Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[CH2:2][CH:3]1[CH2:7][CH2:6][CH2:5][CH2:4]1.CCOCC.[Mg].[CH3:14][N:15]([CH3:28])[C:16]1(C#N)[CH2:25][CH2:24][C:19]2([O:23][CH2:22][CH2:21][O:20]2)[CH2:18][CH2:17]1>C1COCC1>[CH:3]1([CH2:2][C:16]2([N:15]([CH3:28])[CH3:14])[CH2:25][CH2:24][C:19]3([O:23][CH2:22][CH2:21][O:20]3)[CH2:18][CH2:17]2)[CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: ICC1CCCC1
Reactant: CN(C)C1(C#N)CCC2(CC1)OCCO2
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CN(C)C1(CC2CCCC2)CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 6 h

Procedure:
A solution of iodomethylcyclopentane (31.5 g, 150 mmol) in abs. ether (150 ml) was added dropwise to a mixture of magnesium (3.64 g, 150 mmol) in abs. ether (30 ml) in such a manner that the ether boiled slightly. Then the reaction solution was boiled under reflux for 30 min. and cooled to RT, and a solution of 8-dimethylamino-1,4-dioxa-spiro[4.5]decane-8-carbonitrile B-1 (10.5 g, 50 mmol) in abs. THF (100 ml) was added dropwise. The reaction solution began to boil and a white solid precipitated. Boiling was carried out for 6 h under reflux, followed by stirring overnight at RT. For working up of the reaction mixture, 20% NH4Cl solution (200 ml) was added, while cooling with ice, and extraction with ether (3×100 ml) was carried out. The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue that remained was purified by flash chromatography with EA/EtOH (20:1).
Reaction SMILES: [C:1]1([C+:7]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:10]=[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)O2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Na+].[Na+].II.[OH2:33].[OH2:34].O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>CC(C)=O.O>[C:13]1([C:11]2[CH:10]=[C:9]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[O:33][C:12]=2[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:34])[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: c1ccc(-c2cc(-c3ccccc3)o[c+](-c3ccccc3)c2)cc1
Reactant: O
Agent: II
Agent: O=C([O-])[O-]
Agent: O=S([O-])([O-])=S
Solvent: CC(C)=O
Product: O=C(c1ccccc1)c1oc(-c2ccccc2)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 39.5 %

Procedure:
To a mixture of benzaldehyde (2.6 ml, 25.58 mmol) and acetophenone (6 ml, 51.44 mmol) in anhydrous benzene (3 ml), was added boron trifluoride diethyl etherate (8 ml, 63.13 mmol) at RT. The mixture was heated at reflux for 2 h, cooled to RT, acetone was added (5 ml), and the resulting dark red solution was poured into ether (250 ml). A dark yellow precipitate formed, which was isolated and redissolved in acetone (30 ml), ether was added until the yellow solid was formed, isolated and dried to provide 2,4,6-triphenyl-pyranylium (3.87 g, 48%, mw=309). To a suspension of 2,4,6-triphenyl-pyranylium (3.86 g, 12.5 mmol) in acetone (50 ml), was added a solution of Na2CO3 (1.7 g, 16 mmol) in H2O (4.6 ml), and the mixture was stirred at RT for 2 h. To the reaction mixture, iodine (4.1 g, 16.1 mmol) was added, and the resulting mixture was stirred at RT overnight, then poured into a solution of sodium thiosulfate pentahydrate (40.0 g, 160 mmol) in water (250 ml), extracted with CH2Cl2. The organic phase was washed with brine, dried over anhydrous sodium sulfate, decanted, and the organic solution concentrated under reduced pressure. The residue was purified by silica gel chromatography (1% EtOAc in hexane) to provide (3,5-diphenylfuran-2-yl)-phenyl-methanone (intermediate XXVIa, 1.6 g, 19%) as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([C:13]([OH:15])=[O:14])=[C:11]([O:16][CH3:17])[C:10]([O:18][CH3:19])=[C:9]2[C:4]=1[CH:5]1[CH2:20][CH:8]2[CH:7]=[CH:6]1.O[N:22]1[C:26](=[O:27])[CH2:25][CH2:24][C:23]1=[O:28].Cl.CN(C)CCCN=C=NCC>ClCCl>[O:28]=[C:23]1[CH2:24][CH2:25][C:26](=[O:27])[N:22]1[O:14][C:13]([C:12]1[C:3]([O:2][CH3:1])=[C:4]2[C:9](=[C:10]([O:18][CH3:19])[C:11]=1[O:16][CH3:17])[CH:8]1[CH2:20][CH:5]2[CH:6]=[CH:7]1)=[O:15]
Reactant: O=C1CCC(=O)N1O
Reactant: COc1c(OC)c2c(c(OC)c1C(=O)O)C1C=CC2C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COc1c(OC)c2c(c(OC)c1C(=O)ON1C(=O)CCC1=O)C1C=CC2C1
Reaction time: 15 h
Yield: 68.3 %

