Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])(C)(C)C.CCCCCC.I[C:13](=[CH2:22])[CH2:14][C@H:15]1[CH2:19][O:18][C:17]([CH3:21])([CH3:20])[O:16]1.[S:23](Cl)([Cl:26])(=[O:25])=[O:24]>C(OCC)C>[CH3:20][C:17]1([CH3:21])[O:16][C@@H:15]([CH2:14][C:13]([S:23]([Cl:26])(=[O:25])=[O:24])=[CH2:22])[CH2:19][O:18]1
Reactant: C=C(I)C[C@H]1COC(C)(C)O1
Reactant: O=S(=O)(Cl)Cl
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: CCCCCC
Product: C=C(C[C@H]1COC(C)(C)O1)S(=O)(=O)Cl
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
A solution of tert-butyl lithium in hexane (1.7M, 2 eq) is added dropwise to a solution of (S)-4-(2-iodoallyl)-2,2-dimethyl-1,3-dioxolane (1 eq) in diethyl ether at −78° C., and the reaction stirred at −78° C. for 30 min. Sulfuryl dichloride (1 eq) is added, the mixture warmed to room temperature and the solvents removed under reduced pressure.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]([OH:20])[CH2:18][OH:19])[CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]([O:20][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:18][O:19][S:29]([CH3:28])(=[O:31])=[O:30])[CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: OCC(O)c1ccc2cnn(Cc3ccccc3)c2c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCC(OS(C)(=O)=O)c1ccc2cnn(Cc3ccccc3)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 70.7 %

Procedure:
A solution of 1-(1-Benzyl-1H-indazol-6-yl)-ethane-1,2-diol (0.27 g, 1.0 mmol) and Et3N (0.35 mL, 2.5 mmol) in dry CH2Cl2 (5 mL) was cooled in an ice bath before dropwise addition of MsCl (0.155 mL, 2.0 mmol) over 5 min. The resulting mixture was left to stir for 2 h, warming slowly to RT. After dilution with further CH2Cl2, the solution was washed quickly with 1.0 M aq. HCl (20 mL), sat. aq. NaHCO3 (40 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated at 25° C. to afford the crude product. The crude product was part-purified by rapid column chromatography on silica using 1:1 Et2O/CH2Cl2 as eluent, again concentrating at 25° C., giving the title compound (0.30 g, 71%) as an off-white, gummy foam. 1H NMR: (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.42 (s, 1H), 7.34-7.23 (m, 3H), 7.17 (dd, J=18.1, 7.6 Hz, 3H), 5.89 (dd, J=8.5, 3.2 Hz, 1H), 5.66 (d, J=15.8 Hz, 1H), 5.60 (d, J=15.8 Hz, 1H), 4.52 (dd, J=11.8, 8.6 Hz, 1H), 4.40 (dd, J=11.8, 3.2 Hz, 1H), 3.04 (s, 3H), 2.75 (s, 3H). MS (ES+): 425 ([M+H]+), calcd for [C18H20N2O6S2+H]+ 425.1.
Reaction SMILES: [ClH:1].NCCSC1SC=C(C(NC2S[C:16]3[CH:22]=[CH:21][C:20](F)=[CH:19][C:17]=3C=2)=O)N=1.Cl.[NH2:25][CH2:26][CH2:27][S:28][C:29]1[S:30][CH:31]=[C:32]([C:34]([NH:36][CH:37]2[N:41](C)[C:40]3[CH:43]=[C:44](F)[CH:45]=[CH:46][C:39]=3[S:38]2)=[O:35])[N:33]=1>>[ClH:1].[NH2:25][CH2:26][CH2:27][S:28][C:29]1[S:30][CH:31]=[C:32]([C:34]([NH:36][C:37]2[S:38][C:39]3[CH:46]=[C:45]([C:16]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:17]=4)[CH:44]=[CH:43][C:40]=3[N:41]=2)=[O:35])[N:33]=1
Reactant: CN1c2cc(F)ccc2SC1NC(=O)c1csc(SCCN)n1
Reactant: NCCSc1nc(C(=O)Nc2cc3cc(F)ccc3s2)cs1
Agent: Cl
Product: NCCSc1nc(C(=O)Nc2nc3ccc(-c4ccccc4)cc3s2)cs1

