Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][N:20]=[CH:19]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[OH-].[Na+]>ClCCCl>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][N:20]=[CH:19]3)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: Nc1ccc2[nH]ncc2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: c1ccc(CN2CCC(Nc3ccc4[nH]ncc4c3)CC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.3 %

Procedure:
To a solution of 1-benzyl-4-piperidone (7.11 g, 37.6 mmol) in 1,2-dichloroethane (125 ml) were added 5-aminoindazole (5.00 g, 37.6 mmol), sodium triacetoxyborohydride (11.5 g, 52.6 mmol) and acetic acid (2.15 ml, 37.6 mmol) at room temperature, and stirred overnight at room temperature. Then, the reaction solution was poured into a 1N-aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: ethyl acetate/methanol=100/1) to obtain N-(1-benzyl-4-piperidinyl)-1H-indazol-5-amine (8.56 g, 74%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:12]2[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][CH3:20])[CH2:16][CH:17]=2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-])=O.CO>[Pd].C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH3:20])[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[NH2:9]
Reactant: CCCN1CC=C(c2ccc([N+](=O)[O-])c(OC)c2)CC1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCCN1CCC(c2ccc(N)c(OC)c2)CC1
Yield: 84.6 %

Procedure:
Palladium on carbon (10% by weight, 2.5 g) was added to a nitrogen-flushed Fischer-Porter vessel. At least a portion of the 4-(3-methoxy-4-nitrophenyl)-1-propyl-1,2,3,6-tetrahydropyridine from Step B was combined with additional 4-(3-methoxy-4-nitrophenyl)-1-propyl-1,2,3,6-tetrahydropyridine prepared by substantially the same method. Then, a solution of the 4-(3-methoxy-4-nitrophenyl)-1-propyl-1,2,3,6-tetrahydropyridine (9.20 g, 33.3 mmol) in Ethyl acetate (150 mL) followed by methanol (50 mL) were added to the vessel. The reaction was purged and then kept under a hydrogen pressure of 60 psi for 2 d. The pressure was released and the reaction was purged with nitrogen. The reaction was filtered through celite and concentrated to afford 2-methoxy-4-(1-propylpiperidin-4-yl)aniline as a white solid (7.0 g, 85% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.86 (t, J=7.5 Hz, 3 H), 1.44 (dt, J=7.4, 7.4 Hz, 2 H), 1.52-1.63 (m, 2 H), 1.63-1.70 (m, 2 H), 1.90 (td, J=11.6, 2.4 Hz, 2 H), 2.20-2.25 (m, 2 H), 2.30 (tt, J=11.9, 4.0 Hz, 1 H), 2.89-2.94 (m, 2 H), 3.74 (s, 3 H), 4.45 (s, 2 H), 6.53 (s, 2 H), 6.65 (s, 1 H). ESIMS (M+H)+=249.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][N:5]1[C@H:10]([C:11]([NH:13][C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:21])=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6]1.C(O)CO>O>[CH3:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:10]([C:11]([NH:13][C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:21])=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: CCCCN1CCCC[C@H]1C(=O)Nc1c(C)cccc1C
Solvent: O
Solvent: OCCO
Product: CCCCN1CCCCC1C(=O)Nc1c(C)cccc1C
Temperature: 138 °C

Procedure:
A mixture of (S)-bupivacaine (>99% ee, 1.5 g mmol), ethylene glycol (13.5 ml) and water (1.5 ml) was heated at 138° C. for 9 hours. On cooling to ambient temperature crystallisation of a solid occurred. The solid was filtered to give a quantitative yield of bupivacaine which was shown by chiral HPLC analysis to be a 52:48 mixture of (S)-bupivacaine and (R)-bupivacaine.
Reaction SMILES: [O-2].[Zn+2:2].[Mn]([O-])(=O)(=O)=O.[K+].[P:9](=[O:13])([OH:12])([OH:11])[OH:10]>[Zn].O>[P:9]([O-:13])([O-:12])([O-:11])=[O:10].[Zn+2:2].[P:9]([O-:13])([O-:12])([O-:11])=[O:10].[Zn+2:2].[Zn+2:2]
Reactant: O=P(O)(O)O
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Agent: [O-2]
Solvent: O
Product: O=P([O-])([O-])[O-]
Yield: 131.8 %

