Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O>C(O)C>[OH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)=[CH:17][CH:16]=1
Reactant: O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1
Solvent: CCO
Product: Nc1ccc(C=Cc2ccc(O)cc2)cc1
Temperature: 25 °C
Reaction time: 28.5 h

Procedure:
A portion (20.9 grams, 0.0866 mole) of 4-nitro-4'-hydroxystilbene from B. above and ethanol (300 mL) are added to a 400 milliliter heavy walled glass bottle then sparged with nitrogen. After removal of air by nitrogen sparging, Raney nickel catalyst (2.5 grams of a 50% wt. slurry in water at pH 10) is washed one time with ethanol, then added to the slurry in the glass bottle which is then stoppered and multiply purged with hydrogen to replace the nitrogen atmosphere. The bottle is then placed on a shaking type agitator, and pressurized to 46.5 psig (320.6 kPa) hydrogen. Shaking of the pressurized slurry at room temperature (25° C.) commences until 28.5 hours later, the hydrogen pressure reading indicates that 19.6 psig (135.1 kPa) of hydrogen has been consumed. The product slurry is recovered, diluted into dimethylsulfoxide (150 grams) to provide a solution of product containing precipitated Raney nickel, then filtered through a medium porosity fritted glass funnel. The recovered dimethylsulfoxide product solution is rotary evaporated at 130° C. under vacuum to provide a powder product. The powder product is further dried at 100° C. under vacuum of 2 mm Hg to a constant weight of 18.17 grams (99.25% isolated yield) of orange brown colored powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of a portion of the product revealed the presence of absorbances at 3363 (sharp) and 3289 cm-1 (sharp) due to primary amine N--H group stretching and hydroxyl group O--H stretching, complete disappearance of the conjugated nitro group absorbances at 1516 and 1337 (1317 shoulder) cm-1 (sharp) and the ethylene C--H out-of-plane deformation at 965 cm-1. Nuclear magnetic resonance spectroscopy confirmed the integrity of the stilbene ethylenic unsaturated structure.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([NH:12][CH2:13][C@:14]2([F:27])[CH2:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]2)[N:3]=1.[CH3:28][C:29]([N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1)([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:28][C:29]([N:32]1[CH:36]=[C:35]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][CH:8]=[N:9]3)=[C:4]([NH:12][CH2:13][C@:14]3([F:27])[CH2:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]3)[N:3]=2)[CH:34]=[N:33]1)([CH3:31])[CH3:30]
Reactant: CC(C)(C)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@](F)(CNc2nc(Cl)cc3ncccc23)C1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC[C@@](F)(CNc2nc(-c3cnn(C(C)(C)C)c3)cc3ncccc23)C1
Temperature: 130 °C
Yield: 99.9 %

Procedure:
To a solution of 1,1-dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate (1.300 g, 3.29 mmol) in 1,4-dioxane (10 ml) was added 1-(1,1-dimethylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.906 g, 3.62 mmol), caesium carbonate (2.145 g, 6.58 mmol), tetrakis(triphenylphosphine)palladium (0) (0.114 g, 0.099 mmol) and water (2 ml). The reaction mixture was heated in the microwave at 130° C. for 2 h. LCMS shows main peak of product with no starting material. The reaction mixture was filtered through 10 g celite and partitioned between ethyl acetate and water (100 ml×2). The organic layer was washed with brine (100 ml), evaporated the solvent and dissolved in minimum amount of DCM. This was loaded on to a 100 g silica column and purified on SP4 eluting with 20-90% ethyl acetate in cyclohexane over 22 CVs. Appropriate fractions were collected and the solvent was evaporated. The product was dried on high vacuum overnight to give the title compound as a yellow crystalline solid (1.586 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([N:18]=[C:19]=S)[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(OC1CC2C(CC=1)=CC=CC=2N=C=S)C.[N:38]([CH2:41][C:42]([C:44]1[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=1)=[O:43])=[N+]=[N-].N(CC(C1C=CC(C(F)(F)F)=CC=1)=O)=[N+]=[N-]>>[C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([NH:18][C:19]3[O:43][C:42]([C:44]4[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=4)=[CH:41][N:38]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NC1CCc2cccc(N=C=S)c2C1
Reactant: Cc1ccc(C(=O)CN=[N+]=[N-])cc1
Agent: CCOC1=CCc2cccc(N=C=S)c2C1
Agent: [N-]=[N+]=NCC(=O)c1ccc(C(F)(F)F)cc1
Product: Cc1ccc(-c2cnc(Nc3cccc4c3CC(NC(=O)OC(C)(C)C)CC4)o2)cc1
Yield: 82.9 %

