Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=2[N+:16]([O-])=O)=[CH:4][CH:3]=1.[Cl-].[NH4+]>CCO.C1COCC1.[Fe]>[NH2:16][C:10]1[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:9]=1[S:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1
Reactant: O=[N+]([O-])c1cc(O)ccc1Sc1ccc(O)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1cc(O)ccc1Sc1ccc(O)cc1
Yield: 98.4 %

Procedure:
The product from Example 48A (1.34 g, 5.09 mmol) was reacted with iron (1.42 g, 25.48 mmol) and ammonium chloride (409 mg, 1.5 mmol) in 20 mL EtOH/20 ml, THF/6 mL water following the procedure from Example 10E to provide the title compound (1.168 g, 97%).
Reaction SMILES: [OH:1][CH:2]([C:15]1[CH:19]=[CH:18][O:17][C:16]=1[Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:27]1([N:33]=[C:34]=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C)C=O.[Cu]>[C:27]1([NH:33][C:34]([O:1][CH:2]([C:15]2[CH:19]=[CH:18][O:17][C:16]=2[Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CCCCCCCCCCCCC(O)c1ccoc1[Si](CC)(CC)CC
Reactant: O=C=Nc1ccccc1
Agent: [Cu]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCC(OC(=O)Nc1ccccc1)c1ccoc1[Si](CC)(CC)CC

Procedure:
3-(1-Hydroxytridecyl)-2-triethylsilylfuran (Compound 20) is reacted with phenyl isocyanate and copper (2) chloride in dimethylformamide to give 3-(1-phenylcarbamoyloxytridecyl)-2-triethylsilylfuran (Compound 21). Oxidizing the intermediate with singlet oxygen, under similar conditions as in Example 1, and thereafter reduction with sodium borohydride gives 3-(1-phenylcarbamoyloxytridecyl)-2(5H)-furanone (Compound 8).
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[NH2:14].[C:15](=O)([O:18]C)[O:16][CH3:17].O>O1CCCC1.C(OCC)(=O)C>[CH3:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:18])[O:16][CH3:17]
Reactant: COC(=O)OC
Reactant: Cc1ccncc1N
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)Nc1cnccc1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 73.6 %

Procedure:
At about 0° C., potassium tert-butoxide (47 g, 420 mmol, 3.00 equiv.) was added in several batches to a solution of 4-methylpyridin-3-amine (15 g, 139 mmol, 1.00 equiv.) in tetrahydrofuran (400 mL). After stifling the solution for about 30 minutes, dimethyl carbonate (18.8 g, 209 mmol, 1.50 equiv.) was then added. The solution was stirred at ambient temperature for about 16 hours and then water (100 mL) was added. Following standard extractive workup with ethyl acetate (3×200 mL), the crude product was purified by re-crystallization from ethyl acetate/petroleum ether (1:1) to give the title product as a pale yellow solid (17 g; yield=74%). LC-MS: m/z=167 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:21]=[CH:20][C:19]([C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:18][C:3]=1[CH2:4][NH:5][CH2:6][CH2:7][C:8]([N:10]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH3:11])=[O:9].[N:30]#[C:31]Br>CO>[NH2:30][C:31]1[N:5]([CH2:6][CH2:7][C:8]([N:10]([CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[CH3:11])=[O:9])[CH2:4][C:3]2[C:2](=[CH:21][CH:20]=[C:19]([C:22](=[O:29])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:18]=2)[N:1]=1
Reactant: N#CBr
Reactant: CN(C(=O)CCNCc1cc(C(=O)c2ccccc2)ccc1N)C1CCCCC1
Solvent: CO
Product: CN(C(=O)CCN1Cc2cc(C(=O)c3ccccc3)ccc2N=C1N)C1CCCCC1
Temperature: 25 °C

