Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:13])[C:6]2=O.C1COCC1.CO.[BH4-].[Na+]>O>[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][C:5]([CH3:13])=[CH:6]2
Reactant: Cc1cc(Br)c2c(c1)C(=O)C(C)C2
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CC1=Cc2cc(C)cc(Br)c2C1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of 32.5 g (136 mmol) of 4-bromo-2,6-dimethylindan-1-one in 370 ml of a mixture of THF-methanol (2:1, vol.), 11.8 g (312 mmol) of NaBH4 was added in small portions while vigorously stirring for 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 1000 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 700 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 1 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic fractions were evaporated to dryness. The product was isolated by flash chromatography on Silica Gel 60 (40-63 um, d 60 mm, l 150 mm, eluent: hexanes). Yield 24.6 g (81%).
Reaction SMILES: [CH2:1]([CH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:18][CH2:19][NH:20][S:21]([C:24]3[N:25]([CH3:29])[CH:26]=[CH:27][N:28]=3)(=[O:23])=[O:22])[CH:15]=2)[CH2:10][CH:9]1[NH:30]C(=O)OCC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].C(O)C.[ClH:41].C(OCC)C>[Cl-].[Na+].O>[ClH:41].[NH2:30][CH:9]1[CH:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:18][CH2:19][NH:20][S:21]([C:24]3[N:25]([CH3:29])[CH:26]=[CH:27][N:28]=3)(=[O:23])=[O:22])[CH:15]=2)[CH2:10]1
Reactant: CCOC(=O)NC1Cc2ccc(OCCNS(=O)(=O)c3nccn3C)cc2C1Cc1ccccc1
Agent: Cl
Agent: [Cl-]
Agent: [K+]
Solvent: CCOCC
Solvent: CCO
Solvent: O
Product: Cn1ccnc1S(=O)(=O)NCCOc1ccc2c(c1)C(Cc1ccccc1)C(N)C2
Temperature: 90 °C
Reaction time: 1 h

Procedure:
To ethyl 1-benzyl-6-(2-(1-methyl-1H-imidazole-2-sulfonamido)ethoxy)-2,3-dihydro-1H-inden-2-ylcarbamate (26.7 mg, 0.054 mmol; see example 196) was added 2N potassium hydroxide in ethanol (4 mL, 8.00 mmol) and stirred at 90° C. for 1 h. 50% brine was added and extracted twice with dichloromethane. The combined organic layers were washed with brine, dried, filtered and evaporated to obtain a clear oil. Added 2N hydrochloric acid/diethyl ether and stirred at room temperature for 2 h, filtered, washed with diethyl ether and dried to obtain N-(2-(2-amino-3-benzyl-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-2-sulfonamide hydrochloride as a white solid. m=20.2 mg (54%)
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:34]2[CH:50]=[CH:49][C:37]3[N:38]=[C:39]4[C:48]5[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=5[CH:42]=[CH:41][N:40]4[C:36]=3[CH:35]=2)O1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:4]1([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([C:34]4[CH:50]=[CH:49][C:37]5[N:38]=[C:39]6[C:48]7[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=7[CH:42]=[CH:41][N:40]6[C:36]=5[CH:35]=4)[CH:17]=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=[CH:2][CH:3]=1
Reactant: Brc1cccc(-c2nc(-c3ccccc3)cc(-c3ccccc3)n2)c1
Reactant: CC1(C)OB(c2ccc3nc4c5ccccc5ccn4c3c2)OC1(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: c1ccc(-c2cc(-c3cccc(-c4ccc5nc6c7ccccc7ccn6c5c4)c3)nc(-c3ccccc3)n2)cc1
Temperature: 80 °C
Reaction time: 48 h

