Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[N:8]=2)[CH:6]=1.C[Sn](C)(C)[C:31]1[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:4]2[N:5]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C@H:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:15])[N:8]=3)[CH:6]=[C:2]([C:31]3[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=3)[N:3]=2)=[CH:23][CH:24]=1
Reactant: C[Sn](C)(C)c1ccncc1
Reactant: C[C@H](Nc1nccc(-n2cc(Br)nc2-c2ccc(F)cc2)n1)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: C[C@H](Nc1nccc(-n2cc(-c3ccncc3)nc2-c2ccc(F)cc2)n1)c1ccccc1
Yield: 78.4 %

Procedure:
4-Bromo-2-(4-fluorophenyl)-1-(2-[1-(S)-phenylethyl]amino-4-pyrimidyl)imidazole (1.0 g; 2.28 mmol), 4-trimethylstannylpyridine (660 mg; 2.74 mmol) and PdCl2(PPh3)2 (160 mg; 0.228 mmol) are dissolved in xylenes (23 ml) and refluxed for 4 h. The reaction mixture is poured on saturated Na2CO3 solution and extracted with ethyl acetate three times. The combined organic phases were dried over Na2SO4, filtered, evaporated to dryness and purified via SiO2 chromatography (TBME/MeOH/NH3conc 99/9/0.1) to yield the title compound as a yellow foam (780 mg; 68%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[C:5]1[C:10]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])=[C:9]([NH2:16])[C:8]([NH2:17])=[N:7][C:6]=1[CH3:18])[CH3:2].C(O)(=O)C.[N:24]([O-])=O.[Na+]>O>[CH2:1]([O:3][C:4]([C:5]1[C:10]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])=[C:9]2[N:16]=[N:24][NH:17][C:8]2=[N:7][C:6]=1[CH3:18])=[O:19])[CH3:2]
Reactant: CCCCNc1c(N)c(N)nc(C)c1C(=O)OCC
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CCCCNc1c(C(=O)OCC)c(C)nc2[nH]nnc12
Reaction time: 8 h

Procedure:
2.66 g. of 5,6-diamino-4-butylamino-2-methylnicotinic acid ethyl ester (0.01 mol.) are dissolved in 20 ml. of acetic acid and 5 ml. of water. The mixture is cooled to 5° with stirring. At this temperature, a solution of 0.9 g. of sodium nitrite in 5 ml. of water is showly added dropwise. Stirring is continued for an additional 8 hours. The solvent is distilled off and the residue treated with 20 ml. of water and extracted three times with 10 ml. portions of chloroform. The organic layers are dried with sodium sulfate, filtered and evaporated. The crystalline 7-butylamino-5-methyl-3H-[1,2,3]-triazolo-[4,5-b]pyridine-6-carboxylic acid ethyl ester remains and is recrystallized from methanol, yield 2.3 g. (83%), m.p. 188°-189°.
Reaction SMILES: C(O[C:9]1[CH:17]=[CH:16][C:15](CCOS(C2C=CC(C)=CC=2)(=O)=O)=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12])C1C=CC=CC=1>CO.O1CCCC1.[C].[Pd]>[C:11]([NH2:13])(=[O:12])[C:10]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:9]=1
Reactant: Cc1ccc(S(=O)(=O)OCCc2ccc(OCc3ccccc3)c(C(N)=O)c2)cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 260.5 %

Procedure:
2-Benzyloxy-5-[2-(p-toluenesulfonyloxy)ethyl]benzamide (627 mg) was dissolved in methanol (5 ml) and tetrahydrofuran (5 ml), and 10% palladium carbon (wet, 50% water) (169 mg) was added to the solution. The mixture was stirred for 1 hour at room temperature under a hydrogen atmosphere, and the catalyst was filtered off. Removal of the solvent under reduced pressure gave 2-hydroxy-5-[2-toluenesulfonyloxy)ethyl]benzamide (465 mg).
Reaction SMILES: C(=O)C.[CH3:4][C:5]1[N:6]=[C:7]([C:23](=O)[CH3:24])[S:8][C:9]=1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]([CH3:22])([CH3:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=1.[BH3-]C#[N:28].[Na+].CCO.[ClH:33]>O1CCOCC1>[ClH:33].[ClH:33].[CH3:4][C:5]1[N:6]=[C:7]([CH:23]([NH2:28])[CH3:24])[S:8][C:9]=1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]([CH3:22])([CH3:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)c1nc(C)c(-c2ccnc(C(C)(C)C(F)(F)F)c2)s1
Agent: CC=O
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCO
Product: Cc1nc(C(C)N)sc1-c1ccnc(C(C)(C)C(F)(F)F)c1
Reaction time: 1 h

