Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [K].[C:2]1(=[O:12])[NH:6][C:5](=[O:7])[C:4]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]12.[CH2:13](Cl)[CH:14]=[CH2:15]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[CH2:15]([N:6]1[C:2](=[O:12])[C:3]2=[CH:11][CH:10]=[CH:9][CH:8]=[C:4]2[C:5]1=[O:7])[CH:14]=[CH2:13]
Reactant: C=CCCl
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K]
Solvent: CN(C)C=O
Product: C=CCN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 22 h
Yield: 42 %

Procedure:
To a stirred mixture of phthalimide potassium salt (20 g, 108 mmol) and tetrabutylammonium bromide (1.04 g, 3.24 mmol, 0.03 equiv) in anhydrous DMF (75 ml) was added allyl chloride (8.84 ml, 108 mmol) at room temperature, and the mixture was stirred at room temperature for 22 h, resulting in a light-yellow suspension. The reaction was quenched by adding cold H2O (150 ml), and the mixture was stirred for 10 min (an ice bath was applied during this time to aid the precipitation). The resulting white suspension was filtered off, washed with H2O (3×50 ml), and air-dried to give N-allylphthalimide (8.5 g, 42% yield) as white solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][C:18]2[NH:22][C:21]([C:23]3C=CC=CN=3)=[N:20][N:19]=2)=[CH:4][CH:3]=1.[Cl:29]C1C=CC2N(C(CC(NN)=O)=C(C3C=CC=CC=3)N=2)C=1.Cl.C(=N)(N)C>>[Cl:29][C:13]1[CH:14]=[CH:15][C:10]2[N:11]([C:16]([CH2:17][C:18]3[NH:22][C:21]([CH3:23])=[N:20][N:19]=3)=[C:8]([C:5]3[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=3)[N:9]=2)[CH:12]=1
Reactant: NNC(=O)Cc1c(-c2ccccc2)nc2ccc(Cl)cn12
Reactant: Clc1ccc(-c2nc3ccccn3c2Cc2nnc(-c3ccccn3)[nH]2)cc1
Agent: CC(=N)N
Agent: Cl
Product: Cc1nnc(Cc2c(-c3ccccc3)nc3ccc(Cl)cn23)[nH]1

Procedure:
The title compound was prepared according to the experimental described for compound 230 from 2-(6-chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)acetohydrazide and acetimidamide hydrochloride. M/e− 324 for C17H15ClN5 (M+H)+; 1H-NMR (400 MHz, CD3OD) δ 8.43 (s, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.63 (m, 1H), 7.57 (d, J=9.9 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.39 (m, 2H), 4.46 (s, 2H), 2.38 (s, 3H) ppm.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH:19]3[CH2:20][N:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22][CH2:23][CH:18]3[N:6]3[CH2:7][CH:8]([CH3:17])[N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]([CH:11]=1)=[C:5]23.[Cl:29][C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:31]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[Cl:29][C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:31]=1[C:2]1[CH:3]=[C:4]2[CH:19]3[CH2:20][N:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22][CH2:23][CH:18]3[N:6]3[CH2:7][CH:8]([CH3:17])[N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]([CH:11]=1)=[C:5]23
Reactant: OB(O)c1ccc(Cl)cc1Cl
Reactant: CCOC(=O)N1CCC2C(C1)c1cc(Br)cc3c1N2CC(C)N3C(=O)OCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)N1CCC2C(C1)c1cc(-c3ccc(Cl)cc3Cl)cc3c1N2CC(C)N3C(=O)OCC
Temperature: 100 °C
Reaction time: 16 h
Yield: 26.3 %

