Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[N:6]=[C:5]2[N:19]1[C:27]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[CH:21]=[CH:20]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:34]([O:38][C:39](=[O:42])[NH:40][CH3:41])([CH3:37])([CH3:36])[CH3:35].O>O1CCCC1>[C:34]([O:38][C:39](=[O:42])[N:40]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[N:6]=[C:5]2[N:19]1[C:27]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[CH:21]=[CH:20]1)[CH3:41])([CH3:37])([CH3:36])[CH3:35]
Reactant: Fc1ccccc1-c1nc(-n2ccc3cnccc32)c2cc(Br)ccc2n1
Reactant: CNC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Solvent: O
Product: CN(C(=O)OC(C)(C)C)c1ccc2nc(-c3ccccc3F)nc(-n3ccc4cnccc43)c2c1
Temperature: 80 °C
Yield: 61.1 %

Procedure:
6-Bromo-2-(2-fluoro-phenyl)-4-pyrrolo[3,2-c]pyridin-1-yl-quinazoline from step E (0.1 g, 0.23 mmol) was dissolved in tetrahydrofuran (5 ml) in a 50 ml round bottomed flask. Cesium carbonate (0.11 g, 0.35 mmol), Xanphos (0.007 g, 0.002 mmol) and methyl-carbamic acid tert-butyl ester (0.045 g, 0.35 mmol) was then added. The mixture was degassed for 5 mins and tris (dibenzylidineacetone)dipalladium(0) (0.005 g, 0.005 mmol) was added. The resulting solution was then magnetically stirred and the heated to 80° C. for 3 hrs. Water was added and compound extracted into ethyl acetate, dried over sodium sulfate and concentrated in rotary evaporator to yield desired title compound (0.066 g, 58%). MS (ES) 470.1 (M+H)+
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[CH2:4][NH:5][NH2:6].C([O:14][C:15](=O)[CH:16]=[C:17]([NH2:21])OCC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[NH2:21][C:17]1[NH:6][N:5]([CH2:4][C:3]2[CH:7]=[C:8]([CH3:11])[CH:9]=[CH:10][C:2]=2[CH3:1])[C:15](=[O:14])[CH:16]=1
Reactant: Cc1ccc(C)c(CNN)c1
Reactant: CCOC(=O)C=C(N)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Product: Cc1ccc(C)c(Cn2[nH]c(N)cc2=O)c1
Reaction time: 8 h

Procedure:
26.6 g of 2,5-dimethylbenzylhydrazine were added dropwise to a solution of 28.2 g of β-amino-β-ethoxyacrylic acid ethyl ester and 1 g of p-toluenesulphonic acid in 130 ml of ethanol, in the course of which the temperature rose from 25° to 35° C. After stirring overnight, the compound identified above separated out, and was filtered off and recrystallised from ethanol. Melting point: 124°, 20 g (52%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[N:16][C:17]([Cl:20])=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:20][C:17]1[N:16]=[N:15][C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:19][CH:18]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(Cl)nn2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Clc1ccc(N2CCNCC2)nn1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 75.2 %

Procedure:
To an ice cold solution of 4-(6-chloropyridazin-3-yl)piperazine-1-carboxylic acid tert-butyl ester (2.00 g, 6.69 mmol) in dichloromethane (10 mL) was carefully added trifluoroacetic acid (2 mL). The mixture was stirred for 45 minutes at room temperature and then concentrated in vacuo to afford the crude 3-chloro-6-piperazin-1-ylpyridazine (˜1.0 g) which was used in the next reaction without further purification. MS (ES+) m/z 199.1 (M+1).
Reaction SMILES: [NH2:1][CH:2]1[C:12]2[C:13]3[C:5](=[C:6]([C:15]4[CH:20]=[CH:19][C:18]([C:21](OC)=[O:22])=[CH:17][CH:16]=4)[NH:7][C:8]=3[C:9]([Cl:14])=[CH:10][CH:11]=2)[CH2:4][CH2:3]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.CCOCC>O1CCCC1.C(OCC)(=O)C>[NH2:1][CH:2]1[C:12]2[C:13]3[C:5](=[C:6]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][OH:22])=[CH:17][CH:16]=4)[NH:7][C:8]=3[C:9]([Cl:14])=[CH:10][CH:11]=2)[CH2:4][CH2:3]1
Reactant: COC(=O)c1ccc(-c2[nH]c3c(Cl)ccc4c3c2CCC4N)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: C1CCOC1
Product: NC1CCc2c(-c3ccc(CO)cc3)[nH]c3c(Cl)ccc1c23
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.9 %