Procedure:
To a solution of 15 (0.972 g, 3.52 mmol) in dichloromethane (80 mL) was added N-hydroxysuccinimide (0.547 g, 4.75 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.890 g, 4.64 mmol), and the resulting reaction mixture was stirred under dinitrogen for 15 h. The reaction mixture was diluted with dichloromethane (100 mL), washed twice with a 0.01 N HCl solution (50 mL), dried over sodium sulfate, and concentrated under reduced pressure. Purification was performed using silica gel chromatography (dichloromethane→2:1 ethyl acetate/hexanes) to yield 0.898 g (68%) of 3 as a colorless sticky solid. 1H NMR (300 MHz, CDCl3): δ=2.19-2.27 (m, 2H, CH—CH2—CH), 2.89 (bs, 4H, CH2—CH2), 3.86 (s, 3H, O—CH3), 3.92 (s, 3H, O—CH3), 3.95 (s, 3H, O—CH3), 4.19-4.23 (m, 2H, CH—CH(C)—CH2), 6.78-6.85 (m, 2H, HC═CH); 13C NMR (75 MHz, CDCl3): δ=25.9 (CH2—CH2), 47.7 (CH—CH(C)—CH2), 47.9 (CH—CH(C)—CH2), 61.7 (O—CH3), 62.3 (O—CH3), 62.6 (O—CH3), 68.6 (CH—CH2—CH), 137.7, 142.4 (CH═CH), 143.0 (CH═CH), 144.2, 147.9, 149.6, 149.9, 161.4, 169.1; TLC: Rf=0.42 (2:1 ethyl acetate/hexanes); ESI-MS calcd for C19H19NO7 [M+Na]+: 396.1059. found 396.1069.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]1[CH:15]=[C:14]([CH2:16][O:17][CH3:18])[CH:13](O)[CH2:12][N:11]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:27]([O:30][NH:31][S:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N+:41]([O-:43])=[O:42])(=[O:34])=[O:33])[CH:28]=[CH2:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O>C1(C)C=CC=CC=1>[CH2:27]([O:30][N:31]([CH:13]1[CH2:12][N:11]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2])[CH:15]=[C:14]1[CH2:16][O:17][CH3:18])[S:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N+:41]([O-:43])=[O:42])(=[O:34])=[O:33])[CH:28]=[CH2:29]
Reactant: C=CCONS(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: COCC1=C[C@@H](CO[Si](C)(C)C(C)(C)C)N(C(=O)OC(C)(C)C)CC1O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: C=CCON(C1CN(C(=O)OC(C)(C)C)[C@H](CO[Si](C)(C)C(C)(C)C)C=C1COC)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 87.6 %

Procedure:
To a stirred solution of Intermediate 118 (6.2 g, 16.00 mmol), N-(allyloxy)-2-nitrobenzenesulfonamide (4.34 g, 16.80 mmol) and triphenylphosphine (5.03 g, 19.20 mmol) in toluene (140 mL), was added (E)-diisopropyl diazene-1,2-dicarboxylate (3.67 g, 17.60 mmol) at rt. The reaction was stirred at rt over the weekend. The mixture was then concentrated and the residue was purified by silica gel column (120 g, 0-100% Hex/EA) to give the title compound (8.80 g, 88%) as an oil
Reaction SMILES: [CH3:1][N:2]([CH3:32])[CH2:3][C@H:4]([C:13]([NH:15][C@H:16]([C:24]([NH:26][CH2:27][CH2:28][CH:29]([CH3:31])[CH3:30])=[O:25])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:14])[NH:5]C(OC(C)(C)C)=O.[ClH:33]>C(O)(=O)C.C(O)C>[ClH:33].[ClH:33].[CH3:32][N:2]([CH3:1])[CH2:3][C@H:4]([C:13]([NH:15][C@H:16]([C:24]([NH:26][CH2:27][CH2:28][CH:29]([CH3:30])[CH3:31])=[O:25])[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:14])[NH2:5]
Reactant: CC(C)CCNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](CN(C)C)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CC(=O)O
Solvent: CCO
Product: CC(C)CCNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](N)CN(C)C