Procedure:
In a similar manner were prepared: 2-(aminoethylthio)-N-(5-fluorobenzothiol-2-yl) thiazole-4-carboxamide hydrochloride, m.p. 261-263° C. dec. and 2-(aminoethylthio)-N-(3-methyl-5-fluorobenzothiazol-2-yl)thiazole-4-carboxamide hydrochloride, m.p. 276-277° C. dec.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:29][C:30]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:31]=1[CH:32]=O>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:32][C:31]3[C:30]([F:29])=[CH:37][CH:36]=[CH:35][C:34]=3[F:38])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: O=Cc1c(F)cccc1F
Product: Fc1cccc(F)c1CNc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1

Procedure:
The title compound was prepared from {3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amine and 2,6-difluorobenzaldehyde according to the procedure of step 1, Example 66. MS (ESI) m/z 505.
Reaction SMILES: [CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([C:22]([N:24]3[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH3:32][S:33]([C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1)(=[O:35])=[O:34].N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([C:40]3[CH:39]=[CH:38][CH:37]=[C:36]([S:33]([CH3:32])(=[O:35])=[O:34])[CH:41]=3)[C:17]([C:22]([N:24]3[CH2:29][CH2:28][S:27](=[O:30])(=[O:31])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:9][CH2:10]2)[CH2:2][CH2:3][CH2:4]1
Reactant: CS(=O)(=O)c1cccc(B(O)O)c1
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCS(=O)(=O)CC3)cc2c1)N1CCN(C2CCC2)CC1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CS(=O)(=O)c1cccc(-n2c(C(=O)N3CCS(=O)(=O)CC3)cc3cc(C(=O)N4CCN(C5CCC5)CC4)ccc32)c1
Yield: 37 %

Procedure:
The title compound was synthesized in analogy to example 66, from [5-(4-cyclobutyl-piperazine-1-carbonyl)-1H-indol-2-yl]-(1,1-dioxothiomorpholin-4-yl)-methanone (example 202), 3-methylsulfonylphenylboronic acid, copper(II) acetate and pyridine in dichloromethane, to give the desired product as a colorless foam (37%).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])([CH3:3])[CH3:2].[F:11][C:12]1[C:17](F)=[C:16]([F:19])[C:15]([F:20])=[C:14]([F:21])[C:13]=1[F:22].[OH-].[K+].CS(C)=O>O>[F:11][C:12]1[C:17]([O:10][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:1]([CH3:3])[CH3:2])=[C:16]([F:19])[C:15]([F:20])=[C:14]([F:21])[C:13]=1[F:22]
Reactant: Fc1c(F)c(F)c(F)c(F)c1F
Reactant: CC(C)c1ccccc1O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)c1ccccc1Oc1c(F)c(F)c(F)c(F)c1F
Temperature: 80 °C
Reaction time: 48 h

Procedure:
A mixture of 50.0 g (0.36 mol) of 2-isopropylphenol, 137 g (0.72 mol) of hexafluorobenzene, 50.4 g (0.90 mol) of KOH powder, and 1000 ml of DMSO was stirred for 48 h at 80° C. This mixture was cooled to room temperature and then poured in 3000 ml of water. The product was extracted with 4×500 ml of dichloromethane. The combined organic extract was dried over Na2SO4 and then evaporated on Rotavap. The residue was distilled in vacuum, 130-140° C./13 mm Hg.
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[C:5]2[NH:6][C:7]([CH3:11])=[CH:8][C:9](=O)[N:4]2[N:3]=1.P(Cl)(Cl)([Cl:15])=O>>[Cl:15][C:9]1[N:4]2[N:3]=[C:2]([CH3:1])[CH:12]=[C:5]2[N:6]=[C:7]([CH3:11])[CH:8]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc2[nH]c(C)cc(=O)n2n1
Product: Cc1cc(Cl)n2nc(C)cc2n1
Yield: 77 %

Procedure:
2,5-Dimethyl-4H-pyrazolo[1,5-a]pyrimidin-7-one (3.5 g, 21 mmol) in phosphorus oxychloride (20 mL) was stirred at reflux. After 3 hours the dark purple reaction was cooled and then extracted from ice water with ethyl acetate. The combined organic layers were washed with water and saturated aqueous sodium bicarbonate, dried (Na2SO4) and then concentrated under reduced pressure to give the title compound (3.0 g, 77%) as a brown solid: +APcI MS (M+1)+ 182; H NMR (CDCl3) δ: 6.74 (s, 1H), 6.42 (s, 1H), 2.55 (s, 3H), 2.53 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:7](Cl)=[N:6][CH:5]=[CH:4][N:3]=1.[NH2:9][NH2:10].N1C=CC=CC=1>>[Cl:1][C:2]1[C:7]([NH:9][NH2:10])=[N:6][CH:5]=[CH:4][N:3]=1
Reactant: Clc1nccnc1Cl
Reactant: NN
Solvent: c1ccncc1
Product: NNc1nccnc1Cl
Temperature: 60 °C
Reaction time: 2.5 h
Yield: 63.9 %