Procedure:
A portion (170 mg) of the compound obtained in Example 171 was dissolved in anhydrous tetrahydrofuran (10 ml) and to the solution was added lithium aluminum hydride (76 mg). The mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water-containing ether, then water and ethyl acetate, under cooling with ice. The insoluble matter was filtered off, followed by phase separation of the filtrate. The aqueous layer was extracted three times with ethyl acetate. The organic layers were combined, washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (methylene chloride/methanol=2:1) to yield 109 mg (70%) of the titled compound as brown crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:31]=[CH:30][C:5]([CH:6]=[CH:7][CH2:8][N:9]2[CH2:14][CH2:13][C:12](=[C:15]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[CH:19]=[CH:18][C:17]4[CH:26]=[CH:27][CH:28]=[CH:29][C:16]3=4)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[C:32](O)(=[O:36])[CH2:33][CH2:34][CH3:35]>>[C:32]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[CH:7][CH2:8][N:9]2[CH2:10][CH2:11][C:12](=[C:15]3[C:16]4[CH:29]=[CH:28][CH:27]=[CH:26][C:17]=4[CH:18]=[CH:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]3=4)[CH2:13][CH2:14]2)=[CH:30][CH:31]=1)(=[O:36])[CH2:33][CH2:34][CH3:35]
Reactant: CCCC(=O)O
Reactant: Nc1ccc(C=CCN2CCC(=C3c4ccccc4C=Cc4ccccc43)CC2)cc1
Product: CCCC(=O)Nc1ccc(C=CCN2CCC(=C3c4ccccc4C=Cc4ccccc43)CC2)cc1
Yield: 68.5 %

Procedure:
This compound was prepared from 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine (compound 5) and butanoic acid. Yield 68.5%
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[N:8][CH:9]=1)#[C:2][CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:20]1[CH:21]=[CH:22][C:23]2[O:34][C:33]3([CH2:39][CH2:38][CH:37]([O:40][CH3:41])[CH2:36][CH2:35]3)[C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]=2[CH:25]=1.CCO>COCCOC.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:41][O:40][CH:37]1[CH2:38][CH2:39][C:33]2([C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]3[CH:25]=[C:20]([C:6]4[CH:7]=[N:8][CH:9]=[C:4]([C:1]#[C:2][CH3:3])[CH:5]=4)[CH:21]=[CH:22][C:23]=3[O:34]2)[CH2:35][CH2:36]1
Reactant: COC1CCC2(CC1)Oc1ccc(Br)cc1C21N=C(C)C(N)=N1
Reactant: CC#Cc1cncc(B(O)O)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Solvent: O
Solvent: CCO
Product: CC#Cc1cncc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)C2(CCC(OC)CC2)O3)c1
Yield: 41.2 %