Procedure:
To a solution of diethyl 5-bromo-2-methyl-6b,9,10,10a-tetrahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline-3,8(2H,7H)-dicarboxylate (100 mg, 0.22 mmol) in DMF (10 mL) was added 2,4-dichlorophenyl boronic acid (63 mg, 0.33 mmol) and Na2CO3 (58 mg, 0.55 mmol, in 0.4 mL of H2O). The mixture was degassed with a stream of nitrogen for 20 min and then there was added Pd(PPh3)4 (35 mg, 0.03 mmol) and the mixture was stirred at 100° C. for 16 h. The reaction was allowed to cool to ambient temperature and was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine, dried (MgSO4), filtered through Celite and concentrated in vacuo. The residue was purified by flash chromatography (elution with hexanes/ethyl acetate) to afford diethyl 5-(2,4-dichlorophenyl)-2-methyl-6b,9,10,10a-tetrahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline-3,8(2H,7H)-dicarboxylate (30 mg, 29% yield) MS [M+H]+517.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]2[N:10]([C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:9]=[CH:8][CH:7]=[CH:6]2.[N:17]([O-])=[O:18].[Na+].[OH-].[Na+]>C(O)(=O)C.O>[CH3:1][S:2][C:3]1[C:4]([N:17]=[O:18])=[C:5]2[N:10]([C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:9]=[CH:8][CH:7]=[CH:6]2
Reactant: O=N[O-]
Reactant: CCOC(=O)c1c(SC)cc2ccccn12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: CCOC(=O)c1c(SC)c(N=O)c2ccccn12
Yield: 87 %

Procedure:
A solution of 470 mg (2 mmol) of ethyl 2-(methylsulphanyl)-3-indolizinecarboxylate 9 in 10 ml of acetic acid, stirred at 0° C., was admixed dropwise over 10 minutes with a solution of 165 mg of sodium nitrite in 5 ml of water. The reaction mixture was then left with stirring for a further hour. The acidic phase was basified with a solution of 2N NaOH, and then extracted with dichloromethane (25 ml×3). The organic phase was dried over magnesium sulphate, filtered and then concentrated under vacuum to give ethyl 2-(methylsulphanyl)-1-nitroso-3-indolizinecarboxylate 10 (460 mg). m.p: 134-135° C. 1H NMR (CDCl3): δ 9.58 (d, J=6.8 Hz, 1H), 8.45 (d, J=8.5 Hz, 1H), 7.70 (t, J=8.2 Hz, 1H), 7.20 (td, J=7.0, 1.1 Hz, 1H), 4.50 (q, J=7.1 Hz, 2H), 3.05 (s, 3H), 1.52 (t, J=7.1 Hz, 3H). 13C NMR (CDCl3): 161.2, 156.9, 143.4, 135.7, 127.2, 123.7, 118.7, 118.0, 112.9, 61.2, 19.4, 14.4.
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:18][C@H:17]([N:19]=[N+]=[N-])[C:16](=[O:22])[C@H:15]2[C@@:6]1([CH3:30])[CH2:7][CH2:8][C@@H:9]1[C@:14]2([CH3:23])[CH2:13][C@@H:12]([C:24]2[CH:28]=[CH:27][O:26][CH:25]=2)[O:11][C:10]1=[O:29])=[O:4].[NH4+].[Cl-]>C(Cl)Cl.CO.[Zn]>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:18][C@H:17]([NH2:19])[C:16](=[O:22])[C@H:15]2[C@@:6]1([CH3:30])[CH2:7][CH2:8][C@@H:9]1[C@:14]2([CH3:23])[CH2:13][C@@H:12]([C:24]2[CH:28]=[CH:27][O:26][CH:25]=2)[O:11][C:10]1=[O:29])=[O:4]
Reactant: COC(=O)[C@@H]1C[C@H](N=[N+]=[N-])C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: ClCCl
Solvent: CO
Product: COC(=O)[C@@H]1C[C@H](N)C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
Temperature: 25 °C
Reaction time: 3 h
Yield: 81.1 %

Procedure:
A mixture of 38 (0.08 g, 0.19 mmol), Zn dust (0.16 g, 2.45 mmol) and NH4Cl (g, mmol) in a mixture of CH2Cl2/MeOH (1:4, 20 mL) was stirred at room temperature for 3 h. The mixture was filtered and the filtrate was concentrated to dryness under reduced pressure. 2N NaOH (30 mL) was added to the residue and the mixture was extracted with CH2Cl2 (2×20 mL). The combined CH2Cl2 portion was washed with H2O (30 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure afforded 0.06 g (84%) of 39 as a white solid, mp 237-240° C. (EtOAc/n-hexanes.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].N1CCC[CH2:10]1.O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:8])[CH2:4][C:5](=[O:6])[CH2:7][CH3:10]
Reactant: C1CCNC1
Reactant: COC(=O)CC(C)=O
Solvent: O
Solvent: Cc1ccccc1
Product: CCC(=O)CC(=O)OC
Reaction time: 1 h
Yield: 92.3 %