Procedure:
To a solution of 3-(2-amino-5-benzoyl-benzylamino)-N-cyclohexyl-N-methyl-propionamide (3.94 g, 0.0100 mol) in methanol (200 mL) was added cyanogen bromide (1.16 g, 0.0110 mol). The resulting mixture was stirred at room temperature over the weekend and then was heated at reflux for 5 h. The solvent was evaporated to yield a residue that was crystallized from EtOAc (100 mL). The resulting precipitate was filtered and dried to yield crude product that was recrystallized from 2-propanol (50 mL) to yield the title compound, 3-(2-amino-6-benzoyl-4H-quinazolin-3-yl)-N-cyclohexyl-N-methyl-propionamide.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[C:23]([C@H:28]([CH3:32])[C:29]([OH:31])=[O:30])[CH:22]=[CH:21]2.[N+:33]([C:36]([CH3:41])([CH2:39]O)[CH2:37][OH:38])([O-:35])=[O:34]>C(Cl)Cl.C1COCC1>[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[C:23]([C@H:28]([CH3:32])[C:29]([O:31][CH2:39][C:36]([CH3:41])([N+:33]([O-:35])=[O:34])[CH2:37][OH:38])=[O:30])[CH:22]=[CH:21]2
Reactant: CC(CO)(CO)[N+](=O)[O-]
Reactant: COc1ccc2cc([C@H](C)C(=O)O)ccc2c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Solvent: C1CCOC1
Product: COc1ccc2cc([C@H](C)C(=O)OCC(C)(CO)[N+](=O)[O-])ccc2c1

Procedure:
A solution of 1,3-dicyclohexylcarbodiimide (4.23 g, 20.5 mmol), (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.34 g, 18.9 mmol), and 2-nitro-2-methyl-1,3-propanediol (2.56 g, 19.0 mmol) in CH2Cl2 (50 mL) and THF (50 mL) was stirred at ambient temperature overnight. The solvent was evaporated and EtOAc (100 mL) was added to the resulting crude material, cooled in a dry-ice bath and the byproduct, dicyclohexyl urea was removed by filtration. The product was separated by silica gel column chromatography eluting with ethyl acetate/hexane (1:3, Rf=0.1) to give the title compound (a mixture of diasteromers) as an oil (2.77 g, 42% yield). 1H NMR (300 MHz, CDCl3) δ 7.69-7.60 (m, 3H), 7.34-7.3 (m, 1H), 7.14-7.08 (m, 2H), 4.44 (d, J=4.2 Hz, 2H), 3.86 (s, 3H), 3.85 (q, J=7.2 Hz, 1H), 3.7 (m, 1H), 1.55 (d, J=7.2 Hz, 3H), 1.36 & 1.40 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 174.14, 174.02, 157.57, 134.53, 134.51, 133.64, 129.13, 128.7, 127.17, 125.87, 125.84, 119.0, 105.47, 89.53, 89.42, 64.67, 64.52, 64.19, 55.12, 45.04, 18.25, 18.03, 17.82, 17.79. Mass spectrum (API-TIS) m/z 348 (MH)+.
Reaction SMILES: Cl[C:2]1[N:11]=[C:10]([NH2:12])[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[O:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)=[O:23].COCCO>C(N(CC)CC)C>[NH2:12][C:10]1[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=[C:2]([N:27]2[CH2:28][CH2:29][N:24]([C:22]([CH:18]3[CH2:19][CH2:20][CH2:21][O:17]3)=[O:23])[CH2:25][CH2:26]2)[N:11]=1
Reactant: COc1cc2nc(Cl)nc(N)c2cc1OC
Reactant: O=C(C1CCCO1)N1CCNCC1
Solvent: COCCO
Solvent: CCN(CC)CC
Product: COc1cc2nc(N3CCN(C(=O)C4CCCO4)CC3)nc(N)c2cc1OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 86.6 %

Procedure:
Sixty grams (0.25 M) of 2-chloro-4-amino-6,7-dimethoxyquinazoline and 56.8 grams (0.308 M) of N-(2-tetrahydrofuroyl)piperazine were added to a stirred solution of 500 grams of Methyl Cellosolve® (ethylene glycol monomethyl ether) and 37.9 grams of triethylamine. The reaction mixture was heated to and maintained at a temperature of between 115° to 120° C. for 8 hours, and then allowed to cool to room temperature overnight. The Methyl Cellosolve® ether was removed by vacuum distillation, the residue was taken up in 1920 ml of 45° C. filtered water, and the temperature of the solution was readjusted to 45° C. The pH was then adjusted to pH 2.5 with concentrated hydrochloric acid and the solution was mixed for 1 hour. The solution was then filtered and the pH adjusted to pH 8.3 with filtered ammonia water (28%). After heating for 1 hour at 65° C., the solution was cooled to 15° C. and held at a temperature of between 15°-20° C. for 16 hours. The resulting crystalline product was filtered, washed with cold water (15° C.) and dried in vacuo at 65° C. to yield 84 grams of anhydrous base.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].C(=O)([O-])[O-].[K+].[K+].[CH2:16](Br)[CH:17]=[CH2:18].O>CN(C)C=O>[CH2:18]([O:9][C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[F:1])[CH:17]=[CH2:16]
Reactant: Oc1cc(F)ccc1F
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOc1cc(F)ccc1F
Temperature: 80 °C
Reaction time: 1 h

