Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH2:11][CH2:10][C:9]([C:13]([O:15][CH3:16])=[O:14])=[CH:8][C:7]=2[CH:17]=1.B(Br)(Br)Br.C(OCC)C.O>ClCCl>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH2:11][CH2:10][C:9]([C:13]([O:15][CH3:16])=[O:14])=[CH:8][C:7]=2[CH:17]=1
Reactant: COC(=O)C1=Cc2cc(OC)ccc2CCC1
Agent: BrB(Br)Br
Solvent: CCOCC
Solvent: O
Solvent: ClCCl
Product: COC(=O)C1=Cc2cc(O)ccc2CCC1
Temperature: 100 °C
Reaction time: 5 h
Yield: 90.4 %

Procedure:
To methyl 2-methoxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate (5.07 g, 21.8 mmol) dissolved in dichloromethane (100 ml) was added dropwise at −60° C. to −70° C. (inner temperature) boron tribromide (a 1 M solution in dichloromethane, 87 ml), and the resulting mixture was stirred for 5 hours while raising the temperature from −70° C. to room temperature. The reaction mixture was mixed with diethyl ether and water (100 ml) in the order, and was extracted with dichloromethane (100 ml, 50 ml×2). The combined organic layers were dried with anhydrous magnesium sulfate, and were then concentrated under reduced pressure. To the residue dissolved in methanol (150 ml) was added sulfuric acid (0.5 ml), and the resulting mixture was stirred under reflux with heating (100° C.) for 24 hours. The reaction mixture was concentrated under reduced pressure, was mixed with ethyl acetate (150 ml) and was washed with an aqueous saturated solution of sodium chloride (30 ml×3). After drying with anhydrous magnesium sulfate, the organic layer was concentrated under reduced pressure, diisopropyl ether was added to the residue and an insoluble material was collected by filtration. The insoluble material was washed with diisopropyl ether and was then dried under reduced pressure to obtain methyl 2-hydroxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate (4.31 g, 19.7 mmol, 90%).
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:20]3=[CH:21][C:22]4[O:26][CH2:25][O:24][C:23]=4[CH:27]=[C:19]3[O:18][CH2:17]1)[C:5](=[O:16])[N:6]2[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].C(N(CC)CC)C.[NH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1.[C]=O.CN(C)[CH:46]=[O:47]>C(OCC)(=O)C.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:16]=[C:5]1[C:4]2([C:20]3=[CH:21][C:22]4[O:26][CH2:25][O:24][C:23]=4[CH:27]=[C:19]3[O:18][CH2:17]2)[C:3]2[C:2]([C:46]([NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=3)=[O:47])=[CH:10][CH:9]=[CH:8][C:7]=2[N:6]1[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2c(Br)cccc21
Reactant: CN(C)C=O
Reactant: Nc1ccccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C]=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCCCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2c(C(=O)Nc3ccccn3)cccc21
Temperature: 80 °C
Yield: 14 %

Procedure:
A mixture of 4′-bromo-1′-pentylspiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.28 g, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (0.08 g, 10 mole %), triethylamine (0.33 g, 0.50 mL, 3.25 mmol) and 2-aminopyridine (0.12 g, 1.30 mmol) in N,N-dimethylformamide (5.00 mL) was subjected to carbon monoxide (40 Psi). The reaction mixture was heated at 80° C. for 16 h. After cooling down to ambient temperature, the reaction mixture was diluted with ethyl acetate (20.0 mL), washed with water (3×20.0 mL), brine (2×20.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography to give the title compound (0.04 g, 14%) as a solid: 1H NMR (300 MHz, CDCl3) δ 8.52 (d, 1H), 7.87 (br, 1H), 7.69-7.62 (m, 3H), 7.53-7.51 (m, 1H), 7.47-7.38 (m, 3H), 7.04-6.98 (m, 1H), 5.79 (d, 2H), 4.97 (ABq, 2H), 3.84-3.66 (m, 2H), 1.77-1.67 (m, 2H), 1.38-1.33 (m, 4H), 0.90 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 177.5, 158.2, 156.7, 149.2, 143.5, 142.1, 132.2, 132.0, 131.9, 131.8, 129.6, 128.6, 128.4, 121.8, 118.2, 110.7, 102.0, 101.4, 93.9, 79.5, 77.2, 58.5, 40.6, 29.0, 27.0, 22.3, 14.0; MS (ES+) m/z 473.2 (M+2).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH:15]([CH2:18][CH3:19])CO)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[C:20]1([OH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[C:27]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>CN(C)C=O>[O:26]([CH2:27][CH2:19][CH2:18][CH2:15][N:14]1[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=[CH:13]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Oc1ccccc1
Reactant: CCC(CO)n1cnc2c(N)nc3ccccc3c21
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Solvent: CN(C)C=O
Product: Nc1nc2ccccc2c2c1ncn2CCCCOc1ccccc1

