Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:13]=[C:12]2[C:7]([C:8](=[O:22])[C:9]([C:19]([OH:21])=O)=[CH:10][N:11]2[CH2:14][CH2:15][O:16]C=O)=[CH:6][CH:5]=1)[CH3:2].[NH2:23][C:24]1[NH:28][N:27]=[N:26][N:25]=1>CN(C)C=O>[CH2:1]([O:3][C:4]1[N:13]=[C:12]2[C:7]([C:8](=[O:22])[C:9]([C:19]([NH:23][C:24]3[NH:28][N:27]=[N:26][N:25]=3)=[O:21])=[CH:10][N:11]2[CH2:14][CH2:15][OH:16])=[CH:6][CH:5]=1)[CH3:2]
Reactant: Nc1nnn[nH]1
Reactant: CCOc1ccc2c(=O)c(C(=O)O)cn(CCOC=O)c2n1
Solvent: CN(C)C=O
Product: CCOc1ccc2c(=O)c(C(=O)Nc3nnn[nH]3)cn(CCO)c2n1

Procedure:
7-Ethoxy-1(2-formyloxyethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (0.5 g) and N,N'-carbonyldiimidazole (0.4 g) in dimethylformamide (10 ml) were stirred and heated to 80° for 6 hours. 5-Amino-1H-tetrazole (0.42 g) was added and the mixture stirred and heated to 80° for 30 minutes. The solid was collected and dissolved in aqueous sodium hydroxide (10 ml, 2N) and the solution was acidified to pH 1 with dilute hydrochloric acid. The solid was filtered off, washed with water and dried, m.p. above 297° (d). (45 %).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]1[C:14]([CH2:15][OH:16])=[C:13]([CH:17]([CH3:19])[CH3:18])[O:12][N:11]=1.O[C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[C:33]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:32][CH:31]=[CH:30]3)=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]1[C:14]([CH2:15][O:16][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[C:29]4[C:34](=[CH:35][CH:36]=3)[C:33]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:32][CH:31]=[CH:30]4)=[CH:25][CH:26]=2)=[C:13]([CH:17]([CH3:19])[CH3:18])[O:12][N:11]=1
Reactant: CCOC(=O)c1cccc2cc(-c3ccc(O)cc3)ccc12
Reactant: CC(C)c1onc(Cc2c(Cl)cccc2Cl)c1CO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1cccc2cc(-c3ccc(OCc4c(Cc5c(Cl)cccc5Cl)noc4C(C)C)cc3)ccc12
Temperature: 80 °C
Yield: 62.7 %

Procedure:
A solution of [3-[(2,6-dichlorophenyl)methyl]-5-(1-methylethyl)-4-isoxazolyl]methanol (0.105 g, 0.35 mmol), ethyl 6-(4-hydroxyphenyl)-1-naphthalenecarboxylate (0.102 g, 0.35 mmol), triphenylphosphine (0.092 g, 0.35 mmol) and diisopropyl azodicarboxylate (0.063 mL, 0.35 mmol) in toluene (3.5 mL) was placed in microwave reaction tube and heated to 80° C. for 500 seconds. The solution was concentrated and purified by chromatography (silica gel, hexane to 1:4 ethyl acetate:hexanes) to provide the title compound (0.126 g, 60.9% as 0.2 EtOAc). 1H NMR (DMSO-d6): 8.79 (d, J=9 Hz, 1H), 8.28 (d, J=2 Hz, 1H), 8.23 (d, J=8 Hz, 1H), 8.09 (d, J=7 Hz, 1H), 7.98 (dd, J=2, 9 Hz, 1H), 7.81 (d, J=9 Hz, 2H), 7.61 (t, J=8 Hz, 1H), 7.46 (d, J=8 Hz, 2H), 7.32 (t, J=8 Hz, 1H), 7.16 (d, J=9 Hz, 2H), 5.08 (s, 2 H), 4.40 (q, J=7 Hz, 2 H), 4.29 (s, 2 H), 3.34 (septet, J=7 Hz, overlapping H2O 1 H), 1.37 (t, J=7 Hz, 3 H), 1.22 (d, J=7 Hz, 6 H). ESI-LCMS m/z 574 (M+H)+.
Reaction SMILES: [CH2:1]([Sn:5](=[O:10])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[CH3:11][CH:12]([CH3:16])[CH2:13][CH2:14][OH:15]>>[CH2:1]([Sn:5]([CH2:6][CH2:7][CH2:8][CH3:9])([O:15][CH2:14][CH2:13][CH:12]([CH3:16])[CH3:11])[O:10][Sn:5]([CH2:6][CH2:7][CH2:8][CH3:9])([CH2:1][CH2:2][CH2:3][CH3:4])[O:15][CH2:14][CH2:13][CH:12]([CH3:16])[CH3:11])[CH2:2][CH2:3][CH3:4]
Reactant: CC(C)CCO
Reactant: CCCC[Sn](=O)CCCC
Product: CCCC[Sn](CCCC)(OCCC(C)C)O[Sn](CCCC)(CCCC)OCCC(C)C
Temperature: 25 °C
Yield: 99 %