Procedure:
10 g of 2,5-difluorophenol was dissolved in 120 ml of dimethylformamide, and 21 g of potassium carbonate and 8.57 ml of allyl bromide were added to the resulting solution in this order at room temperature. The resulting mixture was stirred at 80° C. for one hour, followed by the addition of water. The resulting mixture was extracted with ethyl acetate, and the organic layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The resulting residue was subjected to silica gel chromatography (developer: 5% ethyl acetate/n-hexane) to give 13 g of the title compound as a colorless oil.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][CH3:13])(=[O:11])=[O:10])=[CH:5][CH:4]=1>ClCCl.[O-2].[O-2].[Mn+4]>[CH:2]([C:3]1[CH:4]=[CH:5][C:6]([S:9]([NH:12][CH3:13])(=[O:11])=[O:10])=[CH:7][CH:8]=1)=[O:1]
Reactant: CNS(=O)(=O)c1ccc(CO)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: CNS(=O)(=O)c1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 39.7 %

Procedure:
Add 4-hydroxymethyl-N-methyl-benzenesulfonamide (0.28 g) to a mixture of manganese dioxide (2.8 g) in 20 mL of dichloromethane. Stir at room temperature overnight and filter over Celite®. Concentrate under reduced pressure to provide (0.11 g, 40%) of the title compound as oil.
Reaction SMILES: [CH2:1]([NH:4][C:5](=[O:7])[CH3:6])[C:2]#[CH:3].C(N)C#C.C(Cl)(=O)C.[F:16][C:17]1[C:18](I)=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21](=[O:26])/[C:20]/2=[CH:27]\[C:28]1[NH:32][CH:31]=[N:30][C:29]=1[CH3:33]>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.CN(C=O)C.CCN(CC)CC>[F:16][C:17]1[C:18]([C:3]#[C:2][CH2:1][NH:4][C:5](=[O:7])[CH3:6])=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21](=[O:26])[C:20]2=[CH:27][C:28]1[NH:32][CH:31]=[N:30][C:29]=1[CH3:33]
Reactant: C#CCNC(C)=O
Reactant: Cc1nc[nH]c1/C=C1\C(=O)Nc2ccc(F)c(I)c21
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C#CCN
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(=O)NCC#Cc1c(F)ccc2c1C(=Cc1[nH]cnc1C)C(=O)N2

Procedure:
Using Method C above, N-propargylacetamide (32.8 mg, 0.34 mmol) (prepared by the reaction of propargylamine (Aldrich) with acetyl chloride and triethylamine in dichloromethane at 0° C. for 3 h) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one (Starting Material 3 supra) (50 mg, 0.135 mmol) using (Ph3P)4Pd (16 mg) and CuI (3 mg) as catalyst in DMF (3 mL) and Et3N (3 mL) as solvent at 80° C. for 5 h to give N-[3-[2,3-dihydro-5-fluoro-3-[(5-methyl-3H-imidazol-4-yl)methylene]-2-oxo-1H-indol-4-yl]-prop-2-ynyl]-acetamide. (Yield 35 mg, 77%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2>CO.[Pt](=O)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH2:8][CH2:7][CH2:6]2
Reactant: COc1ccc2ncccc2c1
Agent: O=[Pt]=O
Solvent: CO
Product: COc1ccc2c(c1)CCCN2
Yield: 66 %

Procedure:
A solution of 218.5 g. of 6-methoxyquinoline in 1750 ml of methanol was hydrogenated at 60 psi over 30 g. of platinum dioxide at 50° overnight. The reaction was filtered and the filtrate concentrated to give an oil. The oil was distilled to give 148.6 g. of 6-methoxy-1,2,3,4-tetrahydroquinoline (66% yield) boiling in the range 123°-125° C. at 8 Torr.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.C1C(=O)N([I:16])C(=O)C1>CN(C=O)C>[Cl:8][C:6]1[C:5]([I:16])=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=1
Reactant: O=C1CCC(=O)N1I
Reactant: Nc1cc(Cl)ccn1
Solvent: CN(C)C=O
Product: Nc1cc(Cl)c(I)cn1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.2 %

