Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:34])[CH2:5][CH:6]([N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([Cl:32])=[C:24]3[C:28]=2[N:27]([CH3:29])[C:26]([CH3:30])=[C:25]3[CH3:31])[C:11]1=[O:33])[CH2:7][CH2:8][CH3:9])C.O.[OH-].[Li+]>C1COCC1.O>[Cl:32][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:12]2[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:10]([CH:6]([CH2:7][CH2:8][CH3:9])[CH2:5][C:4]([OH:34])=[O:3])[C:11]2=[O:33])=[C:28]2[C:24]=1[C:25]([CH3:31])=[C:26]([CH3:30])[N:27]2[CH3:29]
Reactant: CCCC(CC(=O)OCC)n1c(=O)n(Cc2ccc(Cl)c3c(C)c(C)n(C)c23)c2ccccc21
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCCC(CC(=O)O)n1c(=O)n(Cc2ccc(Cl)c3c(C)c(C)n(C)c23)c2ccccc21
Temperature: 25 °C
Yield: 44.1 %

Procedure:
To a stirred solution of 3-[3-(4-Chloro-1,2,3-trimethyl-1H-indol-7-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-hexanoic acid ethyl ester (25 mg, 0.05 mmol) in THF (5 ml) and water (1 ml) was added lithium hydroxide monohydrate (20 mg, 0.48 mmol). The resulting mixture was stirred at ambient temperature until all of the starting material was consumed. After this time the reaction was concentrated to low volume and diluted with water (5 ml) and acetic acid (0.2 ml). The resulting solid was collected via filtration and suspended in acetonitrile/water. The solid was collected once more via filtration and dried on house vacuum at 70° C. to give 10 mg (43%) of the desired product. LCMS (ESMS): m/z 454.96 (M+H+).
Reaction SMILES: N[C:2]1[CH:17]=[CH:16][C:5]2[O:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9](=[O:11])[CH2:10][C:4]=2[CH:3]=1.CS(O)(=O)=O.N([O-])=O.[Na+].[ClH:27]>[Cu]Cl.C(OCC)(=O)C.O>[Cl:27][C:2]1[CH:17]=[CH:16][C:5]2[O:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9](=[O:11])[CH2:10][C:4]=2[CH:3]=1
Reactant: Nc1ccc2c(c1)CC(=O)c1ccccc1O2
Reactant: Cl
Agent: Cl[Cu]
Agent: CS(=O)(=O)O
Agent: O=N[O-]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C1Cc2cc(Cl)ccc2Oc2ccccc21
Temperature: 0 °C
Reaction time: 0.12 h

Procedure:
26.4 G. of 2-amino-10,11-dihydro-dibenz[b,f]oxepin-10-one are dissolved in 230 ml. of 2-N aqueous methanesulfonic acid. The mixture is cooled to 0° C. There is added dropwise thereto over a period of 7 minutes a solution of 10.7 g. of sodium nitrite in 37.5 ml. of water in such a manner that the temperature does not exceed 5° C. The mixture is stirred for an additional 5 minutes at 5° C. Then, this solution of the diazonium methanesulfonate is poured into a mixture of 500 ml. of ethyl acetate and a solution of 37.5 g. of copper (I) chloride in 450 ml. of concentrated hydrochloric acid. The resulting mixture is stirred for an additional 10 minutes at room temperature and the phases are then separated. The ethyl acetate solution is washed several times with saturated aqueous sodium chloride solution, dried over sodium sulfate and evaporated in vacuo. The residue is dissolved in benzene and chromatographed over 400 g. of silica gel. Upon elution with benzene, there is obtained a substance which is crystallized from a small amount of isopropanol and there is obtained 2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-one having a melting point of 60°-61° C.
Reaction SMILES: Br.[Cl:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]2[CH2:15][C:16]([C:29]#[N:30])([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:5][CH:4]=1.C(=O)([O-])[O-:34].[K+].[K+]>S(=O)(=O)(O)O>[C:29]([C:16]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:15][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][N:9]1[CH2:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([Cl:2])=[CH:32][CH:31]=1)(=[O:34])[NH2:30]
Reactant: O=C([O-])[O-]
Reactant: N#CC(CC1CCCCN1CCc1ccc(Cl)cc1)(c1ccccc1)c1ccccc1
Agent: Br
Agent: O=S(=O)(O)O
Agent: [K+]
Product: NC(=O)C(CC1CCCCN1CCc1ccc(Cl)cc1)(c1ccccc1)c1ccccc1
Yield: 65 %

