Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CS(O[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
Reactant: O=[N+]([O-])c1ccc2cn[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(n2ncc3ccc([N+](=O)[O-])cc32)CC1
Yield: 24.6 %

Procedure:
6-Nitro-1H-indazole (12.26 mmol, 2 g), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (12.26 mmol, 3.42 g) and potassium carbonate (24.52 mmol, 3.39 g) were combined and heated to 100° C. in N,N-dimethylformamide (40 mL) for 4 hours. The reaction mixture was diluted with ethyl acetate and washed with water. The organic phase was dried over sodium sulfate and concentrated at reduced pressure. The resulting residue was purified by silica chromatography (eluting with a solvent gradient from 20% ethyl acetate/heptane to 60% ethyl acetate/heptane) to afford the title compound (1.045 g). MS (ESI) m/z 347.2 [M+H]+
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:11][C:10]2[C:5](=[CH:6][C:7]([C:12]#[N:13])=[CH:8][CH:9]=2)[CH:4]2[O:14][CH:3]12.[N+:16]([C:19]1[CH:20]=[CH:21][C:22]2[S:26][C:25]([NH2:27])=[N:24][C:23]=2[CH:28]=1)([O-:18])=[O:17]>>[OH:14][CH:3]1[CH:4]([NH:27][C:25]2[S:26][C:22]3[CH:21]=[CH:20][C:19]([N+:16]([O-:18])=[O:17])=[CH:28][C:23]=3[N:24]=2)[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=2)[O:11][C:2]1([CH3:15])[CH3:1]
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Reactant: Nc1nc2cc([N+](=O)[O-])ccc2s1
Product: CC1(C)Oc2ccc(C#N)cc2C(Nc2nc3cc([N+](=O)[O-])ccc3s2)C1O

Procedure:
Following the procedure in Example 1, using (±)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-cyclopropa[a]naphthalene-6-carbonitrile and 5-nitro-benzothiazol-2-ylamine as starting material, the title compound was prepared as white solid.
Reaction SMILES: [CH3:1][N:2]([CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH:17](F)F)=[CH:12][CH:11]=1)=[O:9])[C:3]([O:5][CH3:6])=[O:4].[CH2:20](OCC)[CH3:21]>>[CH3:1][N:2]([CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:20][CH3:21])=[CH:12][CH:11]=1)=[O:9])[C:3]([O:5][CH3:6])=[O:4]
Reactant: CCOCC
Reactant: COC(=O)N(C)CC(=O)c1ccc(OC(F)F)cc1
Product: CCCOc1ccc(C(=O)CN(C)C(=O)OC)cc1

Procedure:
By substantially following the procedure given in Example 19b, substituting 2-(N-methyl-N-(methoxycarbonyl)amino)-4'-propoxyacetophenone for 2-(N-methyl-N-(methoxycarbonyl)amino)-4'-difluoromethoxyacetophenone and using diethyl ether as solvent and continuing with Example 19dii the expected compound, an oil, bp 150°-160° C. at 0.2 torr, was obtained.
Reaction SMILES: Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.[C:35]([C:37]1[N:41]([CH3:42])[CH:40]=[N:39][CH:38]=1)#[CH:36]>C(N(CC)CC)C.CCOC(C)=O.[Cu]I.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>[CH2:14]([NH:13][C:12]([NH:11][C:8]1[S:9][C:10]2[C:2]([C:36]#[C:35][C:37]3[N:41]([CH3:42])[CH:40]=[N:39][CH:38]=3)=[CH:3][C:4]([C:17]3[CH:22]=[N:21][C:20]([N:23]4[CH2:24][CH2:25][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:27][CH2:28]4)=[N:19][CH:18]=3)=[CH:5][C:6]=2[N:7]=1)=[O:16])[CH3:15]
Reactant: CCNC(=O)Nc1nc2cc(-c3cnc(N4CCC(C)(C(=O)OCC)CC4)nc3)cc(Br)c2s1
Reactant: C#Cc1cncn1C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCNC(=O)Nc1nc2cc(-c3cnc(N4CCC(C)(C(=O)OCC)CC4)nc3)cc(C#Cc3cncn3C)c2s1
Temperature: 80 °C

