Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1C2C(=CC=CC=2)C=[N:3][N:2]=1.[Br:11][C:12]1[CH:13]=[C:14]2[C:19](=O)[O:18][C:16](=[O:17])[C:15]2=[CH:21][CH:22]=1.NN>C(O)(C)C>[Br:11][C:12]1[CH:13]=[C:14]2[C:15](=[CH:21][CH:22]=1)[C:16]([OH:17])=[N:3][N:2]=[C:19]2[OH:18]
Reactant: c1ccc2cnncc2c1
Reactant: O=C1OC(=O)c2cc(Br)ccc21
Agent: NN
Solvent: CC(C)O
Product: Oc1nnc(O)c2cc(Br)ccc12

Procedure:
The synthesis of phthalazine derivatives of general formulas 25-26 may be achieved as outlined in Scheme III. In general, a mixture of 4-bromophthalic anhydride and hydrazine may be refluxed in a suitable solvent, e.g., isopropyl alcohol, to provide 6-bromo-phthalazine-1,4-diol 21 in almost quantitative yield. Compound 21 may then be treated with phosphorus oxychloride to form 1,4-dichloro-6-bromo phthalazine 22. Treatment of compound 22 with a suitable nucleophile (where, for example, Y is NR1R2 or NaOR) affords two isomers of general formulas 23 and 24. Displacement of the bromine atom with a suitable amino or alcohol derivative A-B—X (where, for example, A is alkyl, aryl, arylalkyl, arylheteroalkyl, B is absent, CO, and X is OH, NH2), using a suitable Pd complex derivative in the presence of a base like sodium tert-butoxide in a suitable solvent, affords the desired 6-amino or 6-alkoxy phthalazine derivatives of general formula 25-26.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.ClC(Cl)(O[C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[F:35][C:36]1[C:42]([F:43])=[C:41]([F:44])[CH:40]=[CH:39][C:37]=1[NH2:38].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C(N(CC)CC)C>[F:35][C:36]1[C:42]([F:43])=[C:41]([F:44])[CH:40]=[CH:39][C:37]=1[NH:38][C:27]([NH:22][C:19]1[CH:18]=[CH:17][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:21][CH:20]=1)=[O:33]
Reactant: Nc1ccc(F)c(F)c1F
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccc(F)c(F)c4F)cc3)c2cc1OC
Yield: 22.7 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (50 mg) was dissolved in toluene (5 ml) with heat, after the addition of triethylamine (1 ml), triphosgene (55 mg) was added, and the admixture was refluxed with heat for 3 minutes. 2,3,4-Trifluoroaniline (75 mg) was added to the reaction mixture, and the admixture was refluxed with heat for 20 minutes. After the addition of aqueous sodium hydrogen carbonate, the reaction mixture was extracted 2 times with ethyl acetate, and the organic layer was then washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by reduced-pressure distillation, and the resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 18 mg of the title compound (yield: 23%).
Reaction SMILES: C1(C)C=CC(NC2C=C(C(O)=O)C(NC3C=CC(C)=CC=3)=CC=2C(O)=O)=CC=1.Cl[C:30]1[CH:31]=[C:32]([CH:54]=[CH:55][CH:56]=1)[NH:33][C:34]1[CH:42]=[C:41]([C:43]([OH:45])=O)[C:40]([NH:46][C:47]2[CH:52]=[CH:51][CH:50]=[C:49](Cl)[CH:48]=2)=[CH:39][C:35]=1[C:36](O)=[O:37]>>[CH:50]1[CH:51]=[C:52]2[C:43]([C:41]3[C:40]([NH:46][C:47]2=[CH:48][CH:49]=1)=[CH:39][C:35]1[C:36]([C:31]2[C:32]([NH:33][C:34]=1[CH:42]=3)=[CH:54][CH:55]=[CH:56][CH:30]=2)=[O:37])=[O:45]
Reactant: O=C(O)c1cc(Nc2cccc(Cl)c2)c(C(=O)O)cc1Nc1cccc(Cl)c1
Agent: Cc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(C)cc3)cc2C(=O)O)cc1
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 125 °C
Reaction time: 0.67 h

