Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=O)[C:11]3[CH2:14][CH2:15][CH2:16][C:10]=3[NH:9]2)=[C:4]([F:17])[CH:3]=1.P(Br)(Br)([Br:20])=O.C(N(CC)C1C=CC=CC=1)C.[OH-].[Na+]>O.CN(C)C=O>[Br:20][C:12]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[F:17])[N:9]=[C:10]2[CH2:16][CH2:15][CH2:14][C:11]=12
Reactant: O=P(Br)(Br)Br
Reactant: O=c1c2c([nH]n1-c1ccc(Cl)cc1F)CCC2
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)c1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: Fc1cc(Cl)ccc1-n1nc2c(c1Br)CCC2

Procedure:
A mixture of 6.3 parts of 2-(4-chloro-2-fluorophenyl)-1,4,5,6-tetrahydrocyclopentapyrazol-3(2H)-one, 7.9 parts of phosphorous oxybromide, 3.7 parts of N,N-diethylaniline and 10 parts of N,N-dimethylformamide was refluxed 24 hours and poured into 100 parts of water. After neutralizing with 50% aqueous sodium hydroxide solution, the mixture was extracted twice with 100 parts of diethyl ether. The ether extract was dried over anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 100 mm. Hg at ambient temperature. The crude product was recrystallized from ethanol-water to yield 2.1 parts of 3-bromo-2-(4-chloro-2-fluorophenyl)-2,4,5,6-tetrahydrocyclopentapyrazole melting at 106°-110°.
Reaction SMILES: [C:1](OCC1C=CC=CC=1)(=O)[CH:2]([CH3:4])O.[N:14](C(OCC)=O)=NC(OCC)=O.[CH2:26]([O:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][C:44]([OH:47])=[CH:43][N:42]=2)=[C:37]([F:48])[CH:36]=1)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>>[CH2:26]([O:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH:2]([C:1]#[N:14])[CH3:4])=[CH:43][N:42]=2)=[C:37]([F:48])[CH:36]=1)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCCCCCCCOc1ccc(-c2ccc(O)cn2)c(F)c1
Reactant: CC(O)C(=O)OCc1ccccc1
Reactant: CCOC(=O)N=NC(=O)OCC
Product: CCCCCCCCOc1ccc(-c2ccc(OC(C)C#N)cn2)c(F)c1

Procedure:
Optically active benzyl lactate is etherified by means of diethyl azodicarboxylate (DEAD)/triphenylphosphine with 2-(4-octyloxy-2-fluorophenyl)-5-hydroxypyridine (prepared in accordance with Example 1) and the benzyl group is then split off hydrogenolytically. The acid so obtained is converted as usual into the nitrile (oxalyl chloride, ammonia, thionyl chloride). Optically active 2-(4-octyloxy-2-fluorophenyl)-5-(1-cyanoethoxy)-pyridine is obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([SH:7])=[CH:3][CH:2]=1.[H-].[Na+].C1([OH:16])C=CC=CC=1.F[B-](F)(F)F.[NH2:22][C:23]1[C:66]([Cl:67])=[CH:65][C:26]([C:27]([NH:29][C@H:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38][N+]3C(C4C=CC=CC=4)=CC(C4C=CC=CC=4)=CC=3C3C=CC=CC=3)[CH2:32][C@H:31]2[O:63][CH3:64])=[O:28])=[C:25]([O:68][CH3:69])[CH:24]=1>>[OH2:16].[NH2:22][C:23]1[C:66]([Cl:67])=[CH:65][C:26]([C:27]([NH:29][C@H:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38][S:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:32][C@H:31]2[O:63][CH3:64])=[O:28])=[C:25]([O:68][CH3:69])[CH:24]=1
Reactant: COc1cc(N)c(Cl)cc1C(=O)N[C@H]1CCN(CCC[n+]2c(-c3ccccc3)cc(-c3ccccc3)cc2-c2ccccc2)C[C@H]1OC
Reactant: Oc1ccccc1
Reactant: Sc1ccncc1
Agent: F[B-](F)(F)F
Agent: [H-]
Agent: [Na+]
Product: COc1cc(N)c(Cl)cc1C(=O)N[C@H]1CCN(CCCSc2ccncc2)C[C@H]1OC
Product: O
Temperature: 25 °C
Reaction time: 4 h
Yield: 19 %

