Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][CH2:12][Cl:13]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH2:11][CH2:12][Cl:13])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: ClCCCBr
Product: ClCCCOc1ccc(Br)cc1

Procedure:
Prepared by Procedure U and Scheme AK using 4-bromophenol and 1-bromo-3-chloropropane.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:12]=[N:13][C:14]([S:17]([O-:19])=[O:18])=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.[Na+].Br[CH2:22][C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24].[CH3:31]N(C=O)C>C(OCC)(=O)C.CCCCCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:12]([CH3:31])=[N:13][C:14]([S:17]([CH2:22][C:23](=[O:24])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)(=[O:19])=[O:18])=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1
Reactant: CN(C)C=O
Reactant: O=C(CBr)c1ccccc1
Reactant: O=C(Nc1ccc(F)cc1)c1cnc(S(=O)[O-])nc1
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1nc(S(=O)(=O)CC(=O)c2ccccc2)ncc1C(=O)Nc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 27 %

Procedure:
A solution of sodium 5-(4-fluorophenylcarbamoyl)pyrimidine-2-sulfinate (76 mg, 0.24 mmol) in 2 mL of DMF was treated with 2-bromoacetophenone (48 mg, 0.24 mmol) and stirred at ambient temperature for 3 days. The solution was then diluted with 15 mL ethyl acetate and 5 mL hexane and sequentially washed with 2×5 mL portions of 0.1 M HCl and 5 mL of water. The organic phase was dried using Na2SO4, concentrated and the resultant oil chromatographed through SiO2 (2–5% MeOH/dichloromethane). Recrystallization in ethyl acetate/hexane yielded 26 mg (27%) of the titled compound as yellowish needles. ApcI-MS m/z 414 (MH+), 412 (M−H−).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1Cl)[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18].[C:19]1([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.N1C=CC=CC=1>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:28]1[CH2:29][CH2:30][N:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:26][CH2:27]1)[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(Cl)cc21
Reactant: c1ccc(N2CCNCC2)cc1
Solvent: CC(=O)O
Solvent: c1ccncc1
Product: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(N3CCN(c4ccccc4)CC3)cc21
Yield: 54.9 %

Procedure:
2.15 g of 6,7-dichloro-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid, 6.5 g of 1-phenylpiperazine and 20 cm3 of pyridine were heated under reflux for 16 hours. The solvent was removed in vacuo and the residue was taken up in 20 cm3 of water. The suspension obtained was stirred and brought to pH 7 by the addition of acetic acid. The solid was filtered off and recrystallised from methyl cellosolve. 1.7 g of 6-chloro-1-ethyl-4-oxo-7-(4-phenylpiperazinyl)-1,4-dihydro-quinoline-3-carboxylic acid, m.p. 234°-235° C., were obtained.
Reaction SMILES: [C:1]([C:3]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].O(C)S([C:24](F)(F)F)(=O)=O.C(O)(=O)C>ClCCCl.[Pt](=O)=O>[C:1]([C:3]1([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][N:15]2[CH3:24])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2]
Reactant: COS(=O)(=O)C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CC(C#N)(c2ccccn2)C1
Agent: O=[Pt]=O
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CN1CCCCC1C1(C#N)CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
tert-butyl 3-cyano-3-pyridin-2-ylazetidine-1-carboxylate (14.2 g, 55 mmol) in 1,2-dichloroethane (120 ml) was cooled in an ice-bath and treated with methyl triflate. The reaction was stirred at room temperature for 1 hour then at reflux overnight (no starting material in the solution). The resulting orange/brown precipitate was filtered off and washed with more 1,2-dichloroethane. The solid was then dissolved in ethanol (150 ml) and acetic acid (1.5 eq, 5.5 ml) was added. Platinum dioxide (1.5 g) was added and the reaction hydrogenated on a parr at 40 psi overnight. Tlc and mass spec showed complete conversion. The reaction was filtered under nitrogen and the filtrate was evaporated to dryness to give tert-Butyl 3-cyano-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate as an oil which was used without further purification. m/z (M++H) 280.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5](Br)=[CH:6][CH:7]=1.[C:9]([Si:11]([CH3:14])([CH3:13])[CH3:12])#[CH:10].CC#N.CN(C=O)C>[Cu]I.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.CCN(CC)CC>[CH3:12][Si:11]([CH3:14])([CH3:13])[C:9]#[C:10][C:5]1[N:4]=[CH:3][C:2]([NH2:1])=[CH:7][CH:6]=1
Reactant: C#C[Si](C)(C)C
Reactant: Nc1ccc(Br)nc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1ccc(N)cn1
Temperature: 45 °C
Reaction time: 1.5 h
Yield: 67.9 %