Procedure:
A solution of [3-dimethylamino-N2 -(t-butoxycarbonyl)-D-alanyl]-N-(3-methylbutyl)-L-phenylalaninamide (1.84 g.) in acetic acid saturated with hydrogen chloride (50 ml.) was stirred for one and one half hours at room temperature, then stripped of volatiles under vacuum. A solution of the residue (1.87 g.) in ethyl acetate was washed with saturated aqueous sodium bicarbonate, then saturated aqueous sodium chloride, and filtered. Hydrogen chloride (8.2 millimoles) in ethanol was added and the solution was stripped of volatiles, affording (3-dimethylamino-D-alanyl)-N-(3-methylbutyl)-L-phenylalaninamide dihydrochloride as a gum.
Reaction SMILES: [C:1]([NH:8][CH2:9][CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[N+:14]([C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19]Br)([O-:16])=[O:15].C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[N+:14]([C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][O:11][CH2:10][CH2:9][NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])([O-:16])=[O:15]
Reactant: O=[N+]([O-])c1ccccc1CBr
Reactant: CC(C)(C)OC(=O)NCCO
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCOCc1ccccc1[N+](=O)[O-]
Reaction time: 1 h
Yield: 22.5 %

Procedure:
To a solution of N-Boc-ethanolamine (477 mg) in tetrahydrofuran (10 mL), sodium hydride (118 mg, 60 wt %) was added under ice cooling, and the mixture was stirred at the same temperature for 1 hour under a nitrogen atmosphere. To the reaction mixture, 2-nitrobenzyl bromide (500 mg) was added under ice cooling, and the mixture was stirred at the same temperature for 1 hour, and then further stirred at room temperature for 4 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 80 to 70% hexane in ethyl acetate) to obtain oily tert-butyl (2-((2-nitrobenzyl)oxy)ethyl)carbamate (C11, 154 mg).
Reaction SMILES: [CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].[NH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][N:16]1[C:24]2[C:23]([CH3:25])=[C:22]([CH3:26])[N:21]=[C:20]([NH2:27])[C:19]=2[N:18]=[C:17]1[CH3:28].C(N(CC)CC)C>C(Cl)(Cl)Cl>[NH2:27][C:20]1[C:19]2[N:18]=[C:17]([CH3:28])[N:16]([CH2:15][CH2:14][O:13][CH2:12][CH2:11][NH:10][S:2]([CH3:1])(=[O:5])=[O:3])[C:24]=2[C:23]([CH3:25])=[C:22]([CH3:26])[N:21]=1
Reactant: CS(=O)(=O)OS(C)(=O)=O
Reactant: Cc1nc(N)c2nc(C)n(CCOCCN)c2c1C
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: Cc1nc(N)c2nc(C)n(CCOCCNS(C)(=O)=O)c2c1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 28 %