Procedure:
A solution of 1-(4-chlorophenethyl)-2-(2-cyano-2,2-diphenylethyl)piperidine hydrobromide (Example 26) (122 mg, 0.24 mmol) in 90% sulphuric acid (2 ml) was stirred at 90° C. for 1.5 hours, diluted with ice, basified with excess solid potassium carbonate and extracted into dichloromethane. The combined dichloromethane extracts were dried over sodium sulphate and evaporated. The residue was purified by chromatography on silica using dichloromethane plus 0-5% methanol as eluant. Appropriate fractions were combined and evaporated to give the title compound (70 mg, 65%) as a colourless foam which was characterised as a dihydrate.
Reaction SMILES: O[CH2:2][N:3]1[CH2:7][CH:6]([CH2:8][CH2:9][CH3:10])[CH2:5][C:4]1=[O:11].S(Cl)(Cl)=O.[CH3:16][C:17]1[CH:18]=[N:19][C:20]2[N:21]([N:23]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:25]=2)[CH:22]=1.[Al+3].[Cl-].[Cl-].[Cl-]>C1(C)C=CC=CC=1>[CH3:16][C:17]1[CH:18]=[N:19][C:20]2[N:21]([N:23]=[C:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:25]=2[CH2:2][N:3]2[CH2:7][CH:6]([CH2:8][CH2:9][CH3:10])[CH2:5][C:4]2=[O:11])[CH:22]=1
Reactant: Cc1cnc2cc(-c3ccccc3)nn2c1
Reactant: CCCC1CC(=O)N(CO)C1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CCCC1CC(=O)N(Cc2c(-c3ccccc3)nn3cc(C)cnc23)C1
Temperature: 80 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
To a solution of 1-(hydroxymethyl)-4-propylpyrrolidin-2-one x2 (3.18 mmol, 1 eq, 0.5 g) in toluene (20 ml) is added thionyl chloride (3.5 mmol, 1.1 eq, 0.416 g). The mixture is stirred vigorously overnight at 80° C. After this time, 6-methyl-2-phenylpyrazolo[1,5-a]pyrimidine x122 (3.18 mmol, 1 eq, 0.665 g) and AlCl3 (3.18 mmol, 1 eq, 0.424 g) are successively added. The mixture is stirred at 80° C. for 2 hours. After evaporation of the solvent under reduced pressure, the crude mixture is poured to water and extracted with dichloromethane. The cumulated organic layers are dried over MgSO4, filtered over celite and evaporated under reduced pressure. The crude reaction mixture is purified by chromatography on silicagel (CH2Cl2/MeOH/NH4OH 98/2/0.2 (v/v/v)) and crystallized with AcOEt to afford 0.5 g of 1-[(6-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-one 202.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.[I:20]N1C(=O)CCC1=O>C1COCC1>[NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][C:19]=1[I:20])[CH2:16][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2
Reactant: O=C1CCC(=O)N1I
Reactant: Nc1ccc2c(c1)C[C@@]1(C2)C(=O)Nc2ncccc21
Solvent: C1CCOC1
Product: Nc1cc2c(cc1I)C[C@]1(C2)C(=O)Nc2ncccc21
Reaction time: 18 h

