Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:8]([Cl:13])=[CH:9][C:10]=1[O:11][CH3:12])[CH:6]=O.[C:14]([O:19]CC)(=[O:18])/[CH:15]=[CH:16]/[CH3:17].CC(C)([O-])C.[K+].Cl>CN1CCCC1=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:17][CH:16]=[CH:15][C:14]([OH:19])=[O:18])[C:8]([Cl:13])=[CH:9][C:10]=1[O:11][CH3:12]
Reactant: C/C=C/C(=O)OCC
Reactant: COc1cc(Cl)c(C=O)cc1OC
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN1CCCC1=O
Product: COc1cc(Cl)c(C=CC=CC(=O)O)cc1OC

Procedure:
To a solution containing 10.0 g 3,4 dimethoxy-6-chlorobenzaldehyde and 8 ml of ethyl crotonate in 60 ml of N-methylpyrrolidone 6.0 g of potassium tert.-butoxide was added while stirring . The solution was stirred for 0.5 h more at 20° C. and poured then to a mixture of ice and hydrochloric acid. The solution was extracted with ether. The ether solution was washed with water and extracted with 2.5 N NaOH-solution. The aqueous phase was acidified with hydrochloric acid and the semisolid product was separated. Yield 10.8 g (81%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2([C:12]([O:14]CC3C=CC=CC=3)=[O:13])[CH2:11][CH2:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1>CO.[Pd]>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2([C:12]([OH:14])=[O:13])[CH2:11][CH2:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1
Reactant: O=C(OCc1ccccc1)C1(c2ccncc2)CCCC1
Agent: [Pd]
Solvent: CO
Product: O=C(O)C1(c2ccncc2)CCCC1
Reaction time: 8 h

Procedure:
To a solution of 1-(4-pyridyl)cyclopentanecarboxylic acid, benzyl ester (Step C, 0.36 g, 1.3 mmol) in methanol (10 mL) was added palladium on carbon (10% w/w, 75 mg). The mixture was degassed and filled with hydrogen using a balloon. After stirring overnight, the reaction mixture was filtered through Celite, and the filtrate was concentrated to dryness to afford the title compound. LC-MS: m/e 192 (M+H)+ (0.8 min).
Reaction SMILES: [Br:1][C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[C:10]([O:11][CH2:12][C:13]3[C:18]([N:19]([C:21](=O)[CH3:22])[CH3:20])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:24])[C:5]2=[N:4][C:3]=1[CH3:25].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Br:1][C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[C:10]([O:11][CH2:12][C:13]3[C:18]([N:19]([CH2:21][CH3:22])[CH3:20])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:24])[C:5]2=[N:4][C:3]=1[CH3:25]
Reactant: CC(=O)N(C)c1cccc(Cl)c1COc1cccn2c(Br)c(C)nc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCN(C)c1cccc(Cl)c1COc1cccn2c(Br)c(C)nc12
Temperature: 5 °C
Reaction time: 2 h
Yield: 41.2 %

Procedure:
To a solution of 3-bromo-8-[2-chloro-6-(N-acetyl-N-methylamino) benzyloxy]-2-methylimidazo[1,2-a]pyridine (103 mg) in tetrahydrofuran (2 ml) was added lithium aluminum hydride (16 mg) in several portions at 5° C. After the addition, the mixture was stirred for 2 hours at 5° C. and then quenched with aqueous saturated ammonium chloride solution. The separated organic layer was washed with aqueous saturated ammonium chloride solution, dried, and concentrated in vacuo. The residue was purified by preparative thin-layer chromatography (ethyl acetate:n-hexane =1:2, V/V) to give 3-bromo-8-[2-chloro-6-(N-ethyl-N-methylamino)benzyloxy]-2-methylimidazo[1,2-a]pyridine (41 mg).
Reaction SMILES: [CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([OH:8])[CH:2]=1.CC(C)([O-])C.[K+].C(=O)([O-])[O-].[K+].[K+].[CH2:21]([O:28][CH2:29][N:30]1[C:34]2=[N:35][CH:36]=[CH:37][C:38](Cl)=[C:33]2[CH:32]=[CH:31]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN1C(=O)CCC1>[CH2:21]([O:28][CH2:29][N:30]1[C:34]2=[N:35][CH:36]=[CH:37][C:38]([O:8][C:3]3[CH:4]=[CH:5][C:6]([NH2:7])=[CH:1][CH:2]=3)=[C:33]2[CH:32]=[CH:31]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: Clc1ccnc2c1ccn2COCc1ccccc1
Reactant: Nc1ccc(O)cc1
Agent: CC(C)(C)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: Nc1ccc(Oc2ccnc3c2ccn3COCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 86.5 %