Procedure:
The title compound was prepared using the procedure as described in Example 1H, substituting the product of Example 20F (188 mg, 0.618 mmol) for the product of Example 1F and the product of Example 9A (130 mg, 0.741 mmol) for the product of Example 1G. The crude product was purified by flash chromatography eluting with 2% to 5% CH3OH/CH2Cl2 followed by 60% EtOAc/hexanes which gave 215 mg (83%) of the title compound as a yellow amorphous solid. 1H NMR (DMSO-d6) δ 9.06 (br s, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.45 (d, J=8.1 Hz, 2H), 7.29 (s, 1H), 7.23 (d, J=8.1 Hz, 2H), 7.10 (t, J=7.8 Hz, 1H), 6.98 (br d, 1H), 6.84 (d, J=7.5 Hz, 1H), 3.65 (m, 1H), 3.02 (m, 1H), 2.83 (m, 2H), 2.42 (m, 1H), 2.31 (s, 3H), 1.87 (m, 1H), 1.58 (m, 1H), 1.39 (s, 9H); MS (ESI+) m/z 420 (M+H)+.
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[NH:25]([C:32]([C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][C:35]=1[O:43][CH3:44])=[O:33])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[C:26]1([NH:25][C:32](=[O:33])[C:34]2[CH:39]=[CH:38][C:37]([C:2]3[C:10]4[C:5](=[N:6][CH:7]=[N:8][C:9]=4[NH2:11])[N:4]([C@H:12]4[CH2:17][CH2:16][C@@H:15]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[CH2:14][CH2:13]4)[N:3]=3)=[CH:36][C:35]=2[O:43][CH3:44])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: COc1cc(B(O)O)ccc1C(=O)Nc1ccccc1
Reactant: CN1CCN([C@H]2CC[C@@H](n3nc(I)c4c(N)ncnc43)CC2)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COc1cc(-c2nn([C@H]3CC[C@@H](N4CCN(C)CC4)CC3)c3ncnc(N)c23)ccc1C(=O)Nc1ccccc1

Procedure:
cis-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (148 mg, 0.335 mmol), 4-(anilinocarbonyl)-3-methoxyphenylboronic acid (100 mg, 0.369 mmol), palladium tetrakistriphenyphosphine (23 mg, 0.020 mmol) and sodium carbonate (85 mg, 0.845 mmol) were mixed with ethylene glycol dimethyl ether (4 mL) and water (2 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (95:5) as mobile phase to give cis-N1-Phenyl-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxybenzamide (125 mg, 69%). 1H NMR (CDCl3) δ 1.69 (m, 2H), 1.86 (m, 2H), 2.17 (m, 2H), 2.31 (s, 3H), 2.44 (m, 11H), 4.15 (s, 3H), 4.96 (m, 1H), 5.69 (bs, 2H), 7.14 (m, 1H), 7.37 (m, 2H), 7.45 (m, 2H), 7.68 (m, 2H), 8.41 (m, 2H), 9.77 (s, 1H). LC/MS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.5 mL/min.): MH+ =541.2, Rt=2.58 min.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][N:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH3:13])=[CH:8][C:7]1=[O:14])C.O.[NH2:17][NH2:18]>C(O)C>[CH3:13][C:9]1[CH:10]=[C:11]([CH3:12])[N:6]([CH2:5][C:4]([NH:17][NH2:18])=[O:3])[C:7](=[O:14])[CH:8]=1
Reactant: CCOC(=O)Cn1c(C)cc(C)cc1=O
Reactant: NN
Solvent: O
Solvent: CCO
Product: Cc1cc(C)n(CC(=O)NN)c(=O)c1