Procedure:
Ethyl 1-[5-[7-bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (150 mg, 0.27 mmol), copper(I) iodide (5 mg, 0.027 mmol) and 5-ethynyl-1-methyl-1H-imidazole (56 μl, 0.54 mmol) were dissolved in triethylamine (2 mL) and DMF (1 mL) and the mixture deoxygenated by bubbling N2 through the solution for 20 min. Pd(PPh3)2Cl2, (19 mg, 0.027 mmol) was added and the reaction heated to 80° C. for 4 h under a N2 atmosphere, at the end of which time LCMS indicated product formation. The reaction was diluted with EtOAc, washed with water then brine and the organic layer dried (MgSO4), filtered and the solvent removed in vacuo to give the desired compound.
Reaction SMILES: [C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].Cl[Si:19]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[O:20][Si:21](Cl)([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23]>N1C=CC=CC=1>[OH:3][C@@H:2]1[C@@H:4]2[O:5][Si:19]([CH:29]([CH3:31])[CH3:30])([CH:32]([CH3:34])[CH3:33])[O:20][Si:21]([CH:25]([CH3:27])[CH3:26])([CH:22]([CH3:23])[CH3:24])[O:8][CH2:7][C@H:6]2[O:9][C@H:1]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[O:12]
Reactant: CC(C)[Si](Cl)(O[Si](Cl)(C(C)C)C(C)C)C(C)C
Reactant: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Solvent: c1ccncc1
Product: CC(C)[Si]1(C(C)C)OC[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O[Si](C(C)C)(C(C)C)O1
Temperature: 25 °C
Reaction time: 17 h
Yield: 73 %

Procedure:
Uridine (15, 100.0 g, 409.5 mmol) was co-evaporated to dryness with anhydrous pyridine (600 mL) and re-suspended in anhydrous pyridine (700 mL). To this stirred fine suspension was added 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (135.7 g, 482.5 mmol) over 60 min at ambient temperature. After stirring the fine suspension for 17 h at ambient temperature, the reaction was quenched by adding methanol (20 mL) and then concentrated under reduced pressure. The residue was partitioned between ethyl acetate (1.5 L) and water (2 L). The organic layer was further washed with 5% hydrochloric acid (2×1 L), brine (500 mL), dried over solid sodium sulfate (50 g), filtered and concentrated under reduced pressure to the crude product, ca 250 g. The residue was subjected to a filtration column using silica gel (1.75 kg) and a gradient of ethyl acetate in hexanes 20-65%. The pure product fractions as judged by a homogenous TLC (Rf 0.55 in 1:1 hexanes-ethyl acetate) were combined and concentrated under reduced pressure and dried (40° C., 0.2 mm Hg, 24 h) to afford 145.5 g (76%) of 16 as a white foam solid. An additional fraction (35 g) of slightly impure 16 was also collected. 1H NMR (DMSO-d6) δ (ppm) 11.35 (s, 1H, NH), 7.66 (d, 1H, J=7.6 Hz, H-6), 5.57 (d, 1H, J=4.8 Hz, 2′-OH), 5.50-5.49 (m, 2H, 1′-H and H-5), 4.14-4.18 (m, 3H, 2′,3′,4′-H), 3.97-3.87 (m, 2H, 5′-Ha and Hb), 1.02-0.95 (m, 28H, CH(CH3)2).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH:5]([NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].I[CH2:24][CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27].[OH-].[Li+]>CN1CCCC1=O>[CH2:9]([O:8][C:6](=[O:7])[C:5]([NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])([CH2:24][CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:4]([O:3][CH2:1][CH3:2])=[O:22])[CH3:10]
Reactant: CCOC(=O)C(NC(=O)OCc1ccccc1)C(=O)OCC
Reactant: CCC(CC)CI
Agent: [Li+]
Agent: [OH-]
Solvent: CN1CCCC1=O
Product: CCOC(=O)C(CC(CC)CC)(NC(=O)OCc1ccccc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 48 h
Yield: 33 %