Procedure:
P-Aminophenol (8.4 g, 77 mmol) and potassium t-butoxide (14.4 g, 77 mmol) were dissolved in NMP (150 mL), and potassium carbonate (9 g, 39 mmol) was added thereto. The resulting mixture was stirred at room temperature for 1 hour, and an NMP (10 mL) solution of 1-benzyloxymethyl-4-chloro-1H-pyrrolo[2,3-b]pyridine (20 g, 73.3 mmol) was dropwise added thereto at 180° C. over 15 minutes. Subsequently, the mixture was stirred for 2 hours. The reaction container was cooled, and the content was poured on ice (650 g) and extracted with ethyl acetate (500 mL) three times. The combined organic layer was washed with saturated brine (150 mL) twice, dried, and concentrated. The residue was purified by silica-gel column chromatography (manufactured by Fuji Silysia, BW300, 7.5 cm×25 cm, n-hexane:EtOAc=1:1) to give 4-(1-benzyloxymethyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline (21.9 g) as a light-yellow syrup (yield: 86%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH2:15])=[CH:9][C:8]=1[O:16][CH3:17].C([O-])([O-])=O.[K+].[K+].[I-].[K+].[CH3:29][O:30][C:31](=[O:34])[CH2:32]Br.[ClH:35]>CN(C)C=O.C(OCC)(=O)C>[ClH:35].[CH3:29][O:30][C:31](=[O:34])[CH2:32][NH:15][CH2:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]2[CH:18]=[CH:19][CH:20]=[C:2]([F:1])[CH:3]=2)=[C:8]([O:16][CH3:17])[CH:9]=1
Reactant: COC(=O)CBr
Reactant: COc1cc(CCN)ccc1OCc1cccc(F)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)CNCCc1ccc(OCc2cccc(F)c2)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 39 %

Procedure:
1 g (3.2 mmol) of 2-[4-(3-fluoro-benzyloxy)-3-methoxy-phenyl]-ethylamine, 833 mg (6 mmol) of K2CO3, 50 mg of potassium iodide and 0.27 ml (2.9 mmol) of bromo-acetic acid methyl ester were dissolved in 10 ml of dimethylformamide and the mixture was stirred at room temperature overnight. Solvent was removed, water was added to the residue and the residue was extracted with ethyl acetate. The crude product was purified by flash chromatography (dichloromethane/methanol/NH3 100:0:0→100:2.5:0.25 gradient v:v:v). The product obtained was dissolved in anhydrous hydrochloric acid in ethyl acetate. The solvent was removed and the residue was triturated with diethyl ether. 482 mg (39% yield) of the title compound were obtained as a brown solid.
Reaction SMILES: [N:1]1C=CC=CC=1C(=O)CC(=O)CC(C1C=CC=CN=1)=O.[N:21]1([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([C:32](=O)[CH2:33][C:34](=[O:49])[CH2:35][C:36]([C:38]3[CH:43]=[C:42]([N:44]4[CH2:48][CH2:47][CH2:46][CH2:45]4)[CH:41]=[CH:40][N:39]=3)=O)[CH:27]=2)[CH2:25][CH2:24][CH2:23][CH2:22]1>CO>[N:21]1([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([C:32]3[NH:1][C:36]([C:38]4[CH:43]=[C:42]([N:44]5[CH2:48][CH2:47][CH2:46][CH2:45]5)[CH:41]=[CH:40][N:39]=4)=[CH:35][C:34](=[O:49])[CH:33]=3)[CH:27]=2)[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=C(CC(=O)c1cc(N2CCCC2)ccn1)CC(=O)c1cc(N2CCCC2)ccn1
Reactant: O=C(CC(=O)c1ccccn1)CC(=O)c1ccccn1
Solvent: CO
Product: O=c1cc(-c2cc(N3CCCC3)ccn2)[nH]c(-c2cc(N3CCCC3)ccn2)c1