Procedure:
116 g of acetoacetic acid methyl ester and 75 g of pyrrolidine were boiled in 350 ml of toluene on a water separator until the theoretical quantity of water was separated. The solution was added drop by drop at -40° C. to a suspension of 47 g of sodium amide in 800 ml of liquid ammonia. The ammonia was removed by allowing the temperature of the reaction solution to rise to -20° C., and then, at such temperature, a solution of 114 g of methyl bromide in 500 ml of toluene was added drop by drop. The reaction solution was filtered and the toluene was removed using a rotary evaporator. The residue, after the addition of 700 ml of methylene chloride and 102 g of concentrated hydrochloric acid thereto, was hydrolyzed for 1 hour at ambient temperature. The two phases were separated, the organic phase was dried and the solvent was removed. 120 g of 3-oxopentanoic acid methyl ester (92 percent) was obtained.
Reaction SMILES: Cl[C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([I:15])[CH:12]=[C:11]([F:16])[CH:10]=2)=[O:7])=[CH:4][N:3]=1.[CH2:19]([O:21][C:22](=[O:35])[C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:25][CH:24]=1)[CH3:20].C(OC(=O)C1C=CC(N2CCN(C3C=CC(C(=O)NC4C=CC(C)=C(I)C=4)=CN=3)CC2)=CC=1)C>>[CH2:19]([O:21][C:22](=[O:35])[C:23]1[CH:24]=[CH:25][C:26]([N:29]2[CH2:30][CH2:31][N:32]([C:2]3[CH:18]=[CH:17][C:5]([C:6](=[O:7])[NH:8][C:9]4[CH:14]=[C:13]([I:15])[CH:12]=[C:11]([F:16])[CH:10]=4)=[CH:4][N:3]=3)[CH2:33][CH2:34]2)=[CH:27][CH:28]=1)[CH3:20]
Reactant: CCOC(=O)c1ccc(N2CCNCC2)cc1
Reactant: O=C(Nc1cc(F)cc(I)c1)c1ccc(Cl)nc1
Agent: CCOC(=O)c1ccc(N2CCN(c3ccc(C(=O)Nc4ccc(C)c(I)c4)cn3)CC2)cc1
Product: CCOC(=O)c1ccc(N2CCN(c3ccc(C(=O)Nc4cc(F)cc(I)c4)cn3)CC2)cc1

Procedure:
4-{4-[5-(3-Fluoro-5-iodo-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl ester was prepared from 6-chloro-N-(3-fluoro-5-Iodo-phenyl)-nicotinamide and 4-(piperazin-1-yl)-benzoic acid ethyl ester following a method similar to the one described in the synthesis of 4-{4-[5-(3-iodo-4-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl ester above. The product was isolated after suspension in small volume of EtOAc filtration and a wash with CH3CN. HRMS m/z calcd for C25H24N4O3FI [M+H]+: 575.0950. Found: 575.0947.
Reaction SMILES: [C:1]([C:7]([O:9][CH3:10])=[O:8])#[C:2][C:3](OC)=[O:4].[CH3:11][NH:12][NH2:13]>CCOCC>[OH:4][C:3]1[N:12]([CH3:11])[N:13]=[C:1]([C:7]([O:9][CH3:10])=[O:8])[CH:2]=1
Reactant: CNN
Reactant: COC(=O)C#CC(=O)OC
Solvent: CCOCC
Product: COC(=O)c1cc(O)n(C)n1
Temperature: -5 °C
Reaction time: 1 h

