Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@@H:34]([CH:35]([CH3:37])[CH3:36])[CH2:33][O:32][C:31]4=[O:38])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][N:10](COCC[Si](C)(C)C)[N:9]=1.FC1C=C(C2C=NN3C=CC(N4[C@@H](C(C)C)COC4=O)=NC=23)C=CC=1C1N(COCC[Si](C)(C)C)N=CN=1.FC(F)(F)C(O)=O.N>ClCCl.C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@@H:34]([CH:35]([CH3:36])[CH3:37])[CH2:33][O:32][C:31]4=[O:38])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][NH:10][N:9]=1
Reactant: CC(C)[C@H]1COC(=O)N1c1ccn2ncc(-c3ccc(-c4ncn(COCC[Si](C)(C)C)n4)c(F)c3)c2n1
Agent: CC(C)[C@H]1COC(=O)N1c1ccn2ncc(-c3ccc(-c4ncnn4COCC[Si](C)(C)C)c(F)c3)c2n1
Agent: N
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CC#N
Product: CC(C)[C@H]1COC(=O)N1c1ccn2ncc(-c3ccc(-c4nc[nH]n4)c(F)c3)c2n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 31 %

Procedure:
A mixture of (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one and (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-5-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (0.137 g, 0.255 mmol) was dissolved in dichloromethane (0.55 mL). Trifluoroacetic acid (1.1 mL) was added and the mixture allowed to stir at ambient temperature for 18 hours. The reaction mixture was concentrated with multiple dichloromethane additions to give a crude residue. Acetonitrile (5 mL) and 28% aqueous ammonia (3 mL, 44 mmol) were added and the mixture concentrated with multiple acetonitrile additions to a yellow solid. Purification by normal phase chromatography, eluting with 50-100% EtOAc/dichloromethane, provided (S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (0.032 g, 31%) as a yellow solid. LCMS (APCI+) m/z 408.5 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ 11.24 (broad s, 1H), 8.61 (d, J=7.8 Hz, 1H), 8.43 (s, 1H), 8.26 (t, J=8.2 Hz, 1H), 8.09 (m, 2H), 8.00 (d×d, J=13.8, 1.0 Hz, 1H), 7.87 (d×d, J=8.4, 1.2 Hz, 1H), 4.99-4.96 (m, 1H), 4.50-4.41 (m, 2H), 2.94-2.86 (m, 1H), 1.10 (d, J=7.0 Hz, 3H), 0.94 (d, J=6.8 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:10][CH:11]=[C:12]([C:15]([CH3:17])=O)[C:13]=2[OH:14])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:18][N:19]1[C:23]([CH2:24][NH:25][C:26]([C:28]2[S:29][C:30]([C:33]([NH:35][NH2:36])=[O:34])=[CH:31][CH:32]=2)=[O:27])=[CH:22][CH:21]=[N:20]1.O>CN(C)C=O>[CH3:18][N:19]1[C:23]([CH2:24][NH:25][C:26]([C:28]2[S:29][C:30]([C:33]([NH:35][N:36]=[C:15]([C:12]3[C:13]([OH:14])=[C:9]([C:4]4[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=4)[S:10][CH:11]=3)[CH3:17])=[O:34])=[CH:31][CH:32]=2)=[O:27])=[CH:22][CH:21]=[N:20]1
Reactant: Cn1nccc1CNC(=O)c1ccc(C(=O)NN)s1
Reactant: CC(=O)c1csc(-c2ccc(Cl)c(Cl)c2)c1O
Solvent: O
Solvent: CN(C)C=O
Product: CC(=NNC(=O)c1ccc(C(=O)NCc2ccnn2C)s1)c1csc(-c2ccc(Cl)c(Cl)c2)c1O
Temperature: 70 °C
Yield: 76 %

