Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16]([OH:18])=O)([CH3:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[SH:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=1.N1C=CC=CC=1>ClCCl>[CH3:12][C:2]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16]([S:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=1)=[O:18])([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: O=C(O)c1ccc(S)cc1
Reactant: CCCCCCCCCC(C)(C)c1cc(C(=O)O)ccc1OC
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCCCCCCCC(C)(C)c1cc(C(=O)Sc2ccc(C(=O)O)cc2)ccc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 84 %

Procedure:
Crude 3-(1,1-dimethyldecyl)-4-methoxybenzoic acid, prepared starting with 1.6 g (5 mmoles) of 3-(1,1-dimethyldecyl)-4-methoxybenzoic acid, described in Example 11 of European Patent No. 0.232.199 is dissolved in 20 ml of dichloromethane. The solution is slowly added to a mixture of 771 mg (5 mmoles) of 4-mercaptobenzoic acid and 8 ml of pyridine. The reaction mixture is stirred at ambient temperature for 8 hours, evaporated to dryness, taken up in water, acidified to pH 5 with 1N HCl and extracted o with ethyl ether (500 ml). The organic phase is decanted, washed with water, dried over magnesium sulfate and evaporated to dryness. The resulting residue is purified by chromatography on a silica column, by using as the eluant ethyl ether. 1.92 g (84% yield) of 4-[3-(1,1-dimethyldecyl)-4-methoxybenzoylthio] benzoic acid whose melting point is 186°-187° C. are obtained.
Reaction SMILES: [C:1]([CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([Br:16])=[C:12]([Br:15])[CH:13]=2)[NH:8][C:7](=[O:17])[C:6]1=[O:18])([OH:3])=[O:2].[N+:19](C1C=C(C=CC=1)N)([O-:21])=[O:20].C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[C:1]([CH2:4][N:5]1[C:14]2[C:9](=[C:10]([N+:19]([O-:21])=[O:20])[C:11]([Br:16])=[C:12]([Br:15])[CH:13]=2)[NH:8][C:7](=[O:17])[C:6]1=[O:18])([OH:3])=[O:2]
Reactant: Nc1cccc([N+](=O)[O-])c1
Reactant: O=C(O)Cn1c(=O)c(=O)[nH]c2cc(Br)c(Br)cc21
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Product: O=C(O)Cn1c(=O)c(=O)[nH]c2c([N+](=O)[O-])c(Br)c(Br)cc21
Temperature: 28 °C
Reaction time: 4 h

