Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:24](Br)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11].CC1(C)C(C)(C)OB([C:34]2[CH2:35][CH2:36][CH2:37][N:38]([C:40](=[O:42])[CH3:41])[CH:39]=2)O1.C([O-])(=O)C.[K+].O1CCOCC1>O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:24]([C:36]3[CH2:35][CH2:34][CH2:39][N:38]([C:40](=[O:42])[CH3:41])[CH:37]=3)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11]
Reactant: O=C(c1ccc(Oc2ncccc2Br)cc1)c1nc2ccccc2[nH]1
Reactant: CC(=O)N1C=C(B2OC(C)(C)C(C)(C)O2)CCC1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CC(=O)N1C=C(c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CCC1
Temperature: 80 °C
Reaction time: 16 h
Yield: 0.2 %

Procedure:
To a degassed solution of (1H-benzo[d]imidazol-2-yl)(4-(3-bromopyridin-2-yloxy)phenyl)methanone (706 mg, 1.791 mmol), 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridin-1(2H)-yl)ethanone (0.5 g, 1.991 mmol), potassium acetate (1.5 g, 15.28 mmol), and dioxane (10 mL) was added A-Phos (140 mg, 0.198 mmol). The solution was stirred at 80° C. After 16 hours, the reaction was allowed to cool to room temperature, diluted with H2O (10 mL), and the aqueous layer extracted with DCM (5 mL). The combined organic layers were concentrated in vacuo and purified by Prep TLC (1:1 hexanes/EtOAc) to give 1-(5-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-3,4-dihydropyridin-1(2H)-yl)ethanone (1.6 mg, 3.65 μmol) as a light yellow film. MS (ESI, pos. ion) m/z: 439.0 (M+1). IC50 (uM) +++++.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH:16]=[CH:17][C:18](OCC)=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(F)(F)F.CCOCC.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH:16]=[CH:17][CH2:18][OH:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)C=C[C@H]1CCCN1C(=O)OCc1ccccc1
Agent: CC(C)C[Al+]CC(C)C
Agent: FB(F)F
Agent: [H-]
Solvent: CCOCC
Solvent: C1CCOC1
Product: O=C(OCc1ccccc1)N1CCC[C@@H]1C=CCO
Reaction time: 3 h
Yield: 52.6 %

