Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH:6]=[C:7]2[CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]2=[O:16])=[CH:4][CH:3]=1.[OH:19]O.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[C:7]2[CH2:15][C:14]34[O:19][CH:13]3[CH:12]=[CH:11][CH:10]=[C:9]4[C:8]2=[O:16])=[CH:17][CH:18]=1
Reactant: OO
Reactant: O=C1C(=Cc2ccc(Cl)cc2)Cc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C1C(=Cc2ccc(Cl)cc2)CC23OC2C=CC=C13

Procedure:
Ten grams (0.039 mole) of 2-(p-chlorobenzylidene)-1-indanone is converted to the epoxide in 1 liter of MeOH, using 9.6 g (0.085 mole) of 30% H2O2 and 9.6 ml (0.039 mole) of 16% NaOH, as described in Example 1. Since the starting material is poorly soluble in MeOH it is oxidized as a suspension and the product separates during the course of the reaction (5 hours at 35°-38°). The crude yield is 10 g (94%); m.p. 162°-164°. Crystallization (of 9.7 g) from 70 ml of MeCN gives 8.8 g (86%) of nearly colorless solid; m.p. 165°-167°.
Reaction SMILES: [CH3:1][C:2]([CH3:13])([CH3:12])[C:3](=[N:10][OH:11])[CH:4]([S:7]([CH3:9])=[O:8])[S:5][CH3:6].[CH3:14][N:15]=[C:16]=[O:17]>C(Cl)Cl>[CH3:14][NH:15][C:16]([O:11][N:10]=[C:3]([C:2]([CH3:13])([CH3:12])[CH3:1])[CH:4]([S:7]([CH3:9])=[O:8])[S:5][CH3:6])=[O:17]
Reactant: CSC(C(=NO)C(C)(C)C)S(C)=O
Reactant: CN=C=O
Solvent: ClCCl
Product: CNC(=O)ON=C(C(SC)S(C)=O)C(C)(C)C
Reaction time: 18 h

Procedure:
To 50 mg of 3,3-dimethyl-1-(methylsulfinyl)-1-methylthio-2-butanone oxime in 5 ml of methylene chloride is added 0.5 ml of methyl isocyanate. After standing at room temperature 18 hrs., the solvent was removed to give 53 mg of impure 3,3-dimethyl-1-(methylsulfinyl)-1-methylthio-2-butanone O-[methylaminocarbonyl]oxime. The ir and pmr were identical to that of an authentic sample synthesized independently.
Reaction SMILES: [CH2:1]([N:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)[CH:2]=[CH2:3].[CH2:13]([Mg]Br)[CH:14]=[CH2:15]>C1COCC1>[CH2:1]([NH:4][CH:5]([C:6]1[CH:7]=[CH:8][C:9]([Br:12])=[CH:10][CH:11]=1)[CH2:15][CH:14]=[CH2:13])[CH:2]=[CH2:3]
Reactant: C=CCN=Cc1ccc(Br)cc1
Reactant: C=CC[Mg]Br
Solvent: C1CCOC1
Product: C=CCNC(CC=C)c1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 75.1 %

Procedure:
Allyl-(4-bromo-benzylidene)-amine (1.13 g, 5.0 mmol) is dissolved in THF (15 mL) and the mixture is cooled to 0° C. with an ice bath. Allyl magnesium bromide (6.0 mL, 1.0 M in ethyl ether, 6.0 mmol) is added. The resulting mixture is stirred at 0° C. for 1 hour and warmed to room temperature followed by reaction quenching. EtOAc and water were added and the EtOAc layer is washed with brine and dried. After removal of EtOAc, the product (1.0 g, 75%) is obtained. MS (ESI): 266, 268 (M+1)+1.
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[NH:5][CH:4]([C:16]2[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=2)[CH2:3]1.N1C=CC=CC=1.[F:30][C:31]1[CH:32]=[C:33]([S:37](Cl)(=[O:39])=[O:38])[CH:34]=[CH:35][CH:36]=1>ClCCl>[CH3:1][C:2]1([CH3:23])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:13])[F:14])[CH:10]=2)[NH:5][CH:4]([C:16]2[CH:17]=[C:18]([NH:22][S:37]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([F:30])[CH:32]=3)(=[O:39])=[O:38])[CH:19]=[CH:20][CH:21]=2)[CH2:3]1
Reactant: CC1(C)CC(c2cccc(N)c2)Nc2ccc(C(F)(F)F)cc21
Reactant: O=S(=O)(Cl)c1cccc(F)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC1(C)CC(c2cccc(NS(=O)(=O)c3cccc(F)c3)c2)Nc2ccc(C(F)(F)F)cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.1 %