Procedure:
A mixture of 2-benzyloxycarbonylaminomalonic acid diethyl ester (Bladon, C. M. J. Chem. Soc. Perkin Trans. 1990, 1, 1151–1158) (1.237 g), iodo-2-ethylbutane (1.272 g) and lithium hydroxide (0.287 g) in N-methylpyrrolidone (8 mL) was stirred for 2 days at room temperature and then diluted with ice water. The aqueous solution was extracted with ether and the product purified by chromatography on silica gel to give 2-benzyloxycarbonylamino-2-(2-ethylbutyl)malonic acid diethyl ester (0.520 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:12]2[CH2:13][CH2:14][CH2:15][CH:11]2[NH:10][C:9]1=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:20]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH:12]2[CH2:13][CH2:14][CH2:15][CH:11]2[N:10]([CH3:20])[C:9]1=[O:16])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: CC(C)(C)OC(=O)N1C(=O)NC2CCCC21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1C(=O)N(C(=O)OC(C)(C)C)C2CCCC21
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 106.1 %

Procedure:
To a solution of (3aSR,6aRS)-2-oxo-hexahydro-cyclopentaimidazole-1-carboxylic acid tert-butyl ester (Example 106, step 1) (1.82 g, 8.04 mmol) in 30 ml of DMF was added a 60% suspension of sodium hydride in mineral oil (386 mg, 9.65 mmol, 1.2 equiv.). The suspension was stirred for 45 minutes at room temperature (gas evolution), then iodomethane (0.604 ml, 9.65 mmol, 1.2 equiv.) was added and the mixture was stirred at room temperature overnight. After concentration in vacuo and workup with ethyl acetate/water, 2.05 g of a yellow oil were obtained containing mineral-oil drops which was directly used in the next step without further characterisation.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[F:9][C:10]1[CH:18]=[C:17]2[C:13]([CH2:14][CH2:15][C:16]2=[O:19])=[CH:12][CH:11]=1>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:1][CH:14]1[C:13]2[C:17](=[CH:18][C:10]([F:9])=[CH:11][CH:12]=2)[C:16](=[O:19])[CH2:15]1
Reactant: O=C1CCC(=O)N1Br
Reactant: O=C1CCc2ccc(F)cc21
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=C1CC(Br)c2ccc(F)cc21
Temperature: 25 °C
Yield: 65.8 %

Procedure:
A mixture of N-bromosuccinimide (2.76 g, 15.51 mmoles, Aldrich), benzoyl peroxide (0.01 g, 0.04 mmoles, Aldrich) and 6-fluoro-1-indanone (2.29 g, 15.25 mmoles) in carbon tetrachloride (20 mL) was refluxed under nitrogen for two hours. The mixture was cooled to ambient temperature, filtered, and the solids were washed with dichloromethane. The washings and filtrate were combined, washed successively with 1.0 N sodium hydroxide (2×30 mL), water (2×30 mL) and brine (30 mL), and evaporated in vacuo. The residue was chromatographed on silica gel eluting first with hexane, gradually increasing the polarity to hexane:ethyl acetate (95:5). The fractions containing the major spot were combined and evaporated in vacuo to give a 2.30 g (66%) of 3-bromo-6-fluoro-1-indanone as a yellow oil which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[NH:13][C:12]([C:14]2[N:19]=[C:18]3[N:20]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:21]([N:23]=[CH:24][N:25]([CH3:27])[CH3:26])=[N:22][C:17]3=[CH:16][CH:15]=2)=[C:11]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:10]=1.IC.[C:40]([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[N:13]([CH3:40])[C:12]([C:14]2[N:19]=[C:18]3[N:20]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:21]([N:23]=[CH:24][N:25]([CH3:27])[CH3:26])=[N:22][C:17]3=[CH:16][CH:15]=2)=[C:11]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:10]=1
Reactant: O=C([O-])[O-]
Reactant: CC(C)Cn1c(N=CN(C)C)nc2ccc(-c3[nH]c(-c4c(Cl)cccc4Cl)nc3-c3ccccc3)nc21
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: CC(C)Cn1c(N=CN(C)C)nc2ccc(-c3c(-c4ccccc4)nc(-c4c(Cl)cccc4Cl)n3C)nc21