Procedure:
2-(3,4-Dichlorophenyl)-3-hydroxy-4-methylcarbonylthiophene (50 mg, 0.17 mmol) and 5-hydrazinocarbonylthiophene-2-carboxylic Acid (1-methyl-1H-pyrazol-5-ylmethyl)amide (49 mg, 0.17 mmol) prepared in Reference Synthetic Example 18 were dissolved in N,N-dimethylformamide (0.50 mL) and heated at 70° C. for 24 hours and cooled to room temperature. After addition of water, the precipitated crystals were recovered by filtration, washed with water and chloroform and dried to give the desired product (yield 76%).
Reaction SMILES: [C:1]1([N:7]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27](B4OC(C)(C)C(C)(C)O4)=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)[C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:39][C:40]1[CH:45]=[CH:44][C:43](I)=[CH:42][CH:41]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:39][C:40]1[CH:45]=[CH:44][C:43]([C:27]2[CH:26]=[CH:25][C:24]([C:21]3[CH:20]=[CH:19][C:18]([N:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:8]4[C:17]5[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=5)[CH:11]=[CH:10][CH:9]=4)=[CH:23][CH:22]=3)=[CH:29][CH:28]=2)=[CH:42][CH:41]=1
Reactant: CC1(C)OB(c2ccc(-c3ccc(N(c4ccccc4)c4cccc5ccccc45)cc3)cc2)OC1(C)C
Reactant: Brc1ccc(I)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: Brc1ccc(-c2ccc(-c3ccc(N(c4ccccc4)c4cccc5ccccc45)cc3)cc2)cc1
Temperature: 95 °C
Yield: 90.8 %

Procedure:
A mixture of compound 7 (4.5 g, 9.0 mmol), 1-bromo-4-iodobenzene (5.12 g, 18 mmol), Pd(PPh3)4 (0.52 g, 0.45 mmol) and potassium carbonate (4.436 g, 32 mmol) in dioxane/water (150 ml/30 ml) was degassed and heated at 95° C. overnight. After being cooled to RT, the mixture was poured into dichloromethane (300 ml), washed with brine, dried over Na2SO4, then loaded on silica gel, purified by flash column (hexanes to hexanes/ethyl acetate 20:1) to give a light yellow solid 8 (4.30 g, in 90.7 yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl-].ClC1N(C)CC[NH+]1C.[CH3:26][O:27][C:28]1[C:29](=[O:56])[C:30]([CH3:55])=[C:31]([CH2:37][C:38]2[CH:39]=[CH:40][C:41]([O:47][CH2:48][C:49]3[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=3)=[C:42]([CH:46]=2)[C:43](O)=[O:44])[C:32](=[O:36])[C:33]=1[O:34][CH3:35]>C(Cl)Cl>[CH3:26][O:27][C:28]1[C:29](=[O:56])[C:30]([CH3:55])=[C:31]([CH2:37][C:38]2[CH:39]=[CH:40][C:41]([O:47][CH2:48][C:49]3[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=3)=[C:42]([CH:46]=2)[C:43]([NH:7][C:6]2[CH:8]=[CH:9][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[O:44])[C:32](=[O:36])[C:33]=1[O:34][CH3:35]
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OCc3ccncc3)c(C(=O)O)c2)=C(C)C1=O
Reactant: COc1ccc(N)cc1
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2ccc(OCc3ccncc3)c(C(=O)Nc3ccc(OC)cc3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 32.1 %

Procedure:
p-Methoxyaniline (0.078 g, 0.639 mmol), triethylamine (0.066 g, 0.639 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.108 g, 0.639 mmol) were added to a methylene chloride solution (10 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-(4-pyridylmethyloxy)benzoic acid (0.135 g, 0.318 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=9:1) and then recrystallized from ether to obtain the titled compound (0.054 g, 0.102 mmol, 32%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:17])[CH2:9][C:10]([CH3:16])([CH3:15])[C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Cl[C:42]1[CH:43]=[CH:44][C:45]([N+:50]([O-:52])=[O:51])=[C:46]([O:48][CH3:49])[CH:47]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:49][O:48][C:46]1[CH:47]=[C:42]([C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:17])[CH2:9][C:10]([CH3:16])([CH3:15])[C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=2)[CH:43]=[CH:44][C:45]=1[N+:50]([O-:52])=[O:51]
Reactant: COC(=O)C(C)(C)CC(=O)c1ccc(Br)cc1
Reactant: COc1cc(Cl)ccc1[N+](=O)[O-]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)C(C)(C)CC(=O)c1ccc(-c2ccc([N+](=O)[O-])c(OC)c2)cc1
Temperature: 80 °C
Yield: 48.2 %