Procedure:
A mixture of 3-amino-6-bromopyridine (Alfa Aesar, 1.0 g, 5.8 mmol), ethynyl trimethylsilane (1.7 mL, 17.3 mmol), CH3CN (3 mL), DMF (2 mL) and Et3N (2 mL) was treated with CuI (60 mg, 0.32 mmol) and (Ph3P)4Pd (114 mg, 0.10 mmol) and the mixture stirred at 45° C. for 1.5 h. More ethynyltrimethylsilane (1.7 mL, 17.3 mmol) was added to the reaction and the mixture was stirred for 2 h. The mixture was concentrated in vacuo and the residue partitioned between EtOAc and saturated aqueous NaHCO3 solution. The EtOAc phase was washed with brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography on SiO2 using 0-6% EtOAc/hexanes to give the title compound (0.75 g, 68%) as a brown solid. 1H NMR (DMSO-d6) δ 7.85 (s, 1H), 7.15 (d, 1H, J=8.1 Hz), 6.81 (d, 1H, J=8.1 Hz), 5.76 (s, 2H), 0.19 (s, 9H); MS (ESI+): m/z 191.20 (M+H)+.
Reaction SMILES: [C:1](O)(C(F)(F)F)=O.C(Cl)Cl.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[S:26][C:25]3[C:24](=[O:27])[N:23]([C:28]4[CH:44]=[CH:43][C:31]([O:32][CH2:33][CH2:34][NH:35][C:36](=O)[O:37]C(C)(C)C)=[C:30]([O:45][CH3:46])[CH:29]=4)[CH:22]=[N:21][C:20]=3[CH:19]=2)=[CH:14][CH:13]=1.CC(OC(C)=O)=O.CCN(CC)CC>C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[S:26][C:25]3[C:24](=[O:27])[N:23]([C:28]4[CH:44]=[CH:43][C:31]([O:32][CH2:33][CH2:34][NH:35][C:36](=[O:37])[CH3:1])=[C:30]([O:45][CH3:46])[CH:29]=4)[CH:22]=[N:21][C:20]=3[CH:19]=2)=[CH:16][CH:17]=1
Reactant: O=C(O)C(F)(F)F
Reactant: COc1cc(-n2cnc3cc(-c4ccc(Cl)cc4)sc3c2=O)ccc1OCCNC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CC(=O)OC(C)=O
Product: COc1cc(-n2cnc3cc(-c4ccc(Cl)cc4)sc3c2=O)ccc1OCCNC(C)=O
Reaction time: 2.5 h

Procedure:
A 10% TFA/CH2Cl2 solution (0.5 mL) containing tert-butyl 2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-ethylcarbamate (15 mg, 0.03 mmol) (Example 3) was stirred for 2.5 hr whereupon the volatiles were removed under vacuum. To the residue containing 3-(4-(2-aminoethoxy)-3-methoxyphenyl)-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one was sequentially added CH2Cl2 (0.25 mL), Ac2O (20 mg, 0.2 mmol) and Et3N (74 mg, 0.7 mmol). After standing overnight, the reaction was diluted with aq Na2CO3 and extracted 4× with CH2Cl2. The combined organic layers were washed with brine and dried over Na2SO4. After removal of the solvent the residue was chromatographed on silica gel using 5-10% MeOH/EtOAc to elute the desired acetamide (12 mg). 1H NMR (CDCl3) δ 2.03 (s, 3H), 3.72 (m, 2H), 3.91 (s, 3H), 4.16 (t, 2H, J=4.8 Hz), 6.13 (m, 1H), 6.94 (dd, 1H, J=8.4 Hz, J=2.2 Hz), 6.98 (d, 1H, J=2.2 Hz), 7.02 (d, 1H, J=8.4 Hz), 7.45 (d, 2H, JAB=8.7 Hz), 7.54 (s, 1H), 7.66 (d, 2H, JAB=8.7 Hz), 8.14 (s, 1H); HPLC (Method #1): 3.67 min; LCMS m/z: 498 [M+H].
Reaction SMILES: [ClH:1].Cl.N[C@@H](CC)[C@H](O)[C:6]([NH:8][CH:9]1[CH2:11][CH2:10]1)=[O:7].[NH2:15][C@@H:16]([CH2:19][CH:20]([CH3:22])[CH3:21])[CH2:17][OH:18]>>[ClH:1].[ClH:1].[NH2:15][C@@H:16]([CH2:19][CH:20]([CH3:22])[CH3:21])[C@H:17]([OH:18])[C:6]([NH:8][CH:9]1[CH2:11][CH2:10]1)=[O:7]
Reactant: CC[C@H](N)[C@H](O)C(=O)NC1CC1
Reactant: CC(C)C[C@H](N)CO
Agent: Cl
Product: CC(C)C[C@H](N)[C@H](O)C(=O)NC1CC1