Procedure:
As described for example 112a, (4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester (Shusherina, N. P.; Slavyanova, O. V.; Petrova, L. K.; Levina, R. Ya. Zhurnal Organicheskoi Khimii (1972), 8(2), 387-9) in ethanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 120 h. The mixture was concentrated and crystallized from ethanol/diisopropylether and the title compound was obtained as a white solid (yield. 90%). MS: m/e=218.2 [M+Na]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH:6]=[CH:7][CH:8]=1>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(C=CCCCCC(=O)O)c1
Agent: [Pd]
Solvent: CCO
Product: COc1cccc(CCCCCCC(=O)O)c1
Reaction time: 18 h
Yield: 93 %

Procedure:
After careful purging with argon and still under an atmosphere of argon, 10% palladium on carbon (0.015 g, 0.015 mmol) was suspended in 8 mL ethanol. 7-(3-methoxyphenyl)hept-6-enoic acid (2) was dissolved in 2 mL warm ethanol and injected into the reaction solution and stirring was commenced. The reaction vessel was then purged with hydrogen gas after which a hydrogen balloon was utilized to maintain a hydrogen atmosphere in the reaction vessel while stirring continued for 18 hours. The 10% palladium on carbon was filtered off on diatomaceous earth and the ethanolic filtrate collected and condensed in vacuo to provide the desired product in 93% yield (0.159 g) as a light yellow oil without further purification: 1H NMR (500 MHz, CDCl3) δ 7.24 (q, 1H), 6.79 (q, 3H), 3.83 (s, 3H), 2.63 (t, 2H), 2.39 (t, 3H), 1.69 (m, 4H), 1.41 (m, 4H); 13C NMR (500 MHz, CDCl3) δ 180.48, 159.62, 144.33, 129.24, 120.90, 114.23, 110.93, 100.01, 55.11, 35.96, 34.13, 31.19, 28.94, 24.64.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]([OH:14])=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].CCOC(C)=O.[H][H]>[Pd].CO>[OH:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]([OH:14])=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: COc1ccc(C=CC(=O)O)cc1O
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: COc1ccc(CCC(=O)O)cc1O
Yield: 99 %

Procedure:
The mixture of 3-(3-Hydroxy-4-methoxy-phenyl)-acrylic acid (3 g), 10% Pd/C (0.5 g), EtOAc (50 ml) and MeOH (50 ml) was shaken in Parr apparatus for 5 hs under 30-40 psi of hydrogen. Then the solution was passed through a celite pad and was concentrated to give 3-(3-Hydroxy-4-methoxy-phenyl)-propionic acid (3 g). LC-MS: m/e 197 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[O:30])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][C:15]=1[CH3:16].[CH2:31](O)[CH2:32][OH:33].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]2[O:33][CH2:32][CH2:31][O:30]2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][C:15]=1[CH3:16]
Reactant: COc1cc(CCCCCCC=O)ccc1OCc1nc(-c2ccccc2)oc1C
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: COc1cc(CCCCCCC2OCCO2)ccc1OCc1nc(-c2ccccc2)oc1C
Reaction time: 4 h
Yield: 92.6 %

Procedure:
A mixture of 7-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]heptanal (3.8 g), ethylene glycol (1 g), p-toluenesulfonic acid monohydrate and toluene (50 ml) was stirred for 4 hours under reflux. The reaction mixture was cooled, which was then washed with water and dried (MgSO4), followed by distilling off the solvent under reduced pressure. The residue was subjected to column chromatography on silica gel. From the fraction eluted with ethyl acetate-hexane (1:3), was obtained 2-[6-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]hexyl]-1,3-dioxolan (3.9 g, 94%) as an oily product.
Reaction SMILES: [C:1]([OH:20])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[NH2:21][C:22]([CH3:26])([CH3:25])[CH2:23]O>>[CH3:23][C:22]1([CH3:26])[CH2:25][O:20][C:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[N:21]1
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Reactant: CC(C)(N)CO
Product: CCCCCCCCCCCCCCCCCC1=NC(C)(C)CO1
Yield: 79.7 %

Procedure:
Following example 11, 14.9 g (52.4 mmoles) of octadecanoic acid and 9.34 g (104.8 mmoles) of 2-amino-2-methylpropanol gave 14.1 g (79.7%) of product, b.p. 140°-143° C./0.01 mmHg.
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][C:5]2[C:6](=O)[O:7][C:8](=[O:9])[C:4]=2[CH:3]=1.C[Si](C)(C)[NH:15][Si](C)(C)C>ClC1C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:11][CH:12]=1)[C:6](=[O:7])[NH:15][C:8]2=[O:9]
Reactant: C[Si](C)(C)N[Si](C)(C)C
Reactant: Cc1ccc2c(c1)C(=O)OC2=O
Solvent: Clc1ccccc1
Product: Cc1ccc2c(c1)C(=O)NC2=O
Temperature: 25 °C
Reaction time: 10.5 h

