Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[C:2]([CH2:4]P(=O)(OCC)OCC)#[N:3].[CH3:13][O:14][CH2:15][C@@H:16]1[O:20][C:19](=[O:21])[N:18]([C:22]2[CH:27]=[CH:26][C:25]([CH:28]3[CH2:33][CH2:32][C:31](=O)[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)[CH2:17]1.C(O)(=O)C>C(O)C>[CH3:13][O:14][CH2:15][C@@H:16]1[O:20][C:19](=[O:21])[N:18]([C:22]2[CH:27]=[CH:26][C:25]([CH:28]3[CH2:29][CH2:30][C:31](=[CH:4][C:2]#[N:3])[CH2:32][CH2:33]3)=[CH:24][CH:23]=2)[CH2:17]1
Reactant: COC[C@H]1CN(c2ccc(C3CCC(=O)CC3)cc2)C(=O)O1
Reactant: CCOP(=O)(CC#N)OCC
Agent: [Na]
Solvent: CCO
Solvent: CC(=O)O
Product: COC[C@H]1CN(c2ccc(C3CCC(=CC#N)CC3)cc2)C(=O)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.3 %

Procedure:
0.66 g of sodium were dissolved in 70 ml of ethanol under argon. Thereafter, 5.08 g (=4.51 ml) of diethyl cyanomethylphosphonate dissolved in 20 ml of ethanol were added at 20°. The mixture was stirred at room temperature for 30 minutes and then 2.9 g of (R)-5-methoxymethyl-3-[4-(4-oxo-cyclohexyl)-phenyl]-oxazolidin-2-one were added. Thereafter, the reaction mixture was stirred at reflux for a further 1 hour, cooled to room temperature, adjusted to pH 6 with about 1 ml of glacial acetic acid and evaporated in a vacuum. The residue was dissolved in dichloromethane and washed three times with water, subsequently dried and evaporated. The excess phosphoric ester, which was still present in the residue, was distilled off at a bath temperature of ~100° and 0.03 mm vacuum (bP0.03 34°). The residue remaining (3.2 g) was chromatographed over 250 g of silica gel using medium pressure. Elution was carried out with dichloromethane, dichloromethane/ethyl acetate 20:1. The fractions which were pure according to thin-layer chromatography were combined and concentrated in a vacuum. 2.6 g of mixture of (R)- and (S)-[4-[4-[(R)-5-methoxymethyl-2-oxo-oxazolidin-3-yl]-phenyl]-cyclohexylidene]-acetonitrile (~1:2 E/Z or Z/E) were obtained as a slightly turbid oil. This was used directly for the reduction.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:17](=[O:18])[C:16]3[C:15]4[C:10](=[CH:11][C:12]([C:19]#[N:20])=[CH:13][CH:14]=4)[NH:9][C:8]=3[C:7]([CH3:22])([CH3:21])[C:6]=2[CH:23]=1.N1C=CN=C1.[C:29]([Si:33](Cl)([CH3:35])[CH3:34])([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])O.[Na+]>CN(C=O)C>[C:29]([Si:33]([CH3:35])([CH3:34])[O:1][C:2]1[CH:3]=[CH:4][C:5]2[C:17](=[O:18])[C:16]3[C:15]4[C:10](=[CH:11][C:12]([C:19]#[N:20])=[CH:13][CH:14]=4)[NH:9][C:8]=3[C:7]([CH3:21])([CH3:22])[C:6]=2[CH:23]=1)([CH3:32])([CH3:31])[CH3:30]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC1(C)c2cc(O)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC1(C)c2cc(O[Si](C)(C)C(C)(C)C)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21