Procedure:
2-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)-2-ethylethanol (50 mg, 0.195 mmol) and N,N-dimethylformamide (2 mL) were combined. Phenol (37 mg, 0.390 mmol) and triphenylphosphine (102 mg) were added followed by diethyl azodicarboxylate (67 mg, 0.390 mmol). The resulting solution was sonicated for 1 hour. Analysis by LC-MS showed product and a small amount of starting material. The solvent was removed and the residue was purified by semi-preparative HPLC using Method A. Mass Measurement: TM=332, NM[M+H]+1=333.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Si:13]([CH3:16])([CH3:15])[CH3:14])=[C:6]([CH:12]=1)[C:7]([NH:9][CH2:10][CH3:11])=[O:8].C(N(CC)CC)C.[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1.O>[C:24]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([Si:13]([CH3:15])([CH3:14])[CH3:16])=[C:6]([CH:12]=1)[C:7]([NH:9][CH2:10][CH3:11])=[O:8])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CCNC(=O)c1cc(N)ccc1[Si](C)(C)C
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CCNC(=O)c1cc(NC(=O)c2ccccc2)ccc1[Si](C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of the compound of Example 217 (0.118 g, 0.5 mmol) in CH2Cl2 (10 mL) was added triethylamine (0.14 mL, 1.0 mmol), benzoyl chloride (70 L, 0.6 mmol) and 4-dimethylaminopyridine (12 mg). The reaction was stirred at RT for 16 h, diluted with water, and extracted with ethyl acetate. The extracts were washed with 0.04 N HCl, sat NaHCO3, brine, dried (MgSO4) and concentrated to afford the title compound. The crude product was purified by recrystallization from ethyl acetate/hexanes to afford the title compound as fluffy white crystals (0.129 g, 76%). m.p. 185-187° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:13])=[C:4]([C:10](=[O:12])[CH3:11])[CH:5]=[C:6]([CH2:8]Cl)[CH:7]=1.[C-:14]#[N:15].[Na+]>CS(C)=O.O>[C:10]([C:4]1[CH:5]=[C:6]([CH2:8][C:14]#[N:15])[CH:7]=[C:2]([Br:1])[C:3]=1[OH:13])(=[O:12])[CH3:11]
Reactant: [C-]#N
Reactant: CC(=O)c1cc(CCl)cc(Br)c1O
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(=O)c1cc(CC#N)cc(Br)c1O
Reaction time: 15 h
Yield: 58 %