Procedure:
To a stirred solution of (R)-ethyl 3-(N-benzyloxycarbonylpyrrolidin-2-yl)-2-propenoate (574 g) in tetrahydrofuran (5.7 L) at about -78° C. was added boron trifluoride etherate (295.4 g) and then diisobutylaluminum hydride (1.5M in toluene, 3.91 L, 3.1 eq) added (over two hours) maintaining the temperature below -62° C. The resulting solution was stirred (between -78° and -62° C.) for three hours and then quenched into aqueous citric acid solution (2 kg citric acid in 5 L water plus 4 L ice) over about 40 minutes. The phases were separated and the aqueous phase extracted with ethyl acetate (2×2.1 L). The combined organic solution was dried (over magnesium sulphate) and evaporated, then the residual oil purified by chromatography through silica gel, eluting with mixed ethyl acetate/hexane (9:1 to 4:1) to give the title compound as an oil (260 g), as produced in Example 12A (as an alternative, the residual oil can be purified by chromatography through silica gel eluting with ethyl acetate:hexane (1:1)).
Reaction SMILES: CS(O[CH2:6][C:7]1[C:8]([CH:32]([O:35][CH3:36])[O:33][CH3:34])=[N:9][C:10]2[N:11]([C:17](=[O:31])[NH:18][C:19]3[CH:24]=[C:23]([O:25][CH:26]([CH3:28])[CH3:27])[C:22]([C:29]#[N:30])=[CH:21][N:20]=3)[CH2:12][CH2:13][CH2:14][C:15]=2[CH:16]=1)(=O)=O.[CH3:37][NH2:38]>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[C:29]([C:22]1[C:23]([O:25][CH:26]([CH3:27])[CH3:28])=[CH:24][C:19]([NH:18][C:17]([N:11]2[C:10]3[C:15](=[CH:16][C:7]([CH2:6][NH:38][CH3:37])=[C:8]([CH:32]([O:33][CH3:34])[O:35][CH3:36])[N:9]=3)[CH2:14][CH2:13][CH2:12]2)=[O:31])=[N:20][CH:21]=1)#[N:30]
Reactant: CN
Reactant: COC(OC)c1nc2c(cc1COS(C)(=O)=O)CCCN2C(=O)Nc1cc(OC(C)C)c(C#N)cn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CNCc1cc2c(nc1C(OC)OC)N(C(=O)Nc1cc(OC(C)C)c(C#N)cn1)CCC2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a suspension of (8-((5-cyano-4-isopropoxypyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate (intermediate 167, 2.59 g, 4.98 mmol) in THF (83 ml) was added methylamine 2 M in THF (37.4 ml, 74.70 mmol) at ambient temperature and the reaction mixture was stirred at room temperature for approximately 4 h. The reaction mixture was diluted with saturated aqueous NaHCO3 and DCM. Phases were separated and the water phase was extracted with DCM (2×), organic phases were combined and dried using Na2SO4, filtered and concentrated to yield the title compound as a light yellow solid. (UPLC-MS 3) tR 0.88 min, ESI-MS 455.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 14.00 (s, 1H), 8.37 (s, 1H), 7.95 (s, 1H), 7.61 (s, 1H), 5.51 (s, 1H), 4.88-4.79 (m, 1H), 4.06-4.01 (m, 2H), 3.86 (s, 2H), 3.50 (s, 6H), 2.88-2.80 (m, 2H), 2.49 (s, 3H), 2.03-1.96 (m, 2H), 1.43 (d, 6H).
Reaction SMILES: Cl[C:2]1[C:3]([CH2:14][CH3:15])=[C:4]([CH2:12][CH3:13])[C:5]2[N:6]([C:8]([NH2:11])=[N:9][N:10]=2)[N:7]=1.[O-:16][CH2:17][CH3:18].[Na+].O>C(O)C>[CH2:17]([O:16][C:2]1[C:3]([CH2:14][CH3:15])=[C:4]([CH2:12][CH3:13])[C:5]2[N:6]([C:8]([NH2:11])=[N:9][N:10]=2)[N:7]=1)[CH3:18]
Reactant: CCc1c(Cl)nn2c(N)nnc2c1CC
Reactant: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOc1nn2c(N)nnc2c(CC)c1CC
Reaction time: 0.5 h
Yield: 88.2 %

Procedure:
6-Chloro-7,8-diethyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylamine (W2.014, 0.1 g) was dissolved in ethanol (13 ml) while stirring and under argon. Thereafter, the reaction mixture was admixed with sodium ethoxide (61 mg) and stirred at RT for 1 h, then at 55° C. for 30 min. Subsequently, a further 2 equivalents of sodium ethoxide were added and the mixture was stirred at 55° C. for 4.5 h. After another 1 equivalent of sodium ethoxide had been added, the mixture was stirred at 55° C. for 2.5 h and left to stand over the weekend. The solvent was then drawn off, and the residue was admixed with water and extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and, after the desiccant had been filtered off, dried under reduced pressure. 92 mg of the title compound were obtained. LC-MS rt: 0.80 min [M+H]+: 236.2 (met. b)
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:25]=[CH:24][C:14]([CH:15]=[C:16]([N:21]=[N+]=[N-])[C:17]([O:19][CH3:20])=[O:18])=[CH:13][CH:12]=1>C1(C)C(C)=CC=CC=1>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:25]=[C:24]2[C:14]([CH:15]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[NH:21]2)=[CH:13][CH:12]=1
Reactant: COC(=O)C(=Cc1ccc(OCCOCCOCCO)cc1)N=[N+]=[N-]
Solvent: Cc1ccccc1C
Product: COC(=O)c1cc2ccc(OCCOCCOCCO)cc2[nH]1