Procedure:
627 g (2.7 mol) of dibutyl tin oxide (Sankyo Organic Chemicals Co., Ltd., Japan) and 2000 g (22.7 mol) of 3-methyl-1-butanol (Kuraray Co., Ltd., Japan) were placed in a 5000 mL volumetric pear-shaped flask. The flask was connected to an evaporator (R-144, Shibata Co., Ltd., Japan) to which was connected an oil bath (OBH-24, Masuda Corp., Japan) equipped with a temperature controller, a vacuum pump (G-50A, Ulvac Inc., Japan) and a vacuum controller (VC-10S, Okano Seisakusho Co., Ltd., Japan). The purge valve outlet of this evaporator was connected to a line containing nitrogen gas flowing at normal pressure. After closing the purge valve of the evaporator to reduce pressure inside the system, the purge valve was opened gradually to allow nitrogen to flow into the system and return to normal pressure. The oil bath temperature was set to about 145° C., the flask was immersed in the oil bath and rotation of the evaporator was started. After heating for about 40 minutes in the presence of atmospheric pressure nitrogen with the purge valve of the evaporator left open, distillation of 3-methyl-1-butanol containing water began. After maintaining in this state for 7 hours, the purge valve was closed, pressure inside the system was gradually reduced, and excess 3-methyl-1-butanol was distilled with the pressure inside the system at from 74 to 35 kPa. After the fraction no longer appeared, the flask was taken out of the oil bath. After allowing the flask to cool to the vicinity of room temperature (25° C.), the purge valve was opened gradually and the pressure inside the system was returned to atmospheric pressure. 1173 g of reaction liquid were obtained in the flask. Based on the results of 119Sn—, 1H- and 13C-NMR analyses, 1,1,3,3-tetra-n-butyl-1,3-bis(3-methylbutyloxy) distannoxane was confirmed to have been obtained at a yield of 99% based on dibutyl tin oxide. The same procedure was then repeated 12 times to obtain a total of 10345 g of 1,1,3,3-tetra-n-butyl-1,3-bis(3-methylbutyloxy) distannoxane.
Reaction SMILES: [Si:1]([O:18][CH2:19][C@@H:20]1[CH2:25][O:24][CH2:23][CH2:22][N:21]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.OC[C@@H]1COCCN1C(OC(C)(C)C)=O.C([Si](Cl)(C1C=CC=CC=1)C1C=CC=CC=1)(C)(C)C>>[Si:1]([O:18][CH2:19][C@H:20]1[CH2:25][O:24][CH2:23][CH2:22][N:21]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCOC[C@H]1CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Agent: CC(C)(C)OC(=O)N1CCOC[C@H]1CO
Agent: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Product: CC(C)(C)OC(=O)N1CCOC[C@@H]1CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Yield: 95 %