Procedure:
To a stirred solution of 3-(4,4-dimethyl-6-trifluoromethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenylamine (100 mg, 0.31 mmol) in pyridine (49 mg, 0.62 mmol) and dichloromethane (1.5 mL) at 0° C. was added dropwise a solution of 3-fluoro-benzenesulfonyl chloride (73 mg, 0.37 mmol) in dichloromethane (0.5 mL). The mixture was stirred at room temperature overnight. The mixture was quenched with water (5 mL) and extracted with dichloromethane (5 mL×2). The combined organic layers were dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography on silica gel to afford N-[3-(4,4-dimethyl-6-trifluoromethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenyl]-3-fluoro-benzenesulfonamide (141 mg, 94.6%) as a white solid. MS (ESI+APCI) M+1=479.1.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#N)=[CH:4][CH:3]=1.Cl.[CH3:11][NH:12][CH2:13][CH2:14][NH2:15]>CO>[CH3:11][N:12]1[CH2:13][CH2:14][N:15]=[C:6]1[C:5]1[CH:8]=[CH:9][C:2]([NH2:1])=[CH:3][CH:4]=1
Reactant: CNCCN
Reactant: N#Cc1ccc(N)cc1
Agent: Cl
Solvent: CO
Product: CN1CCN=C1c1ccc(N)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.1 %

Procedure:
To a solution of 4-aminobenzonitrile (5.1 g, 43 mmol) in dry methanol (60 mL) at 0 C, hydrogen chloride gas was bubbled through until saturation was reached. The mixture was then stirred at room temperature overnight. It was concentrated in vacuo. The residue was dissolved in dry methanol (60 mL). To the solution, N-methyl ethylenediamine (19 mL, 216 mmol) was added. The mixture was then heated to reflux for 3 h. After being cooled in fridge overnight, the precipitated product was collected by filtration, then was dried on vacuum to give white solids (3.7 g). MS 176.0 (M+H).
Reaction SMILES: Br[CH:2]1[CH2:17][CH2:16][C:5]2=[C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:7][C:8]([S:9][CH3:10])=[C:4]2[C:3]1=[O:18].[N-:19]=[N+:20]=[N-:21].[Na+]>CN(C)C=O.O>[N:19]([CH:2]1[CH2:17][CH2:16][C:5]2=[C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:7][C:8]([S:9][CH3:10])=[C:4]2[C:3]1=[O:18])=[N+:20]=[N-:21]
Reactant: CCOC(=O)c1sc(SC)c2c1CCC(Br)C2=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1sc(SC)c2c1CCC(N=[N+]=[N-])C2=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 80.7 %

Procedure:
Ethyl 5-bromo-4,5,6,7-tetrahydro-3-methylthio-4-oxobenzo[c]thiophene-1-carboxylate (5.24 g) was suspended in N,N-dimethylformamide (80 ml); a solution of sodium azide (1.95 g) in water (12 ml) was added at 0° C. After the reaction mixture was stirred at room temperature for 4 hours, it was poured over water (50 ml) and extracted with ethyl acetate. The organic layer was washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:9 to 1:2, v/v) to yield ethyl 5-azido-4,5,6,7-tetrahydro-3-methylthio-4-oxobenzo[c]thiophene-1-carboxylate (3.77 g, 80.7%), which was then recrystallized from ethyl acetate-hexane. Colorless needles. Melting point 163-164° C. (decomposed).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[OH:12][C@@H:13]([C@H:15]1[C:21](=[O:22])[N:20]2[C@@H:16]1[CH2:17][C:18]([CH2:36][S:37][CH2:38][CH2:39][NH:40][C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([N+:51]([O-:53])=[O:52])=[CH:47][CH:46]=1)=[O:42])=[C:19]2[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])[CH3:14]>C(Cl)Cl.CS(C)=O>[OH:12][C@@H:13]([C@H:15]1[C:21](=[O:22])[N:20]2[C@@H:16]1[CH2:17][C:18]([CH2:36][S:37]([CH2:38][CH2:39][NH:40][C:41]([O:43][CH2:44][C:45]1[CH:46]=[CH:47][C:48]([N+:51]([O-:53])=[O:52])=[CH:49][CH:50]=1)=[O:42])=[O:9])=[C:19]2[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])[CH3:14]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(CSCCNC(=O)OCc3ccc([N+](=O)[O-])cc3)C[C@H]12
Solvent: ClCCl
Solvent: CS(C)=O
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(CS(=O)CCNC(=O)OCc3ccc([N+](=O)[O-])cc3)C[C@H]12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 89.3 %