Procedure:
To a solution of 2-amino-4-chloropyridine (150 g, 0.78 mol) in DMF (1.5 L) was added NIS (341 g, 1.52 mol) and the reaction mixture stirred at RT for 18 h before being concentrated in vacuo to 300 mL volume. The resultant residue was poured into 10% aqueous sodium thiosulfate solution (1.2 L), stirred for 15 min and the precipitate formed collected by filtration, washed with water then dried at 35° C. in vacuo to give the title compound as a pale brown solid (185 g, 62%). 1H NMR 400 MHz (CDCl3) δ: 8.33 (1H, s), 6.68 (1H, s), 4.52 (2H, s).
Reaction SMILES: [C:1]1([C:7]#[CH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:9][SiH:10]([CH2:12][SiH:13]([Cl:15])[Cl:14])[Cl:11].C1C=CC=CC=1>O1CCCC1>[Cl:9][Si:10]([Cl:11])([CH2:12][SiH:13]([Cl:15])[Cl:14])[CH:8]=[CH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cl[SiH](Cl)C[SiH](Cl)Cl
Reactant: C#Cc1ccccc1
Solvent: c1ccccc1
Solvent: C1CCOC1
Product: Cl[SiH](Cl)C[Si](Cl)(Cl)C=Cc1ccccc1
Reaction time: 8 h
Yield: 27.3 %

Procedure:
Hydrosilation of phenylacetylene with bis(dichlorosilyl)methane in the presence of H2PtCl6 /THF. Into the same apparatus as described in Example 1 were added 1 g of bis(dichlorosilyl)methane, 20 μl of 0.1 M H2PtCl6 in THF (tetrahydrofuran) solution, and 20 ml of dried benzene. The flask content was heated to reflux and 0.52 ml of phenylacetylene was added over a ten minute period. The flask content was refluxed, with stirring, for another 8 hours and then the solvent removed at atmospheric pressure. The products were vacuum distilled at 67 Pa to give a mixture comprising 1.66 g of 3,3,5,5-tetrachloro-1-phenyl-3,5-disilapenta-1-ene (TCD-GC area 27.3%) and 3,3,5,5-tetrachloro-1,7-diphenyl-3,5-disilahepta-1,6-diene (TCD-GC area 26.4%).
Reaction SMILES: [NH:1]([C:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:20])[C:9]=2[CH:8]=[CH:7][CH:6]=1)C(C)=O.[OH-].[Na+]>C(O)C>[NH2:1][C:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:20])[C:9]=2[CH:8]=[CH:7][CH:6]=1
Reactant: CC(=O)Nc1cccc2c1C(=O)c1ccccc1C2=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Temperature: 80 °C
Yield: 95.2 %

Procedure:
363 g (1.37 moles) of 1-acetamino-anthraquinone are stirred into 3.5 kg of ethanol, 150 ml of concentrated sodium hydroxide solution (d = 1.48) are added and the mixture is then heated to the reflux temperature (80° C) for three hours. After cooling to 15° C, the red suspension is suction filtered. The residue is washed on the suction filter with hot water until the filtrate has a neutral reaction. After drying, 291 g of 1-amino-anthraquinone are obtained (yield: 95.2%). Degree of purity: 98 to 99%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:13])[C:6](=[CH:11][CH:12]=1)[C:7]([O:9][CH3:10])=[O:8].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:20](Br)[CH:21]=[CH2:22]>CCOC(C)=O>[CH2:22]([O:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])[CH:21]=[CH2:20]
Reactant: COC(=O)c1ccc(OC)cc1O
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Product: C=CCOc1cc(OC)ccc1C(=O)OC
Reaction time: 2 h