Procedure:
A mixture of 2.8 parts of 4-pyridinethiol, 1.2 parts of a sodium hydride dispersion 50% and 45 parts of phenol was stirred for 4 hours at room temperature. Then there were added 7.5 parts of cis-1-[3-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]propyl]-2,4,6-triphenylpyridinium tetrafluoroborate and 30 parts of phenol. Stirring was continued for 4 hours at reflux. The reaction mixture was extracted five times with 100 parts of a hydrochloric acid solution 1N. The combined acid aqueous phases were treated with potassium hydroxide and extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silic gel using a mixture of trichloromethane and methanol, saturated with ammonia (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 0.88 parts (19%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[3-(4-pyridinylthio)propyl]-4-piperidinyl]benzamide monohydrate; mp. 114.3° C. (compound 59).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]3[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:10]=1[CH3:11])=[O:5])C.[OH-].[Na+].O>CO.O1CCCC1>[CH:18]1([C:15]2[CH:16]=[CH:17][C:12]([N:9]3[C:10]([CH3:11])=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=[N:8]3)=[N:13][CH:14]=2)[CH2:19][CH2:20]1
Reactant: CCOC(=O)c1cnn(-c2ccc(C3CC3)cn2)c1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Cc1c(C(=O)O)cnn1-c1ccc(C2CC2)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.8 %

Procedure:
To a solution of 1-(5-cyclopropylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (14 g) in methanol (70 ml) and tetrahydrofuran (70 ml) were added 4 N aqueous solution of sodium hydroxide (70 ml) and water (50 ml), and stirred at room temperature overnight. After completion of the reaction, the organic solvent was evaporated in vacuo, then water and diethyl ether were added thereto, and the aqueous layer was separated. To the aqueous layer was added concentrated hydrochloric acid under ice-cooling to adjust the layer to pH 5, the precipitated solid was collected by filtration, and dried at 60° C. under air blow to give the titled compound (12.4 g) as a white solid. MS (ESI) m/z: 244 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Cl)=[CH:6][CH:5]=1)([O-:3])=[O:2].[O:12]([S:14]([CH3:16])=[O:15])[Na]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CCO>[CH3:16][S:14]([CH2:8][C:7]1[CH:10]=[CH:11][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)(=[O:15])=[O:12]
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Reactant: CS(=O)O[Na]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: CCO
Product: CS(=O)(=O)Cc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 120.2 %

Procedure:
To a mixture of 4-nitrobenzyl chloride (1 g, 5.8 mmol) and TBAI (0.11 g, 0.29 mmol) in EtOH (12 mL) was added NaOSOCH3 (0.77 g, 6.38 mmol). After heating at reflux for 2 h, the mixture was cooled to room temperature, and the precipitates were collected by filtration to give 1-(methylsulfonylmethyl)-4-nitrobenzene (1.5 g).
Reaction SMILES: Cl[CH2:2][S:3][C:4]1[CH:5]=[C:6]([CH3:10])[CH:7]=[CH:8][CH:9]=1.[F:11][C:12]1[CH:13]=[N:14][C:15](=[O:18])[NH:16][CH:17]=1.C(N(CC)CC)C.[K+].[Br-]>ClCCl>[CH3:10][C:6]1[CH:5]=[C:4]([S:3][CH2:2][N:16]2[CH:17]=[C:12]([F:11])[CH:13]=[N:14][C:15]2=[O:18])[CH:9]=[CH:8][CH:7]=1
Reactant: Cc1cccc(SCCl)c1
Reactant: O=c1ncc(F)c[nH]1
Agent: [Br-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cccc(SCn2cc(F)cnc2=O)c1