Procedure:
5-(Prop-1-ynyl)pyridin-3-ylboronic acid (Intermediate 15, 57.4 mg, 0.36 mmol), (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (9.79 mg, 0.01 mmol), cesium carbonate (233 mg, 0.71 mmol) and 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine (Example 29, 90 mg, 0.24 mmol) were dissolved in a 6:3:1 mixture of DME:EtOH:water (2 mL) and heated at 150° C. in a microwave reactor for 15 min. The mixture was concentrated and the residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL). The layers were separated and the organic layer was dried over MgSO4 and concentrated. Purification of the crude product by preparative chromatography afforded 41 mg of the title compound (42% yield). 1 H NMR (500 MHz, DMSO-d6) δ ppm 1.22 (m, 1 H), 1.46 (m, 3 H), 1.81 (m, 2 H), 1.98 (m, 2 H), 2.09 (s, 3 H), 2.21 (s, 3 H), 3.10 (m, 1 H), 3.22 (s, 3 H), 6.70 (s, 2 H), 6.95 (d, 1 H), 6.99 (d, 1 H), 7.56 (d, 1 H), 7.91 (t, 1 H), 8.47 (d, 1 H), 8.67 (d, 1 H); MS (APCI+) m/z 415 [M+H]+.
Reaction SMILES: COC1C=CC(C[NH:8][C:9]2[C:14]3[C:15]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:16]=4[S:17][C:13]=3[C:12]([C:26]#[N:27])=[CH:11][N:10]=2)=CC=1.O.[OH-].[K+].[O-:33]P([O-])([O-])=O.[K+].[K+].[K+]>OS(O)(=O)=O>[NH2:8][C:9]1[C:14]2[C:15]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:16]=3[S:17][C:13]=2[C:12]([C:26]([NH2:27])=[O:33])=[CH:11][N:10]=1
Reactant: COc1ccc(CNc2ncc(C#N)c3sc4cc(C(F)(F)F)ccc4c23)cc1
Reactant: O=P([O-])([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: NC(=O)c1cnc(N)c2c1sc1cc(C(F)(F)F)ccc12

Procedure:
A solution of 1-[(4-methoxybenzyl)amino]-7-(trifluoromethyl)[1]benzothieno[3,2-c]pyridine-4-carbonitrile in conc. H2SO4 (0.1 M) was stirred at room temperature for 2 h. The mixture was poured into H2O, neutralized with KOH and K3PO4 solution to pH 9. The solid was filtered then swished with boiling H2O to give the title compound.
Reaction SMILES: [CH2:1]([O:4][C:5]([C:7]1[N:8]([NH2:13])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3].[CH:14](=O)[CH2:15][CH:16]([CH3:18])[CH3:17].C([BH3-])#N.[Na+]>CO>[CH2:1]([O:4][C:5]([C:7]1[N:8]([NH:13][CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCOC(=O)c1cc(F)cn1N
Reactant: CC(C)CC=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: C=CCOC(=O)c1cc(F)cn1NCCC(C)C
Temperature: 25 °C
Reaction time: 20 h
Yield: 38.2 %

Procedure:
To a solution of 1-amino-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester (Example 14f, 0.5 g, 2.717 mmol) in methanol (20 mL) were added isovaleraldehyde (0.257 g, 2.988 mmol) and sodium cyanoborohydride (0.256 g, 4.075 mmol). The mixture was stirred for 20 h at 25° C. The solvent was removed in vacuo and the crude product was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes) to afford the desired product, 4-fluoro-1-(3-methyl-butylamino)-1H-pyrrole-2-carboxylic acid allyl ester (0.264 g, 1.039 mmol, 38.2% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 0.91 (3H, s), 0.93 (3H, s), 1.38-1.45 (2H, m), 1.63-1.80 (1H, m), 3.00-3.05 (2H, m), 4.74-4.76 (1H, m), 5.29 (1H, d, J=10.4 Hz), 5.38 (1H, d, J=18.8 Hz), 5.94-6.03 (1H, m), 6.52-6.56 (1H, m), 6.79-6.81 (1H, m).
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([CH3:30])[CH:20]=[C:21]([C:22]4[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][C:23]=4[CH3:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[CH3:31][NH2:32]>>[CH3:29][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([CH3:28])[C:22]=1[C:21]1[C:15]2[O:14][CH:13]([CH2:12][NH:32][CH3:31])[CH2:17][C:16]=2[CH:18]=[C:19]([CH3:30])[CH:20]=1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(C)cc(-c4c(C)cccc4C)c3O2)cc1
Product: CNCC1Cc2cc(C)cc(-c3c(C)cccc3C)c2O1