Procedure:
1.00 g of 5-methyl-2-benzofuran-1,3-dione was suspended in 10 mL of chlorobenzene, to which 1.3 mL of 1,1,1,3,3,3-hexamethyldisilazane was added at room temperature, and this suspension was stirred for 10.5 hours while heating it under reflux. The reaction mixture was cooled to room temperature, and resultant precipitate was filtered out therefrom to yield 0.169 g of 5-methyl-1H-isoindole-1,3(2H)-dione as light yellow solid.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1/[CH:6]=[C:7]1\[C:8](=[O:22])[NH:9][C:10]2[C:15]\1=[CH:14][C:13]([C:16]#[C:17][Si](C)(C)C)=[CH:12][CH:11]=2.[C-]#N.[K+].C(=O)(O)[O-].[Na+]>C(O)C.O1CCCC1.O.[N+]([O-])([O-])=O.[Ag+]>[C:16]([C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:22])/[C:7]/2=[CH:6]\[C:2]1[NH:1][CH:5]=[CH:4][CH:3]=1)#[CH:17]
Reactant: C[Si](C)(C)C#Cc1ccc2c(c1)/C(=C/c1ccc[nH]1)C(=O)N2
Agent: [Ag+]
Agent: O=C([O-])O
Agent: O=[N+]([O-])[O-]
Solvent: O
Solvent: CCO
Solvent: C1CCOC1
Product: C#Cc1ccc2c(c1)/C(=C/c1ccc[nH]1)C(=O)N2
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 96.4 %

Procedure:
To a solution of (Z)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-5-(trimethylsilyl)ethynyl-2H-indol-2-one (940 mg, 3.1 mmol) (from Example 81 above) in 50 mL ethanol and 15 mL tetrahydrofuran (Fisher Scientific) was added dropwise a solution of silver nitrate (1.17 g, 6.89 mmol) in 5 mL water and 15 mL ethanol, during which time a precipitate formed. The mixture was stirred at room temperature for 45 minutes, after which a solution of potassium cyanide (2.18 g, 33.47 mmol) in 8 mL of water was added and the precipitated dissolved. To the solution was then added 50 mL of a saturated aqueous sodium bicarbonate solution followed by 500 mL of water. The product was then filtered off and dried to give (Z)-1,3-dihydro-5-ethynyl-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one (yield 700 mg, 96%), which was recrystallized from EtOAc/Hex to yield 540 mg of the product as yellow crystals.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[CH2:11]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)[CH2:12][CH3:13].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH2:11]([N:14]1[CH2:19][CH2:18][N:17]([C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=2)[CH2:16][CH2:15]1)[CH2:12][CH3:13]
Reactant: CCCN1CCNCC1
Reactant: CC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCCN1CCN(c2ccc(C(C)=O)cc2)CC1
Temperature: 0 °C

Procedure:
A mixture of 33.2 g. of p-fluoroacetophenone, 48.3 g. of N-propylpiperazine and 99.5 g. of potassium carbonate in 100 ml. of dimethyl sulfoxide is stirred and heated at 95° for 4.5 hours, then cooled and poured into ice water. The precipitate of p-(4-propyl-1-piperazinyl)-acetophenone is collected by filtration, washed with water and dried; m.p. 68°-70° after crystallization from hexane.
Reaction SMILES: [C:1]([OH:7])(=[O:6])[CH2:2][C:3](O)=O.C(=O)[C:9]1[O:13][CH:12]=[CH:11][CH:10]=1.O>N1C=CC=CC=1.C(O)C.C(OCC)C>[O:13]1[CH:9]=[CH:10][CH:11]=[C:12]1[CH:3]=[CH:2][C:1]([OH:7])=[O:6]
Reactant: O=Cc1ccco1
Reactant: O=C(O)CC(=O)O
Solvent: CCO
Solvent: c1ccncc1
Solvent: CCOCC
Product: O=C(O)C=Cc1ccco1
Yield: 18.1 %