Procedure:
The DMF solution of 8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 100 mg, 0.331 mmol), imidazole (67.5 mg, 3 eq.) and tert-butylchlorodimethylsilane (92.4 mg, 1.5 eq.) was stirred overnight at room temperature. To the reaction solution, saturated aqueous solution of sodium hydrogen carbonate was added followed by extraction with tert-butylmethyl ether. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white solid, 170 mg, 100%).
Reaction SMILES: Br[C:2]1[O:6][C:5]([CH3:7])=[C:4]([CH:8]=[O:9])[CH:3]=1.[Cl:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[N:15][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>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.O>[Cl:10][C:11]1[CH:12]=[C:13]([C:2]2[O:6][C:5]([CH3:7])=[C:4]([CH:8]=[O:9])[CH:3]=2)[CH:14]=[N:15][CH:16]=1
Reactant: OB(O)c1cncc(Cl)c1
Reactant: Cc1oc(Br)cc1C=O
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: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cc1oc(-c2cncc(Cl)c2)cc1C=O
Reaction time: 8 h
Yield: 49.4 %

Procedure:
A mixture of 5-bromo-2-methylfuran-3-carbaldehyde (1.9 g), 5-chloropyridine-3-boronic acid (1.9 g), tetrakis(triphenylphosphine)palladium(0) (0.6 g), 2N aqueous sodium carbonate solution (12 mL) and 1,2-dimethoxyethane (20 mL) was stirred overnight with refluxing under an argon atmosphere. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (0% ethyl acetate/hexane to 30% ethyl acetate/hexane), and crystallized from ethyl acetate/hexane to give the title compound (1.1 g, 49%) as a yellow solid.
Reaction SMILES: C([Li])CCC.C1([SiH3])C=CC=CC=1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18](/[CH:21]=[C:22](\[CH3:26])/[CH2:23][O:24][CH3:25])=[CH:17][CH:16]=1.[H][H]>C1COCC1>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([CH3:26])[CH2:23][O:24][CH3:25])=[CH:17][CH:16]=1
Reactant: COC/C(C)=C/c1ccc(OC)cc1
Reactant: [H][H]
Agent: [Li]CCCC
Agent: [SiH3]c1ccccc1
Solvent: C1CCOC1
Product: COCC(C)Cc1ccc(OC)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 74 %

Procedure:
In a dry sealable Schlenk flask under an argon atmosphere 0.0573 g (0.096 mmol) of (S,S) -ethylene-1,2-bis(η5 -4,5,6,7-tetrahydro- 1-indenyl)titanium (S)- 1,1'-binaphth -2,2'-diolate was dissolved in THF (10 mL). The vessel was degassed by exposure to vacuum (2×~10 sec) and put under an atmosphere of hydrogen and subsequently cooled to 0° C. in an ice water bath. After equilibration, a solution of n-butyllithium (0.123 mL, 1.52 M in hexanes, 0.187 mmol, 1.95 equiv) was added and the mixture was allowed to stir for 10 min. Phenylsilane (0.030 mL, 0.236 mmol, 2.4 equiv) was then added followed, after 5 minutes, by E-3-(4-methoxyphenyl)-2-methyl-1-methoxy-2-propene (0.345g, 1.92 mmol, 20 equiv). The flask was sealed and the solution moved into a dry box and transferred to a Parr® high pressure reaction vessel containing a magnetic stir bar. The vessel was sealed and moved to a fume hood where it was charged to ~2000 psig with hydrogen and placed in an oil bath at 65° C. The reaction mixture was allowed to stir for 43.5 h. The vessel was cooled to room temperature, vented and opened to air. The reaction mixture was worked up by partitioning between diethyl ether/hexane (1/4) and water and separating the layers. The aqueous layer was extracted twice with ether/hexane and the combined organic layers were dried over MgSO4. The solvent was removed in vacuo and the residue distilled at reduced pressure to yield 0.225g (1.42 mmol, 74%) of 3-(4-methoxyphenyl)-2-methyl-1-methoxypropane which had an ee of 92.7%.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.[C:10]1([CH:16]2[C:19]3([CH2:21][O:20]3)[O:18][CH2:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)Cl>[N:1]1[N:2]([C:19]2([CH2:21][OH:20])[CH:16]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:17][O:18]2)[N:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: c1ccc(C2COC23CO3)cc1
Reactant: c1ccc2[nH]nnc2c1
Solvent: ClCCl
Product: OCC1(n2nc3ccccc3n2)OCC1c1ccccc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 41 %