Procedure:
1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanone ethanone (1.6 g, 4.87 mmol), NH4OAc (5.6 g, 73.1 mmol), and NaBH3CN (1.2 g, 19.5 mmol) were taken up in 40 mL 200 proof EtOH, and heated at 130 C for 10 minutes in a sealed tube. The mixture was concentrated to remove the EtOH. Crude was taken up in 50 ml water+50 mL EtOAc. 6N NaOH was added until aqueous pH was ˜9. Separated layers, and extracted aqueous with EtOAc (50 ml). The combined organic layer was washed with 60 mL brine and dried with Na2SO4. Filtered and concentrated with reduced pressure to give 1.58 g crude tan oil. This material was taken up in 20 mL dioxane. 2.2 eq HCl (4N in dioxane) was added, and stirred 1 h. Yellow ppt was formed. The suspension was concentrated in vacuo to give 1.97 g 1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanamine dihydrochloride salt as a yellow-green solid, which was carried forward without further purification. Major product Anal. RP-HPLC tR=1.23 min. MS m/z 330.1 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-:24].[K+].[K+].OO>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:24])[NH2:22])=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(C#N)cn2)CC1
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(C(N)=O)cn2)CC1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 193.1 %

Procedure:
Combine a solution of 4-(5-cyano-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (1630 mg, 5.38 mmol) in DMSO (50 mL) with potassium carbonate (371 mg, 2.69 mmol). Cool the solution to 0° C. and add slowly hydrogen peroxide (1.61 mL). After 10 min, stir the reaction mixture at room temperature for 2 h. Add water (25 mL) and extract twice with CH2Cl2 (30 mL). Dry the organic layer over sodium sulfate, filter and concentrate to provide the title compound (1669 mg, 97%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[C:18]([F:25])[CH:17]=2)=[N:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1.[P:26]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])([O:28][CH2:29][C@@H:30]([NH2:39])[C:31]1[CH:36]=[C:35]([I:37])[CH:34]=[C:33]([F:38])[CH:32]=1)=[O:27].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN1C(=O)CCC1.C(OCC)(=O)C>[P:26]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])([O:28][CH2:29][C@@H:30]([NH:39][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:16]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([C@H:8]3[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]3)[N:4]=2)=[CH:17][C:18]=1[F:25])[C:31]1[CH:36]=[C:35]([I:37])[CH:34]=[C:33]([F:38])[CH:32]=1)=[O:27]
Reactant: CC(C)(C)OP(=O)(OC[C@@H](N)c1cc(F)cc(I)c1)OC(C)(C)C
Reactant: Nc1ncc([C@H]2CC[C@H](O)[C@@H](F)C2)nc1-c1ccc(C(=O)O)c(F)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: CC(C)(C)OP(=O)(OC[C@@H](NC(=O)c1ccc(-c2nc([C@H]3CC[C@H](O)[C@@H](F)C3)cnc2N)cc1F)c1cc(F)cc(I)c1)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.8 %