Procedure:
Zinc-containing wastes resulting from the production of sodium hydrosulphite in the amount of 1,019 g containing 960 g of zinc oxide and 10 g of metallic zinc are ground in a ball mill by the wet grinding method in the presence of 1,000 g of water, whereafter an additional 2,000 g of water are added thereto along with 143 g of potassium permanganate. Under continuous stirring, the slurry is heated to a temperature of 80° C. and 965 g of phosphoric acid as calculated for 100% H3PO4 are added thereto. The slurry is subjected to filtration after 35 minutes of the heating, the residue is washed and dried to give 2 kg of zinc phosphate (the yield is equal to 97%).
Reaction SMILES: [P:1](=[O:5])([OH:4])([OH:3])[OH:2].[O-2].[Ca+2:7]>O>[P:1]([O-:5])([O-:4])([O-:3])=[O:2].[Ca+2:7].[P:1]([O-:5])([O-:4])([O-:3])=[O:2].[Ca+2:7].[Ca+2:7]
Reactant: O=P(O)(O)O
Agent: [Ca+2]
Agent: [O-2]
Solvent: O
Product: O=P([O-])([O-])[O-]
Yield: 16 %

Procedure:
For example, according to pilot plant tests carried out by the Applicant, in order to produce 1 kg of a CMS-enriched calcium phosphate containing approximately 12% P and approximately 20% Ca, from phosphoric acid containing 57% P2O5, unslaked lime (90% CaO) containing 64,3% Ca and CMS, requires about 482 g (283 ml) H3PO4, about 311 g unslaked lime, about 405 g (311 ml) CMS and about 100 ml water. Similarly, to produce 1 kg of a CMS-enriched calcium phosphate containing approximately 16% P and approximately 18% Ca, requires about 645 g (379 ml) H3PO4, about 280 g unslaked lime, about 384 g (294 ml) CMS and about 100 ml water. Naturally, by varying the quantities of phosphoric acid, unslaked lime and CMS, a CMS-enriched calcium phosphate product having other relative proportions of P and Ca can be produced.
Reaction SMILES: [CH3:1][C:2]1[N:6]([C@H:7]2[CH2:13][C@H:12]3[N:14]([CH2:15][CH2:16][C@H:17]([NH:24][C:25]([CH:27]4[CH2:32][CH2:31][C:30]([F:34])([F:33])[CH2:29][CH2:28]4)=[O:26])[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C@H:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]([CH:35]([CH3:37])[CH3:36])=[N:4][N:3]=1.[P:38](=[O:42])([OH:41])([OH:40])[OH:39]>CC(C)=O>[CH3:1][C:2]1[N:6]([C@H:7]2[CH2:13][C@H:12]3[N:14]([CH2:15][CH2:16][C@H:17]([NH:24][C:25]([CH:27]4[CH2:28][CH2:29][C:30]([F:34])([F:33])[CH2:31][CH2:32]4)=[O:26])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C@H:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]([CH:35]([CH3:37])[CH3:36])=[N:4][N:3]=1.[P:38]([O-:42])([O-:41])([O-:40])=[O:39]
Reactant: O=P(O)(O)O
Agent: Cc1nnc(C(C)C)n1[C@@H]1C[C@H]2CC[C@@H](C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)c1ccccc1
Solvent: CC(C)=O
Product: O=P([O-])([O-])[O-]
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Maraviroc (50 gm) was dissolved in acetone (400 ml) and stirred for 30 minutes at room temperature to obtain a solution. To the solution was added phosphoric acid (11 gm) and stirred for 11 hours at room temperature. The solid obtained was collected by filtration and dried to obtain 55 gm of crystalline form 1 of maraviroc phosphate.
Reaction SMILES: [CH3:1][C:2]1[N:6]([C@H:7]2[CH2:13][C@H:12]3[N:14]([CH2:15][CH2:16][C@H:17]([NH:24][C:25]([CH:27]4[CH2:32][CH2:31][C:30]([F:34])([F:33])[CH2:29][CH2:28]4)=[O:26])[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C@H:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]([CH:35]([CH3:37])[CH3:36])=[N:4][N:3]=1.[P:38](=[O:42])([OH:41])([OH:40])[OH:39]>C(OCC)(=O)C>[CH3:1][C:2]1[N:6]([C@H:7]2[CH2:13][C@H:12]3[N:14]([CH2:15][CH2:16][C@H:17]([NH:24][C:25]([CH:27]4[CH2:28][CH2:29][C:30]([F:34])([F:33])[CH2:31][CH2:32]4)=[O:26])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C@H:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]([CH:35]([CH3:37])[CH3:36])=[N:4][N:3]=1.[P:38]([O-:42])([O-:41])([O-:40])=[O:39]
Reactant: O=P(O)(O)O
Agent: Cc1nnc(C(C)C)n1[C@@H]1C[C@H]2CC[C@@H](C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)c1ccccc1
Solvent: CCOC(C)=O
Product: O=P([O-])([O-])[O-]
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Maraviroc (10 gm) was dissolved in ethyl acetate (100 ml) and stirred for 30 minutes at room temperature. To the solution was added phosphoric acid (2 gm) and stirred for 11 hours at room temperature, filtered. The solid obtained was dried to obtain 11 gm of crystalline form 2 of maraviroc phosphate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH2:14][CH:13]([CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:18][CH2:17]3)[C:11](=[O:12])[C:6]2=[CH:7][C:8]=1[O:9][CH3:10].[P:29](=[O:33])([OH:32])([OH:31])[OH:30]>CC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH2:14][CH:13]([CH2:15][CH:16]3[CH2:17][CH2:18][N:19]([CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:20][CH2:21]3)[C:11](=[O:12])[C:6]2=[CH:7][C:8]=1[O:9][CH3:10].[P:29]([O-:33])([O-:32])([O-:31])=[O:30]
Reactant: O=P(O)(O)O
Agent: COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccccc3)CC1)C2
Solvent: CC(C)=O
Product: O=P([O-])([O-])[O-]
Temperature: 25 °C