Procedure:
A suspension of methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (200 mg, 0.67 mmol), bis(pinacolato)diboron (170 mg, 0.67 mmol), potassium acetate (197 mg, 2.01 mmol), and palladium acetate (5 mg, 0.02 mmol) in N,N-dimethylformamide (4.0 mL) was degassed by bubbling a flow of argon for 30 minutes. The reaction mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, 5-chloro-2-nitroanisole (125 mg, 0.67 mmol), tetrakis(triphenyl-phosphine)palladium(0) (23 mg, 0.02 mmol), and cesium carbonate (327 mg, 1.0 mmol) were added and the reaction mixture was heated at 80° C. for 16 h. The mixture was then cooled to rt, and water was added. The aqueous layer was extracted with ethyl acetate and the combined organic phases were dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure and the residue was purified by flash chromatography (Biotage Flash 40M, 1:3 ethyl acetate/hexane) to afford methyl 4-(3′-methoxy4′-nitro-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (120 mg, 48%). LC-MS ret. time 3.38 min, m/z 371.8 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.19 (s, 6H), 3.36 (s, 2H), 3.51 (s, 3H), 4.02 (s, 3H), 7.21–7.24 (m, 2H), 7.64–7.69 (m, 2H), 7.93 (d, 1H), 8.00–8.04 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[C:6]([CH:14]=[C:15]([NH2:17])[CH:16]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].CCN(CC)CC.[Cl:26][CH2:27][CH2:28][CH2:29][C:30](Cl)=[O:31]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[C:6]([CH:14]=[C:15]([NH:17][C:30](=[O:31])[CH2:29][CH2:28][CH2:27][Cl:26])[CH:16]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:8]
Reactant: O=C(Cl)CCCCl
Reactant: COC(=O)c1cc(N)cc(C(=O)OC(C)(C)C)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(NC(=O)CCCCl)cc(C(=O)OC(C)(C)C)c1
Temperature: 0 °C
Reaction time: 3 h
Yield: 93.7 %

Procedure:
A suspension of 5-amino-isophthalic acid 1-tert-butyl ester 3-methyl ester (D79) (3.4 g, 13.5 mmol, 1 equiv) in CH2Cl2 (25 ml) was treated with NEt3 (2.32 g, 23 mmol, 1.1 equiv) and cooled to 0° C. 4-chlorobutyryl chloride (1.6 g, 15.7 mmol, 1.1 equiv) was added dropwise and the resulting solution was stirred at 0° C. for 3 h then allowed to warm to room temperature and washed with 2N aqueous HCl solution, dried over MgSO4 and concentrated in vacuo. The residue was triturated with iso-hexane and Et2O to give 5-(4-chloro-butanoylamino)-isophthalic acid 1-tert-butyl ester 3-methyl ester (D80) (4.5 g, 94%) as a white solid.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=2)[O:10][CH2:9][CH:8]=1)(=O)=O.[CH:23]1(B2OC(C)(C)C(C)(C)O2)[CH2:25][CH2:24]1.O.[OH-].[Li+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH:23]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=3)[O:10][CH2:9][CH:8]=2)[CH2:25][CH2:24]1
Reactant: CC1(C)OB(C2CC2)OC1(C)C
Reactant: COC(=O)c1ccc2c(c1)C(OS(=O)(=O)C(F)(F)F)=CCO2
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Li+]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)c1ccc2c(c1)C(C1CC1)=CCO2
Temperature: 120 °C

Procedure:
Methyl 4-{[(trifluoromethyl)sulfonyl]oxy}-2H-chromene-6-carboxylate (596 mg, 1.76 mmol), cyclopropylboronic acid pinacol ester (803 μL, 4.40 mmol), lithium hydroxide monohydrate (185 mg, 4.40 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (387 mg, 0.53 mmol) were mixed in a microwave vial and dioxane (4.40 mL) and water (1.50 mL) were added. The reaction mixture was heated to 120° C. for 30 minutes under microwave irradiation before concentrating under vacuum. The crude residue was purified by silica gel chromatography to afford the desired product as a pale-yellow oil.
Reaction SMILES: [SH:1][CH2:2][C:3]([OH:5])=[O:4].C([O-])(O)=O.[Na+].[Br-].[Br:12][C:13]([CH:22]=[N:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:14][NH2+:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl>O.CO>[Br-:12].[C:3]([CH2:2][S:1][C:13]([CH:14]=[N:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:22][NH2+:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([OH:5])=[O:4]
Reactant: O=C(O)CS
Reactant: BrC(C=Nc1ccccc1)=C[NH2+]c1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Br-]
Solvent: CO
Solvent: O
Product: O=C(O)CSC(C=Nc1ccccc1)=C[NH2+]c1ccccc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A mixture of 560 mg (1.85 mmol) of 2-mercaptoacetic acid and 345 mg (4.1 mmol) of NaHCO3 in 3 mL water was heated with stirring at 60° C. for 1 h. Then a solution of 573 mg (1.5 mmol) of 2-bromo-3-phenylimino-1-propenyl(phenyl)ammonium bromide (synthesized as described in EP1221465A1) in 20 mL of methanol was added at 60° C., the mixture was stirred at this temperature for 5 h, cooled to RT, poured into a mixture of 50 g of ice and 1 mL of concentrated hydrochloric acid. The obtained yellow precipitate was filtered and dried.
Reaction SMILES: [CH:1](=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C=O.[CH2:15](NCCCC)CCC.C(O)(=O)CCCCCCCCCCCCCCCCC>>[CH2:15]=[C:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH:1]=[O:12]
Reactant: CCCCCCCCCCC=O
Reactant: CCCCNCCCC
Agent: C=O
Agent: CCCCCCCCCCCCCCCCCC(=O)O
Product: C=C(C=O)CCCCCCCCC
Temperature: 95 °C
Yield: 1583.3 %