Procedure:
A solution of 1-(3-Bromo-5-chloromethyl-2-hydroxy-phenyl)-ethanone 212 (7.6 mmol) in 6 mL DMSO is added dropwise to a suspension of 8.2 mmol of NaCN in 4 mL DMSO. The mixture is stirred for 12-18 h and diluted with 80 mL water to yield a solid. The solid is isolated and recrystallized from ethanol to yield (3-acetyl-5-bromo-4-hydroxy-phenyl)-acetonitrile 213 in a 58% yield.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([C:11](=[O:19])[CH2:12][C:13]([CH3:18])([CH3:17])[O:14]2)=[C:9]([OH:20])[CH:8]=1)(=O)=O.[Cl-].[Li+].[CH:25]([Zn]C(C)C)([CH3:27])[CH3:26].Cl>CN(C)C=O.C1(C)C=CC=CC=1.O>[OH:20][C:9]1[CH:8]=[C:7]([CH2:26][CH2:25][CH3:27])[CH:16]=[C:15]2[C:10]=1[C:11](=[O:19])[CH2:12][C:13]([CH3:18])([CH3:17])[O:14]2
Reactant: CC1(C)CC(=O)c2c(O)cc(OS(=O)(=O)C(F)(F)F)cc2O1
Reactant: CC(C)[Zn]C(C)C
Agent: Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: CCCc1cc(O)c2c(c1)OC(C)(C)CC2=O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
At 0° C., 450 mg (550 μmol) of bis(diphenylphosphino)ferrocenepalladium(II) chloride/dichloromethane complex are added to a solution of 4.25 g (12.5 mmol) of 5-hydroxy-2,2-dimethyl-4-oxo-3,4-dihydro-2H-chromen-7-yl trifluoromethanesulfonate (Example 16A) and 1.59 g (37.5 mmol) of lithium chloride in 80 ml of degassed dimethylformamide. 24.98 ml (24.98 mmol) of a 1 M solution of diisopropylzinc in toluene are then slowly added dropwise. After 10 min of stirring at 0° C., the mixture is warmed to room temperature and stirred at this temperature for a further 5 h. The reaction solution is hydrolyzed carefully with water, acidified with 1 M hydrochloric acid, diluted with 500 ml of water and extracted twice with in each case 500 ml of ethyl acetate. After washing with 100 ml of water and 50 ml of saturated sodium chloride solution, the combined organic phases are dried over magnesium sulfate and concentrated under reduced pressure. Chromatography of the residue on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1) gives the target product as a 2:1 mixture with the isomer 5-hydroxy-2,2-dimethyl-7-propyl-2,3-dihydro-4H-chromen-4-one.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C(N(CC)CC)C.[Cl:19][C:20]([Cl:25])([Cl:24])[C:21](Cl)=[O:22]>ClCCl>[Cl:19][C:20]([Cl:25])([Cl:24])[C:21]([NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2)=[O:22]
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Reactant: Nc1cccc2ncccc12
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1cccc2ncccc12)C(Cl)(Cl)Cl
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 95.1 %

Procedure:
To a solution of 5-aminoquinoline (1.0 g, 6.9 mmol) and triethylamine (1.0 mL, 7.2 mmol) in dichloromethane (40 mL) was added trichloroacetyl chloride (1.4 g, 7.7 mmol) at 0° C., and the mixture was stirred at room temperature for 90 minutes. The reaction solution was concentrated, and to the residue was added ethyl acetate, and the resulting mixture was extracted three times with 1 N hydrochloric acid. The aqueous layers were combined and neutralized with an aqueous saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. The solid was filtered off, and the filtrate was concentrated. The residue was washed with diisopropyl ether and collected by filtration to obtain the title compound (1.9 g, yield 94%) as colorless crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Br:12]N1C(=O)CCC1=O.[C:20]1([P:26]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)(Cl)Cl.C1(C)C=CC=CC=1>[Br-:12].[CH3:7][O:6][C:4]([C:3]1[CH:8]=[CH:9][CH:10]=[CH:11][C:2]=1[CH2:1][P+:26]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:5]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: COC(=O)c1ccccc1C
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)Cl
Solvent: Cc1ccccc1
Product: COC(=O)c1ccccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]

Procedure:
Methyl 2-methylbenzoate was treated successively with N-bromosuccinimide in chloroform and triphenylphosphine in toluene to give (o-methoxycarbonylbenzyl)triphenylphosphonium bromide as a white solid, mp. 230°-234° C., 1H NMR (D6 -DMSO) delta 3.36 (3H,s); 5.47 (2H, br d J 17 Hz) ppm.
Reaction SMILES: C(N)C1[O:6]C=CC=1.C1(C)C=CC(S(NC2C=CN([C@@H:22]3[O:29][C@H:26]([CH2:27][OH:28])[C@@H:24]([OH:25])[CH2:23]3)C(=O)N=2)(=O)=O)=CC=1.C(NC1C=CNC(=O)N=1)C1OC=CC=1.[OH2:48]>>[O:48]=[CH:22][C@@H:23]([C@@H:24]([C@@H:26]([CH2:27][OH:28])[OH:29])[OH:25])[OH:6]
Reactant: NCc1ccco1
Reactant: O
Reactant: Cc1ccc(S(=O)(=O)Nc2ccn([C@H]3C[C@H](O)[C@@H](CO)O3)c(=O)n2)cc1
Agent: O=c1nc(NCc2ccco2)cc[nH]1
Product: O=C[C@H](O)[C@H](O)[C@H](O)CO