Procedure:
The title compound was prepared (0.035 g, 46%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6-dimethylphenyl) 5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.10 g, 0.24 mmol) and methylamine (0.073 g, 2.4 mmol). mp 204-205° C.
Reaction SMILES: Br[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.Cl.Cl.[N:24]1([C:30]2[N:31]=[CH:32][C:33]3[C:38]([CH:39]=2)=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.CCN(C(C)C)C(C)C>CN(C)C=O>[C:16]1([C:3]2[C:2]([N:27]3[CH2:26][CH2:25][N:24]([C:30]4[CH:39]=[CH:38][C:33]5[C:32](=[CH:37][CH:36]=[CH:35][CH:34]=5)[N:31]=4)[CH2:29][CH2:28]3)=[N:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=3)[N:4]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Reactant: c1ccc2cc(N3CCNCC3)ncc2c1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ccc5ccccc5n4)CC3)nc2c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Into a 8-mL sealed tube, was placed methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), 3-(piperazin-1-yl)isoquinoline dihydrochloride (250.8 mg, 0.88 mmol, 2.00 equiv), DIEA (170.3 mg, 1.32 mmol, 3.00 equiv), N,N-dimethylformamide (3 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then quenched by the addition of water. The resulting solution was extracted with 4×30 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 216.6 mg (crude) of methyl 3-(4-(isoquinolin-3-yl)piperazin-1-yl)-2-phenylquinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH3:11])[OH:10])[OH:8])[OH:6])[OH:4].[BrH:12]>C(O)(=O)C.ClCCl>[C:3]([O:10][C@@H:9]1[C@@H:7]([O:8][C:5](=[O:6])[CH3:7])[C@H:5]([O:6][C:9](=[O:10])[CH3:11])[C@@H:3]([CH3:2])[O:4][C@@H:11]1[Br:12])(=[O:4])[CH3:2]
Reactant: Br
Reactant: C[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@@H](Br)O[C@H](C)[C@H]1OC(C)=O
Temperature: 0 °C
Reaction time: 4 h
Yield: 85.4 %

Procedure:
In a 10 mL round bottom flask containing 10 mL of glacial acetic acid was placed 6-deoxyglucose (332.3 mg) and the reaction was cooled to 0° C. Hydrobromic acid in glacial acetic acid (5 mL of a 30 wt. % solution) was added dropwise. The reaction was stirred for 4 hours. The reaction was diluted with 100 mL of dichloromethane and washed with 50 mL ice water and then 50 mL of cold saturated aqueous sodium bicarbonate. The organic layer was dried over magnesium sulfate and filtered. The solvent was removed in vacuo to yield the title compound as a yellow solid (636.5 mg, 85.4%) and the product was used without further purification as in Example 1. MS (FAB) calculated for C12H17O7Br (M−Br) 273.1, found 273.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].Cl[CH2:20][CH2:21][CH:22]1[O:26][C:25](=[O:27])[N:24]([CH3:28])[CH2:23]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>C(O)CCC.CC(O)C>[CH3:28][N:24]1[CH2:23][CH:22]([CH2:21][CH2:20][N:16]2[CH2:17][CH2:18][N:13]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=3)[CH2:14][CH2:15]2)[O:26][C:25]1=[O:27]
Reactant: CN1CC(CCCl)OC1=O
Reactant: COc1cc(N2CCNCC2)cc(OC)c1OC
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCCCO
Solvent: CC(C)O
Product: COc1cc(N2CCN(CCC3CN(C)C(=O)O3)CC2)cc(OC)c1OC
Yield: 42.2 %