Procedure:
A mixture of 2,3-dichloropyrazine (6.26 g, 42.0 mmol) and anhydrous hydrazine (5 mL, 159 mmol) in pyridine (22 mL, 272 mmol) was stirred at 60° C. for 2.5 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The obtained residue was triturated with water. The resulting slurry was filtered, and the collected solid air dried to yield the first crop of the title compound (3.88 g) as a white solid. The filtrate was concentrated in vacuo, the obtained residue was treated by repeating above process to afford additional amount of the product (1.73 g). (total 5.61 g, 92% yield). HPLC/MS (Method C): retention time=0.30 min, [M+H]+=144.8. 1H NMR (500 MHz, DMSO-d6): δ 8.27 (s, 1H), 8.05 (s, 1H), 7.56 (s, 1H), 4.32 (s, 2H); 13C NMR (500 MHz, DMSO-d6) δ 152.62, 140.67, 132.60, 130.01.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][NH2:6].C(N(CC)CC)C.[CH:15]1[C:24]2[CH:23]=[CH:22][CH:21]=[C:20]([S:25](Cl)(=[O:27])=[O:26])[C:19]=2[CH:18]=[CH:17][N:16]=1>C(Cl)(Cl)Cl>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][NH:6][S:25]([C:20]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:24]=2[CH:23]=[CH:22][CH:21]=1)(=[O:26])=[O:27]
Reactant: CN(C)CCCN
Reactant: O=S(=O)(Cl)c1cccc2cnccc12
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CN(C)CCCNS(=O)(=O)c1cccc2cnccc12
Reaction time: 4 h
Yield: 71 %

Procedure:
In 50 ml of a chloroform solution containing 1.4 g of 3-dimethylaminopropylamine and 1.4 g of triethylamine was added dropwise 30 ml of a chloroform solution containing 2.6 g of 5-isoquinolinesulfonyl chloride under cooling with ice. After the dropwise addition of the chloroform solution, the mixed solution was stirred at a temperature of 2° C. to 10° C. for four hours, and the reaction mixture solution was washed with water and dried with anhydrous magnesium sulfate. After the chloroform was distilled therefrom, the residue obtained was subjected to a silica gel column chromatography (silica gel: 70 g; solvent: chloroform) to give 2.38 g of N-(3-dimethylaminopropyl)-5-isoquinolinesulfonamide, i.e., Compound (17) in a yield of 71%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.F[C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9][C:12]2[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=2)=[C:4]([F:10])[CH:3]=1
Reactant: Oc1c(F)cc(Cl)cc1F
Reactant: O=Cc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=Cc1ccc(Oc2c(F)cc(Cl)cc2F)cc1
Temperature: 100 °C
Yield: 69.6 %

Procedure:
To a solution of 4-chloro-2,6-difluorophenol (5.0 g, 30.4 mmol), 4-fluorobenzaldehyde (3.1 mL, 28.9 mmol) in DMF (30 mL), was added K2CO3 (5.0 g, 36.2 mmol). The mixture was heated at 100° C. overnight. After cooling, the reaction mixture was diluted in water, extracted with EA. The organic phase was washed with water and brine, dried over Na2SO4, concentrated, purified by flash chromatography to afford the title compound (5.4 g, 20.10 mmol, 66.1% yield) as a colorless oil. LCMS: rt=3.52 min, [M+H+]=269
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][C:10]2[CH:11]=[C:12]([CH2:16][C:17]#[N:18])[CH:13]=[CH:14][CH:15]=2)=[C:4]([CH3:19])[N:3]=1.[CH2:20]([NH2:25])[CH2:21][CH2:22][CH2:23][CH3:24]>C(O)CCC>[NH2:1][C:2]1[N:3]=[C:4]([CH3:19])[C:5]([CH2:9][C:10]2[CH:11]=[C:12]([CH2:16][C:17]#[N:18])[CH:13]=[CH:14][CH:15]=2)=[C:6]([NH:25][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[N:7]=1
Reactant: CCCCCN
Reactant: Cc1nc(N)nc(Cl)c1Cc1cccc(CC#N)c1
Solvent: CCCCO
Product: CCCCCNc1nc(N)nc(C)c1Cc1cccc(CC#N)c1
Temperature: 110 °C