Procedure:
3-(Chloromethylthio)toluene (6.5 mmol) was added to a solution of 5-fluoropyrimidin-2-one (6.5 mmol) and triethylamine (6.5 mmol) in dichloromethane (75 ml) and the resultant mixture heated under reflux for 2 days. The solvent was then distilled off, the residue triturated with water and the residual material extracted with CCl4. Evaporation of the extracts and crystallisation of the residue from ethyl acetate gave the pure product; 0.40 g (25%), m.p. 124° C. (Found: C57.42; H4.63. Calc. for C12H11FN2OS: C57.59; H4.43) 1H NMR (DMSO d6); δ 2.28 (Me), 5.17(CH2), 7.2 (Ph), 8.05 (H-4), 8.70 (H-6). IR (KBr): 1670 cm-1 (CO), MS [70 eV, m/z (% rel. int.)]: 250 (8,M), 137(11), 136)36), 135(10), 128(7), 127(100), 100(34), 91(9).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:14]([O:15][CH3:16])=[CH:13][C:6]2[CH2:7][C:8](=[O:12])[NH:9][CH:10]=[CH:11][C:5]=2[CH:4]=1>C(O)(=O)C.[Pd]>[CH3:1][O:2][C:3]1[C:14]([O:15][CH3:16])=[CH:13][C:6]2[CH2:7][C:8](=[O:12])[NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1
Reactant: COc1cc2c(cc1OC)CC(=O)NC=C2
Agent: [Pd]
Solvent: CC(=O)O
Product: COc1cc2c(cc1OC)CC(=O)NCC2

Procedure:
A suspension of 21.9 gm (0.1 mol) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one and 1.5 gm of 10% palladium/charcoal in 200 ml of glacial acetic acid is hydrogenated at 50° C. under a hydrogen pressure of 5 bar. After the catalyst has been filtered off, the solvent is concentrated by evaporation in vacuo, and the residue is taken up in methylene chloride. After extraction with sodium bicarbonate solution and washing with water, the product is dried over magnesium sulfate, evaporated, and purified over silica gel with methylene chloride and then with increasing amounts of methanol (up to 10%).
Reaction SMILES: [C:1]([CH:3](C(OCC)=O)[CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[N:14]([CH3:15])[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[C:10]=2[N:23]=1)#[N:2].[OH-].[K+].O.CCOC(C)=O>C(O)CO>[CH3:15][N:14]1[CH2:13][CH2:12][NH:11][C:10]2[N:23]=[C:6]([CH2:5][CH2:4][CH2:3][C:1]#[N:2])[CH:7]=[CH:8][C:9]1=2
Reactant: CCOC(=O)C(C#N)CCc1ccc2c(n1)N(C(=O)OC(C)(C)C)CCN2C
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Solvent: CCOC(C)=O
Product: CN1CCNc2nc(CCCC#N)ccc21
Temperature: 150 °C
Yield: 68.4 %

Procedure:
A mixture of tert-butyl 6-(3-cyano-4-ethoxy-4-oxobutyl)-1-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxylate (5.78 g, 14.88 mmol) and KOH (powder, 1.25 g, 22.32 mmol) in ethylene glycol (30 mL) under N2 was heated at 150° C. for 3 hours. The mixture was cooled to 0° C. and portioned between water and EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. Flash chromatography (silica, 100% EtOAc) yielded a colorless oil (2.2 g, 66% yield). H NMR (CDCl3) δ 2.00 (t, 2H), 2.32 (t, 2H), 2.63 (t, 23H), 2.32 (s, 3H), 3.20 (t, 2H), 3.56 (t, 2H), 6.40 (d, 12H), 6.58(d, 1H), 4.20 (t, 2H), 6.41 (d, 1H), 6.89 (d, 1H).
Reaction SMILES: Cl[S:2]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][C:10](=[O:15])[C:9]3[NH:16][CH:17]=[C:18]([C:19]([OH:21])=[O:20])[C:8]=3[C:7]=2[CH:6]=1)(=[O:4])=[O:3].[Cl:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1>>[Cl:22][C:23]1[CH:29]=[CH:28][C:26]([NH:27][S:2]([C:5]2[CH:14]=[CH:13][C:12]3[NH:11][C:10](=[O:15])[C:9]4[NH:16][CH:17]=[CH:18][C:8]=4[C:7]=3[CH:6]=2)(=[O:3])=[O:4])=[CH:25][CH:24]=1.[CH2:18]([C:19]([O-:21])=[O:20])[CH3:17]
Reactant: Nc1ccc(Cl)cc1
Reactant: O=C(O)c1c[nH]c2c(=O)[nH]c3ccc(S(=O)(=O)Cl)cc3c12
Product: CCC(=O)[O-]
Product: O=c1[nH]c2ccc(S(=O)(=O)Nc3ccc(Cl)cc3)cc2c2cc[nH]c12
Yield: 14.6 %