Procedure:
A stirred vessel is charged with 1000 parts of polyphosphoric acid containing 85.0% P2O5. Then 150 parts of 2,5-di(4-toluidino)terephthalic acid and 50 parts of 2,5-di(3-chloroanilino)terephthalic acid are introduced at 90° C. with stirring over 40 minutes. During this addition the temperature rises to 103° C. The mixture is heated at 125° C. and stirred at 125° C. for 1.5 hours during which ring closure takes place to form the quinacridone. The reaction mixture is then metered into a toothed-disk disperser IKA SD 41 (supplier: Janke u. Kunkel, Staufen) at 13,000 rpm with a stator slot width of 3 mm, with a volume flow of 3.3 parts by volume per hour in a volume flow of 23.5 parts by volume per hour of 70% strength phosphoric acid at 95° C. and is hydrolyzed in 4.3 seconds (a precipitate is formed). During this procedure, the temperature rises to 102° C. Following the hydrolysis the phosphoric acid strength is 74.6%. This gives 6815 parts of mixed-crystal crude pigment suspension. 1315 parts thereof are heated to 130° C. and are stirred at 130° C. for 5 hours. Thereafter, the mixture is cooled to 70° C. and 1116 parts of water at 25° C. are run in with stirring. Following the addition of the water, the phosphoric acid strength is 40%. The mixed-crystal pigment is subsequently filtered off with suction, washed to neutrality with water and dried at 80° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=1.[NH:11]1[CH2:21][CH2:20][CH:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:12]1>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[CH2:21][CH2:20][CH:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:12]2)=[S:10])=[CH:4][CH:3]=1
Reactant: S=C=Nc1ccc(Cl)cc1
Reactant: CCOC(=O)C1CCNCC1
Solvent: ClCCl
Product: CCOC(=O)C1CCN(C(=S)Nc2ccc(Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 4-chlorophenyl isothiocyanate (3.5 g, 20.7 mmol), and ethyl isonipecotate (3.19 mL, 20.7 mmol) in dichloromethane (30 mL) was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure, the residue was triturated with ether and the resulting solid was filtered off and dried to afford the title compound as a white solid, 6.27 g.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:16])([CH3:15])[CH2:9]OS(C)(=O)=O)[C:5]([F:17])=[CH:4][N:3]=1.[N-:18]=[N+:19]=[N-:20].[Na+].[NH4+].[Cl-]>C(O)C.O.CC(OC)(C)C>[N:18]([CH2:9][C:8]([C:6]1[C:5]([F:17])=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=1)([OH:16])[CH3:15])=[N+:19]=[N-:20]
Reactant: CC(O)(COS(C)(=O)=O)c1cc(Br)ncc1F
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CCO
Solvent: COC(C)(C)C
Solvent: O
Product: CC(O)(CN=[N+]=[N-])c1cc(Br)ncc1F
Temperature: 80 °C
Reaction time: 20 h