Procedure:
A 3 L four-necked flask equipped with a stirrer, a thermometer and a reflux condenser was charged with 1043 g (6.0 mol) of n-undecanal, 520 g (6.4 mol) of a 37% by mass formaldehyde aqueous solution, 47 g (0.36 mol) of dibutyl amine and 33 g (0.11 mol) of stearic acid, and the contents in the flask were stirred while heating at 95° C. After the elapse of 30 min. it was confirmed that no n-undecanal was present in the raw mixture, and then the mixture was cooled and separated into two layers. The thus separated organic layer was subjected to distillation treatment, thereby obtaining 1062 g (5.7 mol) of α-methylene undecanal (purity as measured by gas chromatography: 97%) (yield based on theoretical amount: 95%).
Reaction SMILES: FC(F)(F)C(O)=O.[NH2:8][CH2:9][CH:10]([NH:22][C:23](=[O:25])[CH3:24])[C:11]1[C:16]([Cl:17])=[CH:15][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=1.[I:26][C:27]1[CH:31]=[CH:30][S:29][C:28]=1[C:32](O)=[O:33].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.C(N(CC)CC)C>C(O)C>[C:23]([NH:22][CH:10]([C:11]1[C:16]([Cl:17])=[CH:15][C:14]([C:18]([F:19])([F:20])[F:21])=[CH:13][N:12]=1)[CH2:9][NH:8][C:32]([C:28]1[S:29][CH:30]=[CH:31][C:27]=1[I:26])=[O:33])(=[O:25])[CH3:24]
Reactant: CC(=O)NC(CN)c1ncc(C(F)(F)F)cc1Cl
Reactant: O=C(O)c1sccc1I
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: [Cl-]
Solvent: CCO
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)NC(CNC(=O)c1sccc1I)c1ncc(C(F)(F)F)cc1Cl
Yield: 18.7 %

Procedure:
108 mg of N-{2-amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl}acetamide trifluoroacetate (0.0003 mol), 76 mg of 3-Iodo-thiophene-2-carboxylic acid (0.0003 mol), 83 mg of 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (0.0003 mol), 41 μL of triethylamine (0.0003 mol) are stirred in 3 mL of ethanol at room temperature overnight. The reaction mixture is concentrated to dryness and purified on silica to yield to 29 mg of N-{2-(acetylamino)-2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl}-3-iodo-2-thiophenecarboxamide.
Reaction SMILES: [Cl:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[N:5]=[C:4]([CH3:11])[C:3]=1[CH2:12][CH:13](Cl)[CH3:14].[C:16]([NH2:20])([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[Na+].[Na+].Cl.C(O)C>C(O)C>[ClH:1].[C:16]([N:20]1[C:2]2[N:7]3[N:8]=[CH:9][N:10]=[C:6]3[N:5]=[C:4]([CH3:11])[C:3]=2[CH2:12][CH:13]1[CH3:14])([CH3:19])([CH3:18])[CH3:17]
Reactant: Cc1nc2ncnn2c(Cl)c1CC(C)Cl
Reactant: CC(C)(C)N
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1nc2ncnn2c2c1CC(C)N2C(C)(C)C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of 2.4g of 7-chloro-6-(2-chloropropyl)-5-methyl-s-triazolo[1,5-a]pyrimidine, 0.9g of tert-butylamine, 1.8g of sodium carbonate and 20 ml of ethanol was stirred for 3 hours at room temperature and then refluxed for 5 hours. The hot reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by a column chromatography of alumina. To an oily substance thus obtained was added a solution of hydrogen chloride-ethanol and the crystals precipitated thereby were collected by filtration.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[N:9][CH:8]=1)[CH3:2].[H][H]>C(O)C.[Pd]>[CH2:1]([O:3][C:4](=[O:15])[CH2:5][CH:6]([OH:14])[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[N:9][CH:8]=1)[CH3:2]
Reactant: CCOC(=O)CC(=O)c1ccc(C)nc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CC(O)c1ccc(C)nc1
Temperature: 20 °C
Reaction time: 6 h