Procedure:
To a stirred solution of N-carboxymethyl-6,7-dibromo-1,4-dihydroquinoxaline-2,3-dione (100 mg, 0.260 mmol) and m-nitroaniline (40 mg, 0.29 mmol) in dry DMF (2 mL) under N2 at 28° C., DCC (60 mg, 0.29 mmol) was added in one portion. The solution was stirred for 4 h at 28° C. The insoluble solid was filtered and washed with DMF (1 mL). The clear filtrate was then poured into water (30 mL). The precipitated solid was filtered and dried under vacuum (water aspirator) to obtain 65 mg crude product as a yellow powder. The product was purified by Soxhlet extraction in boiling ethanol (20 mL), keeping the oil bath temperature at 120° C., for 4 h. The insoluble material (in the thimble) was dried under vacuum to obtain 30 mg pure (1H NMR) N-(N'-(m-nitrophenyl)carboxamidyl)-methyl-6,7-dibromo-1,4-dihydroquinox-aline-2,3-dione as a white solid (some of the product also ends up being extracted by hot ethanol which accounts for the low yield of pure product). M.p.>300° C. (decomposes). 1H NMR: δ4.98 (s, 1H), 7.45 (s, 1H), 7.61 (d of d seen as a t, J=8.1 Hz) 7.79 (s, 1H), 7.86 (d, 1H, J=9 Hz), 7.91 (d, 1H, J=8.4 Hz), 8.54 (s, 1H), 10.76 (s, 1H), 12.28 (s, 1H). IR (KBr, cm-1): 3444, 3289, 1707, 1686, 1672, 1602. HRMS: Calculated for C16H10BF2N4O5, 495.9018; Observed, 495.9008.
Reaction SMILES: [P:1]([O:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]1[N:23]=[C:22]([C:24]2[C:25]([O:30][C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:38]4[C:47]5[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=5)[C:41]([C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)=[N:40][N:39]=4)=[CH:33][CH:32]=3)=[N:26][CH:27]=[CH:28][CH:29]=2)[CH:21]=[CH:20][N:19]=1)([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].[ClH:54]>O1CCOCC1>[ClH:54].[ClH:54].[P:1]([OH:8])([OH:3])([O:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]1[N:23]=[C:22]([C:24]2[C:25]([O:30][C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:38]4[C:47]5[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=5)[C:41]([C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)=[N:40][N:39]=4)=[CH:33][CH:32]=3)=[N:26][CH:27]=[CH:28][CH:29]=2)[CH:21]=[CH:20][N:19]=1)=[O:2]
Reactant: CC(C)(C)OP(=O)(OCCCNc1nccc(-c2cccnc2Oc2ccc(Nc3nnc(-c4ccccc4)c4ccccc34)cc2)n1)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Product: O=P(O)(O)OCCCNc1nccc(-c2cccnc2Oc2ccc(Nc3nnc(-c4ccccc4)c4ccccc34)cc2)n1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of di-tert-butyl 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propyl phosphate (95 mg, 0.13 mmol) in 1,4-dioxane (3.7 ml, 0.04 M) under nitrogen was added 4M HCl in Dioxane (0.23 mL, 0.91 mmol). Reaction stirred at RT for 18 hrs. The mixture appeared heterogeneous, and the solids were filtered, washed with dioxane and ether, and dried under reduced pressure to afford 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propyl dihydrogen phosphate dihydrochloride as a yellow solid. Mass of the title compound was obtained as the free base: MS m/z=622 [M+H]+. Calc'd for C32H30Cl2N7O5P: 621.6.
Reaction SMILES: [CH3:1][C:2]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])[CH3:3].[CH3:9][C:10]1[N:11]=[CH:12][N:13]([C@@H:15]([CH3:18])[CH2:16][OH:17])[CH:14]=1>C(Cl)Cl>[Si:5]([O:17][CH2:16][C@@H:15]([N:13]1[CH:14]=[C:10]([CH3:9])[N:11]=[CH:12]1)[CH3:18])([C:2]([CH3:4])([CH3:3])[CH3:1])([CH3:7])[CH3:6]
Reactant: Cc1cn([C@@H](C)CO)cn1
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: ClCCl
Product: Cc1cn([C@@H](C)CO[Si](C)(C)C(C)(C)C)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 2.6 %

Procedure:
In a 500-mL round-bottom flask, (S)-2-(4-methyl-1H-imidazol-1-yl)propan-1-ol (12.0 g) and TEA (12 mL) were dissolved in DCM at room temperature. To this solution, TBSCl (21.3 g, 0.141 mol) was added, and the resulting mixture was stirred at room temperature overnight. The mixture was washed with H2O, the organic phase was separated, and the aqueous was extracted with DCM. The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified on a silica gel column eluted with 1/30-1/9 MeOH/DCM, affording a sample (1.20 g), which was further purified by prep-HPLC, to afford the title compound (0.557 g). 1H NMR (CDCl3): δ 7.41 (d, 1H), 6.67-6.65 (m, 1H), 4.16-4.10 (m, 1H), 3.73-3.62 (m, 2H), 2.20 (d, 3H), 1.44 (d, 3H), 0.86 (s, 9H), −0.04 (s, 6H); LCMS: 255 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[CH2:4][CH2:5][CH2:6][C:7]([C:9]1[N:14]=[C:13]([CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:12]([OH:21])=[CH:11][CH:10]=1)=[O:8].Br[CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]/[C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1>>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH2:5][CH2:6][C:7]([C:9]1[N:14]=[C:13]([CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:12]([O:21][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]/[C:30]2[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=2)=[CH:11][CH:10]=1)=[O:8]
Reactant: COC(=O)CCCC(=O)c1ccc(O)c(CCC(=O)OC)n1
Reactant: COc1ccc(/C=C/CCCCBr)cc1
Product: COC(=O)CCCC(=O)c1ccc(OCCCC/C=C/c2ccc(OC)cc2)c(CCC(=O)OC)n1
Yield: 48.5 %