Procedure:
16 g (43.3 mmol) of 2-(3-bromophenyl)-4,6-diphenylpyrimidine and 16.5 g (48 mmol) of 9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz[4,5]-imidazo[2,1-a]isoquinoline are dissolved in 80 ml of toluene and degassed. 281 ml of a degassed 2M K2CO3 and 2.5 g (2.2 mmol) of Pd(OAc)2 are added. The reaction mixture is subsequently stirred at 80° C. for 48 h under protective-gas atmosphere. Additional toluene is added to the cooled solution, which is washed a number of times with water, dried and evaporated. The product is purified by column chromatography on silica gel with toluene/heptane (1:2). Ther purity is 99.9%. Yield: 19.6 g (37 mmol) 77% of theory.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][P:28](=[O:35])([O:32]CC)[O:29]CC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[Si](C)(C)C.O>ClCCl.CO>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][P:28](=[O:29])([OH:32])[OH:35])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOP(=O)(CCCCCCCCCCOCCCCCCCCOCc1ccccc1)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: O=P(O)(O)CCCCCCCCCCOCCCCCCCCOCc1ccccc1
Reaction time: 8 h
Yield: 97.2 %

Procedure:
Diethyl 10-(8-(benzyloxy)octyloxy)decylphosphonate (680 mg, 1.33 mmol) was dissolved in dry dichloromethane (15 mL). Bromotrimethylsilane (0.53 mL, 4.05 mmol) was added via syringe. The reaction was capped with a greased glass stopper and stirred overnight. The volatiles were removed under reduced pressure to yield a yellow oil. This was dissolved in 5:1 methanol:water (10 mL) and stirred 4 hours more. After concentration of the organic, the viscous yellow oil was recrystallized in acetonitrile to yield a white crystalline solid (590 mg, 98% yield). 1H NMR (400.14 MHz, DMSO) δ 7.40-7.19 (m, 5H), 4.42 (2H), 3.39 (t, J=6.48 Hz, 2H), 3.29 (t, J=6.46 Hz, 4H), 1.58-1.34 (m, 10H), 1.34-1.10 (m, 20H). 13C{1H} NMR (100.62 MHz, DMSO) δ 138.7, 128.2 (2C), 127.3 (2C), 127.3, 71.79, 69.91 (2C), 69.59, 30.11 (d, J=16.0 Hz), 29.25, 29.21, 29.20, 29.05, 28.89 (2C), 28.84 (2C), 28.73, 27.55 (d, J=136.5 Hz), 25.76, 25.69, 25.67, 22.74 (d, J=4.5 Hz). 31P{1H} NMR (161.97 MHz, DMSO): δ 27.74. Analysis calculated (found) %: C 65.76 (65.79), H 9.93 (10.00). MS (ESI, m/z): 455 (M−, 100%). Exact mass calculated (found) for [M−H]−, m/z): 455.2932 (455.2932).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:23])[N:7]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:8]([CH3:14])=[N:9]2.[Cl:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][CH:26]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([NH:2][CH2:3][C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]=2[C:6](=[O:23])[N:7]([CH:15]2[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]2=[O:22])[C:8]([CH3:14])=[N:9]3)=[O:30])=[CH:27][CH:26]=1
Reactant: Cc1nc2cccc(CN)c2c(=O)n1C1CCC(=O)NC1=O
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: Cc1nc2cccc(CNC(=O)c3ccc(Cl)cc3)c2c(=O)n1C1CCC(=O)NC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.5 %