Procedure:
Benzotriazole (0.15 g, 1.3 mmol) in dry CH2Cl2 (4 mL) at 0° C. was added to a stirred solution under N2 of 3-phenyl-1,5-dioxaspiro[3.2]hexane (0.21 g, 1.3 mmol) in dry CH2Cl2 (4 mL) at 0° C. The reaction mixture was left to stir for 3 hours at 0° C. It was then concentrated to provide a light brown oil. The residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc 80:20) to give 2-(benzotriazol-2-yl)-2-(hydroxymethyl)-3-phenyloxetane as a white solid (0.15 g, 41%): mp 119-123° C.; IR (film) 3437 (br), 3094, 3064, 2941, 1560, 1499 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J=8.1 Hz, 2H), 7.35 (m, 7H), 5.42 (dd, J=8.7, 7.0 Hz, 1H), 5.20 (dd, J=8.7, 6.0 Hz, 1H), 5.09 (dd, J=6.8, 6.0 Hz, 1H), 4.25 (dd, J=13.0, 7.7 Hz, 1H), 4.20 (dd, J=13.0, 7.0 Hz, 1H), 2.6 (dd, J=7.3, 7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 144.8, 134.3, 129.3, 128.6, 128.5, 127.8, 119.1, 102.2, 69.8, 63.8, 48.8; MS (EI) m/z 281 (M+), 251, 162, 104 (100), 91; HRMS (FAB) calculated for C16H16N3O2 (M++H) m/z 282.1242. Found: 282.1248; Anal. calculated for C16H15N3O2: C, 68.31; H, 5.37; N, 14.94. Found: C, 68.13; H, 5.40; N, 14.97.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:8][C:7](=[O:9])[O:6][C:4](=[O:5])[CH2:3]1.[CH3:11][C:12]([O-:15])([CH3:14])[CH3:13].[K+]>C1COCC1.CCOCC>[C:12]([O:15][C:7](=[O:9])[CH2:8][C:2]([CH3:10])([CH3:1])[CH2:3][C:4]([OH:6])=[O:5])([CH3:14])([CH3:13])[CH3:11]
Reactant: CC1(C)CC(=O)OC(=O)C1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(CC(=O)O)CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 69 %

Procedure:
3,3-Dimethylglutaric anhydride (6.5 g, 45.7 mmol) was dissolved in THF (75 mL) and the t-BuOK, 1M in THF (52.5 mL, 52.5 mmol) was added and the mixture was stirred at room temperature for one hour. The reaction mixture was then diluted with ether, washed with 1N HCl, brine (3×), dried (MgSO4), and concentrated to give 6.8 g (69%) of the desired product as a colorless oil. 1H NMR (DMSO-d6) 12.0 (br s, 1H), 2.22 (s, 4H), 1.39 (s, 9H), 1.03 (s, 6H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:15](=[O:16])[C:14]3=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=[C:13]3[C:12]2=[O:22])[CH:5]=1)([O-])=O.C(O)C.[H][H]>[Pd].CN(C)C=O>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:15](=[O:16])[C:14]3=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=[C:13]3[C:12]2=[O:22])[CH:5]=1
Reactant: [H][H]
Reactant: Cc1ccc2c(c1)C(=O)N(c1cc([N+](=O)[O-])ccc1C)C2=O
Agent: [Pd]
Solvent: CCO
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)C(=O)N(c1cc(N)ccc1C)C2=O