Procedure:
102.3 g (0.72 mol) Dimethyl acetylenedicarboxylate was added to 1000 ml ether and the mixture cooled to -5° C. in an ice-methanol bath. 33 g (0.72 mol) methylhydrazine in 100 ml ether was added dropwise at a rate that the inner temperature did not rise above 0° C. The mixture was stirred for one hour at 0° C., the precipitate suction filtered off, washed with ether and dried at 40° C. in vacuo. The intermediate was immersed in an oil-bath heated to 120° C. The reaction product was recrystallised from methanol.
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[CH2:7][CH2:8][C@@H:9]([C:25](N1[C@H](C)COC1=O)=[O:26])[CH2:10][C@H:11]1[CH2:15][O:14][C:13]([CH3:17])([CH3:16])[N:12]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C1COCC1.CO>[C:1]([O:5][C:6](=[O:34])[CH2:7][CH2:8][C@@H:9]([CH2:25][OH:26])[CH2:10][C@H:11]1[CH2:15][O:14][C:13]([CH3:17])([CH3:16])[N:12]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([CH3:3])([CH3:2])[CH3:4]
Reactant: C[C@@H]1COC(=O)N1C(=O)[C@H](CCC(=O)OC(C)(C)C)C[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)CC[C@@H](CO)C[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 100.3 %

Procedure:
(S)-tert-butyl 4-((R)-5-tert-butoxy-2-((R)-4-methyl-2-oxooxazolidine-3-carbonyl)-5-oxopentyl)-2,2-dimethyloxazolidine-3-carboxylate (4.12 g, 7.36 mmol) was dissolved in 4:1 THF and methanol (200 mL) and cooled to 0° C. Sodium borohydride (557 mg, 2 eq) was added slowly. After 10 min., the mixture was warmed up to rt slowly. The mixture was stirred 2 hr at rt. The mixture was concentrated, redissolved in EtOAc (300 mL), washed with 1% HCl solution (100 mL), brine (60 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by ISCO (40 g column, 10-65% EtOAc in Hexanes gradient, check TLC with Ninhydrin stain) to afford 2.86 g of (S)-tert-butyl 4-((R)-5-tert-butoxy-2-(hydroxymethyl)-5-oxopentyl)-2,2-dimethyloxazolidine-3-carboxylate as a white solid. MS ESI +m/v 410 (M+Na).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][CH2:17][C:18]3[N:19]=[C:20]([CH:23]=[CH:24][C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=4)[O:21][CH:22]=3)=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=[N:2]1.[C:35]([BH3-])#N.[Na+].Cl>C(#N)C>[CH3:35][N:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][CH2:8][CH2:7][CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[N:2]2)=[CH:11][CH:12]=1)[CH2:17][C:18]1[N:19]=[C:20]([CH:23]=[CH:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:29][CH:30]=2)[O:21][CH:22]=1
Reactant: [BH3-]C#N
Reactant: FC(F)(F)c1ccc(C=Cc2nc(CNc3ccc(CCCCn4ccnn4)cc3)co2)cc1
Agent: Cl
Agent: [Na+]
Solvent: CC#N
Product: CN(Cc1coc(C=Cc2ccc(C(F)(F)F)cc2)n1)c1ccc(CCCCn2ccnn2)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of [4-(4-[1,2,3]triazol-1-yl-butyl)-phenyl]-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazol-4-ylmethyl}-amine 2 (0.03 g, 0.06 mmol) in acetonitrile (2 ml) formaldehyde (36%, 0.1 ml) and sodium cyanoborohydride (0.012 g, 0.019 mmol) are added. After stirring at room temperature for 10 min the pH is set to 2 by adding conc. hydrochloric acid and stirring is continued for 2 h. The solvents are evaporated, the crude product suspended in water (10 ml) and the pH adjusted to 9 with aqueous ammonia. The mixture is extracted with ethyl acetate (3×25 ml), the organic phase washed with brine and dried over sodium sulfate. After concentration in vacuo the oily residue is precipitated with heptanes to yield methyl-[4-(4-[1,2,3]triazol-1-yl-butyl)-phenyl]-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazol-4-ylmethyl}-amine 3 as a light yellow solid. Yield 31 mg (100%); m.p. 112–114° C.
Reaction SMILES: [C:1](Cl)(=O)C.[NH2:5][C@H:6]([C:11]([OH:13])=[O:12])[CH2:7][CH2:8][S:9][CH3:10]>CO>[CH3:1][O:12][C:11](=[O:13])[C@@H:6]([NH2:5])[CH2:7][CH2:8][S:9][CH3:10]
Reactant: CSCC[C@H](N)C(=O)O
Reactant: CC(=O)Cl
Solvent: CO
Product: COC(=O)[C@@H](N)CCSC
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
At about 0° C., acetyl chloride (15 mL) was added dropwise to methanol (100 mL). After stirring for about 10 minutes at about 0° C., L-methionine (8.5 g, 57 mmol) was added and the resulting solution was stirred for about 10 minutes. The solution was then heated at reflux for about 4 hours, and then maintained at ambient temperature for about 16 hours. The solvent was removed in vacuo, the resulting residue was dissolved in chloroform (100 mL), and the solution was neutralized to pH 7-8 by the careful addition of a saturated aqueous sodium bicarbonate solution. Following standard extractive workup with chloroform, the resulting residue was kept under high vacuum for about two hours to afford the title product as a colourless oily liquid, which was used directly in the next step without any further purification (crude yield 6 g, 65%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].[C:12]([S-])(=[S:16])OCC.[K+].O.Cl>N1C=CC=CC=1>[N+:8]([C:6]1[CH:5]=[CH:4][C:3]2[O:11][C:12](=[S:16])[NH:1][C:2]=2[CH:7]=1)([O-:10])=[O:9]
Reactant: CCOC(=S)[S-]
Reactant: Nc1cc([N+](=O)[O-])ccc1O
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: c1ccncc1
Product: O=[N+]([O-])c1ccc2oc(=S)[nH]c2c1
Temperature: 120 °C
Reaction time: 6 h
Yield: 168.2 %