Procedure:
The title product (2.0 g, yield: 95%) was prepared using a procedure similar to the one described for the synthesis of INTERMEDIATE 102. (R)-tert-Butyl 3-(hydroxymethyl)morpholine-4-carboxylate (commercially available, 1.0 g, 4.60 mmol) and tert-butylchlorodiphenylsilane (1.4 ml, 5.52 mmol) were used as starting materials. The title product was purified by column chromatography (ISCO, eluting with 0→50% EtOAc/hexanes).
Reaction SMILES: Br[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[N:10][C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:19]2[CH:20]=[C:21]([C:25]3[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:22]=[CH:23][CH:24]=2)O1>>[N:4]1[CH:3]=[C:2]([C:23]2[CH:22]=[C:21]([C:25]3[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:20]=[CH:19][CH:24]=2)[N:6]2[CH:7]=[CH:8][CH:9]=[N:10][C:5]=12
Reactant: Brc1cnc2ncccn12
Reactant: CC1(C)OB(c2cccc(-c3ccccc3C#N)c2)OC1(C)C
Product: N#Cc1ccccc1-c1cccc(-c2cnc3ncccn23)c1
Yield: 60 %

Procedure:
3-Bromoimidazo[1,2-a]pyrimidine (0.29 g, 1.68 mmol) was coupled with 3′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile as described in Example 1 to give 3′-(imidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile (260 mg, 60%) as an off-white powder: δH (360 MHz, CDCl3) 6.97 (1H, dd, J 7 and 4), 7.51 (1H, td, J 1 and 8), 7.59 (1H, dd, J 7 and 1), 7.62-7.73 (4H, m), 7.77-7.78 (1H, m), 7.82 (1H, dd, J 8 and 1), 7.96 (1H, s), 8.60 (1H, dd, J 7 and 2), 8.98 (1H, d, J 7 and 2); m/z (ES+) 297 (M++H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[O:5][C@@H:6]1[CH2:10][CH2:9][N:8]([C:11](OC(C)(C)C)=O)[CH2:7]1.ClC1[N:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:23]=1[C:24]([NH:26][C:27]1([C:30]2[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:32][CH:31]=2)[CH2:29][CH2:28]1)=[O:25]>>[Cl:44][C:41]1[CH:42]=[N:43][C:11]([N:8]2[CH2:9][CH2:10][C@@H:6]([O:5][C:4]3[CH:18]=[CH:19][CH:20]=[C:2]([F:1])[CH:3]=3)[CH2:7]2)=[C:23]([CH:40]=1)[C:24]([NH:26][C:27]1([C:30]2[CH:31]=[CH:32][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:38][CH:39]=2)[CH2:29][CH2:28]1)=[O:25]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](Oc2cccc(F)c2)C1
Reactant: COC(=O)c1ccc(C2(NC(=O)c3cc(Cl)cnc3Cl)CC2)cc1
Product: COC(=O)c1ccc(C2(NC(=O)c3cc(Cl)cnc3N3CC[C@@H](Oc4cccc(F)c4)C3)CC2)cc1
Yield: 106.4 %

Procedure:
The title compound (D205) (96 mg) was prepared according to the experimental procedure described in Description 160 starting from (R)-tert-butyl 3-(3-fluorophenoxy)pyrrolidine-1-carboxylate (D47) (100 mg, 0.355 mmol) and reacting in the second step with methyl 4-(1-(2,5-dichloronicotinamido)cyclopropyl)benzoate (D97) (D021/056/3) (65 mg, 0.177 mmol).
Reaction SMILES: Br[CH2:2][C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:14]=3[C:15]#[N:16])=[CH:11][C:6]=2[O:5][N:4]=1.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>ClCCl>[F:21][C:18]1[CH:19]=[CH:20][C:13]([O:12][C:10]2[CH:9]=[CH:8][C:7]3[C:3]([CH2:2][N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)=[N:4][O:5][C:6]=3[CH:11]=2)=[C:14]([CH:17]=1)[C:15]#[N:16]
Reactant: N#Cc1cc(F)ccc1Oc1ccc2c(CBr)noc2c1
Reactant: C1CCNC1
Solvent: ClCCl
Product: N#Cc1cc(F)ccc1Oc1ccc2c(CN3CCCC3)noc2c1
Reaction time: 2 h
Yield: 94 %