Procedure:
This compound was prepared according to the procedure of Example 2. A mixture of 3.8 g (0.015 mol) of 1-(3,4,5-trimethoxyphenyl)piperazine, 2.5 g (0.015 mol) of 5-(2-chloroethyl)-3-methyl-2-oxazolidinone, 5.3 g (0.05 mol) of anhydrous sodium carbonate and 0.3 g of potassium iodide in 100 mL of 1-butanol gave 2.4 g (42%) of white solid, mp 86°-88° C. (2-propanol).
Reaction SMILES: [C:1]1([N:7]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:8]([O:10][CH2:11][CH2:12][C:13]2[C:22]3[C:17](=[C:18]([O:23][Si:24]([C:37]([CH3:40])([CH3:39])[CH3:38])([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:19]=[CH:20][CH:21]=3)[CH2:16][CH2:15][CH:14]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].OO.C(OCC)(=[O:53])C>O1CCCC1.O>[C:41]1([N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]([O:10][CH2:11][CH2:12][C@@H:13]2[C:22]3[C:17](=[C:18]([O:23][Si:24]([C:37]([CH3:40])([CH3:39])[CH3:38])([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:19]=[CH:20][CH:21]=3)[CH2:16][CH2:15][C@H:14]2[OH:53])=[O:9])[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1
Reactant: CCOC(C)=O
Reactant: CC(C)(C)[Si](Oc1cccc2c1CCC=C2CCOC(=O)N(c1ccccc1)c1ccccc1)(c1ccccc1)c1ccccc1
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)[Si](Oc1cccc2c1CC[C@@H](O)[C@@H]2CCOC(=O)N(c1ccccc1)c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 1-[2-(N,N-diphenylcarbamoyloxy)ethyl]-5-t-butyldiphenylsilyloxy-3,4-dihydronaphthalene (2.0 g) in THF (tetrahydrofuran) (20 ml) was added BH3 (4.8 ml, 1M solution in THF) at 0° C. under N2. After being stirred for 12 hours at the room temperature, 2N--NaOH solution (1.5 ml) and H2O2 (1.0 ml, 35% solution) were added to the solution and stirred for 4 hours. The mixture was poured into a mixture of ethyl acetate and water. The organic layer was washed with 1N--HCl solution, sat. NaHCO3, and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by chromatography on silica gel to afford (trans)-1-[2-(N,N-diphenylcarbamoyloxy)ethyl]-2-hydroxy-5-t-butyldiphenylsilyloxy-1,2,3,4-tetrahydronaphthalene (1.1 g).
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][CH2:9][C:8]1=[CH:7][C:6](=[O:22])[C@H:5]1[CH2:23][C@@H:4]21.C(O)(=O)C>[Zn].C1C=CC=CC=1>[OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][CH2:9][C:8]1=[CH:7][C:6](=[O:22])[CH2:5][C@H:4]2[CH3:23]
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)[C@H]5C[C@H]5[C@@]43CO)[C@@H]1CCC2=O
Agent: [Zn]
Solvent: c1ccccc1
Solvent: CC(=O)O
Product: C[C@@H]1CC(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21CO

Procedure:
19-Hydroxy-1β,2β-methylene-4-androstene-3,17-dione, zinc powder, and acetic acid are heated to their reflux temperature for a period of about 1 hour. Upon cooling of the reaction mixture, benzene is added and the resulting suspension filtered. The filtrate is evaporated to dryness under vacuum and the residue remaining is chromatographed on a silica gel column and eluted with methylenechloride. The eluate is evaporated to dryness and the residue is crystallized from an acetone-hexane solution to yield 19-hydroxy-1β-methyl-4-androstene-3,17-dione.
Reaction SMILES: [C:1]([O-:4])(=O)[CH3:2].[Na+].[Br:6][C:7]1C=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:9](C(Br)Br)[CH:8]=1.Cl>C(O)(=O)C>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:11][C:2]=1[CH:1]=[O:4]
Reactant: CC(=O)[O-]
Reactant: Brc1ccc(-c2ccccc2)c(C(Br)Br)c1
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: O=Cc1cc(-c2ccccc2)ccc1Br
Temperature: 25 °C
Reaction time: 48 h

