred at room temperature for 24 hours and then water was added thereto. The product was extracted with ethyl acetate and the organic layer was washed with water and dried over MgSO4. After concentration under the reduced pressure, the crude product was purified by SiO2 column chromatography. Extraction of the residue with a n-hexane:ethyl acetate (6:1) mixture and concentration gave 4.45 g of the titled compound (yield, 92%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)[CH2:8][C:9]([OH:11])=O)[CH:2]=1.C1C[N:24]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)[CH2:23]C1.F[P-](F)(F)(F)(F)F.CN>C(Cl)Cl>[CH3:23][NH:24][C:9](=[O:11])[CH2:8][CH:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[C:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1
Reactant: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Reactant: O=C(O)CC(c1cccnc1)c1c[nH]c2ncccc12
Agent: CN
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Product: CNC(=O)CC(c1cccnc1)c1c[nH]c2ncccc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61.8 %

Procedure:
To a RT suspension of 3-pyridin-3-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid (810 mg, 3.03 mmol) in DCM (30 mL) was added TEA (0.63 mL, 4.54 mmol) followed by PyBOP (1.73 g, 3.33 mmol) and MeNH2 (2 M in THF, 2.27 mL, 4.54 mmol). After stirring the reaction mixture at RT for 30 min, the beige precipitate was filtered off, and the filtrate was concentrated. The crude residue was purified via flash chromatography (DCM/MeOH/NH4OH) to afford N-Methyl-3-pyridin-3-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-propionamide as a yellow oil (525 mg).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C@@H:8]3[C@@H:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C@@H:7]3[C:6]=2[CH:16]=1.F[C:18]1[CH:27]=[CH:26][N:25]=[C:24]2[C:19]=1[CH2:20][CH2:21][C:22](=[O:28])[NH:23]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[O:28]=[C:22]1[NH:23][C:24]2[N:25]=[CH:26][CH:27]=[C:18]([O:1][C:2]3[CH:3]=[CH:4][C:5]4[O:9][C@@H:8]5[C@@H:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C@@H:7]5[C:6]=4[CH:16]=3)[C:19]=2[CH2:20][CH2:21]1
Reactant: CCOC(=O)[C@@H]1[C@H]2Oc3ccc(O)cc3[C@H]21
Reactant: O=C1CCc2c(F)ccnc2N1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)[C@@H]1[C@H]2Oc3ccc(Oc4ccnc5c4CCC(=O)N5)cc3[C@H]21
Temperature: 120 °C
Reaction time: 2 h
Yield: 65.5 %

Procedure:
The mixture of Intermediate III (400 mg, 1.8 mmol), 5-fluoro-3,4-dihydro-1,8-naphthyridin-2(1H)-one (250 mg, 1.5 mmol) and cesium carbonate (801 mg, 2.3 mol) in DMF (20 mL) was stirred at 120° C. for 2 hrs. The reaction was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The combined organic phase was washed with brine (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with EtOAc:PE=3:1) to obtain the title compound (360 mg, 54.6%) as a white solid.
Reaction SMILES: O[CH2:2][C:3]([NH:6][C:7]([C:9]1[N:10]=[C:11]([C:31]2[C:36]([Cl:37])=[CH:35][CH:34]=[CH:33][C:32]=2[Cl:38])[N:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:21]=3)=[CH:16][C:15]=2[Cl:30])[CH:13]=1)=O)([CH3:5])[CH3:4].C1C=CC=CC=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:46]>CCOC(C)=O>[Cl:30][C:15]1[CH:16]=[C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:21]=2)[CH:18]=[CH:19][C:14]=1[N:12]1[CH:13]=[C:9]([C:7]2[S:46][CH2:2][C:3]([CH3:5])([CH3:4])[N:6]=2)[N:10]=[C:11]1[C:31]1[C:36]([Cl:37])=[CH:35][CH:34]=[CH:33][C:32]=1[Cl:38]
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CC(C)(CO)NC(=O)c1cn(-c2ccc(-c3cccc(S(C)(=O)=O)c3)cc2Cl)c(-c2c(Cl)cccc2Cl)n1
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: CC1(C)CSC(c2cn(-c3ccc(-c4cccc(S(C)(=O)=O)c4)cc3Cl)c(-c3c(Cl)cccc3Cl)n2)=N1
Yield: 17.2 %