Procedure:
Donepezil (3.79 g, dissolved in 70 ml of ethyl acetate) is slowly added to a solution of phosphoric acid (0.29 ml) in acetone (35 ml) with stirring at room temperature. The solid precipitated is filtered and dried at 55° C. under vacuum to give the title compound.
Reaction SMILES: [P:1](=[O:5])([OH:4])([OH:3])[OH:2].C=O.[NH2:8][C:9]([NH2:11])=[O:10]>>[CH2:9]=[O:10].[NH2:8][C:9]([NH2:11])=[O:10].[P:1]([O-:5])([O-:4])([O-:3])=[O:2]
Reactant: O=P(O)(O)O
Agent: C=O
Agent: NC(N)=O
Product: O=P([O-])([O-])[O-]

Procedure:
12 parts by weight of aqueous phosphoric acid (85%) is mixed with 60 parts by weight of aqueous formaldehyde (37%), then 16 parts by weight of urea powder is rapidly added and mixed thereby producing a urea-formaldehyde-phosphate white pre-polymer emulsion. After 10 days the pre-polymer was heated to 50-70 degree C. until the solution became clear, then the resin was poured into a mold and it solidified into a clear solid resin.
Reaction SMILES: [P:1](=[O:5])([OH:4])([OH:3])[OH:2].[OH-].[Mg+2:7].[OH-]>>[P:1]([O-:5])([O-:4])([O-:3])=[O:2].[Mg+2:7].[P:1]([O-:5])([O-:4])([O-:3])=[O:2].[Mg+2:7].[Mg+2:7]
Reactant: O=P(O)(O)O
Agent: [Mg+2]
Agent: [OH-]
Product: O=P([O-])([O-])[O-]

Procedure:
0.66 mol of 30% phosphoric acid was added dropwise to 1 mol of magnesium hydroxide (manufactured by Maruo Calcium Company Limited) at 15 ° C. over 600 seconds under stirring and, thereafter, this was stirred at 80 ° C. for 3 hours to obtain a white slurry. The white slurry was washed and dehydrated with a rotary filter to obtain magnesium phosphate. It was confirmed by X-ray diffraction that the resulting white cake is trimagnesium phosphate.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].[C:13]1([CH3:22])[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:12][C:3]1[CH:4]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:2]=1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH3:22]
Reactant: COC(=O)c1ccc(Br)c(C)c1
Reactant: Cc1ccccc1B(O)O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: COC(=O)c1ccc(-c2ccccc2C)c(C)c1
Temperature: 100 °C
Reaction time: 3.5 h
Yield: 108.2 %