Procedure:
To a solution of (2R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (4.00 g, 15.9 mmol, described in Intermediate 6) in THF (64 mL) at ambient temperature was added N-iodosuccinimide (3.58 g, 15.92 mmol). The reaction mixture was stirred for 18 h, then purified by silica gel chromatography, eluting with EtOAc:hexanes—70:30, to give the title compound. MS: m/z=378 (M+1).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4](Cl)[N:3]=1.[CH3:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(=O)(O)[O-].[Na+]>CN(C=O)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([C:17]3[CH:18]=[CH:19][C:14]([CH3:13])=[CH:15][CH:16]=3)[N:3]=2)=[CH:16][CH:15]=1
Reactant: Cc1ccc(B(O)O)cc1
Reactant: COC(=O)c1cc(Cl)nc(Cl)n1
Agent: Cl[Pd]Cl
Agent: [Fe]
Agent: O=C([O-])O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COC(=O)c1cc(-c2ccc(C)cc2)nc(-c2ccc(C)cc2)n1
Temperature: 80 °C
Reaction time: 16 h
Yield: 52.1 %

Procedure:
To a solution of methyl 2,6-dichloropyrimidine-4-carboxylate (0.39 g, 1.87 mmol) in DMF (15 mL) were added (4-methylphenyl)boronic acid (0.84 g, 6.17 mmol), potassium phosphate tribasic (0.79 g, 3.74 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.15 g, 0.19 mmol). The mixture was heated to 80° C. After 16 h, the mixture was cooled to ambient temperature. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate) gave the title compound (0.31 g). MS 319.2 (M+1).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]1([O:16][C:17]2[CH:18]=[C:19]([CH:25]([OH:35])[CH2:26][C:27]3[C:32]([Cl:33])=[CH:31][N:30]=[CH:29][C:28]=3[Cl:34])[CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH2:15][CH2:14][CH2:13][CH2:12]1.C(N(CC)CC)C>ClCCl.O>[Cl:33][C:32]1[CH:31]=[N:30][CH:29]=[C:28]([Cl:34])[C:27]=1[CH2:26][C:25]([C:19]1[CH:20]=[CH:21][C:22]([O:23][CH3:24])=[C:17]([O:16][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:18]=1)=[O:35]
Reactant: COc1ccc(C(O)Cc2c(Cl)cncc2Cl)cc1OC1CCCC1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)cc1OC1CCCC1
Temperature: -70 °C
Reaction time: 0.33 h

Procedure:
A solution of oxalyl chloride (5.3 mL) in dry dichloromethane (125 mL) at −60° C. is treated portionwise with dimethyl sulfoxide (9.1 mL) in dichloro-methane (20 mL), keeping the temperature below −50° C. The solution is then stirred at −70° C. for 20 minutes and is then treated with a suspension of 1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(3,5-dichloropyrid-4-yl)ethanol (20.5 g; that is prepared as described in Reference Example 63) in dry dichloro-methane (300 mL) during 20 minutes, keeping the temperature below −50° C. After stirring for 30 minutes, the solution is treated with triethylamine (35 mL) and allowed to rise to room temperature. It is then treated with water (250 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts are washed with dilute sulfuric acid (100 mL; 1%), aqueous potassium carbonate solution (100 ml; 5%) and brine (100 mL), dried and concentrated and the resulting residue is recrystallized from a mixture of ethyl acetate and heptane, to give 3-cyclopentyloxy-4-methoxyphenyl 3,5-dichloropyrid-4-ylmethyl ketone (19.6 g), m.p. 119-120° C. [NMR(CDCl3): 8.52(s,2H),7.69 (dd,1H,J=8 Hz),7.57(d,1H,J=2 Hz), 6.95(d,1H,J=8 Hz),4.86 (m,1H),4.64(s,2H), 3.95(s,3H),2.05-1.58(m,8H). Elemental analysis: C,59.8,H,4.95,N,3.63%; calculated: C,60.0; H,5.0, N,3.7%].
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C[Li].[CH2:16]([Si:20]([CH2:23][CH2:24][CH2:25][CH3:26])(Cl)Cl)[CH2:17][CH2:18][CH3:19].[Cl-].[NH4+]>C(OCC)C>[CH2:16]([Si:20]([CH2:12][CH2:11][CH2:10][CH3:9])([CH:23]1[C:13]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[C:6]2[C:24]1=[CH:25][CH:26]=[CH:8][CH:7]=2)[CH:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)[CH2:17][CH2:18][CH3:19]
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Reactant: CCCC[Si](Cl)(Cl)CCCC
Agent: [Cl-]
Agent: [Li]C
Agent: [NH4+]
Solvent: CCOCC
Product: CCCC[Si](CCCC)(C1c2ccccc2-c2ccccc21)C1c2ccccc2-c2ccccc21
Temperature: -78 °C
Reaction time: 8 h