Procedure:
Methyl 4-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]-α-azidocinnamate (IV, EXAMPLE 2, 3.0 g) is dissolved in xylene (86 ml) and quickly heated to reflux. TLC indicates disappearance of starting material, the reaction is cooled to 20°-25° and the material is purified by flash column chromatography eluting with ethyl acetate/hexane (75/25). The appropriate fractions are pooled and concentrated to give the title compound, MS theory=323.1369, found=323.1366.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[O:10][CH3:11].C[C:13]1[N:14]=[CH:15][NH:16][CH:17]=1.[C:18]([O-])([O-])=O.[K+].[K+].[N+](=C(P(=O)(OC)OC)C(=O)C)=[N-]>CN(C=O)C.CCOC(C)=O.C(Cl)Cl>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([N:14]2[CH:13]=[CH:17][N:16]=[CH:15]2)=[C:3]([O:10][CH3:11])[CH:4]=1)#[CH:18]
Reactant: O=C([O-])[O-]
Reactant: COc1cc(C=O)ccc1F
Reactant: Cc1c[nH]cn1
Agent: COP(=O)(OC)C(=[N+]=[N-])C(C)=O
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C#Cc1ccc(-n2ccnc2)c(OC)c1
Temperature: 130 °C
Reaction time: 8 h

Procedure:
A mixture of 4-fluoro-3-methoxybenzaldehyde (1.0 g, 6.5 mmol) in 20 mL of DMF was treated with 4-methylimidazole (1.0 g, 15 mmol) and warmed to 130° C. Stirred overnight. Diluted with EtOAc, washed with sat'd NaHCO3, dried (Na2SO4), concentrated. Dissolved in 20 mL of MeOH, treated with K2CO3 (2.0 g, 14 mmol) and dimethyl (1-diazo-2-oxopropyl)phosphonate (1.5 g, 7.8 mmol) and stirred overnight. Diluted with DCM and washed with water. Dried (Na2SO4), conc. Chromatography on silica (0-20% MeOH/DCM) gave the desired alkyne:
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:19]([O:25][C:26](=[O:28])[CH3:27])[C@@H:18]([CH2:29]I)[O:17][C@@H:6]1[S:7][CH2:8][CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:3])[CH3:2].[N-:31]=[N+:32]=[N-:33].[Na+]>CN(C=O)C>[C:1]([O:4][C@H:5]1[C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:19]([O:25][C:26](=[O:28])[CH3:27])[C@@H:18]([CH2:29][N:31]=[N+:32]=[N-:33])[O:17][C@@H:6]1[S:7][CH2:8][CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](SCC=Cc2ccccc2)O[C@H](CI)[C@H]1OC(C)=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](SCC=Cc2ccccc2)O[C@H](CN=[N+]=[N-])[C@H]1OC(C)=O
Temperature: 85 °C
Reaction time: 24 h

Procedure:
A suspension of 11 (8.0 g) and sodium azide (2.0 g) in DMF (100 ml) is heated with stirring for 24 hours at 85° C. (bath temperature). The solvent is evaporated in vacuo and the residue is partitioned between chloroform and water. The organic layer is separated and washed with water, dried, and evaporated to a thick syrup (7.2 g, 98%): [α]D27 +107±0.5° (C 1.0, chloroform).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[O:23][CH2:22][C:12]3([C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][C:13]3=[O:21])[C:10]=2[CH:11]=1.[NH:24]1[C:32]2[C:27](=CC=C[CH:31]=2)[C:26]2(COC3C=C4C(=[CH:43][C:33]2=3)CCO4)C1=O.Br.BrCC1C=CC=CN=1.ClCC1C=NC(OC)=NC=1>>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[O:23][CH2:22][C:12]3([C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]([CH2:31][C:32]4[CH:27]=[CH:26][CH:33]=[CH:43][N:24]=4)[C:13]3=[O:21])[C:10]=2[CH:11]=1
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)CCO3
Reactant: COCCOc1ccc2c(c1)C1(CO2)C(=O)Nc2ccccc21
Agent: Br
Agent: BrCc1ccccn1
Agent: COc1ncc(CCl)cn1
Product: COCCOc1ccc2c(c1)C1(CO2)C(=O)N(Cc2ccccn2)c2ccccc21

