Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-])=O.C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O.C(OCC)C>[CH2:18]([O:8][C:5]1[CH:4]=[C:3]([C:2]([Cl:1])=[CH:7][CH:6]=1)[NH2:9])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=[N+]([O-])c1cc(O)ccc1Cl
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: Nc1cc(OCc2ccccc2)ccc1Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
4-Chloro-3-nitrophenol (0.13 g) was dissolved in N,N-dimethylformamide (3 mL). To the solution were added potassium carbonate (0.31 g) and benzyl bromide (0.14 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with diethyl ether, and the resulting mixture was washed with water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in tetrahydrofuran (3 mL). To the solution were added methanol (3 mL), nickel(II) bromide (8 mg) and sodium borohydride (85 mg) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was washed with a saturated aqueous sodium hydrogen carbonate solution, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title compound (0.15 g).
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([N:28]1[C:37]2[C:32](=[CH:33][C:34]([NH2:38])=[CH:35][CH:36]=2)[C:31]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)([CH3:39])[CH2:30][C:29]1([CH3:47])[CH3:46])(=[O:27])[CH3:26].[C:48]1([CH3:66])[CH:53]=[CH:52][C:51]([C:54]([O:56][C:57]2[CH:65]=[CH:64][CH:63]=[CH:62][C:58]=2[C:59](O)=[O:60])=[O:55])=[CH:50][CH:49]=1.C(N(CC)C(C)C)(C)C>O1CCCC1>[C:25]([N:28]1[C:37]2[C:32](=[CH:33][C:34]([NH:38][C:59](=[O:60])[C:58]3[CH:62]=[CH:63][CH:64]=[CH:65][C:57]=3[O:56][C:54]([C:51]3[CH:50]=[CH:49][C:48]([CH3:66])=[CH:53][CH:52]=3)=[O:55])=[CH:35][CH:36]=2)[C:31]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)([CH3:39])[CH2:30][C:29]1([CH3:47])[CH3:46])(=[O:27])[CH3:26]
Reactant: Cc1ccc(C(=O)Oc2ccccc2C(=O)O)cc1
Reactant: CC(=O)N1c2ccc(N)cc2C(C)(c2ccccc2)CC1(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(=O)N1c2ccc(NC(=O)c3ccccc3OC(=O)c3ccc(C)cc3)cc2C(C)(c2ccccc2)CC1(C)C

Procedure:
HATU condensation of 1-acetyl-6-amino-4-phenyl-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline (10 mg) with 2-[4-toloyloxy]benzoic acid (8.0 mg) and N,N-diisopropylethylamine (22 l) in tetrahydrofuran (1 ml) was performed according to the method described in example 11.
Reaction SMILES: BrN1C(=[O:7])CCC1=O.Br.[C:10]([O:18][CH:19]([CH3:33])[CH2:20][CH:21]1[CH2:26][O:25][CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:23][CH2:22]1)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C>[C:24]([O:25][CH2:26][CH:21]([CH2:20][CH:19]([O:18][C:10](=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH3:33])[CH2:22][OH:7])(=[O:23])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(CC1COC(c2ccccc2)OC1)OC(=O)c1ccccc1
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: CC(CC(CO)COC(=O)c1ccccc1)OC(=O)c1ccccc1
Reaction time: 1 h
Yield: 29.7 %

Procedure:
To a stirred and ice cooled suspension of 9.344 g (52.5 mM) of N-bromosuccinimide in 250 ml of water are added a drop of conc. hydrobromic acid and 17.125 g of the crude 5-(2-benzoyloxypropan-1-yl)-2-phenyl-1,3-dioxane m4 obtained in the previous reaction dropwise. After standing at 0° C. for another 1 hour, 22 g (260 mM) of sodium bicarbonate is added to the reaction mixture and the product is isolated by ethyl acetate extraction. The ethyl acetate layer is washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated. Purification of the product by column silica gel chromatography using n-hexane-ethyl acetate (1:1) as an eluent gives 7.401 g (29.7% yield from the compound m2) of the titled compound m5 as an oily product.
Reaction SMILES: [CH3:1][N:2]([CH:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)C=C)[C:3]([C@H:5]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][CH:7]=[CH2:8])=[O:4]>C1(C)C=CC=CC=1.Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[CH3:1][N:2]1[C@H:20]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:8]=[CH:7][CH2:6][C@@H:5]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:3]1=[O:4].[CH3:1][N:2]1[C@@H:20]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:8]=[CH:7][CH2:6][C@@H:5]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:3]1=[O:4]
Reactant: C=CC[C@@H](NC(=O)OCc1ccccc1)C(=O)N(C)C(C=C)c1ccccc1
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Solvent: Cc1ccccc1
Product: CN1C(=O)[C@H](NC(=O)OCc2ccccc2)CC=C[C@@H]1c1ccccc1
Product: CN1C(=O)[C@H](NC(=O)OCc2ccccc2)CC=C[C@H]1c1ccccc1
Temperature: 80 °C
Reaction time: 0.83 h
Yield: 83 %