Procedure:
Under the conditions of example 1 D, 70 mg of 5-[3-hydroxy-2-(2-methoxycarbonylethyl)-6-pyridyl]-5-oxopentanoic acid methyl ester is reacted with 58 mg of (1E)-6-bromo-1-(4-methoxyphenyl)-1-hexene, worked up, and the crude product is chromatographed on silica gel with hexane/0-5% ethyl acetate. 52 mg of 5-{2-(2-methoxycarbonylethyl)-3-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-6-pyridyl}-5-oxopentanoic acid methyl ester is obtained as oil.
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:6]=[C:7]([S:16](Cl)(=[O:18])=[O:17])[CH:8]=[CH:9][C:10]=1[NH:11][S:12]([CH3:15])(=[O:14])=[O:13].Cl.[CH3:26][NH:27][CH3:28].[OH-].[Na+].Cl>O1CCOCC1>[CH3:26][N:27]([CH3:28])[S:16]([C:7]1[CH:8]=[CH:9][C:10]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:5]([O:4][C:3]2[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:2]=2[Cl:1])[CH:6]=1)(=[O:18])=[O:17]
Reactant: CNC
Reactant: CS(=O)(=O)Nc1ccc(S(=O)(=O)Cl)cc1Oc1ccc(Cl)cc1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CN(C)S(=O)(=O)c1ccc(NS(C)(=O)=O)c(Oc2ccc(Cl)cc2Cl)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
3-(2,4-Dichlorophenoxy)-4-methylsulphonylaminobenzene-sulphonic acid chloride (1.12 g, 2.6 mmol) was dissolved in dioxan (5 ml) and at 0° C. added dropwise to a solution of dimethylamine hydrochloride (1.10 g, 13.4 mmol) in 1N aqueous NaOH (13 ml, 13 mmol) and dioxan (13 ml). The mixture was stirred for 1 hour at 0° C., acidified with 1N HCl and extracted with ethyl acetate. The combined organic phases were dried over MgSO4 and the solvent was evaporated off. The residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate 6/4). Yield: 0.27 g=24% 13C (100 MHz, DMSO-d6) δ 150.02, 147.24, 133.01, 130.81, 130.42, 129.53, 129.18, 126.03, 123.74, 123.17, 122.57, 115.72, 41.03, 37.59
Reaction SMILES: [N+]([O-])(O)=O.[N+:5]([O:8][CH2:9][CH2:10][NH2:11])([O-:7])=[O:6].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[S:24][C:23](=[O:25])[NH:22][CH:21]2[C:26](O)=[O:27])=[CH:16][CH:15]=1>>[N+:5]([O:8][CH2:9][CH2:10][NH:11][C:26]([CH:21]1[CH:20]([C:17]2[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[CH:19][CH:18]=2)[S:24][C:23](=[O:25])[NH:22]1)=[O:27])([O-:7])=[O:6]
Reactant: NCCO[N+](=O)[O-]
Reactant: COc1ccc(C2SC(=O)NC2C(=O)O)cc1
Solvent: O=[N+]([O-])O
Product: COc1ccc(C2SC(=O)NC2C(=O)NCCO[N+](=O)[O-])cc1