Procedure:
Fluorene (23.27 g, 140 mmol) was dissolved in 100 mL diethyl ether and the solution was cooled to −78° C. Methyllithium (1.4M in diethyl ether, 140 mL) was added dropwise to the stirred solution while maintaining the temperature at −78° C. After the addition was complete, the solution was allowed to warm to room temperature. Stirring was continued overnight. In a separate flask, di-n-butyldichlorosilane (14.9 g, 70 mmol) was dissolved in 50 mL diethyl ether. The temperature was reduced to −78° C., and the solution (prepared above) containing the fluorene anion was added to this stirred solution, dropwise. After the addition was complete, the reaction was allowed to warm slowly to room temperature and stirred overnight. The reaction was then treated with a saturated solution of ammonium chloride, the organic layer was collected and dried over magnesium sulfate, and dried in vacuo. The material was further purified by washing with methanol and drying in vacuo. Yield: 23.39 g (70.7%, 97% purity by GCMS). 1H-NMR (CD2Cl2), d, ppm: 7.81 (d, 4H), 7.30 (m, 12H), 3.95(s, 2H), 1.05(m, 4H), 0.85(m, 10H), 0.5(m, 4H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:12]2[C:20]3[C:19]([OH:21])=[C:18]([C:22]#[N:23])[C:17](=[O:24])[NH:16][C:15]=3[S:14][CH:13]=2)[S:5][C:6]=1[C:7]#[C:8][CH2:9][O:10][CH3:11].CO[CH2:27][CH2:28]OC.C([Sn](CCCC)(CCCC)CCCC)=C>CN(C=O)C>[OH:21][C:19]1[C:20]2[C:12]([C:4]3[S:5][C:6]([C:7]#[C:8][CH2:9][O:10][CH3:11])=[C:2]([CH:27]=[CH2:28])[CH:3]=3)=[CH:13][S:14][C:15]=2[NH:16][C:17](=[O:24])[C:18]=1[C:22]#[N:23]
Reactant: COCCOC
Reactant: COCC#Cc1sc(-c2csc3[nH]c(=O)c(C#N)c(O)c23)cc1Br
Agent: C=C[Sn](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Product: C=Cc1cc(-c2csc3[nH]c(=O)c(C#N)c(O)c23)sc1C#CCOC
Temperature: 100 °C

Procedure:
3-[4-Bromo-5-(3-methoxy-prop-1-ynyl)-thiophen-2-yl]-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carbonitrile (75 mg, 0.18 mmol, Example 183) was dissolved in 2 mL of 1:1 DMF:DME and at rt, vinyl tributyltin (0.2 mmol) was added. The reaction vessel was flushed with N2, capped and heated to 100° C. for 2 h. The reaction mixture was filtered and filtered again through a plug of silica gel. The residue was taken up in 1:1 MeOH : DMSO, filtered and purified by RP-HPLC to provide the title compound. MS (ESI) m/z 367.0 (M−H+); 1H NMR (300 MHz, DMSO-d6) δ ppm 7.67 (s, 1H), 7.44 (s, 1H), 7.04 (s, 1H), 6.98 (s, 1H), 6.83 (dd, 1H), 5.83 (d, 1H), 5.30 (d, 1H), 4.38 (d, 2H), 4.38 (app d, 2H), 3.43 (app d, 3H).
Reaction SMILES: Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[Br:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[C:20]([F:25])[CH:19]=1>C(O)(C)C>[ClH:2].[Br:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:20]([F:25])[CH:19]=1
Reactant: Nc1ccc(Br)cc1F
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Agent: Cl
Solvent: CC(C)O
Product: COc1cc2ncnc(Nc3ccc(Br)cc3F)c2cc1OC
Temperature: 25 °C
Yield: 59.8 %