Procedure:
This compound is prepared in a manner analogous to that described in Example 1, Step 2 for 1,5-di-pyridin-2-yl-pentane-1,3,5-trione, but instead the pyrrolidine-substituted triketone from Example 21 is used. Pure 4,4″-di-pyrrolidin-1-yl-1′H-[2,2′;6′,2″]terpyridin-4′-one can be obtained by recrystallisation from methanol in the form of an almost colourless solid. 1.81-2.05 (m, 8H); 3.17-3.33 (m, 8H); 6.32 (dd, 2H, J=5.7, 2.3 Hz); 6.84 (d, 2H, J=2.3 Hz); 6.90 (s, 2H); 8.19 (d, 2H, J=5.7 Hz). MS (EI pos., 70 eV), m/z=387 ([M+]), 359 (100); 358 (85); 330 (20); 28 (60).
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6](Cl)=[N:7][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]([CH2:21][CH3:22])=[CH:10][C:9]=2[CH3:23])=[O:4].[CH3:25][CH:26]1[CH2:30][CH2:29][CH2:28][NH:27]1>>[CH2:21]([C:11]1[CH:12]=[C:13]2[C:8](=[C:9]([CH3:23])[CH:10]=1)[N:7]=[C:6]([N:27]1[CH2:28][CH2:29][CH2:30][CH:26]1[CH3:25])[C:5]([C:3]([OH:2])=[O:4])=[C:14]2[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:22]
Reactant: CC1CCCN1
Reactant: CCc1cc(C)c2nc(Cl)c(C(=O)OC)c(-c3ccccc3)c2c1
Product: CCc1cc(C)c2nc(N3CCCC3C)c(C(=O)O)c(-c3ccccc3)c2c1

Procedure:
The title compound was prepared in analogy to example 54 step F from 2-chloro-6-ethyl-8-methyl-4-phenyl-quinoline-3-carboxylic acid methyl ester (prepared as described in example 54 step E) and 2-methylpyrrolidine. Light brown solid. MS (ESI): 375.3 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[N:19]=[C:18]([NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:22]3)[N:17]=[C:16]3[C:12]=1[N:13]=[CH:14][N:15]3[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:6][CH2:5]2.[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][C:48](Cl)=[O:49].C(N(C(C)C)CC)(C)C>ClCCl>[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][C:48]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[N:19]=[C:18]([NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])[CH2:23][CH2:22]3)[N:17]=[C:16]3[C:12]=1[N:13]=[CH:14][N:15]3[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:6][CH2:5]2)=[O:49]
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Nc2nc(N3CCc4cc(N)ccc43)c3ncn(C(=O)OC(C)(C)C)c3n2)CC1
Reactant: O=C(Cl)Cc1cccs1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Nc2nc(N3CCc4cc(NC(=O)Cc5cccs5)ccc43)c3ncn(C(=O)OC(C)(C)C)c3n2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
40 mg of product obtained in stage 4 are mixed with 11.4 mg of 2-thiopheneacetyl chloride, 25 μl of diisopropylethylamine and 2 ml of dichloromethane. The mixture is stirred for 1 hour at ambient temperature, and then washing with brine, drying over magnesium sulfate and evaporation to dryness are carried out.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:22])[NH:7][C:8]([N:12]3[CH:16]=[C:15]([C:17]([O:19]CC)=[O:18])[CH:14]=[N:13]3)=[N:9]2)=[CH:4][C:3]=1[N:23]1[CH2:32][CH2:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24]1.[Li+].[OH-]>C1COCC1>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:22])[NH:7][C:8]([N:12]3[CH:16]=[C:15]([C:17]([OH:19])=[O:18])[CH:14]=[N:13]3)=[N:9]2)=[CH:4][C:3]=1[N:23]1[CH2:32][CH2:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24]1
Reactant: CCOC(=O)c1cnn(-c2nc3cc(Cl)c(N4CCc5ccccc5C4)cc3c(=O)[nH]2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1cnn(-c2nc3cc(Cl)c(N4CCc5ccccc5C4)cc3c(=O)[nH]2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 100.3 %