Procedure:
The second step was the reaction of furfurylamine (FIG. 1 V) with 4-N-p-toluenesulfonyl-2′-deoxycytidine (FIG. 1 I). The third step was depended on creating of 4-N-furfurylcytosine (FIG. 1 III), by cleavage of N-glycosyl bond by solution of inorganic acid in water (pH of this solution was about 3). When the reaction ended (what confirmed the dark yellow colour of the reaction mixture, the acid was evaporated or neutralised by water solution of sodium hydroxide where the received salt was lost on reverse column. The major product has shown low solubility in all solvents, but the best solubility was observed in water, and increased with temperature. In this reason, purity on the column was performed in warm water (40-45° C.). The column was referred by aluminum foil, because the decrease temperature of water was carried out to precipitate of the product on the gel. The purification of product was performed two times, because acid degradation of ribose gave a lot of byproducts, obstructed purification.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:18][CH2:17][C:11]3[N:12]=[CH:13][NH:14][C:15](=O)[C:10]=3[CH2:9]2)=[N:6][CH:7]=1.P(Cl)(Cl)([Cl:21])=O.ClCCCl.CN(C)C1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:21][C:15]1[C:10]2[CH2:9][N:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[CH2:18][CH2:17][C:11]=2[N:12]=[CH:13][N:14]=1
Reactant: Cc1ccc(N2CCc3nc[nH]c(=O)c3C2)nc1
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: ClCCl
Solvent: CN(C)c1ccccc1
Product: Cc1ccc(N2CCc3ncnc(Cl)c3C2)nc1

Procedure:
Into a 250 ml round bottom flask was combined 5,6,7,8-tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidin-4(3H)-one (0.250 g, 0.00103 mol), phosphoryl chloride (0.8 mL, 0.008 mol), and 1,2-dichloroethane (10 mL, 0.1 mol). N,N-Dimethylaniline (0.01 g, 0.0001 mol) was added dropwise and the mixture was heated at reflux for 2 hours. The mixture was reduced in vacuo to yield a dark brown oil. The oil was taken up in methylene chloride (50 ml) and poured over ice. The mixture was carefully neutralized using sat sodium bicarbonate. The layers were separated and the organic was dried over sodium sulfate and reduced in vacuo. The mixture was purified by flash chromatography on silica gel using methylene chloride:methanol (0-10%). The combined pure fractions were reduced in vacuo to yield a bright yellow solid. (0.141 g, 52.4%).
Reaction SMILES: [CH2:1]([Mg]Br)[CH3:2].[CH3:5][N:6]1[C:14]2[N:13]=[CH:12][N:11]([CH3:15])C=2C(=O)[N:8]([CH2:17][CH2:18][CH2:19][CH2:20][C:21](=[O:23])[CH3:22])[C:7]1=[O:24].CC[O:27][CH2:28][CH3:29]>>[OH:23][C:21]([CH3:22])([CH2:1][CH3:2])[CH2:20][CH2:19][CH2:18][CH2:17][N:8]1[C:28](=[O:27])[C:29]2[N:11]([CH3:15])[CH:12]=[N:13][C:14]=2[N:6]([CH3:5])[C:7]1=[O:24]
Reactant: CC(=O)CCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Reactant: CC[Mg]Br
Reactant: CCOCC
Product: CCC(C)(O)CCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Yield: 81.1 %

Procedure:
20.0 g (0.15 mol) of ethylmagnesium bromide are taken as a 40% strength solution in ether, and 27.8 g (0.1 mol) of 3,7-dimethyl-1-(5-oxohexyl)-xanthine in 1 liter of dry ether are metered in dropwise at room temperature, while stirring, whereupon a voluminous precipitate forms. The mixture is heated and is subsequently stirred, while boiling gently under reflux, for one hour. It is then worked up as described in the preceding Example 9 to give 25 g of oily crude product (81.1% of theory), which gradually crystallizes completely and is purified by recrystallization from diisopropyl ether, with the addition of a little ethyl acetate, at the boiling point.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC#N.O>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[N:7]=[C:2]([C:15]2[CH:16]=[C:11]([NH2:10])[CH:12]=[CH:13][CH:14]=2)[N:3]=1
Reactant: Cc1cc(C)nc(Cl)n1
Reactant: Nc1cccc(B(O)O)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: Cc1cc(C)nc(-c2cccc(N)c2)n1
Temperature: 150 °C