Procedure:
This compound is prepared according to synthesis 25, from 150 mg (0.46 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid (synthesis 2) and 70 mg (0.55 mmol) of 4-chloro-aniline. After purification by chromatography on silica (eluent dichloromethane/methanol 96/4) then trituration in diethyl ether, 15 mg (7%) of 8-(4-chlorophenylsulfamoyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate is obtained in the form of a white solid.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([CH2:12][C:13]2[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][C:22]([CH2:26][CH3:27])([CH3:25])[CH2:23][CH3:24])[N:7]=1)=[O:5])C.[Li+].[OH-]>CO.C1COCC1.O>[Br:19][C:17]1[CH:16]=[CH:15][C:14]([O:20][CH2:21][C:22]([CH2:26][CH3:27])([CH3:25])[CH2:23][CH3:24])=[C:13]([CH:18]=1)[CH2:12][N:8]1[C:9]([CH3:11])=[CH:10][C:6]([C:4]([OH:5])=[O:3])=[N:7]1
Reactant: CCOC(=O)c1cc(C)n(Cc2cc(Br)ccc2OCC(C)(CC)CC)n1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CCC(C)(CC)COc1ccc(Br)cc1Cn1nc(C(=O)O)cc1C
Temperature: 100 °C

Procedure:
To a solution of 1-[5-bromo-2-(2-ethyl-2-methyl-butoxy)-benzyl]-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester, 22, (0.17 g, 0.38 mmol) in a mixture of MeOH (3 mL) and THF (6 ml) was added a solution of LiOH in 3 ml of H2O. The resulting mixture was heated at 100° C. in an Emrys microwave reactor for 20 minutes. The mixture was poured into water (20 mL) and extracted with EtOAc (3×15 mL). The organic layers were combined, washed with brine (30 mL), dried (MgSO4) and the volatiles were removed in vacuo to yield 1-[5-bromo-2-(2-ethyl-2-methyl-butoxy)-benzyl]-5-methyl-1H-pyrazole-3-carboxylic acid, 23.
Reaction SMILES: [C:1]([C:4]1[CH:28]=[CH:27][C:7]([CH2:8][NH:9][C:10](=[O:26])[C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[NH:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:6][CH:5]=1)([OH:3])=O.Cl.C[N:31](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.O>CN(C)C=O.N>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:10](=[O:26])[C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[NH:20][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)=[CH:27][CH:28]=1)(=[O:3])[NH2:31]
Reactant: CCN=C=NCCCN(C)C
Reactant: O=C(O)c1ccc(CNC(=O)c2cc([N+](=O)[O-])ccc2NC2CCCC2)cc1
Agent: Cl
Agent: N
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: NC(=O)c1ccc(CNC(=O)c2cc([N+](=O)[O-])ccc2NC2CCCC2)cc1
Temperature: 25 °C
Yield: 89.4 %