Procedure:
To a solution of methyl 4-methoxysalicylate (2.0 g, 11 mmol) in DMP (20 mL) at room temperature was added Cs2CO3 (1.3 eq, 4.7 g) and allyl bromide (1.3 eq, 1.23 mL). After 2 hr, reaction mixture was diluted with EtOAc and washed with water (3×), brine (1×). The organic layer was dried over Na2SO4 and concentrated to provide the product as a pale yellow oil. Product was used without further purification.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]([CH2:12][OH:13])[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:14](Cl)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>N1C=CC=CC=1>[CH2:1]([O:8][CH2:9][CH:10]([CH2:12][O:13][C:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCC(O)COCc1ccccc1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccncc1
Product: OC(COCc1ccccc1)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 71.9 %

Procedure:
rac-1-O-Benzylglycerol (5.37 g, 29.5 mmol), trityl chloride (8.31 g, 29.8 mmol) and anhydrous pyridine (35 ml) were placed in a flame-dried 200 ml round-bottomed flask. The reaction mixture was stirred under anhydrous conditions at room temperature for two days. The precipitate which formed was filtered before H2O and ether were added. The ether layer was extracted with H2O, 1N HCl and H2O, and dried (MgSO4). The solvent was removed by reduced pressure to provide a viscous yellow oil. The crude product was purified by column chromatography (180 g silica gel; hexanes:ethyl acetate, gradient 8:1 to 3:1) to yield pure compound 12, rac-1-O-benzyl-3-O-tritylglycerol (9.00 g, 72% yield).
Reaction SMILES: O.S(=O)(=O)(O)O.[F:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1.[Br:17]Br>S([O-])([O-])(=O)=O.[Ag+2].ClCCl>[Br:17][C:9]1[CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[CH:12]=[CH:13][C:8]=1[F:7]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: BrBr
Agent: [Ag+2]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Solvent: ClCCl
Solvent: O
Product: O=[N+]([O-])c1ccc(F)c(Br)c1
Temperature: 10 °C
Yield: 70 %

Procedure:
In a 20 L 4-necked RB flask, fitted with a mechanical stirrer, reflux condenser, add DM water (550 ml), conc. Sulphuric acid (6.2 L, 113 M), 4-fluronitrobenzene(1.0 kg, 7.09 M) at 25-35° C. under stirring. The reaction mixture was cooled to 10° C. and bromine (1.13 kg, 7.06 M) was added to reaction mixture under stirring. The reaction mixture was brought to temp. 25-35° C., silver sulfate (1.1 kg, ˜3.53 M) was added in one portion to the reaction mixture at 25-35° C. and maintained for 30-32 h under stirring. Monitor the progress of the reaction by GC and after ascertaining completion, the reaction mixture was poured slowly into ice cold water (12 L) and dichloromethane (12 L) mixture. Filter the insoluble and wash the inorganic with dichloromethane (2 L). Combine the organic layer, wash with 10% sodium bicarbonate (3 L), water (5 L). The dichloromethane layer was distilled below 40° C. under vacuum and add n-Hexane (4.5 L) to the residue. The resulting mass was stirred at 25-35° C. for 4-5 hr, filter the product and dried in vacuum oven below 35° C. till LOD reaches <1%. The dried product appears as white lustrous crystalline solid, weighs about 1.1-1.2 kg, yield 70-77%, purity 97-98% by HPLC, m.p. 56-58° C. The structure assigned to the product is in agreement with spectral data.
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1.[C:12]1([CH3:26])[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[C:13]=1[CH:20]=[C:21]([C:24]#[N:25])[C:22]#[N:23].C(O)(C)C>N1C=CC=CC=1>[NH2:25][C:24]1[N:3]2[N:4]=[CH:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]2[N:1]=[C:20]([C:13]2[C:12]([CH3:26])=[CH:17][C:16]([CH3:18])=[CH:15][C:14]=2[CH3:19])[C:21]=1[C:22]#[N:23]
Reactant: CCOC(=O)c1c[nH]nc1N
Reactant: Cc1cc(C)c(C=C(C#N)C#N)c(C)c1
Solvent: CC(C)O
Solvent: c1ccncc1
Product: CCOC(=O)c1cnn2c(N)c(C#N)c(-c3c(C)cc(C)cc3C)nc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 155 mg (1 mmol) of 3-amino-4-carbethoxypyrazole and 196 mg (1 mmol) of (mesitylmethylene)malononitrile (Intermediate 3) in 3 mL of anhydrous pyridine was stirred at reflux under air for 3 days and then cooled and concentrated in vacuo. Because LC-MS indicated the presence of considerable dihydro intermediate, 112 mg (0.49 mmol) of 2,3-dichloro-5,6-cyano-1,4-benzoquinone (DDQ) and 3 mL of isopropanol were added to the residue, and the mixture was stirred at ambient temperature for 1 h. The mixture was concentrated in vacuo, and the residue was purified by flash chromatography on silica gel (elution with 2% methanol in dichloromethane) to give the title compound as an orange solid. LC-MS 350 (M+1).
Reaction SMILES: [Cl:1][C:2]1=[C:3]([Cl:9])[C:4]([O:6][C:7]1=O)=[O:5].Cl.[CH3:11][NH2:12].C(O)(=O)C.C[O-].[Na+]>O>[Cl:1][C:2]1[C:7](=[O:6])[N:12]([CH3:11])[C:4](=[O:5])[C:3]=1[Cl:9]
Reactant: O=C1OC(=O)C(Cl)=C1Cl
Reactant: CN
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CN1C(=O)C(Cl)=C(Cl)C1=O
Temperature: 10 °C
Reaction time: 24 h