Procedure:
To a stirred mixture of 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.48 g, 1.4 mmol) in acetonitrile (10 mL), was added 4-chloro-benzoyl chloride (0.27 mL, 2.2 mmol) and N,N-diisopropyl ethylamine (0.62 mL, 3.6 mmol). The mixture was stirred at room temp overnight. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give 4-chloro-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-benzamide as a white solid (390 mg, 62% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, gradient to 95/5 in 5 min, kept for 5 min, 6.18 min (98.0%); mp, 276-278° C.; 1HNMR (DMSO-d6)2.18-2.23 (m, 1H, CHH), 2.58-2.93 (m, 6H, CHCH2, CH3), 4.97-5.08 (m, 2H, CH2NH), 5.26 (dd, J=6, 11 Hz, 1H, CH), 7.33-7.96 (m, 7H, Ar), 9.01 (t, 1H, J=6 Hz, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 23.29, 30.60, 42.21, 56.54, 117.66, 124.16, 125.52, 128.45, 129.17, 132.95, 133.95, 136.13, 140.69, 148.52, 154.84, 161.10, 165.23, 169.54, 172.63. LCMS MH=439, 441; Anal Calcd For C22H19N4O4Cl+0.1H2O: C, 59.96; H, 4.39; N, 12.71; Cl, 8.05. Found: C, 59.80; H, 4.13; N, 12.61; Cl, 8.30.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[NH:23][N:24]=[C:25]([O:26][C@@H:27]4[O:53][C@H:52]([CH2:54][O:55][C:56](=[O:61])[C:57]([CH3:60])([CH3:59])[CH3:58])[C@@H:44]([O:45][C:46](=[O:51])[C:47]([CH3:50])([CH3:49])[CH3:48])[C@H:36]([O:37][C:38](=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40])[C@H:28]4[O:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])[C:18]=23)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:69][C:70]([NH2:72])=[O:71].[I-].[Na+]>CC(C)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[N:23]([CH2:69][C:70](=[O:71])[NH2:72])[N:24]=[C:25]([O:26][C@@H:27]4[O:53][C@H:52]([CH2:54][O:55][C:56](=[O:61])[C:57]([CH3:60])([CH3:59])[CH3:58])[C@@H:44]([O:45][C:46](=[O:51])[C:47]([CH3:48])([CH3:49])[CH3:50])[C@H:36]([O:37][C:38](=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40])[C@H:28]4[O:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:32])[CH3:33])[C:18]=23)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC(=O)CBr
Reactant: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2n[nH]c3nccc(CCc4ccc(OCc5ccccc5)cc4)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Solvent: CC(C)=O
Product: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2nn(CC(N)=O)c3nccc(CCc4ccc(OCc5ccccc5)cc4)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Yield: 80.8 %

Procedure:
To a solution of 4-[2-(4-benzyloxyphenyl)ethyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazolo[3,4-b]pyridine (73 mg) in acetone (4 mL) were added cesium carbonate (56 mg), 2-bromoacetoamide (18 mg) and a catalytic amount of sodium iodide, and the mixture was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=30/1-10/1) to give 4-[2-(4-benzyloxyphenyl)ethyl]-1-carbamoylmethyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazolo[3,4-b]pyridine (63 mg). This material was dissolved in methanol (4 mL). To the solution was added sodium methoxide (28% methanol solution, 0.027 mL), and the mixture was stirred at 50° C. overnight. The reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration. The crystals were washed with methanol and dried under reduced pressure to give 4-[2-(4-benzyloxyphenyl) ethyl]-1-carbamoylmethyl-3-(β-D-glucopyranosyloxy)-1H-pyrazolo-[3,4-b]pyridine (25 mg). To this material were added methanol (1 mL), tetrahydrofuran (1 mL) and 10% palladium-carbon powder (10 mg), and the mixture was stirred at room temperature under 5 a hydrogen atmosphere for 5 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (13 mg).
Reaction SMILES: [N:1]1([CH2:6][CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:13][O:14][CH:15]([O:19][CH3:20])N(C)C>>[CH3:13][O:14][CH:15]([O:19][CH3:20])[N:10]1[CH2:11][CH2:12][CH:7]([CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[CH2:8][CH2:9]1
Reactant: c1cn(CC2CCNCC2)cn1
Reactant: COC(OC)N(C)C
Product: COC(OC)N1CCC(Cn2ccnc2)CC1
Temperature: 100 °C