Procedure:
To a solution of 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acid (3927 mg, 9.3 mmol) in NMP (Volume: 60 mL) was added (S)-2-amino-2-(3-fluoro-5-iodophenyl)ethyl di-tert-butyl phosphate (4740 mg, 9.30 mmol), DIEA (9.75 mL, 55.8 mmol), and then HATU (5304 mg, 13.95 mmol). The reaction mixture was stirred at room temperature for 2 hours followed by LCMS. To the crude reaction was added 850 ml of ethyl acetate washed with saturated bicarbonate (2×), water (3×), saturated salt solution, dried sodium sulfate, filtered and dried to residue. The crude product was purified by silica gel chromatograph 330 g column eluting with 0-70% (EtOAc with 10% MeOH)/heptane. The desired peak was concentrated to constant mass to give 5.75 grams of crude product. The material was re-purified by silica gel chromatograph 330 g column eluting with 0-60% (EtOAc with 10% MeOH)/heptane to give 5.03 grams of crude product. The material was further purified by adding 1200 ml of ethyl acetate to dissolve and 200 ml of heptane, washed with 200 ml of 0.5 N HCl (5×), water, saturated sodium bicarbonate, water (3×), saturated salt solution, dried sodium sulfate, filtered and concentrated to constant mass to give 4.70 grams of desired product, yield used as is. (61% yield over two steps). LCMS (m/z): 805.4 (MH+), 0.99 min. 1H NMR (<cd3od>) d: 7.90 (s, 1H), 7.77-7.86 (m, 1H), 7.68-7.73 (m, 2H), 7.63 (dd, J=11.8, 1.2 Hz, 1H), 7.42-7.52 (m, 1H), 7.26 (d, J=9.5 Hz, 1H), 5.43 (t, J=5.7 Hz, 1H), 4.30-4.49 (m, 1H), 4.28 (t, J=6.3 Hz, 2H), 3.58-3.72 (m, 1H), 2.83 (t, J=11.6 Hz, 1H), 2.27 (dt, J=6.2, 3.1 Hz, 1H), 2.02-2.13 (m, 1H), 1.77-1.94 (m, 2H), 1.58-1.74 (m, 1H), 1.48-1.55 (m, 1H), 1.45 (d, J=5.8 Hz, 18H).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][NH2:10])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[C:17]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)(=[O:19])[CH3:18]>CC(C)=O.O>[C:17]([NH:20][C:21]1[CH:22]=[CH:23][C:24]([S:27]([NH:10][CH2:9][CH2:8][CH2:7][N:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)(=[O:29])=[O:28])=[CH:25][CH:26]=1)(=[O:19])[CH3:18]
Reactant: NCCCN1CCOCC1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)Nc1ccc(S(=O)(=O)NCCCN2CCOCC2)cc1
Temperature: 0 °C
Yield: 61.5 %

Procedure:
To the solution of 2.8 g (0.020 mol) of 3-morpholinopropylamine in 15 ml of acetone, the solution of 3.3 g (0.024 mol) of potassium carbonate in 3 ml of water was added under stirring. To this mixture, 5 g (0.021 mol) of 4-acetamidobenzenesulphonyl chloride XII was added portionwise at the room temperature for 15 min. The mixture was then stirred at the room temperature for another 2 hours. One half of the solvent volume was distilled off from the mixture, the mixture was cooled to 0° C., Obtained solid was separated, washed 3 times with 5 ml of ice water and dried. Afforded 4.2 g (62%) of 4-acetamido-N-(3-morpholinopropyl)benzenesulphonamide XIII, colourless solid, m.p. 97-98° C.
Reaction SMILES: [CH3:1]I.[S:3]=[C:4]1[NH:9][C:8](=[O:10])[CH2:7][C:6](=[O:11])[NH:5]1.[OH-].[Na+]>>[CH3:1][S:3][C:4]1[N:9]=[C:8]([OH:10])[CH:7]=[C:6]([OH:11])[N:5]=1
Reactant: CI
Reactant: O=C1CC(=O)NC(=S)N1
Agent: [Na+]
Agent: [OH-]
Product: CSc1nc(O)cc(O)n1