Procedure:
A mixture of 2-Chloro-4,6-dimethyl-pyrimidine (92 mg, 0.645 mmol, 1 eq.), 3-aminobenzene boronic acid (100 mg, 0.645 mmol, 1 eq.), Na2CO3 (137 mg, 1.29 mmol, 2 eq.), and Pd(PPh3)2Cl2 (23 mg, 0.032 mmol. 5 mol %) in a 1:1 v/v mixture of CH3CN/H2O (2.6 mL) is purged with N2 for 5 minutes and then heated in a microwave at 150° C. for 5 minutes. After cooling to room temperature, the reaction is diluted with EtOAc and sequentially washed with saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic solution is dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (1:1 hexanes/EtOAc) to give 3-(4,6-Dimethyl-pyrimidin-2-yl)-phenylamine as a yellow semisolid. [MS: (ES+) 200.1 (M+1)+].
Reaction SMILES: [F:1][C@:2]12[C@H:19]3[C@@H:10]([C@:11]4([CH3:21])[C:16](=[CH:17][CH2:18]3)[CH2:15][C@@H:14]([OH:20])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@:6]1([CH3:7])[C:5](=[O:22])[CH2:4][CH2:3]2.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.C(O)(=O)C.O>CC(C)=O>[F:1][C@:2]12[C@H:19]3[C@@H:10]([C@:11]4([CH3:21])[C:16]([CH2:17][CH2:18]3)=[CH:15][C:14](=[O:20])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@:6]1([CH3:7])[C:5](=[O:22])[CH2:4][CH2:3]2
Reactant: C[C@]12CC[C@H](O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@]12F
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Solvent: CC(C)=O
Product: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@]12F
Yield: 99.6 %

Procedure:
A solution of 14α-fluoro -3β-hydroxyandrost-5(6)-en-17 -one (93 mg), prepared as described in (i) above, in acetone (20 ml) was treated with Jones reagent (0.10 ml) at 0°-5° for 5 min. Excess Jones reagent was destroyed by the addition of isopropanol (0.2 ml) and water (5 ml) was added. The organic solvents were then evaporated off in vacuo and the aqueous residue was extracted with chloroform. The chloroform was evaporated in vacuo and the thus-obtained residue dissolved in warm methanol (10 ml). The resulting solution was treated with one drop of 2N aqueous sodium hydroxide and warmed on a steam bath for 5 min. The orange solution so obtained was neutralized with acetic acid, water was added, and the organic solvents were evaporated of in vacuo. The residue was extracted with chloroform, and the solution was washed with sodium bicarbonate and water, and then dried. Evaporation of the chloroform in vacuo gave a solid (92 mg) which was chromatographed by p.l.c. (silica gel) eluting with ethyl acetate: hexane (1:1). Recovery of the major band gave the title compound (68 mg), which crystallised from acetone as prisms (58 mg) m.p. 216°-217°; [α]D24 + 181° (c 0.69, CHCl3); λmax (ethanol) 239 nm (ε 12,900); νmax 1740, 1660 and 1615 cm-1 ; the PMR spectrum included signals at δ1.05 (3H, s, 18-Me), 1.22 (3H, s,19-Me) and 5.8 (1H, s, 4-H); FMR φ* + 164.5 ppm (broad multiplet ca 90 Hz wide). (Found: C, 74.82; H, 8.23; F, 6.30, C19H25O2F requires C,74.97; H,8.28; F,6.24%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8](=[O:23])[CH:9]=[C:10]([C:15]2[CH:20]=[C:19]([Cl:21])[CH:18]=[C:17]([Cl:22])[CH:16]=2)[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:4][C:3]=1[CH2:24][N:25]1[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]2[C:26]1=[O:35].[N+:36]([CH3:39])([O-:38])=[O:37].C1CCN2C(=NCCC2)CC1.O>C(#N)C>[Br:1][C:2]1[CH:7]=[C:6]([C:8](=[O:23])[CH2:9][C:10]([C:15]2[CH:20]=[C:19]([Cl:21])[CH:18]=[C:17]([Cl:22])[CH:16]=2)([CH2:39][N+:36]([O-:38])=[O:37])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:4][C:3]=1[CH2:24][N:25]1[C:26](=[O:35])[C:27]2=[CH:34][CH:33]=[CH:32][CH:31]=[C:28]2[C:29]1=[O:30]
Reactant: C[N+](=O)[O-]
Reactant: O=C(C=C(c1cc(Cl)cc(Cl)c1)C(F)(F)F)c1ccc(CN2C(=O)c3ccccc3C2=O)c(Br)c1
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Product: O=C(CC(C[N+](=O)[O-])(c1cc(Cl)cc(Cl)c1)C(F)(F)F)c1ccc(CN2C(=O)c3ccccc3C2=O)c(Br)c1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a solution of 0.80 g of N-[2-bromo-4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-2-butenoyl]phenylmethyl]phthalimide and 0.12 g of nitromethane in 10 mL of acetonitrile, 0.23 g of 1,8-diazabicyclo[5,4,0]-7-undecene was added and the resultant reaction mixture was stirred at room temperature for 15 hours. After the completion of the reaction, 20 mL of water was added to the reaction mixture and the resultant reaction mixture was extracted with ethyl acetate (30 mL×2). The organic phase was dehydrated and dried over a saturated brine and anhydrous magnesium sulfate in this order and the solvent was distilled off under reduced pressure to obtain 0.90 g of the objective substance as a yellow resinoid.
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.I[CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:10][CH3:11])=[CH:6][N:7]=1
Reactant: CCI
Reactant: Oc1ccc(Br)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOc1ccc(Br)nc1
Temperature: 60 °C
Reaction time: 3 h