Procedure:
N-Bromosuccinimide (7.35 g) and benzoyl peroxide (196 mg) were added to a solution of 4-bromo-2-methylbiphenyl (5.0 g) in carbon tetrachloride (150 ml), and the mixture was stirred over night under reflux condition. After cooling to room temperature, the reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with saturated saline solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated therefrom under reduced pressure to give the residue. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain 4-bromo-2-(dibromomethyl)biphenyl (7.9 g). Sodium acetate (9.6 g) was added to a solution of 4-bromo-2-(dibromomethyl)biphenyl in acetic acid (240 ml) and stirred for two days under reflux condition. After cooling to room temperature, 4M hydrochloric acid (50 ml) was added to the reaction mixture, and the resulting mixture was stirred for two hours under reflux condition. After cooling to room temperature, the solvent was evaporated therefrom under reduced pressure to give the residue, ethyl acetate was added to the resulting residue, and the resultant was washed with 1M hydrochloric acid and saturated saline solution in order and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated from the filtrate under reduced pressure to give the residue, and the resulting residue was dried to obtain 4-bromo biphenyl-3-carboaldehyde (5.05 g).
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>COCCOC>[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21]([C:2]2[C:3]3[C:8]([CH:9]=[C:10]4[C:15]=2[CH:14]=[CH:13][CH:12]=[CH:11]4)=[CH:7][CH:6]=[CH:5][CH:4]=3)=[CH:20][CH:19]=1
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: Brc1c2ccccc2cc2ccccc12
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Product: FC(F)(F)c1ccc(-c2c3ccccc3cc3ccccc23)cc1
Temperature: 25 °C

Procedure:
5.1 g (20 mmol) of 9-bromoanthracene, 3.8 g (20 mmol) of 4-trifluoromethylphenylboronic acid, and 244 mg (0.8 mmol) of tri(o-tolyl)phosphine were put into a 100-mL three-neck flask, and nitrogen substitution in the system was carried out. 20 mL of ethylene glycol dimethyl ether (DME) was added to this mixture, and the mixture was stirred under reduced pressure and degassed. After that, 45 mg (0.20 mmol) of palladium acetate(II) and 10 mL (2.0 mol/L) of a potassium carbonate solution were added. This reaction mixture was stirred at 80° C. for 3 hours under nitrogen gas stream. Then, the reaction mixture was cooled to the room temperature, and a solid that was precipitated was collected by suction filtration. The collected solid was dissolved in toluene, and the solution was subjected to suction filtration through Florisil, celite, and then alumina. The filtrate was condensed to obtain a solid, and the solid was recrystallized with ethanol, whereby 5.7 g of a white powdery solid, which was a target matter, was obtained with the yield of 88%.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.[C:7](#[N:10])[CH:8]=[CH2:9]>>[CH3:1][C:2]1[N:3]=[CH:4][N:5]([CH2:9][CH2:8][CH2:7][NH2:10])[CH:6]=1
Reactant: C=CC#N
Reactant: Cc1c[nH]cn1
Product: Cc1cn(CCCN)cn1
Reaction time: 1 h

Procedure:
A mixture of 49.2 g. of 4-methyl-1H-imidazole and 75 ml. of acrylonitrile was heated on a steam bath for 6 hours and then concentrated to remove excess acrylonitrile. The residue was diluted with 400 ml. of methanol and divided into two parts. To each was added 90 ml. of ammonium hydroxide and Raney nickel catalyst. Each portion was then hydrogenated in a Parr apparatus. Each part was filtered, the filtrates combined and concentrated. The residue was concentrated from toluene. This residue was dissolved in tetrahydrofuran, stirred for one hour, filtered, concentrated, then concentrated from toluene, giving 82.2 g. of the desired intermediate as an oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[CH2:9][CH2:10][C:11](=[O:14])[CH2:12]O)=[CH:4][CH:3]=1.C([SiH](CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[O:15][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: O=C(CO)CCC(=O)c1ccc(Br)cc1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Product: OC1CCC(c2ccc(Br)cc2)OC1
Reaction time: 1.42 h
Yield: 84.1 %

Procedure:
To a round bottom flask containing 1-(4-bromophenyl)-5-hydroxypentane-1,4-dione (800 mg, 2.95 mmol) was added DCM (40 ml). The solution was cooled under an ice-bath and a solution of Boron trifluroide (diethyl ether complex, 0.89 ml, 7.00 mmol) was added dropwise. After the addition, triethylsilane (1.11 ml, 6.96 mmol) was also added and the reaction was stirred in an ice-bath for 85 minutes. The mixture was quenched with a saturated of NaHCO3 and was extracted twice with DCM. The combined organic portions was dried over sodium sulfate, filtered and concentrated to afford a crude residue. Column purification afforded the title compound as thick oil (638 mg, 84% conversion). MS (ESI) m/z, non-ionizable. Retention time 1.17 min. (Condition X).