Procedure:
Under a nitrogen atmosphere, methane sulfonic anhydride (550 mg) was added to a solution of 1-[2-(2-aminoethoxy)ethyl]-2,6,7-trimethyl-1H-imidazo[4,5-c]pyridin-4-amine (757 mg, 2.875 mmol), triethylamine (520 μL) and chloroform (11 mL). The reaction mixture was allowed to stir at ambient temperature for about 3 hours. The reaction mixture was diluted with chloroform (20 mL) and washed with saturated sodium bicarbonate solution (10 mL). The organic layer was dried over magnesium sulfate and then concentrated under reduced pressure to provide crude product as a light yellow oil. The oil was purified by column chromatography (10 g of silica gel eluting with 2% methanol in chloroform containing 0.5 % triethylamine). The fractions containing product were combined and concentrated under reduced pressure. The residue was purified using Method A described above to provide 0.2753 g of N-{2-[2-(4-amino-2,6,7-trimethyl-1H-imidazo[4,5-c]pyridin-1-yl)ethoxy]ethyl}methanesulfonamide.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]([OH:13])=[O:12])[CH:5]=[C:6]([CH3:9])[C:7]=1[OH:8].S(=O)(=O)(O)O.[CH3:19]O>>[CH3:19][O:12][C:11](=[O:13])[CH2:10][C:4]1[CH:5]=[C:6]([CH3:9])[C:7]([OH:8])=[C:2]([CH3:1])[CH:3]=1
Reactant: CO
Reactant: Cc1cc(CC(=O)O)cc(C)c1O
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1cc(C)c(O)c(C)c1
Temperature: 70 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
A solution of (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid (5a) (12.4 g, 0.069 mmol) in methanol (300 mL) was treated with concentrated sulfuric acid (6.25 mL). The resulting solution was heated to 70° C. overnight. At this time, the reaction was cooled to room temperature. The reaction was concentrated under vacuum. The residue was diluted with ethyl acetate (700 mL) and was washed with water (2×250 mL). The organics were dried over magnesium sulfate, filtered and concentrated under vacuum to give an orange solid. The solid was slurried in 10% ethyl acetate/petroleum ether and was stirred for 1 h. The solid was collected by filtration, washed with 10% ethyl acetate/petroleum ether, and dried under vacuum overnight. The residue was purified by column chromatography using silica gel eluted with 10-15% ethyl acetate in petroleum ether to afford (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester (6a) (1.93 g, 86%) as an off-white solid; EI(+)-HRMS m/z calcd for C11H14O3 (M+) 194.0943, found 191.0942. Molecular Weight=194.2324; Exact Mass=194.0943
Reaction SMILES: [CH:1]1([N:6]2[C:10]([NH2:11])=[C:9]([C:12]([NH2:14])=[O:13])[C:8]([CH2:15][CH3:16])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:17]([O:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH:22]=O)[CH3:18].C([O-])([O-])=O.[K+].[K+].C(Cl)(Cl)Cl>CS(O)(=O)=O.C(Cl)Cl>[CH:1]1([N:6]2[C:10]3=[N:11][C:22]([C:21]4[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=4[O:19][CH2:17][CH3:18])=[N:14][C:12](=[O:13])[C:9]3=[C:8]([CH2:15][CH3:16])[NH:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CCc1nn(C2CCCC2)c(N)c1C(N)=O
Reactant: CCOc1ccccc1C=O
Agent: CS(=O)(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CCOc1ccccc1-c1nc2n(C3CCCC3)[nH]c(CC)c-2c(=O)n1
Yield: 44.5 %

Procedure:
A mixture of 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (2.0 g, 9 mmol), o-ethoxybenzaldehyde (2.7 g, 18 mmol), methanesulfonic acid (5 drops), and xylenes (50 ml) was refluxed for 48 hours. The reaction mixture was stripped to dryness, and treated with 10% K2CO3 and CHCl3 (100 ml). The layers were separated and the aqueous layer was extracted with chloroform (2×100 ml). The organic layers were combined, and concentrated in vacuo. The dark oil thus obtained was dissolved in CH2Cl2 (30 ml) and combined with silica gel (30 g). The preloaded silica gel was placed on a silica gel column and eluted with Et2O/hexanes (20/80) to Et2O (100%) to afford 1.41 g (45%) of 1-cyclopentyl-3-ethyl-6-(2-ethoxyphenyl)-pyrazolo[3,4-d]pyrimidin-4-one, m.p. 146°-147° C.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:15]([P:23](Cl)(Cl)=[O:24])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>C(Cl)Cl>[CH2:15]([P:23]1(=[O:24])[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH2:1][N:8]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: c1ccc(CNc2ccccc2)cc1
Reactant: CCCCCCCCP(=O)(Cl)Cl
Solvent: ClCCl
Product: CCCCCCCCP1(=O)c2ccccc2CN1c1ccccc1
Yield: 5 %

Procedure:
The procedure of Example 1 was employed utilizing N-benzylaniline and octyl phosphonic dichloride. The reaction of the dilithio compound and the octyl phosphonic dichloride was conducted at -65° C. The crude product produced as a result of the chromatographic separation was dissolved in methylene chloride and separated on a Woelm's neutral alumina column using ethyl acetate as the eluant to yield 1-octyl-2-phenyl-2,3-dihydro-1H-2,1-benzazaphosphole-1-oxide (1.1 g, 5% yield) as a pale yellow oil (nD =1.5502).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:8][NH:9][NH2:10]>>[CH3:8][N:9]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[NH2:10]
Reactant: Brc1ccccn1
Reactant: CNN
Product: CN(N)c1ccccn1
Reaction time: 16 h
Yield: 74.4 %