Procedure:
A mixture of 4-chloro-6,7-dimethoxyquinazoline hydrochloride (130 mg, 0.5 mmol), (prepared as described for the starting material in Example 2), and 4-bromo-2-fluoroaniline (95 mg, 0.5 mmol) in isopropanol (7 ml) was heated at reflux for 2 hours. The mixture was allowed to cool to ambient temperature, the precipitated solid was collected by filtration, washed with isopropanol and ether and dried to give 4-(4-bromo-2-fluoroanilino)-6,7-dimethoxyquinazoline hydrochloride (124 mg, 60%) as an off-white solid. HPLC characteristics:
Reaction SMILES: [N:1]1[C:11]2[NH:10][C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[C:7](=[S:16])[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.F[B-](F)(F)F.[CH3:22][O+](C)C>ClCCl>[CH3:22][S:16][C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[NH:10][C:11]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[N:6]=1
Reactant: S=C1Nc2cccnc2Nc2ccccc21
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Product: CSC1=Nc2cccnc2Nc2ccccc21
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 5H-benzo[e]pyrido[3,2-b][1,4]diazepine-6(11H)-thione (0.106 g, 0.465 mmol) in dichloromethane (5 ml) was added trimethyloxonium tetrafluoroborate (0.076 g, 0.512 mmol). The reaction mixture was stirred at room temperature for 15 minutes and then warmed to 40° C. for 2 hours. The reaction was quenched by adding water (10 ml). The organic layer was separated, dried with sodium sulfate and concentrated to afford the desired product, 6-(methylthio)-11H-benzo[e]pyrido[3,2-b][1,4]diazepine as a dark yellow solid which turned to oil on standing (0.092 g, 82%). The crude product was used in the next step without any further purification. 400 MHz 1H NMR (CDCl3) δ: 7.9-7.85 (m, 1H), 7.60-7.54 (m, 1H), 7.44-7.38 (m, 1H), 7.3-7.22 (m, 1H), 6.98-6.90 (m, 2H), 6.78-6.72 (m, 1H), 6.29 (br s, 1H), 2.53 (s, 3H); LCMS [M+H]: 242.
Reaction SMILES: [N+:1]([C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][C:7]([NH2:13])=[C:6]([NH2:14])[CH:5]=1)([O-:3])=[O:2].O.[F:16][C:17]([F:29])([F:28])[C:18](=O)[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O>>[N+:1]([C:4]1[CH:5]=[C:6]2[C:7](=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[N:13]=[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:18]([C:17]([F:16])([F:28])[F:29])=[N:14]2)([O-:3])=[O:2]
Reactant: Nc1cc([N+](=O)[O-])c([N+](=O)[O-])cc1N
Reactant: O=C(C(=O)C(F)(F)F)c1ccccc1
Solvent: O
Product: O=[N+]([O-])c1cc2nc(-c3ccccc3)c(C(F)(F)F)nc2cc1[N+](=O)[O-]

Procedure:
The title compound was prepared from 4,5-dinitro-1,2-phenylenediamine (890 mg, 4.5 mmol) and 3,3,3-trifluoro-1-phenyl-1,2-propanedione hydrate (1 g, 4.9 mmol) similarly as described in example 144.
Reaction SMILES: [C:1]([NH:4][C@@H:5]([CH3:17])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)(=[O:3])[CH3:2].Cl.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=1[OH:27]>>[C:1]([NH:4][C@@H:5]([CH3:17])[CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([C:12]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=2[OH:27])=[O:14])=[CH:15][CH:16]=1)(=[O:3])[CH3:2]
Reactant: Nc1ccc(O)cc1O
Reactant: CC(=O)N[C@@H](C)COc1ccc(C(=O)O)cc1
Agent: Cl
Product: CC(=O)N[C@@H](C)COc1ccc(C(=O)Nc2ccc(O)cc2O)cc1