Procedure:
The title compound was prepared in analogy to (2S,3S)-3-amino-N-cyclopropyl-2-hydroxypentanamide dihydrochloride, Representative Procedure A, starting with (S)-2-amino-4-methylpentan-1-ol in the first step (A1).
Reaction SMILES: [NH2:1][C:2]1[O:3][CH:4]([CH:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH3:9])[C:5](=[O:7])[N:6]=1.[O:19]1[CH2:23][CH2:22]CC1.C(N(CC)CC)C.[C:31](Cl)(=[O:33])[CH3:32]>O>[C:31]([N:1]([C:23](=[O:19])[CH3:22])[C:2]1[O:3][CH:4]([CH:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH3:9])[C:5](=[O:7])[N:6]=1)(=[O:33])[CH3:32]
Reactant: CC(c1c[nH]c2ccccc12)C1OC(N)=NC1=O
Reactant: C1CCOC1
Reactant: CC(=O)Cl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)N(C(C)=O)C1=NC(=O)C(C(C)c2c[nH]c3ccccc23)O1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
2-amino-5-[1-(indol-3-yl)ethyl]-2-oxazolin-4-one (300 g) was dissolved into tetrahydrofuran (2 ml). Triethylamine (344 μl) and acetyl chloride (123 μl) were added under ice cooling. The mixture was stirred for 2 hours at 0° C. Triethylamine (344 μl) and acetyl chloride (123 μl) were added again. The whole was further stirred for 2 hours. To the reaction mixture was added water and the whole was extracted with ethyl acetate. The extract was washed with brine and dried over magnesium sulfate. Concentration of the solution gave a residue, which was subjected to silica gel chromatography. The eluent with hexane-acetone (1:1) was collected and concentrated to provide the titled compound (40 mg).
Reaction SMILES: [CH2:1]1[C:13]2[N:4]([C:5](=O)[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[CH:12]=2)[CH2:3][CH2:2]1.[BH4-].[Na+]>P(Cl)(Cl)(Cl)=O.CO>[CH2:1]1[CH:13]2[N:4]([CH2:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[CH2:12]2)[CH2:3][CH2:2]1
Reactant: O=c1c2ccccc2cc2n1CCC2
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O=P(Cl)(Cl)Cl
Product: c1ccc2c(c1)CC1CCCN1C2
Temperature: 0 °C
Yield: 41.6 %