Procedure:
A mixture of 1-[7-chloro-6-(3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid, ethyl ester (0.35 g, 0.78 mmol), THF (12 mL), and aqueous 1M LiOH (7.8 mL, 7.8 mmol) was stirred at rt for 16 h. The THF was removed, and the aqueous mixture was cooled in an ice bath. The pH was adjusted to ca. 5 using 1M aqueous HCl, and the resulting precipitate was collected, washed well with water, and dried to afford the titled compound (0.33 g, 99%). MS (ESI): mass calcd. for C21H16ClN5O3, 421.1; m/z found, 422.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6): 13.22-12.69 (br m, 2H), 8.92 (s, 1H), 8.25 (s, 1H), 7.88-7.73 (m, 2H), 7.24-7.16 (m, 4H), 4.31 (s, 2H), 3.39 (t, J=5.6, 2H), 3.00 (t, J=5.5, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[NH:22][C:21](=[O:26])[CH2:20][CH2:19]4)[N:15]=2)[CH:6]=[CH:7][C:8]=1[S:9][CH3:10].C(=O)([O-])[O-:28].[Na+].[Na+]>C(Cl)(Cl)Cl.C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[NH:22][C:21](=[O:26])[CH2:20][CH2:19]4)[N:15]=2)[CH:6]=[CH:7][C:8]=1[S:9]([CH3:10])=[O:28]
Reactant: COc1cc(-c2nc(-c3ccc4c(c3)CCC(=O)N4)cs2)ccc1SC
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: COc1cc(-c2nc(-c3ccc4c(c3)CCC(=O)N4)cs2)ccc1S(C)=O
Reaction time: 1 h

Procedure:
In 150 ml of chloroform-ethanol was suspended 3.40 g of 2-(3-methoxy-4-methylthiophenyl)-4-(3,4-dihydrocarbostyril-6-yl)thiazole. Thereto was added, in small portions, 1.97 g of methachloroperbenzoic acid (80%) under ice-cooling. The mixture was stirred for 1 hour. Then, the mixture was returned to room temperature and stirred overnight. Thereto was added an aqueous sodium carbonate solution. The mixture was extracted with chloroform three times. The combined extract was washed with a saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was distilled off and the resulting crystals were recrystallized from dimethylformamide to obtain 0.50 g of 2-(3-methoxy-4-methylsulfinylphenyl)-4-(3,4-dihydrocarbostyril-6-yl)thiazole as light yellow acicular crystals.
Reaction SMILES: [C:1]([C:5]1[S:19][C:8]2[O:9][C:10]3[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=3[NH:12][C:13](=[O:14])[C:7]=2[CH:6]=1)(=O)[CH2:2][CH3:3].C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[CH2:1]([C:5]1[S:19][C:8]2[O:9][C:10]3[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=3[NH:12][C:13](=[O:14])[C:7]=2[CH:6]=1)[CH2:2][CH3:3]
Reactant: CCC(=O)c1cc2c(s1)Oc1ccccc1NC2=O
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CCCc1cc2c(s1)Oc1ccccc1NC2=O
Temperature: 25 °C
Reaction time: 20 h
Yield: 81.7 %

Procedure:
2-Propionylthieno[2,3-b][1,5]benzoxazepin-4(5H)-one (1.2 g) was dissolved in trifluoroacetic acid (20 ml) and triethylsilane (2 g) was added. The mixture was stirred at room temperature for 20 hours. The solvent was evaporated under reduced pressure and the residue was dissolved in chloroform. The mixture was washed with water and saturated aqueous sodium hydrogencarbonate solution and dried over sodium sulfate. The solvent was evaporated under reduced pressure. To the residue were added chloroform and ethyl acetate and the precipitated crystals were collected by filtration. The obtained crystals were washed with diisopropyl ether to give 2-propylthieno[2,3-b][1,5]benzoxazepin-4(5H)-one (930 mg).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[CH3:14][CH2:15][Mg+].[Br-]>C1COCC1.CN1C(=O)CCC1.CCOCC.C/C(/O)=C/C(C)=O.C/C(/O)=C/C(C)=O.C/C(/O)=C/C(C)=O.[Fe]>[CH2:14]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1)[CH3:15]
Reactant: COC(=O)c1ccc(Cl)cc1OC
Reactant: CC[Mg+]
Agent: [Fe]
Agent: CC(=O)/C=C(/C)O
Agent: [Br-]
Solvent: CN1CCCC1=O
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCc1ccc(C(=O)OC)c(OC)c1
Yield: 50 %