Procedure:
To a solution of benzyl ((1R)-1-{[methyl(1-phenylprop-2-en-1-yl)amino]carbonyl}but-3-en-1-yl)carbamate (3b) (1.01 g) dissolved in Toluene (100 mL) at 80° C. under N2 was added Grubbs catalyst (2nd generation) (113 mg) and the reaction mixture was stirred at 80° C. for 50 min., cooled to RT and concentrated in vacuo. The crude product was directly purified via flash chromatography (gradient—10%, 15%, 20% and 30% EtOAc/hexanes) to give the title compound (3c) (331 mg) and benzyl [(3R,7R)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]carbamate (3d) (453 mg) (combined yield of 83%).
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:10][CH:9]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7].[Cl:36][C:37]1[CH:38]=[C:39]([CH:44]([CH2:56][CH2:57]OS(C)(=O)=O)[CH2:45][N:46]([CH3:55])[C:47](=[O:54])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:40]=[CH:41][C:42]=1[Cl:43].[C:63]([O-:66])([OH:65])=O.[Na+]>C(O)C>[C:6]([OH:54])(=[O:7])/[CH:5]=[CH:27]/[C:63]([OH:66])=[O:65].[F:35][C:2]([F:34])([F:1])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:15][CH2:16][N:17]([CH2:57][CH2:56][CH:44]([C:39]3[CH:40]=[CH:41][C:42]([Cl:43])=[C:37]([Cl:36])[CH:38]=3)[CH2:45][N:46]([CH3:55])[C:47](=[O:54])[C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH2:18][CH2:19]2)[CH2:10][C@@H:9]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7]
Reactant: O=C([O-])O
Reactant: CN(CC(CCOS(C)(=O)=O)c1ccc(Cl)c(Cl)c1)C(=O)c1ccccc1
Reactant: O=C(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)N1CCC(N2CCNCC2)CC1Cc1ccccc1
Agent: [Na+]
Solvent: CCO
Product: CN(CC(CCN1CCN([C@H]2CCN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H](Cc3ccccc3)C2)CC1)c1ccc(Cl)c(Cl)c1)C(=O)c1ccccc1
Product: O=C(O)/C=C/C(=O)O
Yield: 59.8 %

Procedure:
A mixture of compound 15 (0.005 mol), N-[2-(3,4-dichlorophenyl)-4-[(methylsulfonyl)oxy]butyl]-N-methyl benzamide (0.0055 mol) and NaHCO3 (0.0055 mol) in ethanol (50 ml) was stirred and refluxed for 6 hours. The solvent was evaporated, the residue was taken up in water and extracted with CH2Cl2. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2Cl2/CH3OH 100/0, 99/1, 98/2 and 97/3). The pure fractions were collected and the solvent was evaporated. The residue was converted into the fumaric acid salt (1:2) with ethanol. The precipitate was filtered off and dried, yielding 1.42 g (27%) of (±)-cis-N-[4-[4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-1-piperazinyl]-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide (E)-2-butenedioate(1:2) (compound 93).
Reaction SMILES: [CH2:1]([C:3]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:7](=[O:15])[C:6]([C:16]#N)=[CH:5][CH:4]=1)[CH3:2].[OH-:18].[Na+].[OH2:20]>S(=O)(=O)(O)O>[CH2:1]([C:3]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:7](=[O:15])[C:6]([C:16]([OH:20])=[O:18])=[CH:5][CH:4]=1)[CH3:2]
Reactant: [OH-]
Reactant: CCc1ccc(C#N)c(=O)n1-c1ccccc1
Reactant: O
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: CCc1ccc(C(=O)O)c(=O)n1-c1ccccc1
Temperature: 120 °C
Yield: 72 %