Procedure:
A mixture of N-(4-carboxybenzyl)-2-(cyclopentylamino)-5-nitrobenzamide (120 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (90.0 mg) and 1-hydroxybenzotriazole (63.4 mg) in anhydrous dimethylformamide (2 mL) was stirred for an hour at ambient temperature. After addition of 28% ammonia solution (10 drops), the mixture was stirred for 15 hours at ambient temperature and poured into water. The resulting precipitates were collected by filtration, washed with water and purified by a silica gel column chromatography eluting with 10% methanol in chloroform. The obtained product was triturated with diisopropyl ether to give N-(4-carbamoylbenzyl)-2-(cyclopentylamino)-5-nitrobenzamide (107 mg) as yellow powders.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([N:12]1[C:17](=[O:18])[C:16]2[S:19][C:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28](=[NH:31])OC)=[CH:24][CH:23]=3)=[CH:21][C:15]=2[N:14]=[CH:13]1)[CH3:11].[NH2:39][C:40]#[N:41]>CO>[C:40]([NH:41][C:28](=[NH:31])[C:25]1[CH:26]=[CH:27][C:22]([C:20]2[S:19][C:16]3[C:17](=[O:18])[N:12]([C@H:10]([CH3:11])[C@:9]([C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[F:1])([OH:38])[CH2:32][N:33]4[CH:37]=[N:36][CH:35]=[N:34]4)[CH:13]=[N:14][C:15]=3[CH:21]=2)=[CH:23][CH:24]=1)#[N:39]
Reactant: N#CN
Reactant: COC(=N)c1ccc(-c2cc3ncn([C@H](C)[C@](O)(Cn4cncn4)c4ccc(F)cc4F)c(=O)c3s2)cc1
Solvent: CO
Product: C[C@@H](n1cnc2cc(-c3ccc(C(=N)NC#N)cc3)sc2c1=O)[C@](O)(Cn1cncn1)c1ccc(F)cc1F

Procedure:
A solution of (1R,2R)-3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-6-[4-[imino(methoxy)methyl]phenyl]thieno[3,2-d]pyrimidin-4(3H)-one (0.35 mg, 0.652 mmol) (obtained in example 63) and NH2CN (140 mg, 3.26 mmol) in MeOH (15 mL) was refluxed overnight. The solvent was removed by concentration and the residue was partitioned between CHCl3 and 10% NaHCO3 solution. The organic phase was separated, dried over Na2SO4, filtered, concentrated and purified by flash chromatography to give the title compound as a white solid: mp 275°-278° C.; 1H NMR (300 MHz, MeOH-d4) δ (MeOH) 8.61 (s, 1H, N=CH--N), 8.18 (s, 1H, triazole), 8.02 (d, J=8.5, 2H, arom), 7.95 (d, J=8.5, 2H, arom), 7.81 (s, 1H, thiophene), 7.66 (s, 1H, triazole), 7.43 (dt, Jt =6.5, Jd =9, 1H, arom), 7.08 (ddd, Jd =2.5, Jd =8.5, Jd =14, 1H, arom), 6.89 (dt, Jd =2.5, Jt =8.5, 1H, arom), 6.09 (q, J=7.3, 1H, MeCH), 5.09 (d, J=14.2, 1H, CH(H)), 4.19 (d, J=14.2, 1H, CH(H)), 1.33 (d, J=7.3, 3H, CHMe); [α]D =+43.0° (c 0.25, MeOH). Analysis calculated for C26H20F2N8O2S.H2O: C 55.31; H 3.93; N 19.85; S 5.68. Found: C 55.06; H 3.74; N 18.57; S 5.28.
Reaction SMILES: [NH2:1][C:2]1([CH2:18][C:19]([OH:21])=[O:20])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1.S(Cl)([Cl:24])=O.[CH3:26]O>>[ClH:24].[NH2:1][C:2]1([CH2:18][C:19]([O:21][CH3:26])=[O:20])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1
Reactant: CO
Reactant: NC1(CC(=O)O)CCN(C(=O)OCc2ccccc2)CC1
Reactant: O=S(Cl)Cl
Product: COC(=O)CC1(N)CCN(C(=O)OCc2ccccc2)CC1
Product: Cl
Reaction time: 48 h

Procedure:
To a suspension of 300 mg of {4-amino-1-[(benzyloxy)carbonyl]piperidin-4-yl}acetic acid in 6 ml of methanol was added 150 μl of thionyl chloride, followed by stirring for 2 days. The reaction mixture was concentrated under reduced pressure, ether was added thereto, and the resulting solid was collected by filtration and dried to obtain 350 mg of benzyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate hydrochloride.
Reaction SMILES: [OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([O:8][CH2:9]CC)=[O:7])=[CH:4][CH:3]=1.C(O)C(O)C.OCC([C@H]([C@@H]([C@@H](CO)O)O)O)=O.C(O)(C)C>O>[CH3:9][O:8][C:6]([C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:13][CH:12]=1)=[O:7]
Reactant: CCCOC(=O)c1ccc(O)cc1
Agent: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: CC(C)O
Solvent: O
Solvent: CC(O)CO
Product: COC(=O)c1ccc(O)cc1
Yield: 0.2 %