Procedure:
To a solution of methyl 4-chloro-2-methoxybenzoate (example 18d) (4.16 g, 20.8 mmol) in THF (120 mL) and NMP (12 mL) was added under inert atmosphere Iron (III) acetylacetonate (398 mg, 1.17 mmol) giving a red color. Then EtMgBr (29 ml of 1M solution in ether) was added dropwise under vigorous stirring. The mixture turned dark brown and then violet and then was stirred for 15 more min. The reaction was diluted with ether and quenched upon the addition of aq. HCl (1M, 50 mL). The crude product was extracted with ether and the combined organic layers were successively washed with water and brine, dried over MgSO4, filtered and evaporated. The residue was purified on silica gel (Eluent: 30% EtOAc in hexanes) to give methyl 4-ethyl-2-methoxybenzoate (2.01 g, 50%) as an oil. 1H NMR (300 MHz, dMSO): δ 1.20-1.22(t, 3H), 2.65-2.7 (dd, 2H), 3.9 (s, 3H), 6.8 (s, 1H), 6.97 (m, 1H), 7.7 (m, 1H).
Reaction SMILES: [CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[CH3:6][N:7]1[C:11]2[CH:12]=[C:13]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][C:21]=3[CH:22]=[O:23])[CH:14]=[CH:15][C:10]=2[O:9][C:8]1=[O:24]>C1COCC1>[CH:1]1([CH:22]([OH:23])[C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:13]2[CH:14]=[CH:15][C:10]3[O:9][C:8](=[O:24])[N:7]([CH3:6])[C:11]=3[CH:12]=2)[CH2:3][CH2:2]1
Reactant: Cn1c(=O)oc2ccc(-c3cnccc3C=O)cc21
Reactant: Br[Mg]C1CC1
Solvent: C1CCOC1
Product: Cn1c(=O)oc2ccc(-c3cnccc3C(O)C3CC3)cc21
Reaction time: 3 h

Procedure:
Cyclopropylmagnesium bromide (0.5 M in THF, 3.5 mL, 1.8 mmol) was added dropwise to a solution of 3-(3-Methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-pyridine-4-carbaldehyde (150 mg, 0.58 mmol) in THF (1.6 mL) at −36′C. The resulting mixture was stirred at this temperature for 3 h, and the reaction was quenched by the addition of saturated NH4Cl solution. The mixture was diluted with ethyl acetate and water. The organic layer was separated and dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by flash column (MeOH/DCM, v/v, 0-4%) to give the title compound. (67 mg, 39%); ESI-MS m/z 297.2 [M+1]+, Retention time 1.00 min; 1HNMR (CDCl3, 400.342 MHz) δ ppm −0.27-0 (m, 1H), 0.36-0.45 (m, 2H), 0.52-0.57 (m, 1H), 0.96-1.02 (m, 1H), 3.47 (s, 3H), 4.52 (d, J=7.6 Hz, 1H), 7.14 (dd, J=8, 1.6 Hz, 1H), 7.25 (d, J=1.6 Hz, 1H), 7.33 (d, J=: 8 Hz, 1H), 8.18 (d, J=6 Hz, 1H), 8.47 (s, 1H), 8.63 (d, J=6 Hz, 1H).
Reaction SMILES: N1C=CC=CC=1.O=[Si]=O.[CH2:10]([O:12][CH:13]([O:29][CH2:30][CH3:31])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[F:28])[OH:21])[CH3:11]>[O-2].[O-2].[O-2].[Cr+6].ClCCl>[CH2:30]([O:29][CH:13]([O:12][CH2:10][CH3:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[F:28])=[O:21])[CH3:31]
Reactant: CCOC(OCC)c1ccccc1C(O)c1ccccc1F
Agent: [Cr+6]
Agent: O=[Si]=O
Agent: [O-2]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(OCC)c1ccccc1C(=O)c1ccccc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.7 %