Procedure:
A solution of 22 mg of m-chloroperbenzoic acid in 2 ml of methylene chloride was added dropwise to 60 mg of p-nitrobenzyl (5R,6S)-6-[1-(R)-hydroxyethyl]-3-(2-p-nitrobenzyloxycarbonylaminoethyl)thiomethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (53), prepared as described in step (g) of Example 6, in 3 ml of methylene chloride, whilst cooling with ice-water. When the addition was complete, the reaction mixture was stirred at 0°-5° C. for 30 minutes. The resulting mixture containing precipitated material was diluted with 100 ml of ethyl acetate and then the solution was washed successively with a 5% w/v aqueous solution of sodium hydrogen sulphite (once), a saturated aqueous solution of sodium bicarbonate (twice) and a saturated aqueous solution of sodium chloride (three times). The solution was then dried over sodium sulphate, after which the solvents were evaporated under reduced pressure at room temperature, to give a solid substance. This crude substance was dissolved in dimethyl sulphoxide and then reprecipitated by the addition of benzene, to give 55 mg of the title compound as an amorphous powder.
Reaction SMILES: [CH:1]1([N:13]([OH:17])[C:14]([NH2:16])=[O:15])[C:5]2=[CH:6][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[N:4]2[CH2:3][CH2:2]1.[Cl:18]N1C(=O)CCC1=O>C1COCC1>[Cl:18][C:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=2[N:4]2[CH2:3][CH2:2][CH:1]([N:13]([OH:17])[C:14]([NH2:16])=[O:15])[C:5]=12
Reactant: O=C1CCC(=O)N1Cl
Reactant: NC(=O)N(O)C1CCn2c1cc1ccccc12
Solvent: C1CCOC1
Product: NC(=O)N(O)C1CCn2c1c(Cl)c1ccccc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of N-(2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)-N-hydroxy urea (from Example 1, 231 mg, 1 mmol) in THF (9 mL) there was added N-chlorosuccinimide (147 mg, 1.1 mmol) and the mixture was stirred at r.t. for 30 minutes as a clear solution resulted. After evaporation to dryness, the residue was partitioned between H2O and EtOAc. The product obtained from evaporation of the organic fraction was chromatographed on a short column of silica gel, eluting with 5% EtOH in CH2Cl2 to afford a solid which on trituration in Et2O and filtration afforded the title compound as a white solid, m.p.: 192° C. (dec).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C@H:20]1[O:41][C@@H:21]1[C@@H:22]([NH:30][C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].FC(F)(F)C(O)=O>C1COCC1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C@@H:20]([OH:41])[CH2:21][C@@H:22]([NH:30][C:31]([O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:32])[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(N[C@@H](Cc1ccccc1)[C@H]1O[C@@H]1[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)OCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: O=C(N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 58.1 %

Procedure:
A mixture of 39.2 g (71.2 mmol) of (2S,3R,4R,5S)-2,5-bis-(N-(((benzyl)oxy)carbonyl)amino)-3,4-epoxy-1,6-diphenylhexane in 600 ml of THF was treated under N2 atmosphere with 13 g (0.36 mol) of sodium borohydride. The resulting mixture was treated dropwise with 27.7 ml (0.36 mol) of trifluoroacetic acid. After being stirred for 3.5 h at ambient temperature, the resulting mixture was quenched with 1 N aqueous HCl, diluted with water, and stirred for 16 h. The resulting mixture was filtered, washed with water, and dried to provide 22.85 g (58%) of the desired compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][C:10]3=[N:12][N:13]=[C:14](S(C)(=O)=O)[N:9]3[CH:8]=[CH:7][C:6]=2[CH:19]=1.[CH3:20][O-:21].[Na+]>>[CH3:20][O:21][C:14]1[N:9]2[C:10]([CH2:11][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:19][C:6]=3[CH:7]=[CH:8]2)=[N:12][N:13]=1
Reactant: Cc1ccc2c(c1)C=Cn1c(nnc1S(C)(=O)=O)C2
Reactant: C[O-]
Agent: [Na+]
Product: COc1nnc2n1C=Cc1cc(C)ccc1C2