Procedure:
Stir N′-{5-[2-(2,6-dichlorophenyl)-5-phenyl-3H-imidazol-4-yl]-3-isobutyl-3H-imidazo[4,5-b]pyridin-2-yl}-N,N-dimethylformamidine prepared essentially as described in EXAMPLE 63 (0.10 g, 0.188 mmol), iodomethane (0.040 g, 0.282 mmol), and Cs2CO3 (0.09 g, 0.28 mmol) in DMF (1.5 mL) at RT for about 24 h. Extract with EtOAc and wash with water (3×), saturated aqueous NaCl, then dry over Na2SO4. Filter and concentrate to give a mixture of methyl isomers. Purify (silica gel chromatography) eluting with 1:1:0.4 CH2Cl2:acetonitrile:hexanes to give the title compound (0.02 g).
Reaction SMILES: [NH2:1][CH2:2][C:3]1([CH2:8][S:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:7][CH2:6][CH2:5][O:4]1.[Cl:26][CH2:27][CH2:28][CH2:29][S:30](NCC(OC)CSCCCCCCCCCCCCCCCC)(=[O:32])=[O:31]>>[Cl:26][CH2:27][CH2:28][CH2:29][S:30]([NH:1][CH2:2][C:3]1([CH2:8][S:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:7][CH2:6][CH2:5][O:4]1)(=[O:32])=[O:31]
Reactant: CCCCCCCCCCCCCCCCSCC(CNS(=O)(=O)CCCCl)OC
Reactant: CCCCCCCCCCCCCCCCSCC1(CN)CCCO1
Product: CCCCCCCCCCCCCCCCSCC1(CNS(=O)(=O)CCCCl)CCCO1

Procedure:
2-Aminomethyl-2-hexadecylthiomethyltetrahydrofuran IVb1 is allowed to react and worked by the same procedure as described in (4). m.p. 44.5° to 45.5° C. The summary of the experimental condition and the physical data of the prodcut are listed in the Table 7.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[CH3:8].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[N+](C1C=CC([O:28][C:29]([C:31]2[CH:32]=[CH:33][C:34]([O:45][CH3:46])=[C:35]3[O:39][C:38]([C:40]([CH:42]4[CH2:44][CH2:43]4)=[O:41])=[CH:37][C:36]=23)=O)=CC=1)([O-])=O.O>CN(C)C=O>[CH3:8][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:2]=1[NH:1][C:29]([C:31]1[CH:32]=[CH:33][C:34]([O:45][CH3:46])=[C:35]2[O:39][C:38]([C:40]([CH:42]3[CH2:43][CH2:44]3)=[O:41])=[CH:37][C:36]=12)=[O:28]
Reactant: COc1ccc(C(=O)Oc2ccc([N+](=O)[O-])cc2)c2cc(C(=O)C3CC3)oc12
Reactant: Cc1cnccc1N
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)Nc2ccncc2C)c2cc(C(=O)C3CC3)oc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 50.5 %