Procedure:
The mixture of 4.28 g of N-(4-nitro-o-tolyl)-4-methylphthalimide, 200 ml of 95% aqueous ethanol and 0.21 g of 5% palladium on charcoal is hydrogenated at 3.1 atm and 45° until the hydrogen uptake ceases. The resulting suspension is diluted with the minimum amount of dimethylformamide to solubilize the organic material, filtered and evaporated. The residue is taken up in chloroform, the mixture filtered, evaporated and the residue recrystallized from methanol, to yield the N-(4-amino-o-tolyl)-4-methylphthalimide melting at 144°-147°.
Reaction SMILES: C[O-].[Na+].[NH2:4][C:5]([NH2:7])=[S:6].C([O:10][C:11](=O)[CH:12]([NH:18][C:19](=[O:27])[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=1)[C:13](OCC)=[O:14])C>C(O)C>[OH:14][C:13]1[C:12]([NH:18][C:19](=[O:27])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=2)=[C:11]([OH:10])[N:7]=[C:5]([SH:6])[N:4]=1
Reactant: NC(N)=S
Reactant: CCOC(=O)C(NC(=O)c1cccc(C)c1)C(=O)OCC
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1cccc(C(=O)Nc2c(O)nc(S)nc2O)c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 100.8 %

Procedure:
1.5 equivalents of sodium methoxide (30% in methanol) were added to 7.79 g of thiourea in 150 ml of absolute ethanol. A solution of 30 g of 2-(3-methyl-benzoylamino)malonic acid diethyl ester in 100 ml of absolute ethanol was added dropwise, and the mixture was stirred at 60° C. for 2 h. Then the mixture was cooled to 0° C. for 30 min, and the precipitate was filtered off with suction, washed and dried. 28.6 g of the crude title compound were obtained.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][CH:5]=1)=[O:3].[CH3:11][C:12]([Si:15](Cl)([CH3:17])[CH3:16])([CH3:14])[CH3:13].[Na+].[I-].CCN(CC)CC.C([O-])(O)=O.[Na+]>CC#N>[Br:10][C:7]1[CH:8]=[CH:9][C:4]([C:2]([O:3][Si:15]([C:12]([CH3:14])([CH3:13])[CH3:11])([CH3:17])[CH3:16])=[CH2:1])=[CH:5][CH:6]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(=O)c1ccc(Br)cc1
Agent: O=C([O-])O
Agent: [I-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: C=C(O[Si](C)(C)C(C)(C)C)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.4 %

Procedure:
A 250 mL round bottom flask was charged with 4-bromoacetophenone (1.99 g, 10.0 mmol), TBSCl (6.03 g, 40.0 mmol) and NaI (6.00, 40 mmol). The flask was capped with a rubber septum and placed under an atmosphere of Argon. After the addition of 200 mL MeCN, NEt3 (6.13 mL, 44.0 mmol) was introduced and the reaction mixture was stirred for 16 h at rt until TLC monitoring indicated complete conversion. The reaction mixture was poured onto sat. NaHCO3 solution and extracted with EtOAc (3×40 mL). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and evaporated to yield a brown slurry. Hexanes was added and the obtained heterogeneous mixture was filtered through a short plug of silica using hexanes to afford the title compound as a colorless oil (3.02 g, 96% yield). Rf=0.49 (1% EtOc/hexanes); 1H NMR (500 MHz, CDCl3) δ 7.47 (d, J=8.5 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 4.88 (s, 1H), 4.44 (s, 1H), 1.00 (s, 9H), 0.21 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 155.2, 137.0, 131.4, 127.1, 122.4, 91.6, 26.0, 18.5, −4.4; HR-MS(ESI): calcd. For C14H21ObrSi (M+): 312.0545; found: 312.0542.
Reaction SMILES: O[CH2:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.S(Cl)([Cl:26])=O.O>ClCCl>[Cl:26][CH2:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1
Reactant: O=S(Cl)Cl
Reactant: CCCCCCOc1ccc(/C=C/c2ccc(CO)cc2)cc1
Solvent: ClCCl
Solvent: O
Product: CCCCCCOc1ccc(/C=C/c2ccc(CCl)cc2)cc1
Yield: 60 %