Procedure:
The reaction of 8-methyl-3-methylsulfonyl-11H-s-triazolo[3,4-b][3]benzazepine with sodium methoxide yielded 3-methoxy-8-methyl-11H-s-triazolo[3,4-b][3]benzazepine. Colorless prisms (as recrystallized from ethyl acetate), melting point: 148°-149° C.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:15]=[CH:16][CH:17]=2)[O:10][C@H:11]([CH3:14])[CH2:12][OH:13])[N:5]=[C:4]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:3]=1.[OH-].[Na+].Cl[C:25]([O:27][CH2:28][C:29]([Cl:32])([Cl:31])[Cl:30])=[O:26]>CCOC(C)=O.O>[Cl:30][C:29]([Cl:32])([Cl:31])[CH2:28][O:27][C:25](=[O:26])[NH:1][C:2]1[N:6]([C:7]2[CH:17]=[CH:16][CH:15]=[C:9]([O:10][C@H:11]([CH3:14])[CH2:12][OH:13])[CH:8]=2)[N:5]=[C:4]([C:18]([CH3:20])([CH3:19])[CH3:21])[CH:3]=1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Reactant: C[C@H](CO)Oc1cccc(-n2nc(C(C)(C)C)cc2N)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Product: C[C@H](CO)Oc1cccc(-n2nc(C(C)(C)C)cc2NC(=O)OCC(Cl)(Cl)Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 107.6 %

Procedure:
A solution of Intermediate 151b (112 mg, 0.39 mmol) in EtOAc (2.1 mL) was treated with aqueous 1N NaOH (0.7 mL, 0.70 mmol) then 2,2,2-trichloroethyl chloroformate (0.056 mL, 0.41 mmol) and the mixture was stirred at RT for 2.5 h. The mixture was treated with another portion of 2,2,2-trichloroethyl chloroformate (0.015 mL, 0.11 mmol) and stirred at RT for a further 1 h. The mixture was diluted with EtOAc and water and the phases were separated. The aqueous layer was extracted with EtOAc (×2) and the combined organic phase was washed with brine, dried (Na2SO4), and concentrated in vacuo to give a pale red gum (195 mg). The gum was purified by FCC, using 0-40% EtOAc in cyclohexane, to give the title compound as a pale golden gum (134 mg, 74%). LCMS (Method 3): Rt 4.15 min, m/z 464.2, 466.2 [MH+].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([F:27])[CH:21]=2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=O)=[C:4]([CH3:28])[CH:3]=1.Cl.[NH2:30][OH:31].C(=O)([O-])O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([F:27])[CH:21]=2)[CH2:9]/[C:10](/[C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[N:30]\[OH:31])=[C:4]([CH3:28])[CH:3]=1
Reactant: NO
Reactant: Cc1cc(Cl)ccc1C(CC(=O)c1ccc(=O)n(C)c1)c1ccc(O)c(F)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1cc(Cl)ccc1C(C/C(=N\O)c1ccc(=O)n(C)c1)c1ccc(O)c(F)c1

Procedure:
In analogy to example 151, step 3, 5-[3-(4-chloro-2-methyl-phenyl)-3-(3-fluoro-4-hydroxy-phenyl)-propionyl]-1-methyl-1H-pyridin-2-one was reacted with hydroxylamine hydrochloride in the presence of sodium hydrogencarbonate to give the title compound containing <5% of the corresponding Z isomer as a colourless solid, MS (ESI−): m/z=413.0 [M−H]−.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:21]Br)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][NH2:32].O1CCCC1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:21][NH:32][CH3:31])=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CBr)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Reactant: CN
Solvent: C1CCOC1
Product: CNC[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Temperature: 25 °C