Procedure:
10.0 g (0.048 mol) of 6-methyl nicotinoyl acetic acid ethyl ester (distilled) was dissolved in 200 ml of 95 percent ethanol, mixed with 1 g of 5 percent palladium on activated carbon and poured into a 1-liter autoclave. The autoclave was put under 10 bars of hydrogen and stirred at 20° C. The hydrogenation ended after 6 hours. The autoclave was opened, and the reaction solution filtered and evaporated. 10.0 g of 3-hydroxy-3-(2-methyl-5-pyridyl)-propionic acid ethyl ester remained, which according to NMR and DC was pure. The yield, in relation to the 6-methyl nicotinyl acetic acid ethyl ester, was 100 percent.
Reaction SMILES: [CH3:1][C:2]1([CH3:34])[C@@H:4]([C:5]#[C:6][C:7]([O:9]CC(Cl)(Cl)Cl)=[O:8])[C@H:3]1[C:15]([O:17][C@H:18]([C:32]#[N:33])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:20]=1)=[O:16].C(O)(=O)C>[Zn].O>[CH3:1][C:2]1([CH3:34])[C@@H:4]([C:5]#[C:6][C:7]([OH:9])=[O:8])[C@H:3]1[C:15]([O:17][C@H:18]([C:32]#[N:33])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:20]=1)=[O:16]
Reactant: CC1(C)[C@H](C(=O)O[C@H](C#N)c2cccc(Oc3ccccc3)c2)[C@@H]1C#CC(=O)OCC(Cl)(Cl)Cl
Agent: [Zn]
Solvent: CC(=O)O
Solvent: O
Product: CC1(C)[C@H](C(=O)O[C@H](C#N)c2cccc(Oc3ccccc3)c2)[C@@H]1C#CC(=O)O
Reaction time: 1 h
Yield: 96.7 %

Procedure:
5.9 g of powdered zinc were added to a solution of 6.5 g of the product of Step C, 23.4 ml of acetic acid and 2.6 ml of water and the mixture was stirred for one hour and was filtered. The filtrate was decanted and the organic phase was washed with water. The combined aqueous phases were extracted with methylene chloride and the combined organic phases were dried, filtered and evaporated to dryness to obtain 4.7 g of crude (S)α-cyano-3-phenoxy-benzyl(1R,cis)2,2-dimethyl-3-(2-carboxyethynyl)-cyclopropane-carboxylate used as is for the next step.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[C:13](OCC)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]1=[O:23])(=O)C.[CH3:24][O:25][CH2:26][C:27]([NH:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)=[O:28].[OH-].[Na+]>CN(C=O)C.CO>[CH3:24][O:25][CH2:26][C:27]([NH:29][C:30]1[CH:36]=[CH:35][C:33]([NH:34]/[C:13](=[C:6]2\[C:5](=[O:23])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[CH:10][CH:11]=3)/[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:32][CH:31]=1)=[O:28]
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2ccccc21)c1ccccc1
Reactant: COCC(=O)Nc1ccc(N)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CN(C)C=O
Product: COCC(=O)Nc1ccc(N/C(=C2\C(=O)Nc3ccccc32)c2ccccc2)cc1

Procedure:
Prepared analogously to Examples 1 and 39 from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-2-indolinone and 4-methoxymethylcarbonylamino-aniline in DMF and subsequent treatment with sodium hydroxide solution in methanol.
Reaction SMILES: [C:1](O)(=O)C.[N:5]1[C:12]([NH2:13])=[N:11][C:9]([NH2:10])=[N:8][C:6]=1[NH2:7]>[NH4+].[O-][Mo]([O-])(=O)=O.[O-][Mo]([O-])(=O)=O.O>[CH4:1].[C:6]1([NH2:7])[N:8]=[C:9]([NH2:10])[N:11]=[C:12]([NH2:13])[N:5]=1.[C:6]1([NH2:7])[N:8]=[C:9]([NH2:10])[N:11]=[C:12]([NH2:13])[N:5]=1
Reactant: CC(=O)O
Agent: O=[Mo](=O)([O-])[O-]
Agent: Nc1nc(N)nc(N)n1
Agent: [NH4+]
Solvent: O
Product: C