Procedure:
Following the procedure as described in EXAMPLE 5 and making non-critical variations using 5-(2-methoxyethoxy)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one, and 2-(bromomethyl)pyridine hydrobromide to replace 5-(chloromethyl)-2-methoxypyrimidine, 5-(2-methoxyethoxy)-1′-(pyridin-2-ylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one was obtained (65%): mp 140-142° C.; 1H NMR (300 MHz, CDCl3) δ8.57 (d, J=4.8 Hz, 1H), 7.65 (t, J=7.6 Hz, 1H), 7.25-7.11 (m, 4H), 7.06-6.97 (m, 1H), 6.89 (d, J=7.8 Hz, 1H), 6.68-6.62 (m, 1H), 6.59-6.54 (m, 1H), 6.44-6.38 (m, 1H), 5.09 (ABq, 2H), 4.87 (ABq, 2H), 4.11-4.05 (m, 2H), 3.77-3.68 (m, 2H), 3.43 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 177.6, 162.1, 160.7, 155.6, 149.5, 142.1, 137.0, 132.4, 128.8, 123.8, 123.6, 123.5, 122.7, 121.6, 121.1, 109.5, 108.2, 97.3, 80.5, 70.9, 67.6, 59.2, 57.7, 46.1; MS (ES+) m/z 403.0 (M+1).
Reaction SMILES: [CH2:1]([C:3]1[C:4](F)=[C:5]([N+:17]([O-:19])=[O:18])[CH:6]=[C:7]([F:16])[C:8]=1[N:9]1[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1)[CH3:2].[F-].[K+].[CH:23]1([NH2:26])[CH2:25][CH2:24]1>C(OCC)(=O)C>[CH:23]1([NH:26][C:4]2[C:5]([N+:17]([O-:19])=[O:18])=[CH:6][C:7]([F:16])=[C:8]([N:9]3[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]3)[C:3]=2[CH2:1][CH3:2])[CH2:25][CH2:24]1
Reactant: CCc1c(F)c([N+](=O)[O-])cc(F)c1N1CCN(C)CC1
Reactant: NC1CC1
Agent: [F-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: CCc1c(NC2CC2)c([N+](=O)[O-])cc(F)c1N1CCN(C)CC1
Reaction time: 1.5 h

Procedure:
To 3-ethyl-2,5-difluoro-4-(4-methyl-1-piperazinyl)nitrobenzene (1.12 g) are added potassium fluoride (0.24 g), N,N-dimethylsulfoxide (3.5 ml) and cyclopropylamine (0.4 ml), and the mixture is stirred at 80° to 85° C. for 1.5 hour. The reaction mixture is diluted with ethyl acetate, and the organic layer is washed with water and aqueous saturated sodium chloride and dried over magnesium sulfate and then concentrated under reduced pressure to give N-cyclopropyl-2-ethyl-3-(4-methyl-1-piperazinyl)-4-fluoro-6-nitroaniline (1.00 g), as viscous oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:38])[CH:5]([C:19]1[CH:24]=[CH:23][C:22]([O:25][C@H:26]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27]2)=[CH:21][CH:20]=1)[CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][C:11]([C:17]#[N:18])=[CH:12][CH:13]=2)[CH:8]=1)[CH3:2].[NH2-].[Na+]>C(O)C>[CH2:1]([O:3][C:4](=[O:38])[C@H:5]([C:19]1[CH:24]=[CH:23][C:22]([O:25][C@H:26]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27]2)=[CH:21][CH:20]=1)[CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][C:11]([C:17]#[N:18])=[CH:12][CH:13]=2)[CH:8]=1)[CH3:2]
Reactant: CCOC(=O)C(Cc1ccc2ccc(C#N)cc2c1)c1ccc(O[C@H]2CCN(C(=O)OC(C)(C)C)C2)cc1
Agent: [NH2-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)[C@@H](Cc1ccc2ccc(C#N)cc2c1)c1ccc(O[C@H]2CCN(C(=O)OC(C)(C)C)C2)cc1
Yield: 77.7 %