Procedure:
To a solution of methanesulfonic acid 2-(2-bromo-5-fluoro-pyridin-4-yl)-2-hydroxy-propyl ester (10.36 g, 31.6 mmol) in ethanol (160 ml) was added NaN3 (5.13 g, 79.0 mmol) and NH4Cl (8.44 g, 158.0 mmol). The reaction mixture was stirred at 80° C. for 20 h. The reaction mixture was diluted with H2O and TBME and the phases were separated. The aq. phase was twice reextracted with TBME, the combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated. HPLC RtH4=0.89 min; ESIMS: 275, 277 [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 8.20 (d, 1H), 7.80 (d, 1H), 3.81 (d, 1H), 3.65 (d, 1H), 1.61 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([F:9])[CH:3]=1.[Li]CCCC.CN(C)[C:17](=[O:19])[CH3:18].[Cl-].[NH4+]>C(OCC)C>[C:17]([C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([F:9])[CH:3]=1)(=[O:19])[CH3:18]
Reactant: Fc1cc(Br)ccc1Cl
Reactant: CC(=O)N(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Product: CC(=O)c1ccc(Cl)c(F)c1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a solution of 1-bromo-4-chloro-3-fluorobenzene (2.09 g, 10 mmol) in dry diethyl ether (12.0 ml) was added a solution of n-BuLi (1.55M in hexane, 6.77ml, 10.5 mmol) at −78° C. under nitrogen atmosphere. The mixture was allowed to warm to −20_C stirred for 45 min. A solution of N,N-dimethylacetamide (1.04 ml, 11.2 mmol) in diethyl ether (1.5 ml) was added and the mixture stirred for an additional 1 h. The mixture was then allowed to warm to room temperature. After stirring for 3 h, the reaction mixture was poured into saturated aqueous ammonium chloride (20 ml) and extracted with diethyl ether (30 ml×3). The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml), and dried (MgSO4). Removal of solvent gave the title compound as a yellow oil (quant.).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[Sn](Cl)Cl.C(O)C.C([O-])(O)=O.[Na+]>CCOC(C)=O>[NH2:16][C:13]1[CH:14]=[CH:15][C:2]([Cl:1])=[C:3]([CH:12]=1)[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5]
Reactant: O=C(c1ccccc1)c1cc([N+](=O)[O-])ccc1Cl
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1ccc(Cl)c(C(=O)c2ccccc2)c1
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
2-Chloro-5-nitrobenzophenone (1.3 g,5.0 mmol), tin(II) chloride (4.5 g, 20 mmol), and ethanol (20 ml) were mixed and heated at 70° C. for 1 h. After cooling to room temperature, to the reaction mixture were added ice, EtOAc and aqueous NaHCO3 and it was stirred for 30 min. The organic layer was washed with brine and dried over MgSO4. Filtration and evaporation afforded 5-amino-2-Chlorobenzophenone. 1H NMR, 7.85(m,2H), 7.30-7.66 (m,3H7.20 (d,1H,J=8.8 Hz), 6.60-6.80 (m,2H). MS calcd 231.1; MS (M+1) 232.0.
Reaction SMILES: [H-].[Na+].[CH2:3]([C@:6]1([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:11][CH2:10][N:9]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)[CH3:13])[C:8](=[O:21])[NH:7]1)[CH:4]=[CH2:5].[CH3:29]I>C1COCC1>[CH2:3]([C@:6]1([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:11][CH2:10][N:9]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)[CH3:13])[C:8](=[O:21])[N:7]1[CH3:29])[CH:4]=[CH2:5]
Reactant: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)N1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)N1C
Reaction time: 2 h
Yield: 22.6 %

Procedure:
To a suspension of NaH (84 mg, 2.1 mmol) in THF (1 mL) was added a solution of (R)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyl)tetrahydropyrimidin-2(1H)-one (50 mg, 0.120 mmol) in THF (5 mL) at 0° C. The resulting mixture was stirred for 2 h. Then CH3I (50 mg, 0.35 mmol) was added. The mixture was stirred for 3 h. The reaction was quenched with satd aq NH4Cl. The organic phase was separated, and concentrated to give the crude product, which was purified by preparative TLC to afford (R)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyl)-3-methyltetrahydropyrimidin-2(1H)-one (11.7 mg, 23%). LC-MS Method 1 tR=1.403 min, m/z=431; 1H NMR (CDCl3): δ=1.38 (d, 3H), 1.63 (m, 1H), 2.19 (m, 2H), 2.70 (m, 2H), 2.83 (m, 3H), 5.20 (m, 2H), 5.71-5.84 (m, 2H), 6.91 (m, 2H), 7.05 (m, 4H), 7.32 (m, 2H).
Reaction SMILES: [Si:1]([O:8][CH2:9]C1C=CN=C(C#N)C=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:18]([C:21]1[CH:26]=[C:25](Cl)[CH:24]=[CH:23][N:22]=1)(=[O:20])[CH3:19]>>[C:18]([C:21]1[CH:26]=[C:25]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:24]=[CH:23][N:22]=1)(=[O:20])[CH3:19]
Reactant: CC(=O)c1cc(Cl)ccn1
Reactant: CC(C)(C)[Si](C)(C)OCc1ccnc(C#N)c1
Product: CC(=O)c1cc(CO[Si](C)(C)C(C)(C)C)ccn1

Procedure:
The title compound was prepared from 4-(tert-butyldimethylsilyloxymethyl)pyridinecarbonitrile (A. Hadri et al., J. Heterocycl. Chem., 1993, 30, 631) according to the procedure for preparing 2-acetyl-4-chloropyridine described in Example 33.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:16]=3[N:15]=2)[CH2:9]1)C1C=CC=CC=1.Cl.C(Cl)Cl>CO.[Pd]>[Cl:23][C:21]1[CH:20]=[CH:19][C:17]2[NH:18][C:14]([CH:10]3[O:11][CH2:12][CH2:13][NH:8][CH2:9]3)=[N:15][C:16]=2[CH:22]=1
Reactant: Clc1ccc2[nH]c(C3CN(Cc4ccccc4)CCO3)nc2c1
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: ClCCl
Product: Clc1ccc2[nH]c(C3CNCCO3)nc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 26.3 %