Procedure:
Melamine molybdate was prepared in the presence of acetic acid as follows. 10 grams of melamine, 9.52 grams of acetic acid, and 250 ml water were dissolved together by refluxing in a 500 ml roundbottomed flask equipped with a stirrer and water-cooled condenser. 26.95 grams of ammonium dimolybdate was dissolved in 50 ml. hot water and then added to the first solution. A white precipitate formed immediately.
Reaction SMILES: [H-].[Na+].[OH:3]/[N:4]=[C:5](\[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)/[C:6]([O:8]CC)=[O:7].Cl[CH2:19][C:20]1[CH:39]=[CH:38][C:23]([O:24][CH2:25][C:26]2[N:27]=[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[O:29][C:30]=2[CH3:31])=[CH:22][CH:21]=1.Cl.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:31][C:30]1[O:29][C:28]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[N:27][C:26]=1[CH2:25][O:24][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][O:3]/[N:4]=[C:5](\[CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)/[C:6]([OH:8])=[O:7])=[CH:39][CH:38]=1
Reactant: CCOC(=O)/C(Cc1ccccc1)=N/O
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [H-]
Solvent: CN(C)C=O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CO/N=C(\Cc2ccccc2)C(=O)O)cc1
Reaction time: 1 h
Yield: 58 %

Procedure:
Sodium hydride (60% in oil, 127 mg) was added under a nitrogen atmosphere to a solution of ethyl E-2-hydroxyimino-3-phenylpropionate (661 mg) and 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (1.00 g) in N,N-dimethylformamide (10 ml) at room temperature and the mixture was stirred for 1 hour. After adding 1N HCl (5 ml), aqueous sodium bicarbonate was added, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residue was subjected to column chromatography on silica gel to obtain an oil from a fraction eluted with ethyl acetate-hexane (1:3, v/v). This oil was dissolved in tetrahydrofuran (10 ml)-methanol (5 ml), and 1N aqueous solution of sodium hydroxide (4 ml) was added and the mixture was stirred at room temperature for 1.5 hours. 1N HCl (4.5 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residual crystal was recrystallized from ethyl acetate-isopropyl ether to obtain E-2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-3-phenylpropionic acid (844 mg, yield 58%) as colorless crystals. m.p. 143-144° C. (decomposition)
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:8]([CH3:18])=[CH:9][C:10]([CH3:17])=[C:11]([S:13](Cl)(=O)=O)[CH:12]=2)[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[N:3]=1.C(O)C.Cl.O>[Zn].C(OCC)(=O)C>[NH2:1][C:2]1[N:6]([C:7]2[C:8]([CH3:18])=[CH:9][C:10]([CH3:17])=[C:11]([SH:13])[CH:12]=2)[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[N:3]=1
Reactant: Cc1cc(C)c(S(=O)(=O)Cl)cc1-n1nc(C(F)(F)F)nc1N
Agent: Cl
Agent: [Zn]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: O
Product: Cc1cc(C)c(-n2nc(C(F)(F)F)nc2N)cc1S
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 71 %

Procedure:
In a 25-ml eggplant flask provided with a magnetic stirrer was placed 3.3 g (9.3 mmol) of 5-(5-amino-3-trifluoromethyl-1H-1,2,4-triazol-1-yl)-2,4-dimethylbenzenesulfonyl chloride, followed by addition of 3.27 g (50 mmol) of zinc, 10 ml of ethanol and 5 ml (50 mmol) of 35% hydrochloric acid. The mixture was stirred at room temperature for 15 minutes. Then, the mixture was refluxed with heating, for 3 hours. The mixture was cooled to room temperature. Thereto were added 30 ml of water and 30 ml of ethyl acetate to give rise to phase separation. The aqueous phase was extracted with 30 ml of ethyl acetate. The ethyl acetate phase was washed with water and then with a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. Vacuum distillation was conducted to distill off ethyl acetate to obtain a title compound as 1.9 g of oil. Yield: 71%