Procedure:
2-Bromopyridine (5 mL, 52.4 mmol) and methylhydrazine (20 mL, 360 mmol) were mixed together in a flask fitted with a water-condenser. After a few minutes a vigorous exothermic reaction occurred with refluxing of the methylhydrazine. When the reaction had subsided, the mixture was left for 16 hours, and the excess methylhydrazine was removed under reduced pressure. The cooled residue was stirred with aqueous sodium hydroxide solution (30 ml of 20%), and the resulting solution was extracted with ether (3×100 ml). The combined extracts were dried (K2CO3) and purified by silica gel chromatography 0-3% EtOH/CH2Cl2 to give 4.8 g of N-Methyl-N-pyridin-2-yl-hydrazine.
Reaction SMILES: [C:1]([C:4]1[N:5]=[C:6]2[N:11]=[C:10]([CH3:12])[C:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:8]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])[N:7]2[CH:28]=1)(=O)[NH2:2].C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.CCN(CC)CC>C(Cl)Cl>[C:1]([C:4]1[N:5]=[C:6]2[N:11]=[C:10]([CH3:12])[C:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:8]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])[N:7]2[CH:28]=1)#[N:2]
Reactant: Cc1nc2nc(C(N)=O)cn2c(-c2ccc(Cl)cc2Cl)c1C(=O)OC(C)(C)C
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc2nc(C#N)cn2c(-c2ccc(Cl)cc2Cl)c1C(=O)OC(C)(C)C
Reaction time: 2 h
Yield: 103.3 %

Procedure:
To a stirred solution of tert-butyl 2-carbamoyl-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylate (Example 156, Step 1, 50 mg, 0.12 mmol) in CH2Cl2 (3 mL) was added TFAA (50 mg, 0.24 mmol) and Et3N (33 μL, 0.24 mmol). After 2 h, the reaction was extracted with H2O and brine prior to drying over anhydrous MgSO4. Filtration, concentration under reduced pressure afforded tert-butyl 2-cyano-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylate (50 mg, 95% pure) as a yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[C:21]3[C:16](=[C:17]([CH2:22][S:23][CH3:24])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:9][CH2:10][C:11]#[N:12])=[C:4]([CH3:25])[CH:3]=1.ClCCl.ClC1C=CC=C(C(OO)=[O:37])C=1>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[C:21]3[C:16](=[C:17]([CH2:22][S:23]([CH3:24])=[O:37])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:9][CH2:10][C:11]#[N:12])=[C:4]([CH3:25])[CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCc1cccc2c(C(CCC#N)c3ccc(F)cc3C)c[nH]c12
Solvent: CO
Solvent: ClCCl
Product: Cc1cc(F)ccc1C(CCC#N)c1c[nH]c2c(CS(C)=O)cccc12
Temperature: 25 °C
Reaction time: 4 h