Procedure:
2-(3-Bromomethylbenzo[d]isoxazol-6-yloxy)-5-fluorobenzonitrile (4v) (0.295 g, 0.850 mmol) was dissolved in dichloromethane and pyrrolidine was added dropwise (0.18 g, 2.5 mmol). After 2 hours, the reaction was concentrated and partitioned between NaHCO3 (15 mL) and EtOAc (30 mL). The aqueous layer was back extracted with EtOAc and the organic fractions were combined, washed with brine and dried (MgSO4) to provide compound (5v) (0.27 g, 94%) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J=8.6 Hz, 1H), 7.42 (d, J=6.3 Hz, 1H), 7.30-7.26 (m, 1H), 7.11 (s, 1H), 7.07-7.02 (m, 2H), 4.02 (s, 2H), 2.62 (s, 4H), 1.82 (s, 4H); MS (ESI+) m/z 338 (M+H) detected.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[C:5]2[C:18]1[CH2:19][CH2:20][N:21](C(C)C)[CH2:22][CH:23]=1.C([O-])(=O)/C=C/C([O-])=O>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)[CH:6]=[C:5]2[C:18]1[CH2:19][CH2:20][NH:21][CH2:22][CH:23]=1
Reactant: CC(C)N1CC=C(c2cn(-c3ccc(F)cc3)c3ccc(F)cc23)CC1
Agent: O=C([O-])/C=C/C(=O)[O-]
Product: Fc1ccc(-n2cc(C3=CCNCC3)c3cc(F)ccc32)cc1

Procedure:
5-fluoro-1-(4'-fluorophenyl)-3-(1-(2-propyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, fumarate. (Lu 23-167). M.p. 190°-195° C.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9](C)(C)[CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:15][Si:16](C#C)([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(N(CC)CC)C.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][Si:16]([C:10]#[C:9][O:8][C:6](=[O:7])[C:5]1[CH:13]=[CH:14][CH:2]=[CH:3][CH:4]=1)([CH3:18])[CH3:17]
Reactant: CC(C)(C)OC(=O)c1ccc(Br)cc1
Reactant: C#C[Si](C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[Si](C)(C)C#COC(=O)c1ccccc1
Temperature: 100 °C

Procedure:
A mixture containing 1.31 g of tert.-butyl 4-bromobenzoate, 1.0 g of trimethylsilylacetylene, 10 mg of palladium acetate and 15.6 mg of triphenylphosphine in 15 ml of anhydrous triethylamine is heated in a sealed container at 100° C. for 16 hours. After cooling to room temperature, the reaction mixture is diluted with methylene chloride and extracted with water. The organic solution is dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The dark residue is chromatographed as a column of flash silica gel using a 10% ethyl acetate-hexanes mixture as the eluent to give tert.-butyl 4-(trimethylsilylethynylbenzoate as a dark oil: NMR (CDCl3, 300 MHz) delta 0.26 (s, 9H), 1.59 (s, 9H), 7.49 (d, 2H, J=8.23 Hz), 7.91 (d, 2H, J8.23 Hz). This is dissolved in 20 ml of anhydrous methanol, and then treated with 0.1 g of anhydrous potassium carbonate. The mixture is allowed to stir at room temperature under nitrogen for 3 hours. The reaction mixture is diluted with methylene chloride, extracted with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is distilled under reduced pressure (60°-70° C./0.1 mm to give 0.75 g (73% over 2 steps) of tert.-butyl 4-ethynylbenzoate as a white solid: m.p. 71.5°-72° C.; NMR (CDCl3, 80 MHz) delta 1.62 (s, 9H), 3.23 (s, 1H), 7.55 (d, 2H, J=8.11 Hz), 7.96 (d, 2H, J=8.11 Hz); IR (KBr) 3240, 2970, 2100, 1700, 1600, 1450, 1365, 1300, 1250, 1160, 1115, 1015, 845 and 765 cm-1 ; M/S 202 M+), 187, 157, 146, 129, 101, 75 and 57.
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[C:13]1([CH:19]2[CH2:23][CH2:22][CH2:21][S:20]2=[O:24])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:25][N:26]=[C:27]=[S:28].C>CCCCCC.C(O)C.C(OCC)(=O)C.O.O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[CH3:25][NH:26][C:27]([C:19]1([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:23][CH2:22][CH2:21][S:20]1=[O:24])=[S:28]
Reactant: CN=C=S
Reactant: O=S1CCCC1c1ccccc1
Agent: [Li]CCCC
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CNC(=S)C1(c2ccccc2)CCCS1=O
Temperature: 20 °C
Reaction time: 0.25 h
Yield: 47.4 %