Procedure:
To a solution of 1.7 g (5.5 mmole) of (E)-4-hydroxymethyl-4′-hexyloxystilbene (21) in 12 ml of dichloromethane cooled in an ice bath under a nitrogen atmosphere were added dropwise 0.5 ml of thionylchloride in 3 ml of dichloromethane. After 1.5 h 16 ml of water were added and the organic layer was separated. It was washed with 12 ml of brine, dried over MgSO4, and the solvent was evaporated. A white solid was obtained which was recrystallized from 80 ml of a 1:1 mixture of hexane and ethanol. 1.1 g of white crystals were obtained (yield 60%).
Reaction SMILES: [CH3:1][Si:2]([C:5]1([Si](C)(C)C)[CH:9]=[CH:8][CH:7]=[CH:6]1)([CH3:4])[CH3:3].[B:14](Cl)([Cl:16])[Cl:15]>>[CH3:1][Si:2]([C:5]1([B:14]([Cl:16])[Cl:15])[CH:9]=[CH:8][CH:7]=[CH:6]1)([CH3:4])[CH3:3]
Reactant: ClB(Cl)Cl
Reactant: C[Si](C)(C)C1([Si](C)(C)C)C=CC=C1
Product: C[Si](C)(C)C1(B(Cl)Cl)C=CC=C1
Temperature: 25 °C
Yield: 84.7 %

Procedure:
16 g (0.076 mole) of compound 1 were placed in a round bottom flask which was equipped with a dry ice cooling bath. 8.9 g (0.076 mole) BCl3 were condensed at −78° C. in a Schlenk tube and thereafter were added drop-wise to the round bottom flask over a period of 5 minutes. The reaction mixture was slowly heated to room temperature over 1 hour and was then maintained at 55 to 60° C. for a further 2 hours. All the volatile compounds were removed under vacuum (3 mm Hg=4 mbar). Subsequent distillation at 39° C. and 0.012 mbar gave 14.1 g of compound 2 (85% of the theoretical yield). The 1H NMR results agreed with the literature data and showed that a series of isomers had been produced (see J. Organometallic Chem. 169 (1979), 327). 11B NMR (64.2 MHz, C6D6): δ+31.5.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:9]=[C:10]([C:17]([OH:19])=O)[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:20][CH2:21][C:22]([OH:24])=[O:23]>>[O:14]=[C:12]1[C:11]2[C:10](=[CH:9][C:8]([S:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:16][CH:15]=2)[C:17](=[O:19])[N:20]1[CH2:21][C:22]([OH:24])=[O:23]
Reactant: NCC(=O)O
Reactant: O=C(O)c1ccc(Sc2ccccc2)cc1C(=O)O
Product: O=C(O)CN1C(=O)c2ccc(Sc3ccccc3)cc2C1=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 98.1 %

Procedure:
5.62 g of 4-phenylsulfanyl-phthalic acid (20.5 mmol) and 1.55 g of glycine (20.5 mmol) were ground thoroughly together in a mortar. Then the mixture was heated to 210° C. to 220° C. in an oil bath. The molten mass was stirred with a spatula at this temperature for 15 min before it was allowed to cool to ambient temperature in vacuo. 6.30 g of the title compound were obtained; MS-(−)-ion: M−1=311.8; 1H NMR (DMSO-d6): δ=7.82 (d, 1H), 7.46 to 7.62 (m, 7 H), 4.26 (s, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:22]=[CH:21][C:7]2[C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])=[N:9][CH2:10][C:11](=S)[NH:12][C:6]=2[CH:5]=1)([O-:3])=[O:2].[OH:23][CH2:24][C:25]([NH:27][NH2:28])=O>C(O)CCC>[N+:1]([C:4]1[CH:22]=[CH:21][C:7]2[C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])=[N:9][CH2:10][C:11]3[N:12]([C:25]([CH2:24][OH:23])=[N:27][N:28]=3)[C:6]=2[CH:5]=1)([O-:3])=[O:2]
Reactant: NNC(=O)CO
Reactant: O=[N+]([O-])c1ccc2c(c1)NC(=S)CN=C2c1ccccc1F
Solvent: CCCCO
Product: O=[N+]([O-])c1ccc2c(c1)-n1c(CO)nnc1CN=C2c1ccccc1F