Procedure:
50 mg (0.14 mmol) of the compound from Example 46 were introduced into 10 ml of dichloromethane at RT, 35.0 mg (0.14 mmol) of 70% pure meta-chloroperbenzoic acid were added, and the mixture was stirred at RT for 4 h. 2 ml of methanol were added, and the residue after concentration was taken up in dichloromethane and saturated aqueous sodium bicarbonate solution, the phases were separated, the organic phase was washed twice with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, and the organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 24.6 mg (47% of theory) of the title compound as mixture of diastereomers.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([CH3:14])[CH2:10][SiH:11]([Cl:13])[Cl:12])[CH3:2].[CH2:15]=[CH:16][CH2:17][CH2:18][CH:19]=[CH2:20]>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([CH3:14])[CH2:10][Si:11]([CH:15]([Si:11]([Cl:12])([Cl:13])[CH2:10][CH:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:1][CH3:2])[CH3:14])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])([Cl:13])[Cl:12])[CH3:2]
Reactant: C=CCCC=C
Reactant: CCc1ccccc1C(C)C[SiH](Cl)Cl
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: CCCCCC([Si](Cl)(Cl)CC(C)c1ccccc1CC)[Si](Cl)(Cl)CC(C)c1ccccc1CC
Yield: 69.9 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1, 37.5 g (0.153 mole) of 3-(ethylphenyl)-1,1-dichloro-1-silabutane and 100 μl of 1% chloroplatinic acid solution in isopropanol were placed and then 5 g (0.061 mole) of 1,5-hexadiene was added dropwise for 5 min. The solution was reacted for 14 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 24.6 g (190°-192° C./0.03 mmHg) of bis[{2-(ethylphenyl)propyl}dichlorosilyl]hexane in 69.8% yield.
Reaction SMILES: C(OC(=O)[N:7]([CH2:20][CH2:21][CH2:22][CH2:23][N:24]([CH2:32][CH2:33][CH2:34][CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH:53]=[CH:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])=[C:40]([O:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH:72]=[CH:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH3:81])[CH:39]=1)C(OC(C)(C)C)=O)[CH2:8][CH2:9][CH2:10][CH2:11][NH:12]C(OC(C)(C)C)=O)(C)(C)C.[ClH:83]>C(OCC)(=O)C>[ClH:83].[ClH:83].[ClH:83].[ClH:83].[NH2:12][CH2:11][CH2:10][CH2:9][CH2:8][NH:7][CH2:20][CH2:21][CH2:22][CH2:23][NH:24][CH2:32][CH2:33][CH2:34][CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH:53]=[CH:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])=[C:40]([O:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH:72]=[CH:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH3:81])[CH:39]=1
Reactant: CCCCCCCCC=CCCCCCCCCOc1ccc(CNCCCCN(CCCCN(CCCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)cc1OCCCCCCCCC=CCCCCCCCC
Agent: Cl
Solvent: CCOC(C)=O
Product: CCCCCCCCC=CCCCCCCCCOc1ccc(CNCCCCNCCCCNCCCCN)cc1OCCCCCCCCC=CCCCCCCCC
Temperature: 0 °C
Reaction time: 1 h
Yield: 98 %

Procedure:
A concentrated solution of the amine 19 (0.253 g, 0.22 mmol) in ethyl acetate was added cooled to 0° C. A total of 5 mL of a freshly prepared saturated solution of HCl in ethyl acetate was added dropwise and the solution stirred for 1 h at room temperature during which time a white precipitate formed. The ethyl acetate was removed in vacuo and the residue co-evaporated with ethyl acetate and chloroform to give the product 26 as a white powder (0.215 g, 98%); 1H NMR (CD3OD) δ 7.13 (s, 1H, aryl), 7.04 (d, 1H, aryl), 6.98 (d, 1H, aryl), 5.33 (t, 4H, olefinic), 4.12 (m, 2H, benzylic), 4.03 (t, 2H, OCH2), 3.99 (t, 2H, OCH2), 3.08 (m, 10H, 5×CH2), 2.98 (t, 2H, CH2), 2.02 (m, 8H, CH2C═C), 1.89 (m, 16H, 8×CH2), 1.47 (m, 4H, 2×CH2), 1.42-1.19 (m, 40H, 20×CH2), 0.89 (t, 6H, CH3); 13C NMR (300 MHz, D2O) δ 149.74, 148.90, 129.62, 129.46, 123.92, 123.71, 69.36, 68.88, 51.12, 46.68, 38.99, 32.14, 29.97, 29.81, 29.60, 27.36, 26.53, 24.69, 24.22, 23.14, 23.06, 22.84, 14.05; HRMS (FAB): theory for C55H105N4O2 (M+1), 853.8238; found (M+1), 853.8264; Anal. (C55H109Cl4N4O2.0.6H2O): C, H, N.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].Cl[C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([O:22][CH2:23][C:24]2[CH:28]=[CH:27][S:26][CH:25]=2)[N:16]=1>CN(C)C=O.[Cu]I>[CH3:21][C:19]1[CH:20]=[C:15]([O:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=2)[N:16]=[C:17]([O:22][CH2:23][C:24]2[CH:28]=[CH:27][S:26][CH:25]=2)[CH:18]=1
Reactant: Oc1cccc(C(F)(F)F)c1
Reactant: Cc1cc(Cl)nc(OCc2ccsc2)c1
Agent: [Cu]I
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(OCc2ccsc2)nc(Oc2cccc(C(F)(F)F)c2)c1

Procedure:
To a solution containing meta-trifluoromethylphenol (1.70 g, 0.0021×5.0 mol) and sodium hydride (0.42 g, (ca.60% in mineral oil), 0.0021×5.0 mol) in dimethylformamide, 2-chloro-4-methyl-6-(3-thienylmethyloxy)pyridine (0.5 g, 0.0021 mol) and CuI (0.20 g, 0.0021×0.5 mol) were successively added and the resultant solution was refluxed for about 5 hours.