Procedure:
Under a nitrogen atmosphere, 758 ml of pyridine and 469 g of dicalite were added to 6 l of dry dichloromethane. In one portion 469 g of chromium trioxide were added under vigorous stirring. The resulting mixture was stirred at room temperature for 0.5 h, after which a solution of 238 g of 2-(diethoxymethyl)-α-(2-fluorophenyl)-benzenemethanol in 600 ml dry dichloromethane was added. After stirring at room temperature for 2 h, the mixture was filtered. The filtrate was washed with 3×1 l of 1N sodium hydroxide in water and 1 l of water, dried over magnesium sulphate and evaporated to dryness under reduced pressure to yield 224 g of [2-(diethoxymethyl)phenyl](2-fluorophenyl)-methanone as an oil, M.S. (C.I.) (M/Z) 303 [M+H]+.
Reaction SMILES: [Na+].[Cl-].[CH2:3]([C:10](=[C:13]=[CH2:14])[CH2:11][OH:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>ClCCCl.CCOCC>[CH2:3]([C:10](=[C:13]=[CH2:14])[CH:11]=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: C=C=C(CO)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCOCC
Product: C=C=C(C=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 72.4 %

Procedure:
Fe(NO3)3.9H2O (20.3 mg, 0.05 mmol), 1,2-dichloroethane (DCE, 4 mL), 2,2,6,6-tetramethylpiperidinyloxy (TEMPO, 15.6 mg, 0.10 mmol) and NaCl (5.8 mg, 0.10 mmol) were added to a 10 mL-three-necked flask and were stirred for 5 mins at room temperature under oxygen atmosphere. 2-benzylbuta-2,3-dienol (160.6 mg, 1.0 mmol) was dissolved in DCE (1 mL) and then added to the reaction solution dropwise, and the reaction was monitored by TLC till it was complete. Then the reaction solution was diluted with ether (30 mL), dried over anhydrous MgSO4, filtered by a short pad of silica gel, and then concentrated to yield the crude products. Further purification by column chromatography on silica gel (petroleum ether:ethyl acetate=20:1) afforded the target product 2-benzylbuta-2,3-dienal (114.5 mg, 72%). 1H NMR (300 MHz, CDCl3) δ 9.61 (s, 1H), 7.31-7.15 (m, 5H), 5.28 (t, J=2.4 Hz, 2H), 3.52 (t, J=2.6 Hz, 2H); 13C NMR (75.4 MHz, CDCl3) δ 222.50, 191.41, 138.52, 128.84, 128.35, 126.41, 110.62, 80.83, 30.84; IR (neat) 2827, 2728, 1955, 1928, 1677, 1602, 1495, 1454, 1426, 1227, 1144, 1071, 1030 cm−1; MS (EI) m/z 158 (M+, 5.25), 129 (100); HRMS: calcd. for C11H10O (M+): 158.0732. found: 158.07333.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@H:13]1[C@@H:16]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])[NH:15][C:14]1=[O:22].C(N(C(C)C)CC)(C)C.[I:32][C:33]1[CH:38]=[CH:37][C:36]([C:39](Cl)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[CH:35][CH:34]=1>CC(C)=O>[I:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]([NH:12][C@H:13]2[C@@H:16]([O:17][CH2:18][CH:19]([CH3:20])[CH3:21])[NH:15][C:14]2=[O:22])([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[CH:37][CH:38]=1
Reactant: CC(C)CO[C@H]1NC(=O)[C@H]1N
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccc(I)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)=O
Product: CC(C)CO[C@H]1NC(=O)[C@H]1NC(c1ccccc1)(c1ccccc1)c1ccc(I)cc1
Reaction time: 6 h
Yield: 66.8 %