Procedure:
A suspension of 2,3-dihydropyrrolo[1,2-b]isoquinolin-5(1H)-one (10.8 g, 58.3 mmol) [G. M. Coppola, J. Heterocycl. Chem., 1981, 18, 767] in phosphorus oxychloride (100 ml) was heated at reflux for 1.5 h. Upon cooling, the solvent was removed in vacuo to give an oil. This oil was immediately taken up in cold methanol (275 ml) and sodium borohydride (4.0 g) was added portionwise to this solution while maintaining the reaction mixture at 0° C. The solvent was concentrated and the residue was dissolved in water and washed twice with ethyl acetate. The aqueous solution was made basic with potassium carbonate solution and extracted with ethyl acetate. The organic phase was dried (magnesium sulfate) and concentrated to give an oil. Column chromatography on silica gel gave unreacted starting material (3.57 g, 36%) and the title compound (4.2 g, 63% based on recovered starting material) as a light oil; MS 174 (M+H)+ ; NMR (CDCl3) 7.0-7.2 (broad m, 4H), 4.13 (d, 1H, J=15), 3.40 (d, 1H, J=15), 3.27 (dt, 1H), 2.9-3.1 (M, 1H), 2.71 (t, 1H), 1.4-2.4 (m, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@H:15]([NH:21]C(=O)OC(C)(C)C)[C:16]3[NH:20][N:19]=[N:18][N:17]=3)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][C@@H:15]([C:16]3[NH:20][N:19]=[N:18][N:17]=3)[NH2:21])=[CH:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)c1nnn[nH]1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)c1nnn[nH]1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of (S)-tert-butyl 2-(3′-chlorobiphenyl-4-yl)-1-(1H-tetrazol-5-yl)ethylcarbamate (250 mg, 0.625 mmol) in DCM (5 ml) at room temperature was added TFA (2 ml, 26.0 mmol), and the mixture was stirred at room temperature for 0.5 hour. The mixture was concentrated under reduced pressure and obtained the title compound. LCMS (condition A): 300.1 (M+1); retention time=1.20 min.
Reaction SMILES: [CH3:1][CH:2]([CH3:16])[CH2:3][CH2:4][CH:5]([OH:15])[C:6](=[N:13][OH:14])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:17]1([N:23]=[C:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1>[C:17]1([NH:23][C:24]([O:14][N:13]=[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:5]([OH:15])[CH2:4][CH2:3][CH:2]([CH3:16])[CH3:1])=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C=Nc1ccccc1
Reactant: CC(C)CCC(O)C(=NO)c1ccccc1
Solvent: Cc1ccccc1
Product: CC(C)CCC(O)C(=NOC(=O)Nc1ccccc1)c1ccccc1
Reaction time: 1 h

Procedure:
2.2 g (0.01 Mol) of 5-methyl-2-hydroxy-caprophenone-oxime are dissolved in 25 ml of toluene and may be slightly heated in this process. Then 1.2 g (0.01 Mol) of phenylisocyanate are added, with the mixture being swirled. The mixture is allowed to stay for one hour, before the solvent is evaporated under vacuum conditions causing crystallisation of residue. Colourless crystals, between 117° C. and 120° C. in flash point, are obtained by recrystallisation from ethanol or ethanol/water.
Reaction SMILES: C([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[O:10][C:9]([C:18]2[N:19]=[CH:20][C:21]3[C:26]([CH:27]=2)=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:8]1)(C)(C)C.[C:28]([C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1)#[CH:29]>>[CH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[C:18]([C:9]2[O:10][C:11]3[C:16]([C:7](=[N:6][OH:5])[CH:8]=2)=[CH:15][CH:14]=[C:13]([C:29]#[C:28][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)[CH:12]=3)[N:19]=1
Reactant: C#Cc1ccncc1
Reactant: CC(C)(C)ON=c1cc(-c2cc3ccccc3cn2)oc2cc(Br)ccc12
Product: ON=c1cc(-c2cc3ccccc3cn2)oc2cc(C#Cc3ccncc3)ccc12