Procedure:
To a solution of 4-benzyl-2-(5-chloro-1H-benzo[d]imidazol-2-yl)morpholine (2.1 g, 6.41 mmol), and hydrogen chloride (0.234 g, 6.41 mmol) in CH3OH (50 mL) stirred under nitrogen at room temperature was added palladium on carbon (0.068 g, 0.641 mmol). The reaction mixture was stirred under hydrogen at 25° C. for 3 hours. CH2Cl2 was added and the mixture was filtered. The filtrate was evaporated in vacuo and the residue was dissolved in water (10 mL). The crude product was purified via reverse phase chromatography, eluting with 5˜50% of CH3OH in water, to afford the title compound (400 mg) as a white solid. LC-MS (ES) m/z=238 [M+H]+.
Reaction SMILES: Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[C:15](=[O:22])[N:14]4[CH2:23][CH2:24][CH2:25][C@H:13]4[C:12]=23)[N:4]=1.[CH2:26]([NH:29][CH2:30][CH2:31][CH3:32])[CH2:27][CH3:28]>CN(C)C=O>[CH2:26]([N:29]([CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[C:15](=[O:22])[N:14]4[CH2:23][CH2:24][CH2:25][C@H:13]4[C:12]=23)[N:4]=1)[CH2:30][CH2:31][CH3:32])[CH2:27][CH3:28]
Reactant: CCCNCCC
Reactant: O=C1c2ccccc2-n2cnc(-c3noc(CCl)n3)c2[C@@H]2CCCN12
Solvent: CN(C)C=O
Product: CCCN(CCC)Cc1nc(-c2ncn3c2[C@@H]2CCCN2C(=O)c2ccccc2-3)no1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.9 %

Procedure:
A solution of 711 mg (2.0 mmol) of (S)-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in 10 ml of N,N-dimethylformamide was treated with 0.82 ml (6.0 mmol) of dipropylamine and stirred at room temperature under argon for 2 hrs. The solution was evaporated, the residue was triturated in 10 ml of water and the crystals were filtered off. The crude product was chromatographed on 30 g of silica gel (methylene chloride/acetone 9:1, then 4:1). There were obtained 840 mg of (S)-1-(5-dipropylaminomethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one, which was converted with ethereal hydrochloric acid into the hydrochloride. By recrystallization from acetonitrile there were obtained 685 mg (73%) of (S)-1-(5-dipropylaminomethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one hydrochloride (1:1.3) of m.p. 137°-140° (dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[C:7](=[O:13])[N:6](C)[C:5]2(O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.N[OH:24]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[C:7](=[O:13])[N+:6]([O-:24])=[C:5]2[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NO
Reactant: CN1C(=O)N(C)C(O)(c2ccccc2)c2cc(Cl)ccc21
Agent: Cl
Solvent: CCO
Product: Cn1c(=O)[n+]([O-])c(-c2ccccc2)c2cc(Cl)ccc21
Yield: 61 %

Procedure:
A stirred mixture of 3.03 g (0.01 mole) of 6-chloro-3,4-dihydro-4-hydroxy-1,3-dimethyl-4-phenyl-2(1H)-quinazolinone and 2.09 g (0.03 mole) of hydroxylamine hydrochloride in 50 ml of ethanol was refluxed for 5 days. The reaction mixture was cooled, and the solid portion was collected on a filter, washed with ethanol, and dried in air to give 1.75 g (61%) of 6-chloro-1-methyl-4-phenyl-2-(1H)-quinazolinone 3-oxide as yellow crystals: mp 289°-291°; 1H nmr (TFA) δ4.22 ppm (s, 3H) and 7.6-8.5 ppm (m, 8H).
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:30][O:29][C@@:5]2([O:9][C@H:8]3[CH2:10][C@H:11]4[C@@H:16]5[CH2:17][CH2:18][C@@H:19]6[CH2:24][C@@H:23]([OH:25])[CH2:22][CH2:21][C@:20]6([CH3:26])[C@H:15]5[CH2:14][CH2:13][C@:12]4([CH3:27])[C@H:7]3[C@@H:6]2[CH3:28])[CH2:4][CH2:3]1.C[C@H]1CO[C@@]2(O[C@H]3C[C@H]4[C@@H]5CC[C@H]6C[C@@H](O)CC[C@]6(C)[C@H]5CC[C@]4(C)[C@H]3[C@@H]2C)CC1>>[CH3:28][C@@H:6]1[C@:5]2([O:29][CH2:30][CH:2]([CH3:1])[CH2:3][CH2:4]2)[O:9][C@H:8]2[CH2:10][C@H:11]3[C@@H:16]4[CH2:17][CH2:18][CH:19]5[CH2:24][CH:23]([OH:25])[CH2:22][CH2:21][C@:20]5([CH3:26])[C@H:15]4[CH2:14][CH2:13][C@:12]3([CH3:27])[C@@H:7]12
Reactant: C[C@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@@H]5C[C@@H](O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C
Agent: C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C
Product: CC1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CCC5CC(O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C