Procedure:
A procedure similar to that described in Example 1 was repeated, but using 401 mg of N-(2-nitrooxyethyl)amine nitrate and 500 mg of 5-(4-methoxyphenyl)-2-oxothiazolidine-4-carboxylic acid, to obtain 408 mg of the title compound as colorless crystals, melting at 142°-143° C. (after recrystallization from methylene chloride).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[N:19]=[CH:18][N:17]=[C:16]2[NH:25][C:26]1[S:27][C:28]2[CH:34]=[C:33]([NH2:35])[CH:32]=[CH:31][C:29]=2[N:30]=1.ClCCl>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:35][C:33]2[CH:32]=[CH:31][C:29]3[N:30]=[C:26]([NH:25][C:16]4[C:15]5[C:20](=[CH:21][C:22]([O:23][CH3:24])=[C:13]([O:12][CH3:11])[CH:14]=5)[N:19]=[CH:18][N:17]=4)[S:27][C:28]=3[CH:34]=2)=[O:10])=[CH:4][CH:3]=1
Reactant: COc1cc2ncnc(Nc3nc4ccc(N)cc4s3)c2cc1OC
Reactant: O=C=Nc1ccc(Cl)cc1
Solvent: ClCCl
Solvent: CO
Product: COc1cc2ncnc(Nc3nc4ccc(NC(=O)Nc5ccc(Cl)cc5)cc4s3)c2cc1OC

Procedure:
1-(4-Chlorophenyl)-3-[2-(6,7-dimethoxyquinazolin-4-ylamino)benzothiazol-6-yl]urea was prepared from 4-chlorophenyl isocyanate (17.4 mg, 0.113 mmol) and N2-(6,7-dimethoxyquinazolin-4-yl)benzothiazole-2,6-diamine (40 mg, 0.113 mmol) according to GP 3. Preparative TLC of the reaction mixture (dichloromethane:methanol=9:1) furnished a yellowish solid (33.9 mg, 67 μmol, 59%). LC/ESI-MS: m/z=507 [M(35Cl)+H]+; m/z=505 [M(35Cl)−H]−; R′, =3.50 min.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=2)[C:7](=[O:22])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([Br:21])=[CH:10][CH:9]=2)=[O:4].C(N(CC)CC)C.[C:38]1(=[O:45])[O:44][C:42](=[O:43])[CH2:41][CH2:40][CH2:39]1>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:23][C:24]2[CH:25]=[CH:26][C:27]([NH:30][C:38](=[O:45])[CH2:39][CH2:40][CH2:41][C:42]([OH:44])=[O:43])=[CH:28][CH:29]=2)[C:7](=[O:22])[C:8]2[C:13]([C:14]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[CH:12][C:11]([Br:21])=[CH:10][CH:9]=2)=[O:4]
Reactant: COC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1Cc1ccc(N)cc1
Reactant: O=C1CCCC(=O)O1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1Cc1ccc(NC(=O)CCCC(=O)O)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 75.6 %

Procedure:
To a solution of 2-(4-aminobenzyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (139 mg) in tetrahydrofuran (5 ml) were added triethylamine (0.084 ml), glutaric anhydride (51 mg), and the mixture was stirred at room temperature for 24 hrs. The solvent was evaporated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and isopropyl ether was added to the obtained residue and the mixture was crystallized. The obtained crystals were collected by filtration and dried under reduced pressure at 50° C. to give the title compound (131 mg, 76%).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[C:11]2[C:6](=[C:7](Cl)[CH:8]=[C:9]([C:13]([OH:15])=[O:14])[C:10]=2[CH3:12])[S:5](=[O:18])(=[O:17])[CH2:4][CH2:3]1>C(O)C.O.[Zn]>[CH3:1][C:2]1([CH3:19])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13]([OH:15])=[O:14])[C:10]=2[CH3:12])[S:5](=[O:18])(=[O:17])[CH2:4][CH2:3]1
Reactant: Cc1c(C(=O)O)cc(Cl)c2c1C(C)(C)CCS2(=O)=O
Agent: [Zn]
Solvent: CCO
Solvent: O
Product: Cc1c(C(=O)O)ccc2c1C(C)(C)CCS2(=O)=O
Yield: 77.1 %