Procedure:
Using 4-{[(2S)-2-(acetylamino)propyl]oxy}benzoic acid and 4-aminobenzene-1,3-diol hydrochloride, and in the same manner as in Example 2, step C, the title compound was obtained.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:22])[C:7]([C:20]#[N:21])=[CH:8][N:9]2[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[CH:4][C:3]=1[N+:23]([O-:25])=[O:24].[N-:26]=[N+:27]=[N-:28].[Na+]>CS(C)=O>[N:26]([C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:22])[C:7]([C:20]#[N:21])=[CH:8][N:9]2[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[CH:4][C:3]=1[N+:23]([O-:25])=[O:24])=[N+:27]=[N-:28]
Reactant: C[Si](C)(C)CCOCn1cc(C#N)c(=O)c2cc([N+](=O)[O-])c(Cl)cc21
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CS(C)=O
Product: C[Si](C)(C)CCOCn1cc(C#N)c(=O)c2cc([N+](=O)[O-])c(N=[N+]=[N-])cc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 99.9 %

Procedure:
To a solution of 6.0 g (15.8 mmol) of 7-chloro-6-nitro-4-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-3-quinolinecarbonitrile in 120 mL of dimethyl sulfoxide is added 5.13 g (79.0 mmol) of sodium azide and the resulting mixture is stirred at room temperature for 3 hours. The mixture is then heated at 60° C. for 10 minutes, room temperature for 1 hour and then poured on to ice. The solid is collected by filtration, washed thoroughly with water and dried in vacuo to yield 6.1 g of 7-azido-6-nitro-4-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-3-quinolinecarbonitrile as a yellow solid.
Reaction SMILES: C([Li])CCC.[C:6]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1)#[CH:7].CC(C)([O-])C.[K+].Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>O.O1CCCC1.CCCCCC>[C:6]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][C:9]=1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])#[CH:7]
Reactant: C#Cc1cccc2ccccc12
Reactant: CCCCCCBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: C#Cc1c(CCCCCC)ccc2ccccc12
Temperature: -90 °C
Reaction time: 1 h
Yield: 47.2 %

Procedure:
Under a nitrogen atmosphere at −50° C., 1.6 mol/l hexane solution of n-butyllithium was added to 30 ml of a tetrahydrofuran solution containing 3 g of ethynylnaphthalene. After cooling to −90° C., 15 ml of a tetrahydrofuran solution containing 2.5 g of potassium tertiary butoxide was added thereto, and the mixture was stirred at −80° C. for 1 hour and then allowed to warm to 5° C. 3.3 g of bromohexane was added dropwise at −70° C., and the mixture was stirred at 30° C. overnight. 100 ml of water was added dropwise at 0° C., and the compounds generated were extracted with added hexane. The hexane layer was washed thrice with 300 ml of distilled water and dried over anhydrous magnesium sulfate for 24 hours, and the mixture was then filtered and evaporated for removal of the solvent. After column purification and solvent removal, the product was purified by column chromatography while hexane was used as the developing solvent, to give 2.2 g of 1-ethynyl-2-n-hexylnaphthalene.
Reaction SMILES: OC1C(CCC)=C(O)C=CC=1C(=O)C.BrC[C:17]1[CH:26]=[CH:25][CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20]>>[CH3:22][O:21][C:19](=[O:20])[C:18]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:17]=1
Reactant: COC(=O)c1ccccc1CBr
Agent: CCCc1c(O)ccc(C(C)=O)c1O
Product: COC(=O)c1ccccc1