Procedure:
A 3L-three-necked flask fitted with a magnetic stir bar, digital thermocouple/thermometer, nitrogen purge and solid addition funnel was charged with 450 g (269.5 mol) of dichloromaleic anhydride, 191 g (282.8 mol) of methylamine hydrochloride and 1.6 L of acetic acid. The reaction mixture was then cooled to 10° C., and 160 g NaOMe added from the solid addition funnel over 1 hour while keeping the temperature between 10°-12° C. The reaction mixture was allowed to stir at room temperature for 42 hours (24 hours is sufficient) then heated to 100° C. for 3 hours. HPLC analysis at this time indicated that all the starting material had disappeared. The reaction was cooled to room temperature and 2L water was added. The mixture was then cooled to 3°-10° C. for 1 hour and filtered at 4° C. The solids were then rinsed with 2L of cold deionized water. The pale yellow solid dried in an air oven overnight to afford 360 g (75%) yield of the titled compound.
Reaction SMILES: [Na].[O:2]=[C:3]([N:17]1[CH2:22][CH2:21][N:20]2[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]2[CH2:18]1)[CH2:4][C:5](=[O:16])[CH2:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[CH:9][C:8]=1[F:15].[BH4-].[Na+].[NH4+].[Cl-]>CO.C1COCC1>[OH:16][CH:5]([CH2:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[CH:9][C:8]=1[F:15])[CH2:4][C:3]([N:17]1[CH2:22][CH2:21][N:20]2[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]2[CH2:18]1)=[O:2]
Reactant: O=C(CC(=O)N1CCn2c(nnc2C(F)(F)F)C1)Cc1cc(F)c(F)cc1F
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(CC(O)Cc1cc(F)c(F)cc1F)N1CCn2c(nnc2C(F)(F)F)C1
Temperature: -4 °C
Reaction time: 3.5 h

Procedure:
In a 500 mL round bottom flask THF (50 mL) and methanol (100 mL) were taken. To the solution sodium salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-one (2.0 g) was added. It was cooled to −78 to 70° C. in a dry-ice bath. Then NaBH4 (0.7 g) was added in small lots in 10-15 min. It was stirred at −78 to 70° C. for 3-4 h. Reaction mixture was poured into aq. saturated NH4Cl solution at 0-5° C. Product was extracted with ethyl acetate. Organic layer was collected and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-2.0 g, % Y-100%, % Purity by HPLC-95.6%).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][N:17]=1.C(OCC)(=O)C>[C].[Pd].CO>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][CH2:14][CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[O:6][C:2]=2[CH3:1])=[N:17][CH:18]=1
Reactant: Cc1oc(-c2ccccc2)nc1CCOc1ccc([N+](=O)[O-])cn1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(N)cn1
Yield: 93.7 %

Procedure:
A mixture of 2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-nitropyridine (13.4 g), palladium-carbon (5%, 1.5 g), ethyl acetate (200 ml), and methanol (150 ml) was catalytically reduced at room temperature at 1 atm. After the catalyst was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residual crystal was collected by filtration and recrystallized from ethyl acetate-hexane to yield 5-amino-2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]pyridine (11.4 g, 93%) as a brown crystal.