Procedure:
A solution of (R)-8-(benzyloxy)-5-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)quinolin-2(1H)-one (1.5 g, 3.1 mmol) in methylamine/tetrahydrofuran (2.0 M, 16 mL, 32 mmol) was heated in a sealed tube at 100° C. (oil bath) for 3 days. After allowing the mixture to cool to room temperature, it was concentrated and purified via automated flash silica gel chromatography, using a 25 g Silicycle SiliSep flash column (dichloromethane/methanol/ammonium hydroxide). Concentration of the desired fractions under reduced pressure provided the title compound. ES/MS calcd. for C25H35N2O3Si+ 439.2. Found m/z=439.3 (M+H)+.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]1[CH2:24][C:23]2[C@H:18]([CH2:19][CH2:20][C:21](=[O:25])[CH:22]=2)[C@@H:17]2[C@@H:8]1[C@H:9]1[C@@:13]([CH2:15][CH2:16]2)([CH3:14])[C:12](=[O:26])[CH2:11][CH2:10]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)(O)[O-].C(Cl)(Cl)(Cl)[Cl:51]>C(#N)C.ClCCl>[Cl:51][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]1[CH2:24][C:23]2[C@H:18]([CH2:19][CH2:20][C:21](=[O:25])[CH:22]=2)[C@@H:17]2[C@@H:8]1[C@H:9]1[C@@:13]([CH2:15][CH2:16]2)([CH3:14])[C:12](=[O:26])[CH2:11][CH2:10]1
Reactant: ClC(Cl)(Cl)Cl
Reactant: C[C@]12CC[C@H]3[C@@H]([C@H](CCCCCO)CC4=CC(=O)CC[C@@H]43)[C@@H]1CCC2=O
Agent: O=C([O-])O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: ClCCl
Product: C[C@]12CC[C@H]3[C@@H]([C@H](CCCCCCl)CC4=CC(=O)CC[C@@H]43)[C@@H]1CCC2=O

Procedure:
The same product is obtained from 8.05 g of 7α-(5-hydroxypentyl)-estr-4-ene-3,17-dione (Example 1b) by a 3.5-hour reaction with 8.66 g of triphenylphosphine in 85 ml of carbon tetrachloride and 30 ml of acetonitrile at room temperature. The reaction mixture is diluted with dichloromethane, shaken out with saturated bicarbonate solution and with saturated common salt solution, dried with sodium sulfate and concentrated by evaporation in a vacuum. The residue is chromatographed on silica gel with dichloromethane and ethyl acetate, whereby 4.08 g of 7α-(5-chloropentyl)-estr-4-ene-3,17-dione is obtained, [α]D22=+68° (c=0.5% in chloroform)
Reaction SMILES: C=O.[B-][C:4]#N.[Na+].[NH:7]1[CH2:13][CH2:12][C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][C:9]2[CH:19]=[CH:20][CH:21]=[CH:22][C:8]1=2.[OH-].[Na+]>C(#N)C.C(O)(=O)C>[CH3:4][N:7]1[CH2:13][CH2:12][C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][C:9]2[CH:19]=[CH:20][CH:21]=[CH:22][C:8]1=2
Reactant: CCOC(=O)C1=Cc2ccccc2NCC1
Reactant: [B-]C#N
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CC#N
Product: CCOC(=O)C1=Cc2ccccc2N(C)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
A 37% aqueous formaldehyde solution (1.50 g, 18.4 mmol), sodium cyanotrihydroborate (0.12 g, 18.4 mmol) and acetic acid (0.1 ml) were added to a solution in acetonitrile (8 ml) of the ethyl 2,3-dihydro-1H-benz[b]azepine-4-carboxylate (0.40 g, 1.84 mmol) synthesized in Reference Example 5. After stirring at room temperature for 2 hours, the reaction mixture was poured into a 1N aqueous sodium hydroxide solution and extracted twice with diethyl ether. The extract solution was washed twice with a 5% aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: ethyl acetate/n-hexane=4/96) to obtain 0.40 g of ethyl 1-methyl-2,3-dihydro-1H-benz[b]azepine-4-carboxylate.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[CH:7]([NH2:12])[CH2:6][CH2:5]2.[F:13][C:14]([F:25])([F:24])[C:15]([NH:17][C:18]1([C:21](O)=[O:22])[CH2:20][CH2:19]1)=[O:16]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[CH:7]([NH:12][C:21]([C:18]1([NH:17][C:15](=[O:16])[C:14]([F:13])([F:24])[F:25])[CH2:19][CH2:20]1)=[O:22])[CH2:6][CH2:5]2
Reactant: O=C(NC1(C(=O)O)CC1)C(F)(F)F
Reactant: NC1CCc2cc(Br)cc(F)c21
Product: O=C(NC1(C(=O)NC2CCc3cc(Br)cc(F)c32)CC1)C(F)(F)F