Procedure:
Depending on its structure, a given saponin can have a particular biologic property and find use with the present formulation. A variety of structurally related saponins are known, the most variable structural feature being the glycosylation pattern. S. Budavari, ed., The Merck Index, 11th ed., Merck & Co., Inc., Rahway, N.J., 1990, p. 1328. Saponins also may contain additional modifications, such as the sarasaponins which are saponins with asteroid attached, and saponin structure can be modified by any number of enzymatic, chemical and/or mechanical means known in the art. Saponins from Yucca schidigera contain steroidal saponins with the major sapogenins being sarsapogenin and tigogenin. The sarsaponin yields on hydrolysis, sarsasapogenim (sarsasapogenim 5-beta, 20-betaF, 22-deltaF, 25-betaF; also known as spirostan-3-beta-01 and parigenin), glucose and galaetose. The sarasapogenim has a molecular formula of C27H44 O3. Nobel, Park S., Agaves, Oxford Univ. Press, New York, 1994. Accordingly, derivatives of these compounds which produce a formulation having the desired pest growth controlling properties are considered equivalents of the invention. Saponins have diverse activities which are attributable to the chemical make-up of a particular saponin and most typically are dependent on the source form which the saponin is derived. For example, saponins derived from Japanese Camilla control the growth of mosquito larvae. Saponins from sources other than Yucca plants can be used as active agents in insecticidal compositions. As appropriate, it is preferable to select a saponin that increases the pest growth controlling effect of a formulation as compared to a formulation that excludes the saponin.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:11][CH:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:13][C:14]#N.[OH-:22].[Na+].[OH2:24]>C(O)C>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:11][CH:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:13][C:14]([OH:24])=[O:22]
Reactant: O
Reactant: [OH-]
Reactant: COc1cccc(CC(CC#N)c2ccccc2)c1OC
Agent: [Na+]
Solvent: CCO
Product: COc1cccc(CC(CC(=O)O)c2ccccc2)c1OC
Yield: 98 %

Procedure:
4-(2',3'-Dimethoxyphenyl)-3-phenylbutanenitrile (20 g, 71 mmol), from Step 4, was dissolved in 1.5 L of ethanol. Sodium hydroxide (20 g, 0.5 mol) and 200 mL of water were added and the reaction mixture was heated at reflux temperature for 24 h. The solvent was removed in vacuo and 1 L of water plus 1 L of methylene chloride were added to the residue. The layers were separated and the organic layer discarded. The aqueous layer was acidified with concentrated hydrochloric acid and extracted with 3 L of ethyl acetate. The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 21 g (98% yield) of the title compound as an oil; 1H NMR (CDCl3) δ: 2.6-2.7 (m, 2H), 2.9 (d, 2H), 3.4-3.5 (m, 1H), 3.72 (s, 3H), 3.82 (s, 3H), 6.6 (dd, 1H), 6.73 (dd, 1H), 6.88 (t, 1H), 7.1-7.3 (m, 5H).
Reaction SMILES: [CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[C:5]1=[O:14])[CH2:2]C.[CH3:15]C1C=C2C(=CC=1)NC(=O)C2=O.C(Br)C>>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([CH3:15])=[CH:10][CH:11]=2)[C:6](=[O:13])[C:5]1=[O:14])[CH3:2]
Reactant: Cc1ccc2c(c1)C(=O)C(=O)N2
Reactant: CCCN1C(=O)C(=O)c2ccccc21
Solvent: CCBr
Product: CCN1C(=O)C(=O)c2cc(C)ccc21