Procedure:
The product from step (iii) (Ig) was combined with butan-1-ol (25 mL) and pentan-1-amine (4 mL) was added. The reaction mixture was heated to 110° C. for 18 h. The solvents were evaporated and the product purified using chromatography to give the subtitle compound as an orange oil, 600 mg.
Reaction SMILES: [C:1]1([CH:7]([O:14][C:15]([CH:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH:25][C:26](=[O:34])[CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C@H:21]3[S:20][CH2:19][C:18]2=[O:36])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+](=[CH:39][CH2:40][CH2:41][CH3:42])=[N-]>CO.C(OCC)C>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH:25][C:26](=[O:34])[CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[O:36][CH2:39][CH2:40][CH2:41][CH3:42])=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cc1ccccc1)N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)C(=O)CS[C@H]12
Reactant: CCCC=[N+]=[N-]
Solvent: CCOCC
Solvent: CO
Product: CCCCOC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](NC(=O)Cc3ccccc3)[C@H]2SC1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution, cooled to 0° C., of 2.0 g of 7β-phenylacetylamino-cepham-3-one-4ξ-carboxylic acid diphenylmethyl ester in 75 ml of methanol is treated with excess diazo-n-butane in diethyl ether. The mixture is stirred for 15 minutes at 0° C. and is then evaporated under reduced pressure. The oily residue is purified by means of preparative thin layer chromatography (silica gel plates, 6×100 cm; system: toluene/ethyl acetate, 3:1). The layer which is visible under ultraviolet light (λ=254 mμ) is removed and in each case eluted with acetone. This zone (Rf~0.33) yields 3-n-butoxy-7β-phenylacetylamino-3-cephem-4-carboxylic acid diphenylmethyl ester which after crystallisation from a mixture of methylene chloride and diethyl ether is in the form of colourless flakes which melt at 168°-170° C., [α]D20 =+55°±1° (c=0.38 in chloroform); ultraviolet absorption spectrum (in 95% strength aqueous ethanol): λmax =264 mμ (ε=7,300); infrared absorption spectrum (in methylene chloride): characteristic bands at 2.98μ, 5.62μ, 5.81μ, 5.92μ, 6.25μ and 6.62μ.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]=[CH:13][CH:14]=[N:15]N(C)C)=[O:4].C(OC(=O)C)(=O)C.[O:28]=[C:29]1[CH:38]=[CH:37][C:36](=[O:39])[C:35]2[NH:34][C:33](=[O:40])[CH:32]=[CH:31][C:30]1=2>C(#N)C.[Pd]>[OH:40][C:33]1[CH:32]=[CH:31][C:30]2[C:29](=[O:28])[C:38]3[C:12]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=4[NH:5][C:3](=[O:4])[C:2]([F:1])([F:19])[F:20])=[CH:13][CH:14]=[N:15][C:37]=3[C:36](=[O:39])[C:35]=2[N:34]=1
Reactant: CN(C)N=CC=Cc1ccccc1NC(=O)C(F)(F)F
Reactant: O=C1C=CC(=O)c2[nH]c(=O)ccc21
Agent: [Pd]
Solvent: CC(=O)OC(C)=O
Solvent: CC#N
Product: O=C1c2nc(O)ccc2C(=O)c2c(-c3ccccc3NC(=O)C(F)(F)F)ccnc21
Yield: 16.4 %

Procedure:
1.9 g (6.5 mmol) of 4-(2-trifluoroacetamidophenyl)-1-dimethylamino-1-aza-1,3-butadiene, 2.2 mL of acetic anhydride and 1.6 g of Pd/C (10%) are successively added to a solution of 5,8-dioxocarbostyril (1.04 g, 5.9 mmol) in 500 mL of acetonitrile. The reaction medium is refluxed for 15 hours under nitrogen. After evaporating off the solvent on a rotary evaporator, the crude product obtained is purified by flash chromatography on silica (CH2Cl2 and then 95/5 CH2Cl2/MeOH) to give 400 mg of a yellow powder of compound CRL 8249 (or of its oxo tautomer in position 8).
Reaction SMILES: [CH:1]([N:14]1[CH2:17][CH:16](OS(C)(=O)=O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([NH2:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN1C(=O)N(C)CCC1.CCOCC>[CH:1]([N:14]1[CH2:17][CH:16]([NH:30][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)OC1CN(C(c2ccccc2)c2ccccc2)C1
Reactant: NCc1ccccc1
Solvent: CCOCC
Solvent: CN1CCCN(C)C1=O
Product: c1ccc(CNC2CN(C(c3ccccc3)c3ccccc3)C2)cc1
Temperature: 70 °C
Reaction time: 18 h
Yield: 67 %