Procedure:
To a stirred solution of 4-amino-3-methylpyridine (160 mg) in dimethylformamide (10 ml) under an atmosphere of nitrogen was added sodium hexamethyldisilazide (1.0M solution in tetrahydrofuran, 1.5 ml). The reaction mixture was stirred at room temperature for 10 minutes. 2-Cyclopropanecarbonyl-7-methoxy-benzofuran-4-carboxylic acid 4-nitrophenyl ester (280 mg) was then added and stirring continued for 18 h. Water (10 ml) was added and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (150 ml), washed with water (3×50 ml) and washed with brine (50 ml). The combined aqueous layers were extracted with dichloromethane (2×50 ml), the organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica eluting with 5% methanol in dichloromethane followed by trituration with diethyl ether afforded the title compound as an off-white solid (130 mg).
Reaction SMILES: [OH:1][CH2:2][C:3](=[O:17])[CH2:4][CH2:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:9]=[CH:10][CH:11]=1.N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C=O)C>[Si:23]([O:1][CH2:2][C:3](=[O:17])[CH2:4][CH2:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:9]=[CH:10][CH:11]=1)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]
Reactant: COC(=O)Cc1cccc(CCC(=O)CO)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COC(=O)Cc1cccc(CCC(=O)CO[Si](C)(C)C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 94.7 %

Procedure:
To an ice cooled solution of methyl 3-(4-hydroxy-3-oxo-butyl)phenylacetate (472 mg, 2.00 mmol) in DMF (10 ml) was added imidazole (264 mg, 3.88 mmol) followed by tert-butyldimethylsilyl chloride (408 mg, 5.99 mmol). After 30 minutes the ice-bath was removed and then the mixture was stirred overnight at room temperature. The reaction mixture was poured into water (100 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate), and concentrated in vacuo. The residue was purified by silica gel (20 g) column chromatography eluting with hexane/ethyl acetate (10:1) to give methyl 3-[4-(tert-butyldimethylsilyloxy)-3-oxobutyl]phenylacetate (664 mg, 94.9%) as a colorless oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:33])[NH:7][CH2:8][CH2:9][CH2:10][C:11]#[C:12][C:13]1[CH:18]=[C:17]([C:19](=[O:31])[NH:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH3:30])[CH:22]=2)[CH:16]=[CH:15][C:14]=1[NH2:32])([CH3:4])([CH3:3])[CH3:2]>C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.CN(C)C=O>[CH3:30][O:29][C:23]1[CH:22]=[C:21]([NH:20][C:19]([C:17]2[CH:18]=[C:13]3[C:14](=[CH:15][CH:16]=2)[NH:32][C:11]([CH2:10][CH2:9][CH2:8][NH:7][C:6](=[O:33])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:12]3)=[O:31])[CH:26]=[CH:25][C:24]=1[O:27][CH3:28]
Reactant: COc1ccc(NC(=O)c2ccc(N)c(C#CCCCNC(=O)OC(C)(C)C)c2)cc1OC
Agent: Cl[Pd]Cl
Solvent: N#Cc1ccccc1
Solvent: CN(C)C=O
Product: COc1ccc(NC(=O)c2ccc3[nH]c(CCCNC(=O)OC(C)(C)C)cc3c2)cc1OC
Temperature: 80 °C

Procedure:
A 500 mL round bottom flask was charged with {5-[2-amino-5-(3,4-dimethoxy-phenylcarbamoyl)-phenyl]-pent-4-ynyl}-carbamic acid tert-butyl ester (3.0 g, 6.62 mmol), dichlorobis(benzonitrile)palladium (II) (0.514 g, 1.34 mmol), and dimethylformamide (80 mL) and the resulting mixture heated to 80° C. for 24 h. The resulting mixture was then concentrated in-vacuo and the residue via flash silica gel chromatography (Analogix IF-280, SF25-40 g column, gradient 100:0-90:10 CH2Cl2:MeOH) to yield tert-butyl 3-(5-(3,4-dimethoxyphenylcarbamoyl)-1H-indol-2-yl)propylcarbamate. MS (ES+) 454 (M+1); HPLC: Kromasil C18 column (50×2 mm; 3.5μ), gradient 1{tilde over (0)}90% (MeCN+0.16% TFA) in (water+0.2% TFA) over 4 min, tR=3.78 min.
Reaction SMILES: Br[CH2:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][C:4]=1[Cl:11].[C:12]1(=[O:22])[NH:16][C:15](=[O:17])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12.[K]>CN(C=O)C.O>[Cl:11][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:3]=1[CH2:2][N:16]1[C:12](=[O:22])[C:13]2[C:14](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:15]1=[O:17])[CH:7]=[O:8]
Reactant: O=Cc1ccc(CBr)c(Cl)c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: O=Cc1ccc(CN2C(=O)c3ccccc3C2=O)c(Cl)c1
Temperature: 60 °C
Yield: 66.7 %