Procedure:
To 97.5 cc of a 1.6M solution of n-butyllithium in hexane maintained in an atmosphere of argon at a temperature of about -60° C., add, dropwise, over 15 minutes, a solution of 16 g of di-isopropylamine in 90 cc of a mixture of anhydrous hexamethylphosphoric triamide and anhydrous tetrahydrofuran (47:53 v/v) and stir the mixture for 10 minutes. Then add, dropwise, over 15 minutes, a solution of 22.5 g of 2-phenyltetrahydrothiophene-1-oxide in 90 cc of the mixture of anhydrous hexamethylphosphoric triamide and anhydrous tetrahydrofuran (47:53 v/v) and continue to stir the mixture for 20 minutes. Then add, dropwise, over 15 minutes, a solution of 13.6 g of methyl isothiocyanate in 55 cc of the mixture of anhydrous hexamethylphosphoric triamide and anhydrous tetrahydrofuran (47:53 v/v) and continue to stir the mixture for 2 hours, allowing the temperature to increase progressively to 20° C. The reaction mixture is taken up with 450 cc of distilled water and 225 cc of ethyl acetate. The crystals formed are separated by filtration, washed twice with 30 cc (60 cc in total) of ethyl acetate, with 30 cc of di-isopropyl oxide and dried under reduced pressure (15 mm Hg; 2 kPa) at 20° C. A first batch of 16.3 g is thus obtained. The filtrate is separated and the organic phase is washed three times with 50 cc (150 cc in total) of distilled water, dried over anhydrous sodium sulphate, filtered and concentrated to dryness under reduced pressure (15 mm Hg; 2kPa) at 50° C. 30 cc of ethyl acetate is added to the product obtained and the crystals formed are separated by filtration, washed twice with 5 cc (10 cc in total) of di-isopropyl oxide and dried under reduced pressure (15 mm Hg; 2 kPa) at 20° C. A second batch of 1 g is thus obtained. Both batches (17.3 g) are mixed with 0.7 g of the same product, prepared beforehand under the same conditions and dissolved in 500 cc of boiling ethanol. Activated charcoal is added to the solution thus obtained; the solution is filtered while hot, cooled, then set aside for 15 hours at a temperature of about 5° C. The crystals formed are separated by filtration, washed with 20 cc of ethanol, then twice with 25 cc (50 cc in total) of di-isopropyl oxide and dried under reduced pressure (1 mm Hg; 0.13 kPa) at 50° C. 15 g of N-methyl-2-phenyltetrahydrothiophene-2-carbothioamide-1-oxide, with a melting point of 236° C., is thus obtained.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:8]([CH:10]=[C:11]([C:13]([O:15]CC)=O)[N:12]=2)[CH:9]=1)([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.ON1C2N=CC=CC=2N=N1>C1(C)C=CC=CC=1.CC(C)([O-])C.[Zr+4].CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:8]([CH:10]=[C:11]([C:13]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:15])[N:12]=2)[CH:9]=1)([CH3:2])[CH3:3]
Reactant: Nc1ccccc1
Reactant: CCOC(=O)c1cn2cc(C(C)C)ccc2n1
Agent: [Zr+4]
Agent: CC(C)(C)[O-]
Agent: On1nnc2cccnc21
Solvent: Cc1ccccc1
Product: CC(C)c1ccc2nc(C(=O)Nc3ccccc3)cn2c1
Yield: 15.2 %