Procedure:
2-[4-[[(3S)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]oxy]phenyl]-3-(7-cyano-2-naphthyl)propionic acid ethyl ester (1.90 g, 3.7 mmol) was heated and dissolved in ethanol (6 ml), and the resultant solution was cooled to room temperature with stirring to settle crystals. Subsequently, sodium amide (22 mg, 0.6 mmol) was added thereto, followed by stirring at the same temperature for 30 minutes, then sodium amide (22 mg, 0.6 mmol) was further added, followed by stirring for 18 hours. The crystals were collected through filtration to obtain 1.48 g of the title compound (78% yield). The diastereomer purity of the crystals was 92.3%.
Reaction SMILES: I[C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][C:8](I)=[CH:9][CH:10]=3)[C:5]([CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])([CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:34]1([NH:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[CH:42]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>[Cu]>[C:34]1([N:40]([C:41]2[CH:42]=[C:43]([CH3:47])[CH:44]=[CH:45][CH:46]=2)[C:2]2[CH:14]=[CH:13][C:12]3[C:11]4[C:6](=[CH:7][C:8]([N:40]([C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=5)[C:41]5[CH:42]=[C:43]([CH3:47])[CH:44]=[CH:45][CH:46]=5)=[CH:9][CH:10]=4)[C:5]([CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])([CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:4]=3[CH:3]=2)[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: COC(=O)CCC1(CCC(=O)OC)c2cc(I)ccc2-c2ccc(I)cc21
Reactant: Cc1cccc(Nc2ccccc2)c1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COC(=O)CCC1(CCC(=O)OC)c2cc(N(c3ccccc3)c3cccc(C)c3)ccc2-c2ccc(N(c3ccccc3)c3cccc(C)c3)cc21
Temperature: 150 °C

Procedure:
A mixture of 17.0 grams of 2,7-diiodo-9,9-bis[2-(methoxycarbonyl)ethyl]fluorene, 4.3 grams of copper bronze, 12.5 grams of potassium carbonate in 30 milliliters of Soltrol 220 was mechanically stirred and heated to 150° C. under a nitrogen atmosphere. Fifteen (15.0) grams of molten N-phenyl-m-toluidine was added dropwise at this temperature. After addition, the resulting mixture was heated at 210° C. under reflux for 24 hours. The hot reaction mixture was filtered, and the filter cake was washed several times with hot cyclohexane. The combined filtrate was evaporated under reduced pressure to give a brown residue which was purified by column chromatography on silica gel to afford 15.2 grams of pure 2,7-bis(phenyl-m-tolylamino)-9,9-bis[2-(methoxycarbonyl)ethyl]-fluorene, melting point 159° to 160° C.
Reaction SMILES: [C@@H:1]1([NH:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([C:28]5[N:32]=[CH:31][N:30](C(C6C=CC=CC=6)(C6C=CC=CC=6)C6C=CC=CC=6)[N:29]=5)[CH:26]=4)[N:21](C4CCCCO4)[N:20]=3)[CH:14]=2)=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1>[NH:29]1[C:28]([C:25]2[CH:26]=[C:27]3[C:22](=[CH:23][CH:24]=2)[NH:21][N:20]=[C:19]3[C:15]2[CH:14]=[C:13]([C:11]([NH:10][C@@H:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3][CH2:2]3)=[O:12])[CH:18]=[CH:17][CH:16]=2)=[N:32][CH:31]=[N:30]1
Reactant: O=C(N[C@H]1CCc2ccccc21)c1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: O=C(N[C@H]1CCc2ccccc21)c1cccc(-c2n[nH]c3ccc(-c4ncn[nH]4)cc23)c1
Temperature: 50 °C
Yield: 8.5 %