Procedure:
To a N2 purged 50 mL round bottom flask attached with condenser was added 1-(3-Chloro-3′-methanesulfonyl-biphenyl-4-yl)-2-(2,6-dichloro-phenyl)-1H-imidazole-4-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (140 mg, 236 μmol), anhydrous benzene (14 mL) and P2S5 (500 mg, 2.25 mmol). The reaction solution was stirred at reflux for 1 hr. The reaction solution was diluted with EtOAc (100 mL) and filtered through a Buchner funnel to remove excess P2S5. The filtrate was washed with aq. 0.1 N NaOH. The organic phase was partitioned, dried over Na2SO4, filtered, concentrated in vacuo, and chromatographed through a 25 g SiO2 column using a gradient of 100% Hexane to 80% EtOAc to afford 24 mg (17% yield) of title compound. MS (ESI) 590.0, 592.0, 594.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (t, J=2 Hz, 1H), 8.21 (t, J=2 Hz, 1H), 8.17 (d, J=2 Hz, 1H), 8.14 (d, J=8 Hz, 1H), 8.10 (d, J=8 Hz, 1H), 7.99 (d, J=8 Hz, 1H), 7.95 (d, J=8 Hz, 1H), 7.78-7.85 (m, 2H), 7.74 (t, J=8 Hz, 1H), 7.49-7.61 (m, 3H), 7.43 (d, J=8 Hz, 1H), 3.36 (br s, 2H), 3.26 (s, 3H), 1.48 (s, 6H).
Reaction SMILES: [CH2:1]1[CH2:11][C:9](=[O:10])[C:8]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:2]1.[H-].[Na+].[C:14](=O)([O:18]CC)[O:15][CH2:16][CH3:17].Cl>O>[O:10]=[C:9]1[C:8]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:2][CH2:1][CH:11]1[C:14]([O:15][CH2:16][CH3:17])=[O:18]
Reactant: CCOC(=O)OCC
Reactant: O=C1CCCc2ccccc21
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)C1CCc2ccccc2C1=O
Yield: 57.6 %

Procedure:
A suspension of 10 g (0.0684 mole) of α-tetralone, 3.56 g (0.0890 mole) of 60% sodium hydride and 32 g (0.2709 mole) of diethyl carbonate was heated under reflux for 1 hour, then poured into water, adjusted with conc. hydrochloric acid to a pH of 1 to 2, and extracted with ether. The ether layer was washed with water and then dried over magnesium sulfate. After evaporation of the solvent, the crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9/1) to obtain 8.6 g of ethyl 1,2,3,4-tetrahydro-1-oxo-2-naphthalenecarboxylate, which was dissolved in tetrahydrofuran (220 ml) and then 1.90 g (0.0475 mole) of 60% sodium hydroxide was added under ice-cooling. After stirring for 30 minutes, 10.0 g (0.0599 mole) of ethyl bromoacetate was added, followed by stirring for 3 hours at room temperature. The reaction mixture was poured into ice-water, extracted with ether, and then the extract was subjected to washing with water, drying and solvent evaporation in a conventional manner. The crude product obtained was purified by silica gel column chromatography (hexane/ethyl acetate=5/1) to obtain 9.03 g of the following ethyl 2-ethoxycarbonyl-1,2,3,4-tetrahydro-1-oxo-2-naphthaleneacetate ##STR13##
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[C:10](=[O:11])[CH2:9][C:8]([CH3:13])([CH3:12])[CH2:7][C:5]=2[N:6]=1.[Br:14][C:15]1[CH:16]=[C:17]([S:21](Cl)(=[O:23])=[O:22])[S:18][C:19]=1[Cl:20]>>[Br:14][C:15]1[CH:16]=[C:17]([S:21]([NH:1][C:2]2[S:3][C:4]3[C:10](=[O:11])[CH2:9][C:8]([CH3:13])([CH3:12])[CH2:7][C:5]=3[N:6]=2)(=[O:23])=[O:22])[S:18][C:19]=1[Cl:20]
Reactant: CC1(C)CC(=O)c2sc(N)nc2C1
Reactant: O=S(=O)(Cl)c1cc(Br)c(Cl)s1
Product: CC1(C)CC(=O)c2sc(NS(=O)(=O)c3cc(Br)c(Cl)s3)nc2C1