Procedure:
Was prepared in an analogous manner to 1-propylindoline-2,3-dione using commercially available 5-methyl isatin (purchased from Fisher Scientific) and ethyl bromide (purchased from Fisher Scientific). 1H-NMR δ 7.42-7.38 (m, 2H), 6.80 (d, 1H), 3.77 (q, 2H), 2.34 (s, 3H), 1.31 (t, 3H).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH2:7][CH2:6][CH2:5][C:4]1=[O:8].[CH3:9][N:10]([CH3:21])[C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>O1CCOCC1>[CH3:9][N:10]([CH3:21])[C:11]1[CH:12]=[CH:13][C:14]([S:17]([N:3]2[CH2:7][CH2:6][CH2:5][C:4]2=[O:8])(=[O:19])=[O:18])=[CH:15][CH:16]=1
Reactant: O=C1CCCN1
Reactant: CN(C)c1ccc(S(=O)(=O)Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CN(C)c1ccc(S(=O)(=O)N2CCCC2=O)cc1
Reaction time: 1 h

Procedure:
3.44 g of sodium hydride (at 55-60% in oil) is added to a solution comprising 6.11 g of 2-pyrrolidinone and 200 cm3 of dioxan, with agitation for one hour at ambient temperature. 15.76 cm3 of 4-dimethylaminobenzenesulphonyl chloride [Beritche 43, 3038 (1910)]in solution in 250 cm3 of dioxan is added drop by drop, with agitation for one hour at ambient temperature. The sodium chloride is filtered off on celite, the dioxan is evaporated off under reduced pressure, the residue is crystallized from acetone and 3.90 g of expected product is obtained.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([N:31]4[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]4)[CH2:27][CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17]C(=O)OC(C)(C)C)=[CH:13][CH:12]=3)[C:3]=12.FC(F)(F)C(O)=O>ClCCl>[NH2:17][C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([N:31]4[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]4)[CH2:27][CH2:26]3)[N:9]=2)=[CH:16][CH:15]=1
Reactant: CN1CCN([C@H]2CC[C@@H](n3nc(-c4ccc(NC(=O)OC(C)(C)C)cc4)c4c(N)ncnc43)CC2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN1CCN([C@H]2CC[C@@H](n3nc(-c4ccc(N)cc4)c4c(N)ncnc43)CC2)CC1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 93.5 %

Procedure:
Cis-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)carbamate (4.0 g, 0.0079 mol) was triturated in anhydrous dichloromethane (75 mL) and the reaction mixture was cooled to 0° C. Trifluoroacetic acid (10 mL) was added dropwise and the resulting solution was warmed up to ambient temperature and stirred under an atmosphere of nitrogen for 1.5 hours. The solvents were removed under reduced pressure, the residue suspended in water (70 mL) and basified with saturated aqueous sodium bicarbonate solution. It was extracted with dichloromethane (3×150 mL), the combined organic extracts were dried with magnesium sulfate and the solvent was removed under reduced pressure to yield cis-3-(4-aminophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3.0 g, 0.00739 mol) as an off-white solid.
Reaction SMILES: [CH3:1][C:2]([CH3:6])=[CH:3][CH:4]=O.[CH3:7][C:8]([CH3:10])=[O:9]>[O-2].[Zn+2]>[CH3:1][C:2](=[CH:3][CH:4]=[CH:7][C:8](=[O:9])[CH3:10])[CH3:6]
Reactant: CC(C)=O
Reactant: CC(C)=CC=O
Agent: [O-2]
Agent: [Zn+2]
Product: CC(=O)C=CC=C(C)C
Temperature: 180 °C
Yield: 93 %

Procedure:
A mixture of 50 parts of 3,3-dimethylacrolein, 100 parts of acetone and 12 parts of zinc oxide is heated for 3 hours at 180° C and a pressure of 45 atmosphere in a vibrated autoclave. The reactor is then cooled and the mixture is fractionally distilled. 52.5 parts of 2-methyl-2,4-heptadien-6-one is obtained in a yield of 93% of theory based on 3,3-dimethylacrolein at a conversion 76% of theory and with a boiling point of 92° C at 15 mm Hg.