Procedure:
To a stirred solution of N-((1S)indanyl)(3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenyl methyl)(1,2,4-triazol-3-yl)](1H-indazol-3-yl)}phenyl)carboxamide (0.277 g, 0.371 mmol) was added dioxane (4.0 mL) and aqueous 6 N hydrochloric acid (4.0 mL) and the mixture heated at 50° C. for 5.5 h. The mixture was cooled and poured into saturated sodium bicarbonate (50 mL). The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated. Addition of ethyl acetate (5 mL) initiated crystal growth and the ethyl acetate phase was pipetted off. The crystals were filtered. Purification by preparative HPLC (30-80% acetonitrile/water) followed by washing with saturated sodium bicarbonate and extraction with ethyl acetate gave the title compound (0.0133 g, 9% yield). 1H NMR (CD3OD) δ 8.81 (s, 1H), 8.54 (m, 1H), 8.39 (br s, 1H), 8.24 (d, 1H), 8.13 (d, 1H), 7.96 (m, 1H), 7.70 (m, 2H), 7.37 (m, 1H), 7.27 (m, 1H), 7.22 (m, 2H), 5.70 (t, 1H), 3.09 (m, 1H), 2.93 (m, 1H), 2.61 (m, 2H), 2.09 (m, 1H). ES-MS (m/z) 421 [M+1]+.
Reaction SMILES: CCN(C1C=CC(N=NC2C(C(O)=O)=CC=CC=2)=CC=1)CC.CCN1C2C(=CC=CC=2)C=C/C/1=C\C1C2C(=CC=CC=2)[N+](CC)=CC=1.[I-].CO[C:51]1[C:56](F)=[C:55](F)[C:54]([C:59]([C:67]([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)([C:69]2[C:74](F)=[C:73](F)[C:72](OC)=[C:71](F)[C:70]=2F)[OH:68])([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[OH:60])=[C:53](F)[C:52]=1F>CC(C)=O.COCCO>[C:69]1([C:67]([C:59]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)([C:54]2[CH:53]=[CH:52][CH:51]=[CH:56][CH:55]=2)[OH:60])([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[OH:68])[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1
Reactant: COc1c(F)c(F)c(C(O)(c2ccccc2)C(O)(c2ccccc2)c2c(F)c(F)c(OC)c(F)c2F)c(F)c1F
Agent: CCN(CC)c1ccc(N=Nc2ccccc2C(=O)O)cc1
Agent: CCN1/C(=C/c2cc[n+](CC)c3ccccc23)C=Cc2ccccc21
Agent: [I-]
Solvent: COCCO
Solvent: CC(C)=O
Product: OC(c1ccccc1)(c1ccccc1)C(O)(c1ccccc1)c1ccccc1
Temperature: 160 °C

Procedure:
Ethyl red (2.0 mg), 1,1'-diethyl-2,4'-cyanine iodide, was dissolved in 2.0 ml. of acetone/2-methoxyethanol. Then, 50 mg of 4,4"-dimethoxy-2,3,5,6,2",3",5",6"-octafluorobenzopinacol was added. The solution was mixed with 1.0 ml of 20 percent polysulfonamide polymer solution (acetone/2-methoxyethanol (1:1)). The solution was mixed and coated on poly(ethylene terephthalate) film base at a wet thickness of 0.098 mm. It was allowed to dry at 49° C. for 15 minutes. The dye in the film had λ max at 565 nm, and at 530 nm, the optical density was 1.8 and 0.93, respectively. The film was heated at 160° C. for 10 seconds. The optical density of the heated film was 0.20 at λ=565 and 0.18 at 530 nm. The reduction in the dye density was 89 percent and 81 percent, at the two wavelengths. The same results were obtained after the film had been held in storage at room temperature for 6 months.
Reaction SMILES: C(N(CC)CC)C.[C:8](=[O:19])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])OC(C)(C)C.ClCCl.[NH:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1>O>[C:15]([O:14][C:8]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)=[O:19])([CH3:16])([CH3:17])[CH3:18]
Reactant: O=C1CCNCC1
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(=O)CC1