Procedure:
6-Ethyl-2-oxo-1-phenyl-1,2-dihydropyridine-3-carbonitrile (395 mg, 1.76 mmol) was dissolved in conc. sulfuric acid (0.4 mL) and water (0.4 mL), and the mixture was stirred with heating at 120° C. for 7 hr. 1N Aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was washed with ethyl acetate. 1N Hydrochloric acid was added to the aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was washed with ethyl acetate to give the title compound (310 mg, 72%) as a colorless solid.
Reaction SMILES: C([O:6][C:7]1[C:13]([Cl:14])=[C:12]([Cl:15])[C:10]([OH:11])=[C:9]([Cl:16])[C:8]=1[Cl:17])CCCC.Cl[C:19]1[C:20](=O)[C:21](C#N)=C(C#N)[C:23](=O)[C:24]=1Cl>CO>[CH2:23]([C:13]1([Cl:14])[CH:12]([Cl:15])[C:10](=[O:11])[C:9]([Cl:16])=[C:8]([Cl:17])[C:7]1=[O:6])[CH2:24][CH2:19][CH2:20][CH3:21]
Reactant: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Reactant: CCCCCOc1c(Cl)c(Cl)c(O)c(Cl)c1Cl
Solvent: CO
Product: CCCCCC1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C1Cl
Reaction time: 2 h

Procedure:
To a solution of 110 mg (0.388 mmol) of 3 in methanol, 880 mg (10 eq) of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was added. The reaction mixture was stirred for 2 hr, and then the solvent was removed. Silicagel chromatography (hexane:EA=20:1) gave 4 as an orange solid with quantitative yield.
Reaction SMILES: [C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([NH2:14])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.C(O[C:23]1(O[Si](C)(C)C)[CH2:25][CH2:24]1)C.[BH4-].[Na+].C(=O)([O-])O.[Na+]>CO.O1CCCC1>[CH:23]1([NH:14][C:10]2[CH:9]=[C:8]([NH:7][C:6](=[O:15])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:13]=[CH:12][CH:11]=2)[CH2:25][CH2:24]1
Reactant: CCOC1(O[Si](C)(C)C)CC1
Reactant: CC(C)(C)OC(=O)Nc1cccc(N)c1
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)(C)OC(=O)Nc1cccc(NC2CC2)c1
Temperature: 60 °C
Reaction time: 4 h
Yield: 59.1 %

Procedure:
To a solution of tert-butyl(3-aminophenyl)carbamate (6.91 g, 33.2 mmol) in methanol (30 mL) were added acetic acid (5.69 mL, 99.5 mmol) and [(1-ethoxycyclopropyl)oxy](trimethyl)silane (7.98 mL, 39.8 mmol), and the mixture was stirred at 60° C. for 4 hr. The reaction mixture was concentrated under reduced pressure. A solution of the obtained residue in tetrahydrofuran (20 mL) was added dropwise to a suspension of sodium tetrahydroborate (2.51 g, 66.4 mmol) and boron trifluoride diethyl ether complex (8.33 mL, 66.4 mmol) in tetrahydrofuran (30 mL) (the suspension was stirred in advance at room temperature for 1 hr) at 0° C. over 30 min, and the mixture was stirred at room temperature for 2.5 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (100 mL), and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with saturated brine (20 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5→90/10), and the fractions containing the object product were concentrated under reduced pressure to give the title compound (4.87 g, 59%) as a colorless solid.
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:38])=[C:11]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([N:24]5[CH2:29][C@@H:28]6[CH2:30][C@H:25]5[CH2:26][N:27]6[C:31](OC(C)(C)C)=O)[CH:20]=4)[N:15]=[CH:14]3)[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.C=O>C(O)=O.O.C(=O)(O)[O-].[Na+]>[CH:1]1([NH:4][C:5](=[O:6])[C:7]2[CH:8]=[CH:9][C:10]([CH3:38])=[C:11]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([N:24]5[CH2:29][C@@H:28]6[CH2:30][C@H:25]5[CH2:26][N:27]6[CH3:31])[CH:20]=4)[N:15]=[CH:14]3)[CH:12]=2)[CH2:3][CH2:2]1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1-n1cnc2ccc(N3C[C@@H]4C[C@H]3CN4C(=O)OC(C)(C)C)cc2c1=O
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=CO
Product: Cc1ccc(C(=O)NC2CC2)cc1-n1cnc2ccc(N3C[C@@H]4C[C@H]3CN4C)cc2c1=O
Yield: 54.8 %