Procedure:
To a solution of methanesulfonic acid 1-benzhydrylazetidin-3-yl ester (0.32 g, 1 mmol) in N,N′-dimethylpropyleneurea (0.5 ml) was added benzylamine (0.5 ml, 5 mmol), and the mixture was stirred at 70° C. for 18 h. It was then cooled to room temperature and diluted with ether (30 ml). The resulting suspension was filtered and the ether solution was evaporated. The residue was partitioned between hexanes and water, and hexanes solution was washed with saturated sodium bicarbonate solution and dried over anhydrous sodium sulfate. It was then filtered through a pad of silica gel, and the filter pad was eluted with a 1:1 mixture of ether-hexanes. Evaporation of solvents followed by trituration with isooctane gave 0.22 g of a white solid; m.p. 73-75° C.; MS (ES) m/z 329.0 (MH+); HRMS (EI) Calcd. for C23H24N2 (M+): 328.1940, Found: 328.1936.
Reaction SMILES: [Br:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)=[CH:5][CH:4]=1.[C:18](=O)(O)[O-].[Na+].COS(OC)(=O)=O>CC(C)=O>[CH3:18][N:13]1[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][Br:1])=[CH:4][CH:5]=1
Reactant: O=C([O-])O
Reactant: BrCc1ccc(-c2nc3ccccc3[nH]2)cc1
Agent: [Na+]
Solvent: COS(=O)(=O)OC
Solvent: CC(C)=O
Product: Cn1c(-c2ccc(CBr)cc2)nc2ccccc21
Temperature: 40 °C
Reaction time: 3 h

Procedure:
To a stirred solution of 143.6 g (0.5 mole) of 2-(4-bromomethylphenyl)benzimidazole and 42.0 g (0.5 mole) of sodium bicarbonate in 85% aqueous acetone is added 66.0 g (0.5 mole) of dimethylsulfate dropwise. The mixture is stirred at 40° C. for about 3 hours until thin-layer chromatography indicates that the reaction is complete. The solvent is removed in vacuo, and the solid product is washed with water to eliminate sodium salts and purified by recrystallization from benzene.
Reaction SMILES: [C:1]([N:5]([C:7](=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16](=[C:20]([Cl:22])[Cl:21])[C:17](Cl)=[O:18].C(N(CC)CC)C>C(Cl)Cl>[C:1]([N:5]([C:7](=[O:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[NH:6][C:17]([C:16]([Cl:15])=[C:20]([Cl:22])[Cl:21])=[O:18])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)N(N)C(=O)c1ccccc1
Reactant: O=C(Cl)C(Cl)=C(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)N(NC(=O)C(Cl)=C(Cl)Cl)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred solution of 1-t-butyl-1-benzoylhydrazine (1.5 g, 0.008M) in methylene chloride at 5° C. was added, simultaneously and separately, trichloroacryloylchloride (1.7 g, 0.009M) and triethylamine (0.9 g, 0.009M). After addition, the reaction was warmed to room temperature and stirred for 3 hours. The flask's contents were diluted with 50 ml methylene chloride and washed with water (3×75 ml) and brine solution (1×75 ml). The organic layer was dried over magnesium sulfate and the solvent removed under vacuum to afford N'-t-butyl-N-(1,2,2-trichlorovinyl)carbonyl-N'-benzoylhydrazine as a white solid product.
Reaction SMILES: [CH2:1]([CH:4]1[C:9](=[O:10])[CH:8]([CH2:11][CH:12]=[CH2:13])[C:7](=[O:14])[C:6]([NH:15][C:16]([C@@H:18]2[CH2:22][CH2:21][CH2:20][C@H:19]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=O)=[C:5]1[NH2:29])[CH:2]=[CH2:3].[OH-].[K+]>C(O)C.O>[CH2:11]([CH:8]1[C:9](=[O:10])[CH:4]([CH2:1][CH:2]=[CH2:3])[C:5]2[NH:29][C:16]([CH:18]3[CH2:22][CH2:21][CH2:20][CH:19]3[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[N:15][C:6]=2[C:7]1=[O:14])[CH:12]=[CH2:13]
Reactant: C=CCC1C(=O)C(NC(=O)[C@@H]2CCC[C@H]2c2ccccc2)=C(N)C(CC=C)C1=O
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: C=CCC1C(=O)c2nc(C3CCCC3c3ccccc3)[nH]c2C(CC=C)C1=O
Yield: 52.4 %