Procedure:
2.7 ml (20.0 mmol) of triethylamine, 1.84 g (8.45 mmol) of di-t-butyl carbonate and 30 ml of dichloromethane were added to 1.0 g (5.0 mmol) of 4-piperidone, and the resultant mixture was stirred for 19 hours. The reaction solution was diluted with water. After the extraction with dichloromethane, the organic layer was washed with 1 N aqueous hydrochloric acid solution and then with a saturated Aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain 1-t-butoxycarbonyl-4-piperidone. Separately, 80 ml of tetrahydrofuran and methyl 4-(diethoxyphosphorylmethyl)benzoate were added to 241 mg (6.0 mmol) of sodium hydride under cooling with ice, and the resultant mixture was stirred for 30 minutes and then at room temperature for 30 minutes. Crude 1-t-butoxycarbonyl-4-piperidone obtained as described above was added to the mixture, and they were stirred for 20 hours. The reaction solution was diluted with water. After the extraction with ethyl acetate, the organic layer was washed with water and then with a saturated Aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by the silica gel column chromatography to obtain the title compound.
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][CH2:7][OH:8])=[N+:2]=[N-:3].[H-].[Na+].Cl[CH2:12][C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].Cl>O1CCCC1.C(#N)C.O>[N:1]([CH2:4][CH2:5][CH2:6][CH2:7][O:8][CH2:12][C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N+:2]=[N-:3]
Reactant: CCOC(=O)CC(=O)CCl
Reactant: [N-]=[N+]=NCCCCO
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)COCCCCN=[N+]=[N-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 31.4 %

Procedure:
A solution of 4-azidobutanol (6.8 g) in tetrahydrofuran (100 ml) was added dropwise over 30 minutes to a suspension of sodium hydride (5.4 g; 60% dispersion in oil) in tetrahydrofuran (100 ml). The mixture was stirred at room temperature for 30 minutes and then treated with a solution of ethyl 4-chloroacetoacetate (9.7 g) in tetrahydrofuran (150 ml) dropwise over 30 minutes. The mixture was stirred at room temperature for 16 hours, poured into water and the pH adjusted to 3-4 with 2M hydrochloric acid. The aqueous solution was extracted with ethyl acetate (3×200 ml) and the organic layer was dried (MgSO4) and evaporated to give an oil which was taken up in acetonitrile and washed with petrol. The solvent was evaporated to dryness and the residue was chromatographed on silica eluting with a mixture of petrol and methylene chloride. Fractions containing the product were evaporated to give ethyl 4-(4-azidobutoxy)acetoacetate as a yellow oil (4.5 g). Methyl 3-aminocrotonate (2.2 g) and 2-chlorobenzaldehyde (2.7 g) in methanol (50 ml) were added and the mixture was heated under reflux for 5 hours and then evaporated. The residue was chromatographed on silica eluting with a mixture of petrol and ethyl acetate to give 2-(4-azidobutoxy)methyl-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (5.9 g) as a yellow oil. The product was taken up in methanol (70 ml) and stirred at room temperature for 16 hours under 1 atmosphere of hydrogen in the presence of 5% palladium on calcium carbonate catalyst (2.0 g). The reaction mixture was filtered and concentrated. The residue was treated with a solution of fumaric acid (1.0 g) in methanol. The resulting precipitate was collected, treated with 2M ammonium hydroxide and extracted with methylene chloride (2×25 ml). The organic layer was washed with water, dried (MgSO4), filtered and evaporated to give 2-(4-aminobutoxy)methyl-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (2.2 g) as a yellow oil. The product was used in the next stage without further purification.