Procedure:
A solution of tert-butyl(1S,4S)-5-(3-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-oxo-3,4-dihydroquinazolin-6-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.30 g) and 38% aqueous formaldehyde (0.42 ml) in formic acid (5 ml) was stirred at 90° C. for 16 hours. The reaction mixture was diluted with water and sodium bicarbonate added, evacuated to dryness. The residue was partitioned between methylene chloride and saturated NaHCO3 solution. The organic phase was washed with water and dried (magnesium sulphate). The residue was purified by column chromatography on an ion exchange column (isolute SCX-2 column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methylene chloride and then a 49:1 mixture of methanol and aqueous ammonia solution to give the title compound (0.137 g); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.70 (m, 2H), 1.96 (m, 1H), 2.14 (s, 3H), 2.32 (s, 3H), 2.57 (d, 1H), 2.87 (m, 2H), 3.29 (d, 1H), 3.45 (m, 1H), 3.56 (s, 1H), 4.50 (d, 1H), 7.13 (d, 1H), 7.26 (m, 1H), 7.52 (d, 1H), 7.61 (d, 1H), 7.81 (m, 1H), 7.90 (m, 1H), 7.99 (s, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 430.
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][N:8]1[C:13](=[O:14])[C:12]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH:16]=[C:17]([CH3:18])[C:11]=2[N:10]([CH3:27])[C:9]1=[O:28])(=O)C.O[Li].O>C1COCC1.O.C(Cl)Cl>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:15]2[C:12]3[C:13](=[O:14])[N:8]([CH2:7][CH2:6][CH2:5][OH:4])[C:9](=[O:28])[N:10]([CH3:27])[C:11]=3[C:17]([CH3:18])=[CH:16]2)=[CH:25][CH:24]=1
Reactant: CC(=O)OCCCn1c(=O)c2c(c(C)cn2Cc2ccc(Cl)cc2)n(C)c1=O
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Solvent: ClCCl
Product: Cc1cn(Cc2ccc(Cl)cc2)c2c(=O)n(CCCO)c(=O)n(C)c12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 41.9 %

Procedure:
To a solution of 3-(5-(4-chlorobenzyl)-1,7-dimethyl-2,4-dioxo-1H-pyrrolo[3,2-d]pyrimidin-3 (2H,4H,5H)-yl)propyl acetate (40 mg, 0.099 mmol) in THF (5 mL) and water (5 mL) was added LiOH.H2O (4.74 mg, 0.198 mmol). The reaction was stirred at RT for 30 min then diluted with DCM (5 mL) and water (5 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1,7-dimethyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (15 mg, 41.9% yield) as a white solid. 1H NMR (DMSO-d6) δ: 7.38 (d, J=8.4 Hz, 2H), 7.26 (s, 1H), 7.22 (d, J=8.4 Hz, 2H), 5.45 (s, 2H), 4.44 (t, J=5.3 Hz, 1H), 3.95-3.82 (m, 2H), 3.56 (s, 3H), 3.45-3.39 (m, 2H), 2.26 (s, 3H), 1.73-1.58 (m, 2H). LCMS: MH+ 362 and TR=2.343 min.
Reaction SMILES: C([O:4][CH2:5][CH:6]([N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[CH2:7][O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)(=O)C.[OH-].[K+]>CO.O>[N:19]1([CH:6]([CH2:7][O:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11][CH:10]=2)[CH2:5][OH:4])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: CC(=O)OCC(COc1cccc2ccccc12)N1CCCCC1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: OCC(COc1cccc2ccccc12)N1CCCCC1