Procedure:
A mixture of 6-bromopyridin-3-ol (7.58 g), iodoethane (5.23 mL), potassium carbonate (9.03 g), and DMF (80 mL) was stirred at 60° C. for 3 hr. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (7.58 g) as a pale yellow solid.
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
Reaction time: 0.67 h
Yield: 99 %

Procedure:
672 g (2.7 mol) of dibutyltin oxide (made by Sankyo Organic Chemicals Co., Ltd., Japan) and 1900 g (21.5 mol) of 3-methyl-1-butanol (made by Kuraray Co., Ltd, Japan) were put into a 3000 mL flask. The flask containing the mixture, which was a white slurry, was attached to an evaporator (R-144, made by Sibata, Japan) having a temperature regulator-equipped oil bath (OBH-24, made by Masuda Corporation, Japan), a vacuum pump (G-50A, made by Ulvac, Japan) and a vacuum controller (VC-10S, made by Okano Works Ltd., Japan) connected thereto. The outlet of a purge valve of the evaporator was connected to a line for nitrogen gas flowing at normal pressure. The purge valve of the evaporator was closed, and the pressure in the system was reduced, and then the purge valve was gradually opened, so as to pass nitrogen into the system, and thus return the system to normal pressure. The oil bath temperature was set to approximately 145° C., and the flask was immersed in the oil bath and rotation of the evaporator was commenced. With the purge valve of the evaporator left open, rotational agitation and heating were carried out for approximately 40 minutes at normal pressure, whereupon the liquid mixture boiled, and hence distilling off of water-containing 3-methyl-1-butanol began. This state was maintained for 7 hours, and then the purge valve was closed, and the pressure in the system was gradually reduced, and excess 3-methyl-1-butanol was distilled off with the pressure in the system at from 74 to 35 kPa. Once distillate stopped coming off, the flask was lifted out from the oil bath. The reaction liquid was a transparent liquid. After lifting the flask out from the oil bath, the purge valve was gradually opened, so as to return the pressure in the system to normal pressure. 880 g of reaction liquid was obtained in the flask. According to 119Sn-, 1H-, and 13C-NMR analysis results, the product 1,1,3,3-tetrabutyl-1,3-bis(3-methylbutyloxy)-distannoxane was obtained at a yield of 99% based on the dibutyltin oxide. The same procedure was repeated twelve times, thus obtaining a total of 10350 g of 1,1,3,3-tetrabutyl-1,3-bis(3-methylbutyloxy)-distannoxane.