Procedure:
Methyl iodide can be added to a solution of 2-thioxo-dihydropyrimidine-4,6(1H,5H)-dione and aqueous sodium hydroxide to provide 2-(methylthio)pyrimidine-4,6-diol. The reaction is typically performed in a solvent such as but not limited to ethanol, and may require the use of heat. Addition of phosphorus oxychloride to 2-(methylthio)pyrimidine-4,6-diol will provide 4,6-dichloro-2-(methylthio)pyrimidine. The reaction is typically done at elevated temperature without an additional solvent. 4,6-Dichloro-2-(methylthio)pyrimidine can be added to a mixture of diisopropylamine and n-butyl lithium, followed by the addition of dry carbon dioxide gas to provide 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylic acid. The reaction is typically performed at reduced temperature in a solvent such as but not limited to tetrahydrofuran. A mixture of 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylic acid and thionyl chloride can be refluxed together and concentrated, followed by the addition of aqueous ammonia at reduced temperature in a solvent such as but not limited to tetrahydrofuran to provide 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxamide. A compound of formula (1A) wherein B, R2, R3, and m are as described herein, can be reacted with 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxamide in the presence of a base such as but not limited to N,N-diisopropylethylamine to provide compounds of formula (4). The reaction typically requires the use of heat and a solvent such as but not limited to 1,4-dioxane. Compounds of formula (5) can be prepared by reacting compounds of formula (4) with hydrazine hydrate. The reaction is typically performed at ambient temperature in a solvent such as but not limited to 1,4-dioxane. Methyl orthoformate can be reacted with compounds of formula (5) to provide compounds of formula (6). The reaction may require the use of heat. Compounds of formula (7), which are representative of the compounds of Formula (I), can be prepared by reacting compounds of formula (6) with an organozinc compound of formula (2A), wherein Z, A, R1, and n are as described herein and XA is a halide. The reaction typically involves the use of heat and a nickel or palladium catalyst such as but not limited to bis(triphenylphosphine)palladium(II) dichloride or tetrakis(triphenylphosphine)palladium(0) in a solvent such as but not limited to N-methylpyrrolidone, tetrahydrofuran, or mixtures thereof.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:17][N:18]1[C:26]2[C:21](=[CH:22][C:23]([CH2:27][NH2:28])=[CH:24][CH:25]=2)[CH:20]=[CH:19]1.CCN(C(C)C)C(C)C>CC(O)C>[CH:14]1([C:12]2[NH:11][N:10]=[C:9]([NH:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:28][CH2:27][C:23]4[CH:22]=[C:21]5[C:26](=[CH:25][CH:24]=4)[N:18]([CH3:17])[CH:19]=[CH:20]5)[N:7]=3)[CH:13]=2)[CH2:16][CH2:15]1
Reactant: Cn1ccc2cc(CN)ccc21
Reactant: Clc1nccc(Nc2cc(C3CC3)[nH]n2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Cn1ccc2cc(CNc3nccc(Nc4cc(C5CC5)[nH]n4)n3)ccc21
Temperature: 120 °C

Procedure:
A microwave vial was charged with 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (160 mg, 0.68 mmol), 296 (800 mg, 5.59 mmol), DIPEA (1 ml), and IPA (5.0 mL), sealed and heated at 120° C. for 18 h. It was concentrated and purified by SiO2 chromatography, and then preparative HPLC to afford 30 mg (12%) of I-33 as white solid.
Reaction SMILES: CC1C=CC(S(O[CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[CH2:24]([NH2:26])[CH3:25].C(#N)C>C(CC(C)(C)C)(C)C.CCOC(C)=O.CO>[F:23][C:19]1[C:17]2[O:18][C@@H:13]([CH2:12][NH:26][CH2:24][CH3:25])[CH2:14][O:15][C:16]=2[CH:22]=[CH:21][CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2COc3cccc(F)c3O2)cc1
Reactant: CCN
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CC(C)CC(C)(C)C
Product: CCNC[C@H]1COc2cccc(F)c2O1

Procedure:
Preparation according to Example 5 using [(2R)-8-fluoro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (4.0 g, 11.8 mmol), ethanamine (5 ml, 70% in water) and ACN (10 ml). Flash column chromatography (Isooctane/EtOAc/MeOH) yielded 2.0 g of the title compound. MS m/z (rel. intensity, 70 eV) 211 (M+, 17), 70 (10), 59 (4), 58 (bp), 56 (4).
Reaction SMILES: [N:1]1([C:7]2[N:12]=[C:11]([NH:13]C(OC)=O)[N+:10]([O-:18])=[C:9]([NH:19][C:20]([O:22][CH3:23])=[O:21])[CH:8]=2)[CH2:6][CH:5]=[CH:4][CH2:3][CH2:2]1.C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O.CO>[NH2:13][C:11]1[N+:10]([O-:18])=[C:9]([NH:19][C:20]([O:22][CH3:23])=[O:21])[CH:8]=[C:7]([N:1]2[CH2:2][CH:3]=[CH:4][CH2:5][CH2:6]2)[N:12]=1
Reactant: COC(=O)Nc1cc(N2CC=CCC2)nc(NC(=O)OC)[n+]1[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: ClC(Cl)Cl
Product: COC(=O)Nc1cc(N2CC=CCC2)nc(N)[n+]1[O-]
Reaction time: 0.5 h