Procedure:
A mixture of methyl 4-bromo-3-methylbenzoate (25.0 g, 110 mmol), o-tolylboronic acid (16.5 g, 120 mmol) and potassium carbonate (50 g, 360 mmol) in dioxane:water (300 mL:200 mL) was purged with nitrogen for 1 hour. [1,1′-bis(Diphenylphosphino)ferrocene]dichloropalladium [II] (4.5 g, 5.5 mmol) was added and the reaction mixture heated to 100° C. with vigorous stirring for 3.5 hours. The cooled reaction mixture was filtered through Celite and the cake washed with ethyl acetate (500 mL). The combined organic phases were washed with 1 M aqueous sodium hydroxide (500 mL) and brine (500 mL), dried over anhydrous potassium carbonate, filtered and concentrated in vacuo to afford a dark oil (28.6 g). Purification by flash chromatography using 2% ethyl acetate in hexanes as solvent provided the title compound (24.7 g) as a pale yellow oil.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[C:10]([CH3:16])=[N:9][CH2:8][CH2:7]2>CO.[Pd]>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH:10]([CH3:16])[NH:9][CH2:8][CH2:7]2
Reactant: COc1cc2c(cc1OC)C(C)=NCC2
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: COc1cc2c(cc1OC)C(C)NCC2
Reaction time: 18 h
Yield: 70 %

Procedure:
A solution of 3,4-dihydro-6,7-dimethoxy-1-methylisoquinoline hydrochloride (58.4 g, 0.24 m) in 1 liter of methanol and 5% Pd/C (5 g) were combined under nitrogen in a pressure bottle and the mixture hydrogenated at 40 psi and ambient temperature on a Parr apparatus for 18 hr. The catalyst was removed by filtration and the solvent evaporated. The residue was dissolved in H2O (1 liter), basified to pH 11 with 50% NaOH and extracted with CHCl3 (3×300 ml). The extracts were dried over MgSO4 and evaporated to dryness (aspirator, then high vacuum) to give 1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline, 35.2 g (70% yield).
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[K+].CO.ClCCl>O1CCCC1>[C:6]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1)#[CH:5]
Reactant: C[Si](C)(C)C#Cc1ccc(-c2ccccn2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: C#Cc1ccc(-c2ccccn2)cc1
Yield: 80 %

Procedure:
The strategy for a sample convergent synthesis of a highly branched first generation organometallic dendrimer of the invention is shown in FIGS. 1 and 2. Taking FIG. 1 as an example, 2-(4-iodophenyl)pyridine (1) was prepared in a 40% yield by reaction of the mono-lithiated 1,4-diiodobenzene with 2-fluoropyridine. Trimethylsilylacetylene was then coupled with (1) under Sonogashira conditions to afford 2-(4-trimethylsilylethynylphenyl)pyridine (2) in an 89% yield. The acetylene was easily deprotected with either tetra-n-butylammonium fluoride in tetrahydrofuran or by treatment with aqueous potassium hydroxide in a methanol/dichloromethane mixture. Both methods gave 2-(4-acetylenylphenyl)pyridine (3) in an isolated yield of 80%. The dendronised ligand (5) was then formed by reaction of 3 with 2,3,4,5-tetraphenylcyclopentadienone (4). The reaction was heated at 220° C. for two to three hours using diphenyl ether as the solvent after which (5) was isolated in a 93% yield. The complexation of (5) to form the fac-tris(2-phenylpyridyl)iridium (III) cored dendrimer utilised the standard two step procedure. In the first step 2.5 equivalents of (5) was reacted with iridium trichloride trihydrate in aqueous 2-ethoxyethanol heated at reflux to give a mixture of the bis-iridium bis-chloro dimer and unreacted ligand. This mixture was then reacted with an excess of (5) in the presence of silver trifluoromethylsulfonate in diglyme at 130° C. to give, after purification, the desired dendrimer (6) in a 63% yield for the two steps. Gel permeation chromatography (GPC) showed that the dendrimer was mono-disperse and the facial nature of the dendrimer was confirmed by 1H NMR by comparison with spectra reported for other dendrimers with fac-tris(2-phenylpyridyl)iridium (III) cores.
Reaction SMILES: [C:1]([O:20][CH2:21][C@@H:22]([OH:35])[CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][C:37](C)([O-])[CH3:38].[K+].C(Br)C=C>C1COCC1.CCCCCC>[C:1]([O:20][CH2:21][C@@H:22]([O:35][CH2:38][CH:37]=[CH2:36])[CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CC(C)(C)[O-]
Reactant: COc1ccc(COCC[C@H](O)COC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: C=CCBr
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C=CCO[C@@H](CCOCc1ccc(OC)cc1)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 98.8 %