Procedure:
The title compound was prepared from 2-amino-5,5-dimethyl-5,6-dihydro-1,3-benzothiazol-7(4H)one (53 mg) and 4-bromo-5-chlorothiophene-2-sulfonyl chloride (80 mg) as described in the synthetic METHOD B to give a white-yellow solid (47.1 mg) with purity >90%: MS (pos) m/z 455.2, 457.2.
Reaction SMILES: [OH:1][N:2]=[CH:3][C:4]1[C:12]2[C:7](=[C:8]([CH3:14])[CH:9]=[CH:10][C:11]=2[CH3:13])[NH:6][C:5]=1[C:15]([O:17][CH3:18])=[O:16].CI.[C:21](=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:21][O:1][N:2]=[CH:3][C:4]1[C:12]2[C:7](=[C:8]([CH3:14])[CH:9]=[CH:10][C:11]=2[CH3:13])[NH:6][C:5]=1[C:15]([O:17][CH3:18])=[O:16]
Reactant: COC(=O)c1[nH]c2c(C)ccc(C)c2c1C=NO
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC#N
Product: CON=Cc1c(C(=O)OC)[nH]c2c(C)ccc(C)c12
Yield: 24.8 %

Procedure:
A mixture of 0.8 g (3.25 mmol) of methyl 3-(hydroxyiminomethyl)-4,7-dimethylindole-2-carboxylate, 0.60 g (4.23 mmol) of methyl iodide, 0.59 g (4.23 mmol) of potassium carbonate and 20 ml of acetonitrile was refluxed for 19 hours. After potassium carbonate was removed by filtration, acetonitrile was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, washed with water three times and dried over anhydrous magnesium sulfate. The crude crystals were purified by silica gel column chromatography to provide 210 mg of light yellow crystals. Yield: 25%
Reaction SMILES: [N+:1]([C:4]1[O:8][C:7]([CH:9]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[Cl:11][CH:12]([Cl:16])C(Cl)=O.C(N(CC)CC)C>C1C=CC=CC=1>[Cl:11][C:12]([Cl:16])=[CH:9][C:7]1[O:8][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1
Reactant: O=Cc1ccc([N+](=O)[O-])o1
Reactant: O=C(Cl)C(Cl)Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: O=[N+]([O-])c1ccc(C=C(Cl)Cl)o1
Reaction time: 0.5 h

Procedure:
To a stirred mixture of 14.1 g of 5-nitro-2-furaldehyde and 22.1 g of dichloroacetyl chloride in 300 ml of benzene was added dropwise at 25°-30° over a 30-minute period a solution of 15.2 g of triethylamine in 50 ml of benzene. The mixture then was stirred at 25°-30° for an additional 30 minutes and then for 90 minutes at reflux. After cooling, the mixture was filtered and the filtrate was washed and dried, concentrated under reduced pressure and Claisen distilled to give a liquid product, b.p.: 88°-98° at 0.3 torr. (mainly 90°-95°). This material was crystallized from acetone/petroleum ether to give 1 as a light yellow solid, m.p.: 74°-75°.
Reaction SMILES: [C:1]([C:5]1[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=1[NH2:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Br:18][CH2:19][CH2:20][C:21](Cl)=[O:22].O>ClCCl>[Br:18][CH2:19][CH2:20][C:21]([NH:7][C:6]1[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=1[C:1]([CH3:4])([CH3:2])[CH3:3])=[O:22]
Reactant: CC(C)(C)c1ccccc1N
Reactant: O=C(Cl)CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)c1ccccc1NC(=O)CCBr
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-tert-butylaniline (Aldrich, 24.7 g, 166 mmol) was dissolved in dichloromethane (100 mL) and potassium carbonate (47.0 g, 340 mmol) was added. 3-Bromopropionyl chloride (29.1 g, 170 mmol) in dichloromethane (50 mL) was added dropwise and the mixture stirred for 3 hours at ambient temperature. Water was added slowly to quench the mixture, and the organic layer was separated and washed twice with water, dried with magnesium sulfate, filtered, and concentrated under reduced pressure to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.32 (s, 9H), 2.97 (t, J=6.44 Hz, 2H), 3.74 (t, J=6.27 Hz, 2H), 7.00-7.06 (m, 1H), 7.16-7.25 (m, 2H), 7.36-7.42 (m, 1H), 9.35 (s, 1H). MS (DCI) m/z 284.0 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[CH:6]=1.[C:11](Cl)(=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1>>[CH3:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[C:6]=1[C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: Cc1cc2ccccc2o1
Product: COc1ccc(C(=O)c2c(C)oc3ccccc23)cc1