Procedure:
A solution of 344 mg of ethyl 6-isopropylimidazo[1,2-a]pyridine-2-carboxylate, 152 mg of aniline, 40 mg of 1-hydroxy-7-azabenzotriazole (HOAt) and 316 mg of zirconium tert-butoxide in 5 ml of toluene is stirred at ambient temperature for 16 hours in a microwave tube. The medium is concentrated to dryness under reduced pressure and the residue is chromatographed on a silica cartridge, elution being carried out with a mixture of dichloromethane and ethyl acetate (50/50). The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure to give 63 mg of 6-isopropyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in the form of a white solid.
Reaction SMILES: [Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13]([CH:15]1[CH2:19][C:18](=[O:20])[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[CH2:16]1)=[O:14].Br[CH2:30][C:31]([CH3:33])=[CH2:32].[NH4+].[Cl-]>C1COCC1>[CH3:11][O:12][C:13]([C:15]1([CH2:32][C:31]([CH3:33])=[CH2:30])[CH2:19][C:18](=[O:20])[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[CH2:16]1)=[O:14]
Reactant: C=C(C)CBr
Reactant: COC(=O)C1CC(=O)N(c2c(C)cccc2C)C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C=C(C)CC1(C(=O)OC)CC(=O)N(c2c(C)cccc2C)C1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 52.5 %

Procedure:
LHMDS (1 M solution in THF, 83 mL, 83 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (17 g, 68.83 mmol) in THF (170 mL). After 5 min, 3-bromo-2-methylpropene (13.8 mL, 136.8 mmol) was added slowly at −50° C. and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (50 mL) was added, and the aqueous was extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried (Na2SO4) and evaporated. The residue was purified by automated flash chromatography (SiO2, 20→60% MTBE/hexanes) to give 1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (10.9 g, 53% yield). LC-MS: R, (retention time): 2.44 min, MS: (ES) m/z 302.1 (M+H+).
Reaction SMILES: [N:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][C@H:5]1[CH3:18])=[N+]=[N-]>CO.[Pd]>[NH2:1][C@@H:4]1[CH2:9][CH2:8][C@@H:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:6][C@H:5]1[CH3:18]
Reactant: C[C@@H]1C[C@H](NC(=O)OC(C)(C)C)CC[C@H]1N=[N+]=[N-]
Agent: [Pd]
Solvent: CO
Product: C[C@@H]1C[C@H](NC(=O)OC(C)(C)C)CC[C@H]1N
Yield: 93.2 %

Procedure:
tert-Butyl [(1R*,3R*,4R*)-4-azido-3-methylcyclohexyl]carbamate (example C10; 1.2 g; 4.7 mmol) is dissolved in MeOH (20.0 mL) and pressure hydrogenated over Pd (10% on charcoal; 0.1 g) at 20 bar and ambient temperature over night. After filtration through a pad of celite the solvent is removed under reduced pressure to yield 1.0 g of the title compound as off-white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[O:12][C:10](=[O:11])[C:6](=[CH:7][O:8]C)[C:4](=[O:5])[O:3]1.Cl.CCOCC>C(Cl)(Cl)Cl>[CH3:1][C:2]1([CH3:13])[O:3][C:4](=[O:5])[C:6](=[CH:7][OH:8])[C:10](=[O:11])[O:12]1
Reactant: COC=C1C(=O)OC(C)(C)OC1=O
Agent: Cl
Solvent: CCOCC
Solvent: ClC(Cl)Cl
Product: CC1(C)OC(=O)C(=CO)C(=O)O1
Temperature: 25 °C