Procedure:
In accordance with well known procedures, (see Batista-Parra, A. et al. Heterocycles, 2003, 60, 1367), a suspension of 2-amino-4-nitrophenol (1.54 g, 10 mmol) and potassium O-ethyl carbonodithioate (1.68 g, 10.5 mmol) in dry pyridine (10 mL) was stirred at 120° C. for 6 h, and then at room temperature for 16 h. The solution was poured into water and aqueous hydrochloric acid was added. The resulting precipitate was collected by filtration, washed with dilute aqueous hydrochloric acid, followed by water and then dried in the vacuum oven to afford 3.3 g (84%) of the title compound.
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[F:9][C:10]([F:22])([F:21])[O:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1>>[F:9][C:10]([F:21])([F:22])[O:11][C:12]1[CH:17]=[C:16]([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=2)[CH:15]=[CH:14][CH:13]=1
Reactant: OB(O)c1cccc(OC(F)(F)F)c1
Reactant: Nc1ccc(Br)cc1
Product: Nc1ccc(-c2cccc(OC(F)(F)F)c2)cc1
Yield: 63.5 %

Procedure:
The title compound (280 mg) was prepared from 4-bromoaniline (300 mg, 1.74 mmol) and 3-(trifluoromethoxy)phenylboronic acid (466 mg, 2.26 mmol) as a pale-yellow liquid.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]1[CH2:24][C@@:22]2([CH3:23])[C@@H:18]([CH2:19][CH:20]=[C:21]2[O:25]C(=O)C)[C@H:17]2[C@H:8]1[C:9]1[CH:10]=[CH:11][C:12]([O:29][C:30](=[O:32])[CH3:31])=[CH:13][C:14]=1[CH2:15][CH2:16]2.C([O-])(=O)C.[Na+].[Br:38]N1C(=O)CCC1=O.O>CN(C)C=O>[C:30]([O:29][C:12]1[CH:11]=[CH:10][C:9]2[C@@H:8]3[C@H:17]([C@H:18]4[C@@:22]([CH2:24][CH:7]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Cl:1])([CH3:23])[C:21](=[O:25])[CH:20]([Br:38])[CH2:19]4)[CH2:16][CH2:15][C:14]=2[CH:13]=1)(=[O:32])[CH3:31]
Reactant: CC(=O)OC1=CC[C@H]2[C@@H]3CCc4cc(OC(C)=O)ccc4[C@H]3C(CCCCCCl)C[C@]12C
Reactant: O=C1CCC(=O)N1Br
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)Oc1ccc2c(c1)CC[C@@H]1[C@@H]2C(CCCCCCl)C[C@]2(C)C(=O)C(Br)C[C@@H]12
Yield: 228.4 %