Procedure:
2-isoquinolin-3-yl-7-(pyridin-4-yl)ethynyl-chromen-4-one oxime was prepared in 6% overall yield using the method described in example 24, starting from 7-bromo-2-isoquinolin-3-yl-chromen-4-one O-tert-butyl oxime (example 2B) and 4-ethynylpyridine. The title compound was isolated as a yellow solid and as a 95/5 mixture of Z/E oxime isomers.
Reaction SMILES: C([O:4][C:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[C:6]=1[CH2:28][CH3:29])(=O)C.C1C=C(Cl)C=C(C(OO)=[O:38])C=1.C(Cl)Cl>C(OC(C)C)(C)C.CO>[OH:38][C@@H:8]1[C:7]2[C@:20]([CH3:23])([CH2:21][CH2:22][C:5](=[O:4])[C:6]=2[CH2:28][CH3:29])[C@@H:19]2[C@H:10]([C@H:11]3[C@@:15]([CH2:17][CH2:18]2)([CH3:16])[C@@H:14]([O:24][C:25](=[O:27])[CH3:26])[CH2:13][CH2:12]3)[CH2:9]1.[OH:38][C@H:8]1[C:7]2[C@:20]([CH3:23])([CH2:21][CH2:22][C:5](=[O:4])[C:6]=2[CH2:28][CH3:29])[C@@H:19]2[C@H:10]([C@H:11]3[C@@:15]([CH2:17][CH2:18]2)([CH3:16])[C@@H:14]([O:24][C:25](=[O:27])[CH3:26])[CH2:13][CH2:12]3)[CH2:9]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCC1=C(OC(C)=O)CC[C@@]2(C)C1=CC[C@H]1[C@@H]3CC[C@H](OC(C)=O)[C@@]3(C)CC[C@@H]12
Solvent: CO
Solvent: CC(C)OC(C)C
Solvent: ClCCl
Product: CCC1=C2[C@@H](O)C[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Product: CCC1=C2[C@H](O)C[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Reaction time: 8 h
Yield: 105 %

Procedure:
To a stirred solution of 3,17β-diacetoxy-4-ethylandrosta-3,5-diene (1.08 g) in EtOH/H2O 95/5 (13.7 ml), mCPBA (1.0 g) was added. After 8 h at RT, DCM (150 ml) was added and the mixture was washed with 10% Na2SO3 aqueous solution, 5% aqueous NaHCO3 solution, and brine. The organic phase was dried over Na2SO4, and evaporated to dryness. The crude reaction mixture was purified by flash chromatography (SiO2, n-hexane/EtOAc 60/40) to give a mixture 6α-hydroxy-17β-acetoxy-4-ethylandrost-4-en-3-one and 6β-hydroxy-17β-acetoxy-4-ethylandrost-4-en-3-one (0.53 g, 52%).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[CH:19]([S:22](Cl)(=[O:24])=[O:23])([CH3:21])[CH3:20]>>[F:8][C:7]1[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])=[C:5]([NH:18][S:22]([CH:19]([CH3:21])[CH3:20])(=[O:24])=[O:23])[CH:4]=[CH:3][C:2]=1[F:1]
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Reactant: CC(C)S(=O)(=O)Cl
Product: CC(C)S(=O)(=O)Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Yield: 39 %

Procedure:
According to the general procedure A, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene-1,2-diamine was reacted with isopropylsulfonyl chloride to obtain the desired product. Yield: 39%. 1H-NMR (500 MHz, CDCl3): δ=7.50-7.43 (m, 1H), 7.35-7.34 (m, 1H), 7.27-7.26 (m, 1H), 7.15-7.09 (q, 1H, J=1.6 Hz), 6.62 (s, 1H, br), 6.22-6.18 (q, 1H, J=1.5 Hz), 5.65 (s, 1H, br), 3.30-3.28 (m, 1H), 1.38-1.37 (d, 6H, J=1.2 Hz); m/z=469 [M−I]−.
Reaction SMILES: [CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=[O:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.[CH3:12][Mg]Cl.[Cl-].[NH4+]>C1COCC1>[CH3:12][C:7]1([OH:10])[CH2:6][CH2:5][C:4]2([O:3][CH2:2][CH2:1][O:11]2)[CH2:9][CH2:8]1
Reactant: C[Mg]Cl
Reactant: O=C1CCC2(CC1)OCCO2
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC1(O)CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 3 h
Yield: 59.3 %