Procedure:
A mixture of 4-[(1H-imidazol-1-yl)methyl]-piperidine (5 g, 0.03 M) and dimethylformamide dimethylacetal (40 ml) was heated at 100° C. for 8 hrs. Removal of the excess of dimethylformamide dimethylacetal gave 4-[(imidazol-1-yl)methyl]-1-piperidine carboxaldehyde dimethylacetal (6.33 g) which was dissolved in methylene chloride (25 ml) and added to the mixture of 6-aminopenicillanic acid (5.15 g, 0.024 M) and diisopropylethylamine (3.14 ml) in methylene chloride (90 ml) at 0° C. The reaction was stirred at 0° C. for 1 hr and room temperature for 3 hrs. The solvent was then removed and water (80 ml) was added. After being washed with ethylacetate, the aqueous solution, acidified to pH 3, was purified on Sephadex LH 20 columns to give [2S-(2alpha,5alpha,6beta)]-6-[[[4-(1H-imidazol-1-yl-methyl)-1-piperidinyl]methylene]amino]-3,3 -dimethyl-6-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (5.2 g, 55% yield).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH:12]([C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH3:13])[CH2:11][O:10]1.[NH:20]1[CH:24]=[N:23][CH:22]=[N:21]1.[Na].C(OCC)(=O)C>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:10])([CH:12]([C:14]1[N:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[CH3:13])[CH2:11][N:20]1[CH:24]=[N:23][CH:22]=[N:21]1
Reactant: c1nc[nH]n1
Reactant: CC(c1ncccn1)C1(c2ccc(F)cc2F)CO1
Agent: [Na]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(c1ncccn1)C(O)(Cn1cncn1)c1ccc(F)cc1F

Procedure:
Treatment of the product of part (iii) (0.80 g) with 1H-1,2,4-triazole, sodium salt (0.82 g) in N,N-dimethylformamide according to the method of Example 12(iv), followed by chromatography of the crude product on silica gel using ethyl acetate as eluant, first gave, after combination and evaporation of appropriate fractions, the title compound, diastereoisomeric pair A, (0.26 g), m.p. 193°-195° (from dichloromethane/ether).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4](=[O:18])[C:5]([C:16]#[N:17])=[C:6]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[C:8](=[O:15])[C:7]=12.IC.[C:21](=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:1][C:2]1[N:3]([CH3:21])[C:4](=[O:18])[C:5]([C:16]#[N:17])=[C:6]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[C:8](=[O:15])[C:7]=12
Reactant: O=C([O-])[O-]
Reactant: Cc1[nH]c(=O)c(C#N)c2c1C(=O)c1ccccc1-2
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Solvent: O
Product: Cc1c2c(c(C#N)c(=O)n1C)-c1ccccc1C2=O

Procedure:
A mixture of 20 parts of 3,9-dihydro-1-methyl-3,9-dioxo-2H-indeno[2,1-c]pyridine-4-carbonitrile, 114 parts of iodomethane, 15 parts of potassium carbonate, and 475 parts of N,N-dimethylformamide is heated at 55°-60° for 2 hours, then diluted with 1500 parts of water. The precipitate which forms is filtered off, dried in air, and crystallized from a mixture of methanol and N,N-dimethylformamide to give 3,9-dihydro-1,2-dimethyl-3,9-dioxo-2H-indeno[2,1-c]-pyridine-4-carbonitrile melting at 271°-273.5°. The product has the formula ##STR13##
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][C:9]1[C:14]([CH3:15])=[C:13]([N+:16]([O-:18])=[O:17])[CH:12]=[C:11]([Br:19])[C:10]=1F)([CH3:4])([CH3:3])[CH3:2].[NH:22]1[CH:26]=[CH:25][CH:24]=[N:23]1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>C(OCC)(=O)C.O>[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][C:9]1[C:14]([CH3:15])=[C:13]([N+:16]([O-:18])=[O:17])[CH:12]=[C:11]([Br:19])[C:10]=1[N:22]1[CH:26]=[CH:25][CH:24]=[N:23]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: c1cn[nH]c1
Reactant: Cc1c([N+](=O)[O-])cc(Br)c(F)c1CNC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1c([N+](=O)[O-])cc(Br)c(-n2cccn2)c1CNC(=O)OC(C)(C)C
Temperature: 100 °C
Reaction time: 2 h
Yield: 62 %