Procedure:
0.88 Gram (2.90 mmol) of 4,4,5-trimethyl-8-chlorothiochroman-6-carboxylic acid-1,1-dioxide was dissolved in ethanol having a water content of 60%, 0.55 g (8.70 mmol) of a zinc powder was added, and the mixture was refluxed under heat for 5 hours. After the completion of the reaction, 50 ml of water was added, the zinc powder was removed by filtration, and the remainder was extracted with ethyl acetate. The extract was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The ethyl acetate was distilled off under reduced pressure to give 0.60 g (yield 78%) of 4,4,5-trimethylthiochroman-6-carboxylic acid-1,1-dioxide.
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[CH2:3][S:4]([NH:7][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:21]([CH3:22])[N:20]=[C:19]([CH2:23][NH:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:18]=2)[CH:12]=1)([CH3:10])[CH3:9])(=[O:6])=[O:5].[CH:34](=O)[CH3:35]>CC#N.CC(O)=O>[F:33][C:2]([F:1])([F:32])[CH2:3][S:4]([NH:7][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:21]([CH3:22])[N:20]=[C:19]([CH2:23][N:24]([CH2:34][CH3:35])[C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[CH:18]=2)[CH:12]=1)([CH3:9])[CH3:10])(=[O:6])=[O:5]
Reactant: Cn1nc(CNc2ccc(F)cc2)cc1-c1cccc(C(C)(C)NS(=O)(=O)CC(F)(F)F)c1
Reactant: CC=O
Solvent: CC(=O)O
Solvent: CC#N
Product: CCN(Cc1cc(-c2cccc(C(C)(C)NS(=O)(=O)CC(F)(F)F)c2)n(C)n1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 11.4 %

Procedure:
NaB(CN)H3 (16 mg, 0.25 mmol) was added to a stirred solution of 2,2,2-trifluoro-N-[1-(3-{3-[(4-fluorophenylamino)methyl]-1-methyl-1H-pyrazol-5-yl}phenyl)-1-methylethyl]ethanesulfonamide (Example 3) (61 mg, 0.13 mmol) and acetaldehyde (11 mg, 0.25 mmol) in MeCN (5 mL), and AcOH (1 drop) and the mixture was stirred at RT for 16 hours. The mixture was concentrated under reduced pressure and then partitioned between NaHCO3 solution (20 mL) and EtOAc (70 mL). The organics were washed with brine (20 mL) and concentrated under reduced pressure whilst dry loading onto MgSO4. This residue was then purified by column chromatography on silica eluting with 100% Et2O and then by normal phase preparative HPLC to yield the desired product (7.6 mg, 12%). 1H NMR (CDCl3, 500 MHz) δ 7.55-7.48 (2H, m), 7.45 (1H, t, J=7.6 Hz), 7.32 (1H, d, J=7.6 Hz), 6.91 (2H, t, J=9 Hz), 6.78-6.71 (2H, m), 6.13 (1H, s), 4.91 (1H, s), 4.44 (2H, s), 3.85 (3H, s), 3.50-3.39 (4H, m), 1.80 (6H, s), 1.18 (3H, t, J=7.1 Hz). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%).
Reaction SMILES: [C:1]([C:5]1[CH:26]=[CH:25][C:8]([C:9]([NH:11][NH:12][C:13](=O)[C:14]2[CH:19]=[CH:18][C:17]([C:20]([O:22][CH3:23])=[O:21])=[CH:16][CH:15]=2)=O)=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:28].C(O)C.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[CH3:23][O:22][C:20](=[O:21])[C:17]1[CH:18]=[CH:19][C:14]([C:13]2[S:28][C:9]([C:8]3[CH:25]=[CH:26][C:5]([C:1]([O:3][CH3:4])=[O:2])=[CH:6][CH:7]=3)=[N:11][N:12]=2)=[CH:15][CH:16]=1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: COC(=O)c1ccc(C(=O)NNC(=O)c2ccc(C(=O)OC)cc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CCO
Product: COC(=O)c1ccc(-c2nnc(-c3ccc(C(=O)OC)cc3)s2)cc1