Procedure:
In the manner given in Example 11, a solution of 1,3-dihydro-8-nitro-5-(o-fluorophenyl)-2H-1,4-benzodiazepine-2-thione in n-butyl alcohol is heated to reflux with hydroxyacetic acid hydrazide to give 9-nitro-1-(hydroxymethyl)-6-(o-fluorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([C:11]([OH:13])=[O:12])[OH:10])[OH:8])[OH:6])[OH:4].[NH2:14][C@H:15]([C:21]([OH:23])=[O:22])[CH2:16][CH2:17][C:18]([OH:20])=[O:19].CO>[Ni].O>[C:11]([CH:9]([OH:10])[CH:7]([OH:8])[CH:5]([OH:6])[CH:3]([OH:4])[CH2:2][NH:14][C@H:15]([C:21]([OH:23])=[O:22])[CH2:16][CH2:17][C:18]([OH:20])=[O:19])([OH:13])=[O:12]
Reactant: N[C@@H](CCC(=O)O)C(=O)O
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(=O)O
Agent: [Ni]
Solvent: O
Solvent: CO
Product: O=C(O)CC[C@H](NCC(O)C(O)C(O)C(O)C(=O)O)C(=O)O

Procedure:
As starting material D-glucuronic acid and L-(+)-glutamic acid were used. The reductive amination was carried out using Raney nickel as a catalyst and heating for 2 hours to 50° C. and for 4 hours to 70° C. The product obtained had a melting point of 90° C. (with sintering) an RF -value of 0.70 (determined on DC-finished plates of silica gel G (Merck) with a transporting liquid made up of 70 parts by volume of methanol and 30 parts by volume of water).
Reaction SMILES: Br[C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]2[CH:10]([C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=3)[N:11]([C:14]3[N:15]([CH3:21])[N:16]=[C:17]([CH3:20])[C:18]=3[F:19])[C:12](=[O:13])[C:4]=2[CH:3]=1.[CH3:30][O:31][C:32]1[N:37]=[C:36]([O:38][CH3:39])[C:35](B(O)O)=[CH:34][N:33]=1.BrC1N(C(C)C)C2C(C3C=CC(Cl)=CC=3)N(C3C=C(Cl)C=CC=3C)C(=O)C=2C=1.COC1C(B2OC(C)(C)C(C)(C)O2)=CN=C(N)N=1>>[CH3:30][O:31][C:32]1[N:37]=[C:36]([O:38][CH3:39])[C:35]([C:2]2[N:6]([CH:7]([CH3:8])[CH3:9])[C:5]3[CH:10]([C:22]4[CH:23]=[CH:24][C:25]([C:26]#[N:27])=[CH:28][CH:29]=4)[N:11]([C:14]4[N:15]([CH3:21])[N:16]=[C:17]([CH3:20])[C:18]=4[F:19])[C:12](=[O:13])[C:4]=3[CH:3]=2)=[CH:34][N:33]=1
Reactant: Cc1nn(C)c(N2C(=O)c3cc(Br)n(C(C)C)c3C2c2ccc(C#N)cc2)c1F
Reactant: COc1ncc(B(O)O)c(OC)n1
Agent: COc1nc(N)ncc1B1OC(C)(C)C(C)(C)O1
Agent: Cc1ccc(Cl)cc1N1C(=O)c2cc(Br)n(C(C)C)c2C1c1ccc(Cl)cc1
Product: COc1ncc(-c2cc3c(n2C(C)C)C(c2ccc(C#N)cc2)N(c2c(F)c(C)nn2C)C3=O)c(OC)n1