Procedure:
A solution of 6.2 g of 11-(5-chloropentyl)-3,17-diacetoxy-estra-1,3,5(10),16-tetraene in 95 ml of dimethylformamide is mixed at 0° C. first with 9.05 ml of sodium acetate solution (10%) and then with 2.6 g of N-bromosuccinimide, and it is stirred for one hour. Then, it is mixed with water, extracted with ethyl acetate, washed with sodium sulfate solution as well as common salt solution, dried on sodium sulfate and evaporated to the dry state in a vacuum. 15.3 g of crude 3-acetoxy-16-bromo-11-(5-chloropentyl)-estra-1,3,5(10)-trien-17-one is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH3:36])=[C:6]([CH:34]=1)[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([C:16]([NH:18][CH:19]([CH2:31][CH3:32])[C:20]([NH:22]CC(OC(C)(C)C)=O)=[O:21])=[O:17])[CH2:12][C:11](=[O:33])[NH:10][CH2:9]1.Cl.C(OC(=O)CN)(C)(C)C.N[C:48]1[CH:49]=[C:50]([CH:58]=[CH:59][CH:60]=1)[C:51]([O:53]C(C)(C)C)=[O:52]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH3:36])=[C:6]([CH:34]=1)[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([C:16]([NH:18][C@H:19]([CH2:31][CH3:32])[C:20]([NH:22][C:48]2[CH:49]=[C:50]([CH:58]=[CH:59][CH:60]=2)[C:51]([OH:53])=[O:52])=[O:21])=[O:17])[CH2:12][C:11](=[O:33])[NH:10][CH2:9]1
Reactant: CCC(NC(=O)N1CC(=O)NCC(Cc2cc(Cl)ccc2OC)C1=O)C(=O)NCC(=O)OC(C)(C)C
Reactant: CC(C)(C)OC(=O)c1cccc(N)c1
Agent: CC(C)(C)OC(=O)CN
Agent: Cl
Product: CC[C@@H](NC(=O)N1CC(=O)NCC(Cc2cc(Cl)ccc2OC)C1=O)C(=O)Nc1cccc(C(=O)O)c1

Procedure:
Instead of the starting material compound of Example 220, that is, the glycine tert-butyl ester hydrochloride, tert-butyl 3-aminobenzoate was used for the similar procedure as in Example 220 and Example 245 to obtain the title compound.
Reaction SMILES: [N+:1]([C:4]1[NH:5][CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2].C(=O)(O)[O-].[Na+].Br[CH2:15][CH2:16][CH:17]=[C:18]([CH3:20])[CH3:19]>CN(C)C=O.O>[CH3:19][C:18]([CH3:20])=[CH:17][CH2:16][CH2:15][N:5]1[CH:6]=[CH:7][N:8]=[C:4]1[N+:1]([O-:3])=[O:2]
Reactant: CC(C)=CCCBr
Reactant: O=[N+]([O-])c1ncc[nH]1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)=CCCn1ccnc1[N+](=O)[O-]
Temperature: 65 °C
Reaction time: 16 h

Procedure:
To a solution of 2-nitroimidazole (3.0 g, 27 mmol) in dry dimethylformamide (25 mL), was added anhydrous sodium bicarbonate (4.2 g, 50 mmol) followed by 5-bromo-2-methyl-2-pentene (5.0 g, 30.67 mmol). The reaction mixture was heated at 60-70° C. with stirring under nitrogen for 16 hours. Solvent dimethylformamide and the unreacted bromide were removed under reduced pressure (<1 mm) at 50-60° C. to yield a paste which was dissolved in water (50 mL) and extracted with ethyl acetate (5×50 mL). The combined organic extracts were dried and concentrated to give a brown oil which was recrystallized from petroleum ether (b.p. 40-60° C.) to yield a yellow solid. Yield: 4.8 g, m.p. 51-52° C. 1H NMR (CDCl3) δ1.55 (s, 3H, CH3), 1.75 (s, 3H, CH3), 2.7 (q, 2H, olefinic CH2), 4.5 (t, 2H, N—CH2), 5.2 (t, 1H, olefinic H), 7.1 (s, 1H, imidazole H), 7.2 (s, 1H, imidazole H). M.S. [M+H]+ 196, [M+NH4]+ 213.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]=1[Si](C)(C)C)(=O)=O.[F-].[Cs+].C([O:27][P:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)C.C(#N)C>CCOC(C)=O>[CH:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:15]=[CH:16][C:7]=1[P:28](=[O:27])([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: CCOP(c1ccccc1)c1ccccc1
Reactant: C[Si](C)(C)c1c(OS(=O)(=O)C(F)(F)F)ccc2ccccc12
Agent: [Cs+]
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: O=P(c1ccccc1)(c1ccccc1)c1ccc2ccccc2c1