Procedure:
10 G. of dimethyl 6-[3,6-dihydro-1(2H)-pyridyl]-2,4-pyrimidinedicarbamate-3-oxide are dissolved in 350 ml. of chloroform and 100 ml. of methanol. The solution obtained is treated with 5 g. of sodium carbonate in 100 ml. of water and the resulting mixture is stirred at room temperature for 80 hours. The mixture is then diluted with 250 ml. of water and adjusted to pH 12.5 with concentrated sodium hydroxide. The mixture is then stirred for 30 minutes and then the two phases are separated. The aqueous phase is extracted twice with methylene chloride. The combined organic extracts are dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue is chromatographed over silica gel using a mixture of chloroform and ethanol (90:10) for the elution, there being obtained pure methyl 2-amino-6-[3,6-dihydro-1(2H)-pyridyl]-4-pyrimidinecarbamate-3-oxide having a melting point of 174°-176° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-])=O)[C:3]=1[CH2:11][C:12]([OH:14])=O>C(O)(=O)C.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[CH2:11][C:12](=[O:14])[NH:8]2
Reactant: O=C(O)Cc1c(F)cccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CC(=O)O
Product: O=C1Cc2c(F)cccc2N1
Yield: 67.8 %

Procedure:
(2-fluoro-6-nitrophenyl)acetic acid (3.3 g, 16.6 mmol) was dissolved in acetic acid (20 mL) and hydrogenated over palladium on carbon (10%, 0.5 g) at 50 psi for 24 hours. The catalyst was removed by filtration through the Celite® reagent, which was washed with methanol, and the combined organics were then evaporated. The reaction mixture was then dissolved in ethanol (100 mL), 50 mg of para-toluenesulfonic acid was added, and the mixture heated under reflux for 1 hour. The mixture was poured into water, extracted with ethyl acetate, dried over magnesium sulfate, and evaporated. The solid was triturated with hexane/ethyl acetate (95/5) to give 1.7 g, 67% of 4-fluoro-1,3-dihydro-2H-indol-2-one: HRMS [M+H]+=152.0515
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[C:14]#[CH:15].[N+:20]([C:23]1[CH:30]=[C:29]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)=[O:33])[CH:28]=[CH:27][C:24]=1[CH:25]=[O:26])([O-:22])=[O:21].C(O)(=O)C>O1CCCC1>[OH:26][CH:25]([C:24]1[CH:27]=[CH:28][C:29]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)=[O:33])=[CH:30][C:23]=1[N+:20]([O-:22])=[O:21])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: Cc1ccc(C(=O)Nc2ccc(C=O)c([N+](=O)[O-])c2)cc1
Reactant: C#CC(=O)OCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Solvent: CC(=O)O
Product: CCOC(=O)C#CC(O)c1ccc(NC(=O)c2ccc(C)cc2)cc1[N+](=O)[O-]
Reaction time: 0.5 h
Yield: 90.3 %

Procedure:
To a solution of diisopropylamine (0.11 ml, 0.82 mmole) in tetrahydrofuran (2 ml) at -78° C. was added under the argon atmosphere 1.5N butyllithium (0.51 ml, 0.77 mmole), and the mixture was stirred for 30 minutes. Next, to this reaction mixture were added ethyl propiolate (93 μl, 0.92 mmole) followed by a solution of 2-nitro-4-(p-toluoylamino)-benzaldehyde (144.5 mg, 0.51 mmole), and the mixture was further stirred at -78° C. for 1 hour. After a solution of acetic acid (90 μl, 1.58 mmole) in tetrahydrofuran (1 ml) was added to the reaction mixture, it was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, water, a saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous saline in this sequence. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure to give ethyl 4-hydroxy-4-(2-nitro-4-(p-toluoylamino)-phenyl)-2-butynoate as an oil (176 mg). The product thus obtained was dissolved in toluene (2 ml), 4-methoxybenzylazide (250 mg, 1.53 mmole), and the mixture was stirred with heating at 100° C for 5 hours. The reaction mixture was cooled to room temperature, the resulting crystalline products were filtered to give the 1 : 1 mixture of ethyl 4-(hydroxy-(2-nitro-4-(p-toluoylamino)phenyl)methyl)-1-(4- methoxybenzyl)-1,2,3-triazole-5-carboxylate (a-i) and ethyl 5-(hydroxy-(2-nitro-4-(p-toluoylamino)phenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylate (a-2) (103.4 mg, 37%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=O)[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.Cl.[OH:18][NH3+:19].O>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[N:19][OH:18])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: O=C(Cn1cncn1)c1ccc(Cl)cc1Cl
Reactant: [NH3+]O
Agent: Cl
Solvent: CCO
Solvent: O
Product: ON=C(Cn1cncn1)c1ccc(Cl)cc1Cl
Yield: 42.8 %