Procedure:
A mixture of the compound (233 mg) obtained in Example 7c, pyrazole (53 mg), sodium carbonate (82 mg) and dimethylformamide (6 ml) was stirred at 100° C. for 2 hours. Water was added to the reaction mixture and extraction with ethyl acetate was conducted. The organic layer was washed with brine, dried with anhydrous magnesium sulfate and then concentrated at reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3) to give the titled compound (yield, 62%).
Reaction SMILES: C([O-])(=O)C.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].C(=O)=O.[C:19]([C@:27]([C:42]([OH:44])=[O:43])([OH:41])[C@:28]([C:33](=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([OH:32])[C:29]([OH:31])=[O:30])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[C:45](#[N:47])[CH3:46]>O.C(O)C>[C:33]([C@:28]([C:29]([OH:31])=[O:30])([OH:32])[C@:27]([C:19](=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([OH:41])[C:42]([OH:44])=[O:43])(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[NH2:47][C@@H:45]1[CH2:25][C@H:20]([CH2:19][OH:26])[CH:21]=[CH:46]1
Reactant: CC#N
Agent: CC(=O)[O-]
Agent: O=C(O)[C@](O)(C(=O)c1ccccc1)[C@](O)(C(=O)O)C(=O)c1ccccc1
Agent: O=C=O
Solvent: O
Solvent: CCO
Product: N[C@H]1C=C[C@@H](CO)C1
Temperature: 25 °C

Procedure:
(±)-cis-4-Acetamidocyclopent-2-enemethyl acetate [U.S. Pat. No. 4,268,672] (14.88 g, 0.073 mol) and barium hydroxide octahydrate (46.19 g), 0.146 mol) were refluxed in water (300 ml) under nitrogen for 18 hours. The resulting solution was neutralised with carbon dioxide. The precipitate was washed with water, then ethanol. The combined filtrate was evaporated to a syrup, (acetic acid salt of (±)-4-amino-2-cyclopentene-1-methanol) which converted to free amine by stirring with an excess of Amberlite IRA-400 (OH-) resin in water. The resin was filtered off, washed with water, and the filtrate-wash evaporated to a pale yellow syrup which was dried by evaporation of portion of ethanol. Such a sample of amine (2.26 g, 20.0 mmol) and dibenzoyl-D-tartaric acid (Aldrich, 3.62 g, 10.0 mmol as 99%) were dissolved in hot absolute ethanol (35 ml). Refluxing acetonitrile (ca. 150 ml) was added to the cloud point and the solution was allowed to cool slowly to room temperature. The white needles which formed were recrystallized three times from the same solvent combination to give title compound as white plates (1.07 g, 37%); m.p. 160°-162°; [α]D20 +66.9°, [α]43620 +165°, [α]36520 +325° (c=0.28, methanol). X-ray crystallography of this salt allowed the absolute configuration of the cation to be fixed by the known configuration of the D-dibenzoyl tartaric acid dianion. This salt crystallized in the space group C2 with one C6H12NO cation and one-half C18H14O8 dianion as the asymmetric unit.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[N:13]=[C:12](Cl)[C:11]([C:15]([O:17][CH3:18])=[O:16])=[CH:10][N:9]=1.Cl.[CH3:20][NH2:21]>O.CC(C)=O>[Cl:7][C:8]1[N:13]=[C:12]([NH:21][CH3:20])[C:11]([C:15]([O:17][CH3:18])=[O:16])=[CH:10][N:9]=1
Reactant: COC(=O)c1cnc(Cl)nc1Cl
Reactant: CN
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CNc1nc(Cl)ncc1C(=O)OC
Reaction time: 1 h