Procedure:
The title compound was prepared in analogy to the procedure described for Example 25 but 4-[2-bromo-5-(4-fluoro-2,5-dimethyl-2H-pyrazol-3-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-6-yl]-benzonitrile (Intermediate BJ) and 2,4-dimethoxypyrimidine-5-boronic acid were used instead of 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one and 4-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine respectively. ESI-MS: tR=1.00 min, [M+H]+ 516 (LC-MS 1).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]#[N:8].C[O-].[Na+].[NH:12]([C:14]([CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)=O)[NH2:13].C(O)(=O)C>CO>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[NH:13][N:12]=[C:14]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[N:8]=1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)NN)CC1
Reactant: N#Cc1cnccn1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(c2n[nH]c(-c3cnccn3)n2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of pyrazinecarbonitrile (2.0 g, 19 mmol) in methanol (20 mL) was treated with sodium methoxide in methanol (25 wt %, 1.3 mL, 5.7 mmol) at room temperature. After 30 minutes, a solution of tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate (4.6 g, 19 mmol) in methanol (20 mL) was added and the reaction was heated to reflux for 19 hours. The reaction mixture was concentrated, dissolved in ethoxyethanol (50 mL) and heated to reflux for 22 hours. The reaction was cooled to room temperature, quenched with acetic acid (0.38 mL, 6.6 mmol) and concentrated. The residue was suspended in ether and filtered to give tert-butyl 4-(5-pyrazin-2-yl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate as a solid. HRMS (M+H+): observed=331.1876, calculated=331.1877; 1H NMR (400 MHz, CD3OD): δ 9.29 (d, J=1.6 Hz, 1H), 8.70 (dd, J=2.4, 1.6 Hz, 1H), 8.64 (d, J=2.4 Hz, 2H), 4.19-4.15 (m, 2H), 3.15-3.09 (m, 1H), 2.97 (m, 2H), 2.07-2.03 (m, 2H), 1.84-1.75 (m, 2H), 1.48 (s, 9H).
Reaction SMILES: [CH3:1][N:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:3](=[O:11])[C:4]1[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=1)[OH:6].Br[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:1][N:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:3]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[O:6][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[O:11]
Reactant: CCOC(=O)CBr
Reactant: CN(C(=O)c1ccccc1O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccccc1C(=O)N(C)c1ccccc1
Yield: 97.9 %

Procedure:
A solution of N-methyl-N-phenylsalicylamide (13.5 g.), ethyl bromoacetate (10 g.) and anhydrous potassium carbonate (8.4 g.) in N,N-dimethylformamide (90 ml.) was stirred at room temperature for 7 hours. The resultant mixture was added to water and extracted with diethyl ether, and the extract was washed with 10% aqueous solution of sodium hydroxide and water in turn, dried over magnesium sulfate and then evaporated under reduced pressure to give oily ethyl 2-[2-(N-methyl-N-phenylcarbamoyl)phenoxy]acetate (18.23 g.).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[S:9][CH:10]=1)=[O:5])[CH3:2].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].CCN(C(C)C)C(C)C>O1CCOCC1>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:8]2[S:9][CH:10]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[N:7]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
Reactant: CCOC(=O)c1csc(Br)n1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1csc(N2CCN(C(=O)OC(C)(C)C)CC2)n1

Procedure:
A mixture of 2-bromo-thiazole-4-carboxylic acid ethyl ester (1.4 g, 5.93 mmol), piperazine-1-carboxylic acid tert-butyl ester (1.16 g, 1.05 eq.) and DIPEA (1.15 g, 1.5 eq.) in 1,4-dioxane (20 mL) was heated to reflux overnight. After cooling, the solvent was removed in vacuo. The crude product was purified on silica gel (EtOAc:hexanes=1:4) to afford the desired product as a pale yellow solid.