Procedure:
106.8 g (0.44 mol) of 1-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-yl)-ethan-1-one were dissolved in 780 ml of ethanol, 48 g of hydroxylammonium hydrochloride were added and the mixture was heated under reflux for 5 hours. Thereafter, 1,000 ml of water were added, and the reaction mixture was filtered. 51 g (45% of theory) of 1-(2,4-dichlorophenyl)-1-oximino-2-(1,2,4-triazol-1-yl)-ethane of melting point 165°-170° C. were obtained. ##STR8##
Reaction SMILES: Br[C:2]1[C:8]([Cl:9])=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[Cl:10].[Cu][C:12]#[N:13]>CN(C=O)C>[NH2:6][C:5]1[CH:7]=[C:8]([Cl:9])[C:2]([C:12]#[N:13])=[C:3]([Cl:10])[CH:4]=1
Reactant: N#C[Cu]
Reactant: Nc1cc(Cl)c(Br)c(Cl)c1
Solvent: CN(C)C=O
Product: N#Cc1c(Cl)cc(N)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
The title compound was prepared from the reaction of 4-bromo-3,5-dichloroaniline (6.88 g, 28.6 mmol) and Copper(I)cyanide (2.56 g, 28.6 mmol) in DMF (48 mL) under microwave irradiation at 190° C. for 1 h. After the completion of the reaction, the mixture was cooled to RT and quenched with 200 mL of 12% ammonia solution. The resultant mixture was stirred for 30 min at RT and the precipitate was filtered, washed with water and dried under vacuum. Yield 3.725 g. 1H NMR (400 MHz; d6-DMSO): δ 6.70 (s, 1H), 6.79 (s, 1H).
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[Cl-].[Al+3].[Cl-].[Cl-].[CH2:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:13][CH2:14][CH2:15][CH3:16]>>[CH2:12]([C:17]1[CH:18]=[CH:19][C:20]([C:1]([CH2:2][CH2:3][C:4]([OH:6])=[O:5])=[O:7])=[CH:21][CH:22]=1)[CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCc1ccccc1
Reactant: O=C1CCC(=O)O1
Agent: [Al+3]
Agent: [Cl-]
Product: CCCCCc1ccc(C(=O)CCC(=O)O)cc1

Procedure:
Succinic anhydride (8.6 g; 0.1 mole) is reacted with pentylbenzene (100 ml) and aluminum chloride (29 g; 0.22 mole) and the product isolated by the manner described in Example 3. Recrystallization from aqueous ethanol gives 3-(4-n-pentylbenzoyl)propanoic acid (17 g) as colorless crystals, m.p. 98°-100° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]23[CH2:17][CH2:16][CH2:15][C:14]2=[CH:13][N:12]([CH3:18])[CH2:11][CH2:10]3)[CH:6]=[CH:7][CH:8]=1>[Pt]=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@@:9]23[CH2:17][CH2:16][CH2:15][C@@H:14]2[CH2:13][N:12]([CH3:18])[CH2:11][CH2:10]3)[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(C23CCCC2=CN(C)CC3)c1
Agent: O=[Pt]
Product: COc1cccc([C@@]23CCC[C@@H]2CN(C)CC3)c1

Procedure:
Following the procedure set forth in Example 5, 4a-(3-methoxyphenyl)-2-methyl-3,4,4a,5,6,7-hexahydro-2-pyrindine was hydrogenated over platinum oxide to provide a 60:40 mixture of trans-4-a-(3-methoxyphenyl)-2-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-2-pyrindine and the corresponding cisosomer. The trans isomer was crystallized as the picrate salt. The cis isomer was isolated as the free base, namely cis-4a-(3-methoxyphenyl)-2-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-2-pyrindine; M.P.=40°-43° C.