Procedure:
In analogy to the procedure described for the preparation of intermediate A-1 [B] and A-1 [C], (rac)-5-bromo-7-fluoro-indan-1-ylamine has been coupled with 1-(2,2,2-trifluoroacetamido)cyclopropanecarboxylic acid (intermediate A-1 [A]) to give 1-(2,2,2-trifluoro-acetylamino)-cyclopropanecarboxylic acid ((rac)-5-bromo-7-fluoro-indan-1-yl)-amide, which was subsequently reacted with 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) to yield the title compound as light yellow amorphous solid. MS: 455.2 (M−H−).
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])([O-:4])=[O:3].[N:12]1([C:17]#[N:18])[CH2:16][CH2:15][CH2:14][CH2:13]1.ClC1C=CC=CC=1>O>[N+:2]([C:5]1[CH:6]=[C:7]([NH:8][C:17]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[NH:18])[CH:9]=[CH:10][CH:11]=1)([O-:4])=[O:3]
Reactant: N#CN1CCCC1
Reactant: Nc1cccc([N+](=O)[O-])c1
Agent: Cl
Solvent: O
Solvent: Clc1ccccc1
Product: N=C(Nc1cccc([N+](=O)[O-])c1)N1CCCC1

Procedure:
Samples of 3-nitroaniline hydrochloride, 15.5 g, and 1-pyrrolidinecarbonitrile, 9.6 g, were combined with 12 ml of chlorobenzene, and the mixture was warmed to reflux for three hours, and then allowed to cool. The resulting solid mass was taken up in 200 ml of hot water, and the chlorobenzene layer was separated. The aqueous layer was washed with 30 ml of chloroform and the combined organic layers were washed with 50 ml of water. The aqueous layers were combined, warmed, treated with charcoal and filtered hot. The filtrate was allowed to cool, and made strongly basic with 50% sodium hydroxide. This basic mixture was extracted with 200 ml of chloroform. The chloroform extract was concentrated on a steam bath to 150 ml, then diluted with hexanes to 300 ml, and stirred until yellow solids formed, giving 17 g of the N-(3-nitrophenyl)-1-pyrrolidinecarboximidamide. m.p. 117-118° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][C:5]1[C:6]([Cl:25])=[C:7]([C:21]([Cl:24])=[CH:22][CH:23]=1)[CH2:8][O:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[C:17]([CH3:20])[CH:16]=[CH:15]2.N1C=CC=CC=1.[C:32](OC(=O)C)(=[O:34])[CH3:33]>ClCCl>[C:32]([NH:1][CH2:2][CH2:3][O:4][C:5]1[C:6]([Cl:25])=[C:7]([C:21]([Cl:24])=[CH:22][CH:23]=1)[CH2:8][O:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[C:17]([CH3:20])[CH:16]=[CH:15]2)(=[O:34])[CH3:33]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccc2cccc(OCc3c(Cl)ccc(OCCN)c3Cl)c2n1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)NCCOc1ccc(Cl)c(COc2cccc3ccc(C)nc23)c1Cl
Reaction time: 0.5 h
Yield: 49.1 %

Procedure:
To a solution of 8-[3-(2-aminoethoxy)-2,6-dichlorobenzyloxy]-2-methylquinoline (11 mg) in dichloromethane were added pyridine (3.46 g) and acetic anhydride (4.47 mg), and the mixture was stirred for 30 minutes. The reaction mixture concentrated, and the reside was purified by preparative thin-layer chromatography (dichloromethane:methanol=10:1, V/V) to give 8-[3-(2-acetamidoethoxy)-2,6-dichlorobenzyloxy]-2-methylquinoline (6 mg) as an amorphous powder.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N:18]2[C:22](=[O:23])[C:21]3=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]3[C:19]2=[O:28])=[C:13]([N+:15]([O-])=O)[CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H][H]>C(OCC)(=O)C.[Pd]>[Si:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N:18]2[C:19](=[O:28])[C:20]3=[CH:27][CH:26]=[CH:25][CH:24]=[C:21]3[C:22]2=[O:23])=[C:13]([CH:14]=1)[NH2:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(N2C(=O)c3ccccc3C2=O)c([N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc(N2C(=O)c3ccccc3C2=O)c(N)c1
Yield: 89 %

Procedure:
A suspension of 5-(tert-butyldimethylsilyloxy)-2-phthalimido-1-nitrobenzene (5.00 g, 12.5 mmol) and 10% palladium-on-carbon (2.5 g) in ethyl acetate (60 mL) was stirred under 1 atm of hydrogen for 16 h. The mixture was filtered through a pad of diatomaceous earth and concentrated in vacuo to yield 4.1 g (89%) of the title compound.