Procedure:
To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (3.8 g, 14 mmol) in DMF (40 mL) was added potassium pthalimide (3.54 g, 19.14 mmol), and the mixture was heated at 60° C. for 6 h. The reaction mixture was cooled to ambient temperature and diluted with water (100 mL). The solid obtained was separated by filtration and dried under vacuum to afford the title compound as a white solid (2.8 g, 60%): mp 123-126° C.; 1H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 298.03 ([M−H]−).
Reaction SMILES: [C:1]1([C:7]([NH:20][CH:21]2[C:40](=[O:41])[N:23]3[CH:24]([C:29]4[N:33](CCC(OC)=O)[N:32]=[N:31][N:30]=4)[C:25]([CH3:28])([CH3:27])[S:26][C@H:22]23)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N12CCCC1=CCCN2>C(Cl)(Cl)Cl>[C:1]1([C:7]([NH:20][CH:21]2[C:40](=[O:41])[N:23]3[CH:24]([C:29]4[NH:30][N:31]=[N:32][N:33]=4)[C:25]([CH3:27])([CH3:28])[S:26][C@H:22]23)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)CCn1nnnc1C1N2C(=O)C(NC(c3ccccc3)(c3ccccc3)c3ccccc3)[C@H]2SC1(C)C
Agent: C1=C2CCCN2NCC1
Solvent: ClC(Cl)Cl
Product: CC1(C)S[C@@H]2C(NC(c3ccccc3)(c3ccccc3)c3ccccc3)C(=O)N2C1c1nnn[nH]1
Reaction time: 3 h
Yield: 71 %

Procedure:
To a stirred solution of 600 mg. of 6-(triphenylmethylamino)-2,2-dimethyl-3-(1-[2-methoxycarbonylethyl]tetrazol-5-yl)penam (containing ca 4.5% of methanol) in 1 ml. of chloroform, is added a solution of 375.2 mg. of diazabicyclo[4.3.0]non-5-ene in 0.5 ml. of chloroform. Stirring is continued for a further 3 hours, and then the solution is diluted with a further 2 ml. of chloroform. The latter solution is washed quickly with 5 ml. of 2N hydrochloric acid, and then a further 5 ml. of 2N hydrochloric are added. The resulting mixture is cooled to ca 0° C., and the solid which precipitates is filtered off, giving 323 mg. (71% yield) of the title compound. The NMR spectrum (DMSO-d6) of the product shows absorptions at 7.40 ppm (m, 15H), 5.30 ppm (s, 1H), 4.60 ppm (m, 2H), 1.58 ppm (s, 3H) and 0.78 ppm (s, 3H).
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C(C)=C(S(O)(=O)=O)C(C)=C(N)C=2C)=[CH:4][C:3]=1S(O)(=O)=O.N1C(Cl)=NC(Cl)=NC=1Cl>N1C=CC=CC=1>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Cc1c(N)c(C)c(S(=O)(=O)O)c(C)c1Sc1cc(S(=O)(=O)O)c(N)c2c1C(=O)c1ccccc1C2=O
Agent: Clc1nc(Cl)nc(Cl)n1
Solvent: c1ccncc1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
1-Amino-4-(3'-amino-2',4',6'-trimethyl-5'-sulfophenylthio)anthraquinone-2-sulfonic acid (23.7 parts), cyanuric chloride (9.3 parts) and 1-aminobenzene-3-β-sulfatoethylsulfone (14.1 parts) were subjected to condensation reactions one after another in an aqueous medium in a usual manner, followed by a condensation reaction with pyridine (4.5 parts) at 60° to 70° C. under a weak acid condition. Thereafter, salting out of the reaction mixture gave an anthraquinone compound of the following formula (free acid form). ##STR580##
Reaction SMILES: O[C@H:2]1[CH2:7][C@@H:6]([CH3:8])[S:5][C:4]2[S:9][CH:10]=[CH:11][C:3]1=2.[CH2:12]([NH:14][S:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N+:24]([O-:26])=[O:25])(=[O:17])=[O:16])[CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>C(Cl)Cl>[CH2:12]([N:14]([C@H:2]1[CH2:7][C@H:6]([CH3:8])[S:5][C:4]2[S:9][CH:10]=[CH:11][C:3]1=2)[S:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N+:24]([O-:26])=[O:25])(=[O:16])=[O:17])[CH3:13]
Reactant: C[C@@H]1C[C@H](O)c2ccsc2S1
Reactant: CCNS(=O)(=O)c1ccccc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCN([C@H]1C[C@H](C)Sc2sccc21)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 2.5 °C
Yield: 43.9 %