Procedure:
A method for the preparation of an insecticidal gel composition comprising, admixing at 25° C. to 95° C. on a weight basis 14% to 22% of the gellant α-hydro-Ω-hydroxy-poly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer having an average molecular weight 12,500, mp 56° C., Brookfield viscosity of 3100 at 77° C., surface tension of a 0.1% aqueous solution: 40.6 dynes/cm; 0.15% to 0.5% propyl p-hydroxybenzoate; 0% to 30% propylene glycol; 0.5% to 6% of a C17 -C19 unsaturated fatty acid; a C7 -C17 saturated fatty acid or a mixture of the fatty acids; 1% to 5% of formula (I) insecticide ##STR4## 10% to 40% high fructose (55%) corn syrup; 0% to 10% isopropyl alcohol; 0.2% to 0.5% methyl p-hydroxybenzoate and 25% to 60% of water to obtain a composition having water to gellant ratios of 2.3/1 to 3.0/1 and a viscosity of 1.4×106 centipoise to 2.1×106 centipoise in a temperature range of 25° C. to 45° C.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)=[O:4].C1N2CN3CN(C2)C[N:18]1C3.C(Cl)(Cl)[Cl:28]>>[ClH:28].[NH2:18][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)=[O:4]
Reactant: ClC(Cl)Cl
Reactant: C1N2CN3CN1CN(C2)C3
Reactant: O=C(CBr)c1ccc(-c2ccccc2)cc1
Product: Cl
Product: NCC(=O)c1ccc(-c2ccccc2)cc1
Temperature: 48 °C
Reaction time: 4 h

Procedure:
To 400 ml of chloroform in a 3 liter flask equipped with a mechanical stirrer was added 50 g of 2-bromo-4'-phenylacetophenone and 26.4 g of hexamethylenetetramine. The solution was stirred at 48° C. for 4 hours, then cooled to 20° C., and the resulting solid collected and washed with a small amount of absolute ethanol. The solid was suspended in a solution of 270 ml of absolute ethanol and 134 ml of concentrated hydrochloric acid and stirred at 20° C. for 22 hours. This solid was collected washed with 100 ml of water and dried at 75° C. in vacuo, giving 54.9 g of the desired compound as a white solid, mp 260° C.
Reaction SMILES: Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:8]=2[C:21]=1[CH3:22].[NH2:23][C:24]1[C:29]([C:30]#[N:31])=[C:28](Cl)[N:27]=[CH:26][N:25]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:23][C:24]1[C:29]([C:30]#[N:31])=[C:28]([NH:14][C@H:12]([C:10]2[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:8]3[C:21]([CH3:22])=[C:4]([F:3])[CH:5]=[CH:6][C:7]=3[N:11]=2)[CH3:13])[N:27]=[CH:26][N:25]=1
Reactant: Cc1c(F)ccc2nc([C@H](C)N)n(-c3ccccn3)c12
Reactant: N#Cc1c(N)ncnc1Cl
Agent: Cl
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1c(F)ccc2nc([C@H](C)Nc3ncnc(N)c3C#N)n(-c3ccccn3)c12
Temperature: 90 °C
Yield: 48.5 %

Procedure:
To a solution of (S)-1-(6-fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (300 mg, 0.87 mmol) in IPA (10 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (135 mg, 0.87 mmol) and DIPEA (448 μL, 2.62 mmol) and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc). The product was triturated with diethyl ether then subjected to HPLC purification (C18, 10-90% MeCN in H2O, 0.1% formic acid, 20 min gradient) to give 289 as a white solid (164 mg, 48%). 1H NMR 400 MHz 6 (DMSO-d6): 8.55 (1H, br s), 8.00-7.91 (1H, m), 7.81-7.73 (1H, m), 7.70-7.60 (1H, m), 7.53 (1H, dd, J=8.7, 4.6 Hz), 7.55-7.45 (1H, m), 7.21-7.09 (1H, m), 7.06 (1H, dd, J=10.3, 8.7 Hz), 5.65-5.13 (1H, m), 1.63 (3H, s), 1.46 (3H, d, J=6.7 Hz). LCMS (Method K): RT=3.40 min, [M+H]+=389
Reaction SMILES: [H-].[Na+].[C:3]12([C:13]3[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=3[OH:20])[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH2:4]1)[CH2:10]2.[CH3:21]I.O>C1COCC1>[C:3]12([C:13]3[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=3[O:20][CH3:21])[CH2:4][CH:5]3[CH2:11][CH:9]([CH2:8][CH:7]([CH2:6]3)[CH2:12]1)[CH2:10]2
Reactant: Oc1ccc(Br)cc1C12CC3CC(CC(C3)C1)C2
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(Br)cc1C12CC3CC(CC(C3)C1)C2
Temperature: 20 °C
Reaction time: 2 h