Procedure:
1-(trimethylsilyl)naphthalen-2-yl trifluoromethanesulfonate (25 mg, 0.071 mmol), Cesium Fluoride (60 mg, 0.395 mmol), Ethoxydiphenylphosphane (68 mg, 0.287 mmol), Acetonitrile (1 ml): Reaction Time: 16 h; Rf: 0.4 (1:3 EtOAc:Pet Ether); Thick oil; 19.5 mg, 83%; 1H NMR (400 MHz, CDCl3, TMS) δ 8.28 (d, J=13.8 Hz, 1H), 7.95-7.84 (m, 3H), 7.79-7.40 (m, 13H); 13C NMR (100 MHz, CDCl3, TMS) δ 134.7 (d, J=2.3 Hz), 134.0 (d, J=9.3 Hz), 133.0, 132.3, 132.1 (d, J=10.0 Hz), 132.0 (d, J=1.5 Hz), 131.3 (d, J=243.5 Hz), 128.9, 128.5 (d, J=12.3 Hz), 128.4, 128.2, 127.4 (d, J=87.9 Hz), 126.8 (d, J=10.8 Hz); 31P NMR (162 MHz, CDCl3) δ 29.3; HRMS-ESI (m/z) calcd (C22H17OP+H)+: 329.1090. found: 329.1086; Known compound, Lit. Y. -L. Zhao, G. -J. Wu, Y. Li, L. -X. Gao, F.-S. Han, Chem. Eur. J. 2012, 18, 9622.
Reaction SMILES: O=[C:2]([CH2:8][CH3:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[C:12]=1[NH:19][NH2:20].C1C=CC=CC=1>O>[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[C:12]=1[NH:19][N:20]=[C:2]([CH2:8][CH3:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: NNc1c(Cl)cc(Cl)cc1Cl
Reactant: CCOC(=O)C(=O)CC
Solvent: O
Solvent: c1ccccc1
Product: CCOC(=O)C(CC)=NNc1c(Cl)cc(Cl)cc1Cl

Procedure:
A reaction mixture consisting of 11 g. (0.085 mole) ethyl 2-oxobutyrate, 17 g. (0.077 mole) (2,4,6-trichlorophenyl)hydrazine, and 200 ml. benzene was heated at the reflux temperature with a Dean and Stark water trap attached to the reaction vessel. When all the water produced by the reaction had been removed, the benzene was removed by evaporation under reduced pressure. The oily residue that remained was dissolved in hot technical hexane, and this solution was allowed to cool. Crystals of the desired product separated and 15.2 g. were recovered. Recrystallization from methanol gave an analytical sample of ethyl 2-oxobutyrate 2-(2,4,6-trichlorophenyl)hydrazone having a melting point at 97° to 99° C.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([CH:10]=[O:11])[C:4]=2[CH:3]=[CH:2]1.[CH2:12]([N+](CCCC)(CCCC)CCCC)CCC.CI>C(Cl)Cl.[OH-].[Na+]>[CH3:12][N:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([CH:10]=[O:11])[C:4]=2[CH:3]=[CH:2]1
Reactant: O=Cc1cccc2[nH]ccc12
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CI
Product: Cn1ccc2c(C=O)cccc21
Yield: 98.7 %

Procedure:
34 g of indol 4-carboxaldehyde in 800 ml of methylen chloride were mixed for 4 hours at ambient temperature with 79.5 g of tetrabutyl ammonium hydrogeno sulfate and 16.04 ml of methyl iodide in 400 ml of 5N sodium hydroxide and 300 ml of methylene chloride were added, followed by decanting and extraction was effected with methylene chloride. The organic phase was washed with a saturated aqueous solution of sodium chloride, dried and concentrated to dryness. The residue was chromatographed on silica (eluant: methylene chloride) to obtain 36.8 g of the expected product melting at <40° C.