Procedure:
To a solution of Compound 5 (10 grams, 21.4 mmoles) in dry THF (250 ml), a solution of 1M of potassium t-butoxide (Aldrich) (27.8 ml, 27.8 mmoles) in THF was added, under argon atmosphere. The mixture was stirred at room temperature for 5 minutes and, thereafter, allyl bromide (Aldrich) (7.4 ml, 85.5 mmoles) was added. The mixture was stirred for 18 hours at 55° C. The solvent was thereafter evaporated to dryness and the residue was extracted with ethyl acetate (250 ml) and washed with water and brine. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure. The resulting yellowish oily residue was purified by silica gel chromatography, using 1:2 (v:v) ethyl acetate:hexane as eluent, 10.75 grams (99% yield) of Compound 6 were obtained as an oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:11]([F:14])([F:13])[F:12])=[C:8]([OH:10])[CH:9]=1)([O-])=O>CO.[C].[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:11]([F:12])([F:13])[F:14])=[C:8]([OH:10])[CH:9]=1
Reactant: O=[N+]([O-])c1ccc(C(F)(F)F)c(O)c1
Agent: [Pd]
Solvent: CO
Product: Nc1ccc(C(F)(F)F)c(O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.9 %

Procedure:
To a solution of 5-nitro-2-(trifluoromethyl)phenol (2.22 g, 10.7 mmol) in methanol (30 mL) was added 10% palladium-carbon (440 mg), and the mixture was stirred at room temperature for 8 hr under a hydrogen atmosphere (1 atm). The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was crystallized from ethyl acetate/hexane to give the title compound (1.59 g, 84%) as a pale-brown solid.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH2:10](Cl)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[OH-].[Na+].C1C=CC=CC=1>O>[CH2:10]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: c1ccc2[nH]ccc2c1
Reactant: ClCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: O
Product: c1ccc(Cn2ccc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 70 %

Procedure:
Indole (1.17 g, 0.01 mol) was added to a mixture of benzyl chloride (1.90 g, 0.015 mol), 50% aqueous sodium hydroxide solution (5 ml), benzene (10 ml) and 0.5 mmol of compound 1. The mixture was stirred at 60°-70° C. for 5 hours, then cooled to room temperature and diluted with water (10 ml). The organic layer was separated, washed with diluted hydrochloric acid, water and dried over anhydrous magnesium sulphate. The solvent and excess of benzyl chloride were removed under vacuo and the residue was chromatographed on silica gel using n-hexane to give the N-benzylindole (70%), m.p.: 43°-45° C.
Reaction SMILES: C(N1[CH2:13][CH2:12][NH:11][CH2:10]C1)(OC(C)(C)C)=O.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:31]=[N:32][NH:33][CH:34]=3)=[CH:26][CH:25]=2)[CH:22]=O)=[CH:17][CH:16]=1>>[N:11]1([CH2:22][CH:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:31]=[N:32][NH:33][CH:34]=3)=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=2)[CH2:10][CH2:13][CH2:12]1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=CC(c1ccc(Cl)cc1)c1ccc(-c2cn[nH]c2)cc1
Product: Clc1ccc(C(CN2CCC2)c2ccc(-c3cn[nH]c3)cc2)cc1