Procedure:
Methylene chloride (130.5 mL), cis-4-hydroxy-5,6-dihydro-6-methyl-4-H-thieno-[2,3-b]-thiopyran (10.44 g), N-ethyl-2-nitrobenzene-sulfonamide (16.78 g) and triphenyl-phosphine (20.61 g) are mixed under nitrogen atmosphere. The mixture is cooled at 0-5° C. and diisopropyl azadicarboxylate (16.6 mL) is added, maintaining the temperature. The temperature is allowed to rise to 20-25° C. and is maintained until completing the transformation (2 hours). The resulting mixture is treated with 5% NaOH (100 mL). The resulting organic phase is vacuum distilled to dryness and the residue is chromatographed, obtaining 9.8 g of trans-4-[N-ethyl-N-(2-nitrobenzenesulfonyl)amino]-5,6-dihydro-6-methyl-4-H-thieno-[2,3-b]-thiopyran.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]#[N:10])=[C:4](Cl)[N:3]=1.[CH2:12]([NH:14][CH2:15][CH3:16])[CH3:13]>C(OCC)C>[Cl:8][C:6]1[C:5]([C:9]#[N:10])=[C:4]([N:14]([CH2:15][CH3:16])[CH2:12][CH3:13])[N:3]=[C:2]([N:14]([CH2:15][CH3:16])[CH2:12][CH3:13])[N:7]=1
Reactant: N#Cc1c(Cl)nc(Cl)nc1Cl
Reactant: CCNCC
Solvent: CCOCC
Product: CCN(CC)c1nc(Cl)c(C#N)c(N(CC)CC)n1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred solution of 6.3 grams of 2,4,6-trichloro-5-pyrimidinecarbonitrile in 150 ml of diethyl ether at 10° was added dropwise 8.8 grams of diethylamine in 150 ml of diethyl ether. Upon complete addition, the reaction mixture was allowed to warm to room temperature, where it was stirred for 16 hours. The reaction mixture was heated under reflux for 1 hour, then cooled to room temperature. The reaction mixture was washed with water, and the diethyl ether layer was separated. The aqueous layer was washed with diethyl ether. The ether layers were combined and dried over magnesium sulfate. The mixture was filtered, and the filtrate was evaporated under reduced pressure to a residue. The residue was recrystallized from petroleum ether to give crude 4-chloro-2,6-bis(diethylamino)-5-pyrimidinecarbonitrile. This crude material was dissolved in diethyl ether, and 4.4 grams of diethylamine was added.