Procedure:
A suspension of 2-piperidino-3-(1-naphthyloxy)-1-propanol acetate (6.4 g), 15% KOH in methanol (10 ml), methanol (10 ml) and water (20 ml) is heated at reflux for 1 hour. The reaction mixture is concentrated to dryness. The residue is taken up in diethyl ether. The ether extract is washed with water and concentrated to give the title compound as an oil, γmaxEtOH 319 nm (ε = 1780), 305 nm (ε = 3330), 288 nm (ε = 6340), 230 nm (ε = 30,600), 212 nm (ε = 44,180).
Reaction SMILES: [H][H].[C:3]1([C:9](=[C:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]#[N:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:25]C1C=CC(C#N)=CC=1.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1>>[Br:25][C:6]1[CH:5]=[CH:4][C:3]([C:9](=[C:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:10]#[N:11])=[CH:8][CH:7]=1
Reactant: [H][H]
Reactant: N#CC(=C(c1ccccc1)c1ccccc1)c1ccccc1
Reactant: N#Cc1ccc(Br)cc1
Agent: O=C(c1ccccc1)c1ccccc1
Product: N#CC(=C(c1ccccc1)c1ccccc1)c1ccc(Br)cc1

Procedure:
A related material was prepared in which the vinylic hydrogen of C(DPVBi)4 is substituted with a cyano group. The stabilized LUMO of the cyano-substituted triphenylethene fragment (2,3,3-triphenylacrylonitrile) is expected to enhance electron injection and transport as is observed for CN-PPV.38 Knovenagle condensation between 4-bromobenzonitrile and benzophenone gives 2-(4-bromophenyl)-3,3-diphenylacrylonitrile (Scheme 4). Metathesis of the bromine atom for boronpinacolate proceeds in good yield using the method of Miyaura.39 In this case metathesis of bromine using the n-BuLi/B(OiPr)3 protocol is not compatible with the sensitive cyano functionality. Five equivalents of 2-(4-pinacolatoboron-phenyl)-3,3-diphenylacrylonitrile react smoothly with tetrakis(4-bromophenyl)methane using the optimized Pd(dppf)Cl2 catalyzed coupling conditions to yield tetrakis(4,4′-(3,3-diphenylacrylonitrile)-1,1′-biphenyl)methane, C(DPAB)4 in 82% yield, following purification by flash chromatography. Compound C(DPAB)4 has been fully characterized and the details can be found in the Examples.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[C:6]([C:8]1[N:16]=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([OH:12])=O)=[O:7].[Cl:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([Cl:33])[C:24]=1[NH:34][NH2:35].O>C1(C)C=CC=CC=1>[Cl:22][C:23]1[CH:28]=[C:27]([C:29]([F:31])([F:30])[F:32])[CH:26]=[C:25]([Cl:33])[C:24]=1[NH:34][N:35]=[C:10]([OH:12])[C:9]1[CH:13]=[CH:14][CH:15]=[N:16][C:8]=1[C:6](=[O:7])[C:5]1[CH:17]=[CH:18][CH:19]=[C:3]([C:2]([F:1])([F:21])[F:20])[CH:4]=1
Reactant: O=C(O)c1cccnc1C(=O)c1cccc(C(F)(F)F)c1
Reactant: NNc1c(Cl)cc(C(F)(F)F)cc1Cl
Solvent: O
Solvent: Cc1ccccc1
Product: O=C(c1cccc(C(F)(F)F)c1)c1ncccc1C(O)=NNc1c(Cl)cc(C(F)(F)F)cc1Cl
Temperature: 25 °C
Yield: 9 %