Procedure:
19.1 g of potassium carbonate in 50 ml water are added dropwise to 13 g of 2,4-dichloro-5-methoxycarbonyl-pyrimidine and 4.7 g of methylamine-hydrochloride in 500 ml acetone at 0 to 5° C. within one hour. Then the mixture is stirred for one hour in an ice bath. The acetone is largely removed in vacuo and the residue is distributed between water and ethyl acetate. Then the aqueous phase is extracted twice more with ethyl acetate. The combined organic phases are dried and evaporated down. The residue is separated by chromatography through a silica gel column with cyclohexane/ethyl acetate (2:1).
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CS(C)=O>[CH:1]1[C:3]2[C:2](=[C:1]3[C:2]([CH:4]=2)=[CH:1][C:3]2=[C:4]4[C:3](=[CH:4][C:2]2=[CH:1]3)[CH:4]=[CH:3][CH:2]=[CH:1]4)[CH:4]=[CH:3][CH:2]=1
Reactant: [Li]CCCC
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Product: C1=c2ccccc2=c2cc3c(cc21)=c1ccccc1=C3

Procedure:
Groups of Ar1-(Ey)a can be prepared by preparation of a 2,8-dibromo-6,12-dihydroindeno [1,2-b]fluorene using the process of Reaction Scheme IX. In step (1), Suzuki coupling of 2-(2,5-dimethylphenyl)-4,4,5,5-tetramethyl[1,3,2]dioxaborolane (CCLXXX) with commercially available 2-bromo-9-fluorenone (CCLXXIX) provides 2-(2,5-dimethylphenyl)fluoren-9-one (CCLXXXI). Commercially available 2-bromo-p-xylene is converted to 2-(2,5-dimethylphenyl)-4,4,5,5-tetramethyl [1,3,2]dioxaborolane (CCLXXX) by treatment with butyl lithium and reaction of the lithiated intermediate with 2-isopropoxy-4,4,5,5-tetramethyl [1,3,2]dioxaborolane. In step (2), 2-(2,5-dimethylphenyl)fluoren-9-one (CCLXXXI) can be converted to 2-bromo-7-(4-bromo-2,5-dimethylphenyl)fluoren-9-one (CCLXXII) with bromine in chloroform at 0° C. Regiospecific bromination at the 4′-position of the phenyl ring is directed by the 5′-methyl and fluorene substituents. In step (3), 2-bromo-7-(4-bromo-2,5-dimethylphenyl)fluoren-9-one (CCLXXII) can undergo potassium permanganate oxidation to provide 2-bromo-5-(7-bromo-9-oxo-9H-fluoren-2-yl)-terephthalic acid (CCLXXIII). Ring closure, in step (4), to 2,8-dibromo-6,12-dioxa-6,12-dihydroindeno [1,2-b]fluorene-3-carboxylic acid (CCLXXXIV) is effected by treatment with sulfuric acid. Reduction of 2,8-dibromo-6,12-dioxa-6,12-dihydroindeno [1,2-b]fluorene-3-carboxylic acid (CCLXXXIV), in step (5), with red phosphorus provides 2,8-dibromo-6,12-dihydroindeno[1,2-b]fluorene-3-carboxylic acid (CCLXXXV). In step (6), alkylated by reaction with butyl lithium followed by an R3-halide or by phase transfer methods utilizing, for example, benzyltriethylammonium chloride in dimethylsulfoxide, followed by 50% aqueous sodium hydroxide and then R3-Br provides the indeno[1,2-b]fluorene derivative of Formula CCLXXXVI. Treatment of the indeno[1,2-b]fluorene of Formula CCLXXXVI with thionyl chloride gives the reactive acyl chloride intermediate of Formula CCLXXXVII. The oxadiazole, thiadiazole, or triazole may be formed at the acyl chloride group of the acyl chloride intermediate via a benzhydrazide intermediate as in Reaction Schemes II-IV or by direct coupling with a tetrazole as in Reaction Scheme I. In step (8), for example, the oxadiazole of Formula CCLXXXVIII is provided by reaction of the acyl chloride intermediate of Formula CCLXXXVII with 5-(4-octyloxyphenyl)-1H-tetrazole as in Reaction Scheme I.