Procedure:
To a suspension of sodium hydride (80% in oil, 4.32 g, 144 mmol) in 50 ml of THF, there are slowly added, while maintaining the temperature at 20° C., 36.8 g (120 mmol) of 2-(1-adamantyl)-4-bromophenol. The mixture is stirred for 1 hour at ambient temperature at which point 9 ml (144 mmol) of methyl iodide are added. The mixture is then stirred for 2 hours at 20° C., poured into water, extracted with ether, dried and evaporated. The product is purified by passage through a silica column (10×30 cm), eluting with a mixture of hexane (90%) and dichloromethane (10%). On evaporation, 26.2 g of a white solid are obtained. Yield--68%. Melting point: 138°-139° C.
Reaction SMILES: Br[C:2]1[N:3]([CH2:13][C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[C:4]2[N:5]=[C:6]([NH2:12])[NH:7][C:8](=[O:11])[C:9]=2[N:10]=1.NC(N)=[S:21]>CN(C=O)C>[NH2:12][C:6]1[NH:7][C:8](=[O:11])[C:9]2[NH:10][C:2](=[S:21])[N:3]([CH2:13][C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)[C:4]=2[N:5]=1
Reactant: NC(N)=S
Reactant: Nc1nc2c(nc(Br)n2Cc2cccs2)c(=O)[nH]1
Solvent: CN(C)C=O
Product: Nc1nc2c([nH]c(=S)n2Cc2cccs2)c(=O)[nH]1

Procedure:
A mixture of 8-bromo-9-[(2-thienyl)methyl]guanine (see Example 5) (2.0 g; 6.13 mmol), DMF (250 ml), and thiourea (0.93 g; 12.26 mmol) was heated under reflux for 20 hours and then the solvent was evaporated to dryness under reduced pressure. The residue was dissolved in 1N NaOH, treated with charcoal, filtered, and acidified with glacial AcOH to give a pale yellow solid. Analytical sample was prepared by repeating the purification process, yield 709 mg; mp >280° C.
Reaction SMILES: [Cl:1][C:2]1[N:9]=[C:8]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[CH:7]=[C:6]([CH3:17])[C:3]=1[C:4]#[N:5].[Cl:18][C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[O:21][CH2:22][CH2:23][NH2:24].C(=O)([O-])O.[Na+].CS(C)=O>O>[ClH:1].[Cl:18][C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[O:21][CH2:22][CH2:23][NH:24][C:2]1[N:9]=[C:8]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[CH:7]=[C:6]([CH3:17])[C:3]=1[C:4]#[N:5]
Reactant: Cc1cc(Nc2cc(C)c(C#N)c(Cl)n2)n[nH]1
Reactant: NCCOc1ccccc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: Cc1cc(Nc2cc(C)c(C#N)c(NCCOc3ccccc3Cl)n2)n[nH]1
Product: Cl
Temperature: 100 °C
Reaction time: 27 h

Procedure:
Compound A (200 mg, 813 μmol), 2-(2-chlorophenoxy)ethylamine (280 μl) and sodium hydrogencarbonate (683 mg) were added to DMSO (6 ml), and the mixture was stirred at 100° C. for 27 hr. After stirring, the reaction mixture was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate. This was converted to hydrochloride to give the object compound of 2-(2-(2-chlorophenoxy)ethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-methylnicotinonitrile hydrochloride (18 mg).