Procedure:
1,2-di(4-Carbomethoxybenzoyl)hydrazine (A), prepared as in Example 1, in pyridine was refluxed with phosphorus pentasulfide for 15 hours. The mixture was cooled and poured into 20% ethanol. After the solution was neutralized with sodium bicarbonate, the product, dimethyl-4,4'-(1,3,4-thiadiazol-2,5-diyl)dibenzoate (D), was obtained by filtration (m.p. 268°-270°, yiled 60%). Then III was obtained by reacting D in a similar manner as in Example 1 (m.p. >300°, 60%).
Reaction SMILES: [CH3:1][C@@H:2]([O:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25]C(=O)C)=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].C1(C)C=CC=CC=1.CN>CO>[CH3:1][C@@H:2]([O:10][C:11]([C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:20]=[CH:21][C:22]([OH:25])=[CH:23][CH:24]=2)=[CH:17][CH:18]=1)=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCC[C@@H](C)OC(=O)c1ccc(-c2ccc(OC(C)=O)cc2)cc1
Agent: CN
Solvent: CO
Solvent: Cc1ccccc1
Product: CCCCCCC[C@@H](C)OC(=O)c1ccc(-c2ccc(O)cc2)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A reactor was charged with 14 g (36 mmol) of (R)-1-methyloctyl-4′-acetoxybiphenyl-4-carboxylate and 150 ml of toluene, 5.7 g of a methanol solution containing 40% methylamine (73 mmol % of methylamine) was dropwise added, and a mixture was stirred at room temperature for 3 hours.
Reaction SMILES: [F:1][C:2]([F:25])([C:7]1[CH:8]=[CH:9][C:10]2[O:15][C:14]([CH2:18][F:19])([CH2:16][F:17])[CH:13]=[C:12]([C:20](=S)[NH:21][CH3:22])[C:11]=2[CH:24]=1)[C:3]([F:6])([F:5])[F:4].C(I)C.[H-].[Na+].[N:31]#[C:32][NH2:33].Cl>O1CCCC1>[C:32]([NH:33][C:20]([C:12]1[C:11]2[CH:24]=[C:7]([C:2]([F:25])([F:1])[C:3]([F:4])([F:5])[F:6])[CH:8]=[CH:9][C:10]=2[O:15][C:14]([CH2:18][F:19])([CH2:16][F:17])[CH:13]=1)=[N:21][CH3:22])#[N:31]
Reactant: CNC(=S)C1=CC(CF)(CF)Oc2ccc(C(F)(F)C(F)(F)F)cc21
Reactant: N#CN
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCI
Solvent: C1CCOC1
Product: CN=C(NC#N)C1=CC(CF)(CF)Oc2ccc(C(F)(F)C(F)(F)F)cc21
Yield: 49 %