Procedure:
A solution of (3S,4R)-3-amino-4-(isobutoxy)azetidin-2-one para-toluenesulfonate (180 mg, 0.54 mmol) in acetone (8 mL) containing diisopropylethylamine ( 1.1 mmol) was treated with a solution of (4-iodophenyl)diphenylmethyl chloride (218 mg, 0.54 mmol), prepared as described by Tschitschibabin, Chem. Ber. 44, 450 (191 1), in acetone (98 mL). The solution was stirred for 6 h and partitioned between water and dichloromethane. The combined organic phases were dried (magnesium sulfate), concentrated, and the residue was chromatographed on silica gel eluted with 15% ethyl acetate:hexane to give the title compound (190 mg, 67%). MS(ES) m/e 527 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH:9][CH3:10])[N:3]=1.CCN(C(C)C)C(C)C.[CH3:20][C@@H:21]1[CH2:26][O:25][CH2:24][CH2:23][NH:22]1>C(O)C>[Cl:8][C:6]1[CH:7]=[C:2]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][C@H:21]2[CH3:20])[N:3]=[C:4]([NH:9][CH3:10])[N:5]=1
Reactant: CNc1nc(Cl)cc(Cl)n1
Reactant: C[C@@H]1COCCN1
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CNc1nc(Cl)cc(N2CCOC[C@H]2C)n1
Temperature: 100 °C
Reaction time: 48 h
Yield: 68.7 %

Procedure:
To a solution of 4,6-dichloro-N-methyl-2-pyrimidinamine (2 g, 11.23 mmol) in ethanol (50 mL) in a 200-mL RBF were added Hunig's base (5.89 mL, 33.7 mmol) and (3R)-3-methylmorpholine (1.546 g, 11.23 mmol). The reaction mixture was stirred at 100° C. in a sealed tube on a stirrer hotplate for 2 days. The reaction was concentrated in vacuo, and the residue was dissolved in EtOAc (200 mL) and washed with water (50 mL). The organic layer was dried over Na2SO4, filtered, then concentrated to afford the title compound (1.873 g) as a white solid. LC-MS (ES) m/z=243 [M+H]+.
Reaction SMILES: [C:1]([NH:4][C:5]1[N:9]([C:10]2[CH:15]=[C:14]([S:16][CH2:17][C:18]([F:21])([F:20])[F:19])[C:13]([CH3:22])=[CH:12][C:11]=2[F:23])[N:8]=[C:7]([O:24][C:25]([F:40])([F:39])[C:26]([F:38])([F:37])[C:27]([F:36])([F:35])[C:28]([F:34])([F:33])[C:29]([F:32])([F:31])[F:30])[CH:6]=1)(=[O:3])[CH3:2].ClC1C=CC=C(C(OO)=[O:49])C=1>C(Cl)(Cl)Cl>[C:1]([NH:4][C:5]1[N:9]([C:10]2[CH:15]=[C:14]([S:16]([CH2:17][C:18]([F:19])([F:20])[F:21])=[O:49])[C:13]([CH3:22])=[CH:12][C:11]=2[F:23])[N:8]=[C:7]([O:24][C:25]([F:39])([F:40])[C:26]([F:37])([F:38])[C:27]([F:35])([F:36])[C:28]([F:33])([F:34])[C:29]([F:30])([F:31])[F:32])[CH:6]=1)(=[O:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(=O)Nc1cc(OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)nn1-c1cc(SCC(F)(F)F)c(C)cc1F
Solvent: ClC(Cl)Cl
Product: CC(=O)Nc1cc(OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)nn1-c1cc(S(=O)CC(F)(F)F)c(C)cc1F
Reaction time: 0.5 h
Yield: 77.2 %

Procedure:
0.12 g of 5-acetylamino-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-(1,1,2,2,3,3,4,4,5,5,5-undecafluoropentyloxy)pyrazole was dissolved in 10 mL of chloroform, and 44 mg of m-chloroperbenzoic acid (purity: 75%) was added under cooling with ice. After stirring for 30 minutes under cooling with ice, the solution was washed with an aqueous sodium thiosulfate solution and then washed with an aqueous potassium carbonate solution, and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane=1:1) to obtain 0.095 g of 5-acetylamino-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylsulfinyl)phenyl}-3-(1,1,2,2,3,3,4,4,5,5,5-undecafluoropentyloxy)pyrazole.