Procedure:
Malonic acid (104 g; 1 mole) was dissolved in a mixture of furfural (96 g; 1 mole), pyridine (72 ml) and ethanol (10 ml) and pumped through the CMR (15 ml/min; 165° C.; 1200 kPa). The product mixture was diluted with diethyl ether (200 ml) and washed with 5% aqueous sulphuric acid (4×200 ml) to remove most of the pyridine. The remaining solution was evaporated to dryness on a rotary evaporator and the resultant 2-furanacrylic acid (25 g; 18% yield) crystallised from water m. p. 141° C. The MS was in close agreement with spectrum in the MS library. For a convention preparation see ref.18.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]([N+:11]([O-])=O)[C:8]([O:14][CH3:15])=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[CH:16][C:17]#[N:18].C(N(CC)CC)C>C(OCC)(=O)C.[C].[Pd]>[NH2:11][C:9]1[C:8]([O:14][CH3:15])=[C:7]2[C:3]([CH2:4][CH2:5][C:6]2=[CH:16][C:17]#[N:18])=[CH:2][CH:10]=1
Reactant: COc1c([N+](=O)[O-])cc(Br)c2c1C(=CC#N)CC2
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COc1c(N)ccc2c1C(=CC#N)CC2
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 99.9 %

Procedure:
(4-Bromo-7-methoxy-6-nitro-2,3-dihydro-1H-inden-1-ylidene)acetonitrile (47.0 mg, 0.152 mmol) and triethylamine (22.3 μL, 0.160 mmol) were dissolved in ethyl acetate (1.5 mL), a 10% palladium-carbon powder (10 mg) was added, and the mixture was stirred at room temperature for 1.5 hr under a hydrogen atmosphere. The catalyst was filtered off using celite, and the filtrate was concentrated under reduced pressure to give the title compound (30.4 mg, yield 100%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17](CC3C=CC=CC=3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].CCOC(C)=O>CCO.[Pd]>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]2)=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(C)(C)OC(=O)Nc1ccc(N2CCNCC2)cc1
Reaction time: 72 h
Yield: 53.3 %

Procedure:
A solution of [4-(4-benzyl-piperazine-1-yl)-phenyl)-carbamic acid tert-butyl ester (43.5 g) in EtOH (1 L) containing Pd/C 10% (4 g) was hydrogenated at room temperature. After 72 hours, the catalyst was removed by filtration and the filtrate was evaporated under reduced pressure. The oily residue was then purified by flash chromatography eluting with AcOEt/isopropylamine (90/10) and the solid obtained was recristallized from AcOEt to give the title compound (17.5 g) as white crystals.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2N=C(C)S[C:6]=2[N:7]=1.[CH3:13][C:14]1[S:15]C2C(=O)NC(=O)NC=2[N:24]=1>>[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[S:15][C:14]([CH3:13])=[N:24][C:6]=2[N:7]=1
Reactant: Cc1nc2[nH]c(=O)[nH]c(=O)c2s1
Reactant: Cc1nc2c(Cl)nc(Cl)nc2s1
Product: Cc1nc2nc(Cl)nc(Cl)c2s1

Procedure:
Prepared using the method used in the preparation of 5,7-dichloro-2-methyl-thiazolo[5,4-d]pyrimidine using 2-methyl-4H-thiazolo[4,5-d]pyrimidine-5,7-dione in place of 2-methyl-4H-thiazolo[5,4d]pyrimidine-5,7-dione. The title compound was obtained as an solid solid (140 mg, 28%).
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[N:7]1[C:14]([Cl:15])=[N:13][C:11](Cl)=[N:10][C:8]=1[Cl:9].[CH2:16]([NH:19][CH2:20][CH:21]=[CH2:22])[CH:17]=[CH2:18].[OH-].[Na+]>O1CCOCC1>[Cl:15][C:14]1[N:7]=[C:8]([Cl:9])[N:10]=[C:11]([N:19]([CH2:20][CH:21]=[CH2:22])[CH2:16][CH:17]=[CH2:18])[N:13]=1
Reactant: C=CCNCC=C
Reactant: Clc1nc(Cl)nc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: C=CCN(CC=C)c1nc(Cl)nc(Cl)n1
Temperature: 60 °C
Reaction time: 3 h
Yield: 50 %