Procedure:
Next, this methoxy methylene Meldrum's acid (25 g, 0.13 mol) was dissolved in chloroform (200 ml), followed by adding 2N-HCl (50 ml), agitating the mixture at room temperature, allowing it to still standing, separating the chloroform layer, saturating the aqueous layer with sodium chloride, extracting the solution with chloroform, combining the extract solution with the previously obtained chloroform solution, drying over anhydrous magnesium sulfate, filtering off the drying agent, and distilling off chloroform under reduced pressure to obtain raw formyl Meldrum's acid as residue, adding ether thereto, filtering off, further washing with ether, vaporizing the remaining ether and recrystallizing the resulting crystals from a mixed solvent of dichloromethanehexane to obtain formyl Meldrum's acid in the form of colorless crystals (20.5 g, yield 89%) having a m.p. of 95°-96° C.
Reaction SMILES: Br[C:2]1[C:10]2[C:9](=[O:11])[N:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[N:7]=[CH:6][C:5]=2[S:4][CH:3]=1.[N:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>>[N:20]1[CH:25]=[CH:24][C:23]([C:2]2[C:10]3[C:9](=[O:11])[N:8]([CH2:12][CH2:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=4)[N:7]=[CH:6][C:5]=3[S:4][CH:3]=2)=[CH:22][CH:21]=1
Reactant: OB(O)c1ccncc1
Reactant: O=c1c2c(Br)csc2cnn1CCc1ccccn1
Product: O=c1c2c(-c3ccncc3)csc2cnn1CCc1ccccn1
Yield: 33.1 %

Procedure:
The title compound was prepared in analogy to the process described in Example 3.5 starting from 3-bromo-5-(2-pyridin-2-yl-ethyl)-5H-thieno[2,3-d]pyridazin-4-one and pyridine-4-ylboronic acid. Yield: 33.1%.
Reaction SMILES: OO.C([OH:7])(C)(C)C.C=CCCCCC.[O:15]([CH:17]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:18][OH:19])O>[W].C(OC)(C)(C)C>[O:19]([CH2:18][CH:17]([OH:15])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[OH:7]
Reactant: CCCCCC(CO)OO
Reactant: CC(C)(C)O
Agent: [W]
Agent: C=CCCCCC
Agent: OO
Solvent: COC(C)(C)C
Product: CCCCCC(O)COO
Temperature: 40 °C
Yield: 22 %

Procedure:
To a 50 mL flask equipped with a magnetic stirrer and a reflux condenser were added 800 mg of the tungsten-containing mesoporous silicate prepared in Example 1, 800 mg of a 60% by weight aqueous hydrogen peroxide solution, 2 g of tert-butanol and 400 mg of 1-heptene, and the mixture was stirred and maintained at an inner temperature of 40° C. for 16 hours to react these materials. To the resulting reaction mixture was added 5 g of methyl tert-butyl ether, and the mixture was stirred, and then allowed to stand. The supernatant organic layer was analyzed by LC, and it was found that 2-hydroperoxy-l-hydroxyheptane and 1-hydroperoxy-2-hydroxyheptane were produced. When the organic layer was analyzed by GC, 2-hydroperoxy-1-hydroxyheptane and 1-hydroperoxy-2-hydroxyheptane were thermally decomposed at an injection inlet, and detected as 1-hexanal. Then, the yield of 1-hexanal was determined by GC analysis (internal standard method), and this was regarded as the yield of 2-hydroperoxy-1-hydroxyheptane and 1-hydroperoxy-2-hydroxyheptane. Yield: 22%. The recovery of 1-hexene was 67%.