Procedure:
A suspension of 2-(3-trifluoromethylbenzoyl)nicotinic acid (1.5 g) and 2,6-dichloro-4-trifluoromethylphenylhydrazine (1.87 g) in toluene was stirred at reflux with azeotropic removal of water (using a Dean Stark apparatus) for 6.5 hours. The mixture was cooled to room temperature and then washed with 2N hydrochloric acid and water. The organic phase was dried and evaporated. The crude product was purified by column chromatography to yield a yellow gum which was triturated in hexane to yield the title compound as a pale yellow solid (0.24 g), m.p. 92°-96° C.
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3](N)=O.F[B-](F)(F)F.C([O+](CC)CC)C.[F:19][CH2:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([NH:27][C:28]2[C:33]([NH2:34])=[CH:32][N:31]=[C:30]3[CH:35]=[CH:36][S:37][C:29]=23)[CH2:23][CH2:22]1>O1CCCC1.C(O)C>[F:19][CH2:20][C@H:21]1[CH2:22][CH2:23][C@H:24]([N:27]2[C:28]3=[C:29]4[S:37][CH:36]=[CH:35][C:30]4=[N:31][CH:32]=[C:33]3[N:34]=[C:3]2[C@H:2]([OH:1])[CH3:6])[CH2:25][CH2:26]1
Reactant: C[C@@H](O)C(N)=O
Reactant: Nc1cnc2ccsc2c1N[C@H]1CC[C@H](CF)CC1
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCO
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CC[C@H](CF)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of (2R)-2-hydroxypropanamide (0.184 g, 2.07 mmol) and triethyloxonium tetrafluoroborate (0.371 g, 1.95 mmol) in tetrahydrofuran (2.8 mL) was stirred at room temperature for 2 h. The solvent was removed and the residue dissolved in ethanol (1.2 mL) and added to a suspension of N7-[trans-4-(fluoromethyl)cyclohexyl]thieno[3,2-b]pyridine-6,7-diamine (0.18 g, 0.64 mmol) in ethanol (4.3 mL). The resulting mixture was stirred at 80° C. for 1 h. The solvent was removed and the residue was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (0.10 g, 50%). LCMS calculated for C17H21FN3OS (M+H)+: m/z=334.1. Found: 334.1.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:25])[N:9]3[CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([O:18]C(C)(C)C)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31]O>CCO.CCO.CCO.CCO.[Ti]>[Cl:1][C:2]1[C:7]2[C:8](=[O:25])[N:9]3[CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([O:18][CH2:31][C:30]3[CH:33]=[CH:34][CH:35]=[C:28]([O:27][CH3:26])[CH:29]=3)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)c1ncn2c1[C@@H]1CCN1C(=O)c1c(Cl)cccc1-2
Reactant: COc1cccc(CO)c1
Agent: [Ti]
Solvent: CCO
Product: COc1cccc(COC(=O)c2ncn3c2[C@@H]2CCN2C(=O)c2c(Cl)cccc2-3)c1
Reaction time: 5 h

Procedure:
A mixture of 3.6 g (10 mmol) of tert.butyl (S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate, 1.7 g (7.2 mmol) of tetraethyl orthotitanate and 20 ml of 3-methoxybenzyl alcohol is stirred at 120° for 5 hours, a small amount of solvent being removed in vacuo three times during this time. The excess 3-methoxybenzyl alcohol is subsequently distilled off in a high vacuum, the residue is taken up in 30 ml of chloroform, the chloroform solution is treated with 25 ml of water, stirred for 1.25 hours and filtered through siliceous earth. The organic phase is separated, the aqueous phase is extracted once with chloroform, the combined chloroform extracts are dried over magnesium sulphate and evaporated. The crude product is chromatographed on silica gel while eluting with ethyl acetate. By recrystallization from ethyl acetate/n-hexane there is obtained m-methoxybenzyl (S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][ 1,4]benzodiazepine-1-carboxylate of melting point 126°-127°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][N:4]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[Cl:33][C:34]1[CH:35]=[C:36]([CH:41]2[CH2:45][NH:44][CH2:43][CH:42]2[C:46](=[O:48])[CH3:47])[CH:37]=[CH:38][C:39]=1[Cl:40]>C(Cl)Cl>[Cl:33][C:34]1[CH:35]=[C:36]([CH:41]2[CH2:45][N:44]([C:7]([C:6]3[CH:5]=[N:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=3)=[O:9])[CH2:43][CH:42]2[C:46](=[O:48])[CH3:47])[CH:37]=[CH:38][C:39]=1[Cl:40]
Reactant: COc1ccc(C(=O)O)cn1
Reactant: CC(=O)C1CNCC1c1ccc(Cl)c(Cl)c1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)N2CC(C(C)=O)C(c3ccc(Cl)c(Cl)c3)C2)cn1
Yield: 56.1 %

Procedure:
To a stirred solution of 6-methoxy-nicotinic acid (0.53 g, 3.40 mmol) in CH2Cl2 (15 mL) were added EDC (0.659 g, 3.40 mmol), HOBt (0.465 g, 3.40 mmol) and Et3N (0.59 mL, 4.3 mmol). After one hour at RT was added 1-[(3SR,4RS)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethanone (XIII-1) (0.74 g, 2.90 mmol) and stirring was continued over night. The reaction mixture was then poured onto water and extracted with CH2Cl2. The combined organic phases were dried over Na2SO4 and concentrate under vacuo. Flash chromatography (SiO2, EtOAc/H, 1:1) afforded 0.64 g (57%) of the title product as a white solid. ES-MS m/e: 393.1 (M+H+).