Procedure:
By following the procedure described in Example 33B but replacing bis-(4-chloro-phenyl)-acetaldehyde and N—BOC-piperazine with (4-Chloro-phenyl)-[4-(1H-pyrazol-4-yl)-phenyl]-acetaldehyde and anticline, the title compound was obtained. LC/MS: (PS-B3) Rt 2.99 [M+H]+ 338.09. 1H NMR (Me-d3-OD) δ 3.57-3.60 (1H, m), 3.63-3.70 (2H, m), 3.71-3.77 (1H, m), 4.01 (2H, m), 4.14 (2H, m), 4.40 (1H, t), 7.40 (4H, br s), 7.49 (2H, d), 7.73 (2H, d), 8.69 (2H, br s).
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][C:5]=1[N:13]([CH3:15])[CH3:14].Br[CH2:17][CH2:18][CH2:19][Cl:20].C(N)=O>CN(C)C=O.O>[Cl:20][CH2:19][CH2:18][CH2:17][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][C:5]=1[N:13]([CH3:14])[CH3:15]
Reactant: CC(=O)c1ccc(O)c(N(C)C)c1
Reactant: ClCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: NC=O
Product: CC(=O)c1ccc(OCCCCl)c(N(C)C)c1
Temperature: 3 °C
Reaction time: 0.75 h
Yield: 179 %

Procedure:
To a suspension of sodium hydride (2.3 g, 48.5 mmol of 50% oil dispersion) with dimethylformamide (75 ml), and cooled to 3° C. in an ice-salt bath and under a stream of nitrogen was added, dropwise, 1-(4-hydroxy-3-dimethylaminophenyl)ethanone (8.7 g, 48.5 mmol) dissolved in dimethylformamide (150 ml) so that the temperature did not go over 7° C. After the addition was over, the bath was removed and the reaction was stirred at ambient temperature for 45 minutes. The ice bath was reapplied and a solution of 1-bromo-3-chloropropane (8.4 g, 53.4 mmol) in dimethy]formamide (25 ml) was added dropwise. After the addition was complete, the reaction was stirred for 18 hours at ambient temperature under nitrogen. The reaction was chilled to 7° C. in an ice bath and water (200 ml) was carefully added. After stirring for 5 minutes, the aqueous mixture was extracted with ethyl acetate (5×200 ml). The ethyl acetate extract was washed with water (2×50 ml), dried with MgSO4, and concentrated to yield 22.2 g of a black oily liquid. The compound was purified by prep HPLC, and combination of appropriate fractions gave 5.0 g of brown oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([OH:12])[CH:6]=[CH:5]2.[Si:13](Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(N(CC)CC)C>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH:8]=2)[CH:3]=1
Reactant: Oc1ccc2cc(Br)ccc2c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc2cc(Br)ccc2c1
Temperature: 0 °C
Yield: 84.1 %

Procedure:
To a solution of 6-bromo-2-naphthol (3.00 g, 13.5 mmol) in 67 ml of methylene chloride were added 4-dimethylaminopyridine (0.164 g, 1.34 mmol) and t-butyldimethylsilyl chloride (2.64 g, 17.5 mmol). The solution was cooled to 0° C. and triethylamine (2.60 ml, 18.7 mmol) was added. After 1.5 hours the reaction mixture was diluted with ethyl acetate and washed successively with saturated NH4Cl, H2O, and brine. Drying (MgSO4), evaporation, and purification by flash chromatography through 130 g of silica gel (1:4 CH2Cl2 /hexane) yielded 3.83 g (85%) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([OH:12])[CH:6]=[CH:5]2.[Si:13](Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH:6]=[CH:5]2
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Oc1ccc2cc(Br)ccc2c1
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)Oc1ccc2cc(Br)ccc2c1
Temperature: 0 °C
Yield: 94.8 %

Procedure:
A solution of 6-bromo-naphthalen-2-ol (18.0 g, 80.7 mmol), t-butyldimethylsilyl chloride (14.6 g, 96.8 mmol), triethyl amine (12.3 g, 121.0 mmol), and DMAP (0.75 g) in THF (400 mL) was stirred at room temperature overnight. The reaction was taken up in ethyl acetate and washed with 1N HCl (2×) and brine, dried over magnesium sulfate, and concentrated to give an oil. The product was crystallized from acetonitrile cooled to 0° C. to give (6-Bromo-naphthalen-2-yloxy)-tert-butyl-dimethyl-silane (25.8 g, 95%) as an off-white solid.