Procedure:
2-Methylbenzofuran (7.25 g., 0.055 mol.) was acylated with 15.7 g. (0.092 mol.) of anisoyl chloride according to the procedure described in Example 10 to give 2-methyl-3-(4'-methoxybenzoyl)benzofuran.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][O:5][N:6]1[CH:14]=[N:13][C:12]2[C:11](=[O:15])[NH:10][C:9]([NH2:16])=[N:8][C:7]1=2.[C:17](OC(=O)C)(=[O:19])[CH3:18].CN(C)C=O>CN(C)C1C=CN=CC=1.C(O)C>[C:17]([O:1][CH2:2][CH2:3][CH2:4][O:5][N:6]1[CH:14]=[N:13][C:12]2[C:11](=[O:15])[NH:10][C:9]([NH2:16])=[N:8][C:7]1=2)(=[O:19])[CH3:18]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1nc2c(ncn2OCCCO)c(=O)[nH]1
Agent: CN(C)c1ccncc1
Solvent: CCO
Solvent: CN(C)C=O
Product: CC(=O)OCCCOn1cnc2c(=O)[nH]c(N)nc21
Temperature: 20 °C
Reaction time: 3 h
Yield: 67 %

Procedure:
A mixture of 9-(3-hydroxyprop-1-oxy)guanine (150 mg, 0.67 mmol), 4-dimethylaminopyridine (15.6 mg, 0.13 mmol), acetic anhydride (0.25 ml, 2.65 mmol) and N,N-dimethylformamide (5 ml) was stirred at 20° C. for 3 hours and then ethanol was added. After a further 15 minutes the solvent was evaporated under reduced pressure and the residue was chromatographed on silica gel (eluted with chloroform-ethanol, 4:1), yielding the title compound (120 mg, 67%). Recrystallisation from methanol-water gave 9-(3-acetoxy-prop-1-oxy)guanine (82 mg, 46%). IR: υmax (KBr) 3330, 3168, 1736, 1696, 1648, 1602, 1589, 1391 cm-1. 1H NMR: δH [(CD3)2SO] 1.98 (2H, quintet, J=6.3, 6.6 Hz, CH2CH2CH2), 2.02 (3H, s, ##STR14## 4.17 (2H, t, J=6.6 Hz, CH2ON), 4.32 (2H, t, J=6.3 Hz, ##STR15## 6.60 (2H, br.s, D2O exchangeable NH2), 7.94 (1H, s, H-8), 10.69 (1H, br.s, D2O exchangeable, H-1). Found: C, 44.99; H, 4.93; N, 26.20% M+ 267.0964 C10H13N5O4 requires C, 44.93; H, 4.91; N, 26.21% M+ 267.0968.
Reaction SMILES: [CH:1]([C:4]1[N:9]=[CH:8][C:7]([CH:10]=O)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(O)(=O)[CH2:13][C:14]([OH:16])=[O:15].N1CCCCC1>N1C=CC=CC=1>[CH:1]([C:4]1[N:9]=[CH:8][C:7]([CH:10]=[CH:13][C:14]([OH:16])=[O:15])=[CH:6][CH:5]=1)([CH3:2])[CH3:3]
Reactant: O=C(O)CC(=O)O
Reactant: CC(C)c1ccc(C=O)cn1
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: CC(C)c1ccc(C=CC(=O)O)cn1
Temperature: 110 °C
Reaction time: 2 h
Yield: 84.3 %

Procedure:
A mixture of 3.7 g of the crude 6-isopropyl-3-pyridinecarbaldehyde, 3.9 g of malonic acid, 0.5 ml of piperidine, and 18 ml of pyridine is stirred at 110° C. for 2 hours. The reaction mixture is concentrated, and 5 ml of water is added. The resulting precipitate is collected to give 4.0 g of the title compound.