Procedure:
A mixture of 0.14 g of 6-pentafluoroethyl-2,2-bis(fluoromethyl)-N-methyl-2H-1-benzopyran-4-carbothioamide, 0.31 g of ethyl iodide, 0.017 g of sodium hydride and 5 ml of tetrahydrofuran was refluxed with heating for 45 minutes. To the reaction mixture were added 0.081 g of cyanamide and 0.017 g of sodium hydride and the resultant mixture was refluxed with heating for 22 hours. To the reaction mixture was added a small amount of hydrochloric acid and the mixture was concentrated under reduced pressure. The resultant residue was subjected to silica gel column chromatography (developing solution, ethyl acetate:hexane=1:1) to obtain 0.07 g of N-cyano-6-pentafluoroethyl-2,2-bis(fluoromethyl)-N'-methyl-2H-1-benzopyran-4-amidine with a melting point of 178°-179° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].[CH:19]1([NH2:22])[CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C1COCC1>ClCCCl>[CH:19]1([NH:22][CH:15]2[CH2:16][CH2:17][N:12]([C:5]3[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:13][CH2:14]2)[CH2:21][CH2:20]1
Reactant: COc1cc(N2CCC(=O)CC2)ccc1[N+](=O)[O-]
Reactant: NC1CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCCl
Product: COc1cc(N2CCC(NC3CC3)CC2)ccc1[N+](=O)[O-]
Yield: 93.2 %

Procedure:
1-(3-Methoxy-4-nitrophenyl)piperidin-4-one (INTERMEDIATE 18, 0.70 g, 2.80 mmol), cyclopropanamine (0.160 g, 2.80 mmol) and sodium triacetoxyborohydride (0.889 g, 4.20 mmol) in DCE (15 mL)/THF (5 mL) were stirred at 25° C. for 2 h. The reaction mixture was concentrated in vacuo. The crude residue was taken up in EtOAc and washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by chromatography on silica gel (10% MeOH/EtOAc) to give the title product (0.76 g, 93%). m/z 292.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][N:5]=[C:6]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.[CH3:21][C:22]([Si:25](Cl)([CH3:27])[CH3:26])([CH3:24])[CH3:23].N1C=CN=C1.O>CN(C=O)C>[CH3:21][C:22]([Si:25]([CH3:27])([CH3:26])[O:1][CH2:2][CH2:3][NH:4][N:5]=[C:6]([C:14]1[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=1)[CH2:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)([CH3:24])[CH3:23]
Reactant: OCCNN=C(Cc1ccncc1)c1ccc(F)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCNN=C(Cc1ccncc1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98 %

Procedure:
To a solution of the 1-(4-fluorophenyl)-2-(4-pyridinyl)ethanone (2-hydroxyethyl)hydrazone prepared in step 1 (2.73 g, 0.01 mol) and (1,1-dimethylethyl)dimethylsilyl chloride (1.5 g, 0.01 mol) in 25 mL of DMF was added imidazole portionwise. The reaction mixture was stirred at room temperature overnight. Water was added and extracted with ethyl acetate, the organic layer was washed with water, washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 3.8 g of crude product, 1-(4-fluorophenyl)-2-(4-pyridinyl)ethanone [2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]hydrazone, as a yellow oil that was used in the next step without further purification.
Reaction SMILES: [BrH:1].C(O[CH:6]1[S:23][CH2:22][C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]([O:13][C:14](=[O:16])[CH3:15])[C@H:7]1[O:8][C:9](=[O:11])[CH3:10])(=O)C>C(O)(=O)C.ClC(Cl)C>[C:9]([O:8][C@@H:7]1[C@@H:12]([O:13][C:14](=[O:16])[CH3:15])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[CH2:22][S:23][C@H:6]1[Br:1])(=[O:11])[CH3:10]
Reactant: Br
Reactant: CC(=O)OC1SC[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Br
Reaction time: 2.5 h
Yield: 39 %

Procedure:
3.50 ml of a 30% solution of hydrobromic acid in glacial acetic acid are added at 10° C. to a solution of 2.10 g (6.3.10-3 mol) of 1,2,3,4-tetra-O-acetyl-5-thio-D-xylopyranose in 10 cm3 of dichloroethane. After 2 to 3 h, the reaction medium is hydrolyzed, washed with a solution of sodium bicarbonate and dried over sodium sulfate (Na2SO4) and the solvent is evaporated off to dryness under reduced pressure. 0.87 g (yield: 39%) of the expected product is obtained after precipitation in ether.