Procedure:
Dissolve trans-2-phenylcyclopentanecarboxylic acid (3,5-diallyl-2-amino-4,6-dioxo-cyclohex-1-enyl)amide (300 mg, 0.76 mmol) in ethanol (100 ml), add 10% potassium hydroxide (100 ml) and heat the reaction to 60° C. for 4 hours. Cool the reaction and dilute with water (200 ml). Acidify with concentrated hydrochloric acid and extract with diethyl ether (400 ml). Rinse the organic extract with water (200 ml), saturated sodium chloride (200 ml), dry over anhydrous magnesium sulfate, filter and concentrate under vacuum. Purify the residue by radial chromatography (40% to 50% ethyl acetate/hexane, 2 mm plate) to provide 5,7-diallyl-2-(2-phenylcyclopentyl)-1,7-dihydrobenzoimidazole-4,6-dione (149 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:11][S:12]([O-:14])=[O:13].[Na+]>CS(C)=O>[Cl:1][C:2]1[CH:9]=[C:8]([S:12]([CH3:11])(=[O:14])=[O:13])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: O=Cc1ccc(F)cc1Cl
Reactant: CS(=O)[O-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CS(=O)(=O)c1ccc(C=O)c(Cl)c1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
A suspension of 2-chloro-4-fluorobenzaldehyde (24.9 g, 0.16 mol) and dry sodium methanesulfinate (17.9 g, 0.175 mmol) in dry DMSO (60 ml) is stirred at 90° C. overnight. The reaction mixture is allowed to cool to room temperature and then poured onto ice-water (400 ml). The resulting precipitated is collected by filtration and dried under high vacuum to yield the titled compound as a yellow powder.
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH2:20][OH:21])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[CH2:9][CH2:10][C:11]2=[O:22])[CH2:3]1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.O>CC(C)=O>[CH3:13][C@:12]12[CH2:14][CH2:15][C@H:16]3[C@@H:7]([CH2:6][CH2:5][C@@H:4]4[C@:17]3([CH:20]=[O:21])[CH2:18][CH2:19][C:2](=[O:1])[CH2:3]4)[C@@H:8]1[CH2:9][CH2:10][C:11]2=[O:22]
Reactant: C[C@]12CC[C@H]3[C@@H](CC[C@H]4C[C@@H](O)CC[C@@]43CO)[C@@H]1CCC2=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(C)=O
Product: C[C@]12CC[C@H]3[C@@H](CC[C@H]4CC(=O)CC[C@@]43C=O)[C@@H]1CCC2=O
Reaction time: 0.25 h

Procedure:
To a solution of 3β,19-dihydroxy-5α-androstan-17-one in acetone chilled to 10° C. is added exactly two equivalents of Jones reagent. After standing for 15 minutes the upper acetone layer is poured into water with vigorous stirring. The solid which forms is filtered, air dried and crystallized from hexane to yield 5α-androstane-3,17,19-trione.
Reaction SMILES: O=[C:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1.[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:18][Mg]Br>[Pd]>[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:18][CH:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1
Reactant: Fc1ccc(C[Mg]Br)cc1F
Reactant: COC(=O)c1cc2c([nH]1)CCC2=O
Agent: [Pd]
Product: COC(=O)c1cc2c([nH]1)CCC2Cc1ccc(F)c(F)c1

Procedure:
The title compound was synthesized from methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate in two steps. First, methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.60 g, 3.35 mmol) was reacted with 3,4-difluorobenzylmagnesium bromide (0.25 M in diethyl ether, 33.5 mL, 8.4 mmol) according to General Procedure 3. The resulting olefin was then converted to the title compound by hydrogenation according to General Procedure 6 (5% Pd on carbon). The crude product was purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-40% EtOAc/heptane to afford the title compound: 0.100 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.98-2.18 (m, 1 H) 2.48-2.64 (m, 1H) 2.64-2.83 (m, 4H) 3.27 (quin, J=7.00 Hz, 1H) 3.81 (s, 3H) 6.29-6.41 (m, 1H) 6.89 (ddd, J=6.19, 4.14, 2.03 Hz, 1H) 6.94-7.14 (m, 2H) 9.01 (br. s, 1H).