Procedure:
After 10.6 g (0.10 mol) of sodium carbonate and 20.0 g (0.10 mol) of cyanuric chloride were added and dissolved into 140 g of 1,4-dioxane, 9.9 g (0.10 mol) of diallylamine was gradually added thereinto and further, 4.2 g (0.10 mol) of caustic soda was added thereinto. By generating the heat of reaction, the temperature of reaction solution was raised to about 60° C. and the reaction was continued at the temperature for 3 hours. Thereafter, the reaction mixture was cooled and filtered to remove the sodium chloride generated as the byproduct. The obtained filtrate was distilled under reduced pressure to recover the solvent. Therefore, 18.3 g (0.05 mol) of 4,6-dichloro-2-diallylamino-1,3,5-triazine was obtained.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10]([C:19]([NH:21][NH2:22])=[O:20])=[C:9]1[CH:23]([CH3:25])[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:27](=N)(OCC)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CCO>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10]([C:19]2[O:20][C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:22][N:21]=2)=[C:9]1[CH:23]([CH3:25])[CH3:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=N)c1ccccc1
Reactant: COc1ccc2c(c1)c(C(=O)NN)c(C(C)C)n2Cc1ccccc1
Agent: Cl
Solvent: CCO
Product: COc1ccc2c(c1)c(-c1nnc(-c3ccccc3)o1)c(C(C)C)n2Cc1ccccc1
Temperature: 80 °C
Reaction time: 4 h

Procedure:
To a solution of 1-benzyl-2-isopropyl-5-methoxy-1H-indole-3-carbohydrazide (Compound 35, 25 mg, 0.074 mmol) in EtOH (2.0 ml) was added ethyl benzimidate hydrochloride (Fluka, 21 mg, 0.11 mmol). The mixture was stirred at 80° C. for 4 h and was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 0-30% EtOAc-hexanes to yield 2-(1-benzyl-2-isopropyl-5-methoxy-1H-indol-3-yl)-5-phenyl-1,3,4-oxadiazole (Compound 36) as a white solid.
Reaction SMILES: Cl.[NH2:2][C:3]1[N:12]=[C:11]([NH2:13])[C:10]2[C:5](=[N:6][CH:7]=[C:8]([CH2:14][N:15]([C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=3)[CH3:16])[N:9]=2)[N:4]=1.NC1N=C(N)C2C(=NC=C(CN(C3C=CC(C(O)=O)=CC=3)C)N=2)N=1.C(N(CC)C(C)C)(C)C.C(P(=O)(OCC)OCC)#N.[NH2:69][CH2:70][CH2:71][CH2:72][CH2:73][NH2:74].C([O-])(O)=O.[Na+]>CN(C=O)C>[NH2:69][CH2:70][CH2:71][CH2:72][CH2:73][NH:74][C:21](=[O:22])[C:20]1[CH:19]=[CH:18][C:17]([N:15]([CH2:14][C:8]2[N:9]=[C:10]3[C:5](=[N:6][CH:7]=2)[N:4]=[C:3]([NH2:2])[N:12]=[C:11]3[NH2:13])[CH3:16])=[CH:25][CH:24]=1
Reactant: NCCCCN
Reactant: CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)O)cc1
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Agent: O=C([O-])O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)NCCCCN)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a suspension of 4-[N-(2,4-diamino-6-pteridinylmethyl)-N-methylamino]benzoic acid hemihydrochloride (250 mg, 0.73 mmol) in dry DMF (20 ml) were added N,N-diisopropylethylamine (250 μl, 1.46 mmol, 2 equiv) and diethyl cyanophosphonate (225 μl, 1.46 mmol, 2 equiv). Dissolution occurred rapidly and the reaction was stirred for 4 hours at room temperature. 1,4-Diaminobutane (367 μl, 3.65 mmol, 5 equiv) and N,N-diisopropylethylamine (250 μl, 1.46 mmol, 2 equiv) were then added and the solution was stirred 45 minutes at room temperature. The completion of reaction was verified by HPLC, and solid NaHCO3 was added. The solvent was then evaporated under reduced pressure and the residue suspended in a small amount of methanol. Addition of dilute aqueous NH4OH was then followed by filtration and a rinse with water gave the product upon drying to yield 153 mg (53%): MS m/z (M+H) 396, HPLC Rt=3.80 min.