Procedure:
1-(2,4-dihydroxy-3-propylphenyl)ethanone was allowed to react with methyl 2-bromomethylbenzoate according to the procedure of Example 69 and the product was purified by recrystallization from hexane to give 2-[4-acetyl-3-hydroxy-2-propylphenoxy)methyl]benzoic acid methyl ester, the title compound, m.p. 90°-93°, in 78% yield. Analysis Calculated for C20H22O5 : C, 70.16, H, 6.48. Found: C, 69.97; H, 6.36.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[N:12]=[N:13]N(C3C=CC(N4C=CC=CC4=O)=CC=3)[CH:15]=2)=[O:8])=[CH:4][CH:3]=1.[I:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[C:32]([F:37])[CH:31]=1>>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[N:12]=[N:13][N:34]([C:33]3[CH:35]=[CH:36][C:30]([I:29])=[CH:31][C:32]=3[F:37])[CH:15]=2)=[O:8])=[CH:4][CH:3]=1
Reactant: Nc1ccc(I)cc1F
Reactant: O=C(NCc1cn(-c2ccc(-n3ccccc3=O)cc2)nn1)c1ccc(Cl)s1
Product: O=C(NCc1cn(-c2ccc(I)cc2F)nn1)c1ccc(Cl)s1

Procedure:
The title compound was prepared by the same procedure for compound 35 described in Example 290 in Scheme 5, using 4-iodo-2-fluoroaniline in place of 4-iodoaniline. MS found for C14H9ClFIN4OS as (M+H)+ 462.0, 464.0
Reaction SMILES: [CH:1]1([CH2:6][C:7]2([N:17]([CH3:19])[CH3:18])[CH2:16][CH2:15][C:10]3(OCC[O:11]3)[CH2:9][CH2:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1>S(=O)(=O)(O)O>[CH:1]1([CH2:6][C:7]2([N:17]([CH3:18])[CH3:19])[CH2:8][CH2:9][C:10](=[O:11])[CH2:15][CH2:16]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CN(C)C1(CC2CCCC2)CCC2(CC1)OCCO2
Agent: O=S(=O)(O)O
Product: CN(C)C1(CC2CCCC2)CCC(=O)CC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
5% sulfuric acid (600 ml) was added at room temperature to (8-cyclopentylmethyl-1,4-dioxa-spiro[4.5]dec-8-yl)-dimethyl-amine (13.4 g, 50 mmol), and the mixture was stirred for 3 d at RT. The reaction mixture was extracted with ether (2×50 ml). Then the aqueous phase was rendered alkaline with 5N NaOH, while cooling with an ice bath, and extraction with dichloromethane (3×50 ml) was carried out. The organic phase was dried over Na2SO4 and concentrated to dryness in vacuo.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[O:15][CH:16]=[CH:17][CH:18]=3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(=O)([O-])[O-].[K+].[K+].Cl[C:26]([O:28][CH2:29][C:30]([Cl:33])([Cl:32])[Cl:31])=[O:27]>O1CCOCC1>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[O:15][CH:16]=[CH:17][CH:18]=3)[N:10]=2)=[CH:3][C:2]=1[NH:1][C:26](=[O:27])[O:28][CH2:29][C:30]([Cl:33])([Cl:32])[Cl:31]
Reactant: Nc1cc(-c2nc(-c3ccco3)no2)ccc1Cl
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: O=C(Nc1cc(-c2nc(-c3ccco3)no2)ccc1Cl)OCC(Cl)(Cl)Cl
Yield: 39.9 %

Procedure:
To a mixture of 5-(3-amino-4-chlorophenyl)-3-(2-furanyl)-1,2,4-oxadiazole (0.75 g) and 0.58 g of potassium carbonate in 25 ml of dioxane is added 0.80 g of 2,2,2-trichloroethyl chloroformate. The resulting mixture is heated at reflux for 2 hours, and concentrated to dryness. 50 ml of water is added to the residue and the resulting mixture is extracted three times with chloroform. The extracts are dried over magnesium sulfate, filtered and concentrated to dryness. The residue is absorbed on an alumina column and eluted with benzene to give 0.50 g of the title compound, melting point 114°-116°C.