Procedure:
1,4-cyclohexandione mono-ethylene ketal (1.0 g, 6.4 mmol) was dissolved in THF (30 ml), followed by addition of MeMgCl (3.0M solution in THF, 2.6 ml, 7.7 mmol) at 0° C., and then the resulting mixture was stirred at room temperature under nitrogen stream for 3 hours. A saturated aqueous ammonium chloride solution was added to the resulting reaction liquid, followed by extraction with MC (50 ml×2). The organic layer was dried over anhydrous sodium sulfate, followed by filtration and concentration, and then the residue thus obtained was subjected to MPLC (50% EtOAc/Hexanes), to obtain 654 mg of white solid (59%).
Reaction SMILES: [CH:1]1[C:6]([CH2:7][C@H:8]([NH2:12])[C:9]([OH:11])=[O:10])=[CH:5][C:4]([OH:13])=[C:3]([OH:14])[CH:2]=1.S(Cl)(Cl)=O.[CH2:19](O)[CH3:20]>>[CH3:19][CH2:20][O:10][C:9]([C@@H:8]([NH2:12])[CH2:7][C:6]1[CH:1]=[CH:2][C:3]([OH:14])=[C:4]([OH:13])[CH:5]=1)=[O:11]
Reactant: CCO
Reactant: N[C@@H](Cc1ccc(O)c(O)c1)C(=O)O
Solvent: O=S(Cl)Cl
Product: CCOC(=O)[C@@H](N)Cc1ccc(O)c(O)c1
Temperature: 5 °C

Procedure:
Levodopa (50 g.) was added in portions to a cooled (2-8° C.) solution of 30 ml. thionyl chloride in 250 ml. absolute ethanol. The resulting mixture was heated to 40° C. for 16 hours and then the volatiles were removed in vacuo. The residue was dissolved in 50 ml. of water and diluted with a solution of 20 g. of sodium bicarbonate, 26 g. of sodium sulfate and 50 mg. of ascorbic acid in 400 ml. of water. The pH of the resulting solution was carefully adjusted to pH 7 with 10% aqueous sodium hydroxide and it was extracted with deaerated ethyl acetate containing 0.01% BHT.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.C([Li])CCC.CCCCCC.CN(C)[CH:24]=[O:25]>O1CCCC1.O>[CH:24]([C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2)=[O:25]
Reactant: Brc1cccc2cc[nH]c12
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: O
Product: O=Cc1cccc2cc[nH]c12
Temperature: -70 °C
Reaction time: 0.25 h

Procedure:
A solution of 7-bromoindole [Tet. Lett. 30, 2129 (1989)] (12.75 g, 0.065 mole) in dry tetrahydrofuran (230 ml) was cooled in a dry ice-acetone bath and 2.5M n-butyl lithium in hexane (78 ml, 0.195 mole) added dropwise over 1 hour, maintaining the reaction temperature below -60° C. The reaction mixture was stirred for a further 15 minutes at -70° C., then allowed to warm to 5° C. After 30 minutes at 5° C., the reaction was recooled to -70° C. and dimethylformamide (25 ml, 0.325 mole) added dropwise at a rate to maintain the temperature below -65° C. The mixture was allowed to warm to room temperature slowly, then was poured into water and extracted into diethyl ether. The combined dry extracts were washed with brine, dried and evaporated. Recrystallisation from 80°-100° C. petroleum ether with charcoal treatment yielded the product as fawn-coloured crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([S:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]O)[CH:25]=3)[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.C1(C)C(S([Cl:50])(=O)=O)=CC=CC=1.O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([S:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][Cl:50])[CH:25]=3)[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: COc1ccc(-c2nc(SCc3cccc(CO)c3)[nH]c2-c2ccc(OC)cc2)cc1
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(-c2nc(SCc3cccc(CCl)c3)[nH]c2-c2ccc(OC)cc2)cc1

Procedure:
Part C. A solution of the alcohol prepared above (5.96 g, 13.8 mmol), diisopropylethylamine (2.90 mL, 16.6 mmol) and toluenesulfonyl chloride (2.89 g, 15.2 mmol) in tetrahydrofuran (30 mL) was heated to reflux for 18 hours. The mixture was cooled, and poured into water (150 mL). This was extracted with methylene chloride (2×150 mL), and the extracts were combined, dried over magnesium sulfate and evaporated. The residual oil was separated by flash chromatography (3:7 ethyl acetate-hexane)to afford the product, 4,5-bis (4-methoxyphenyl)-2-[3-(chloro-methyl)benzyl]thio-1H-imidazole, as a foam upon vacuum pumping (2.24 g, 4.96 mmol, 36%). 1H NMR (CDCl3): 8.94 (1H, br s); 7.70-7.09 (8H, m); 6.84 (4H, d, J=8.8 Hz); 4.51 (2H, s); 4.19 (2H, s); 3.81 (6H, s).
Reaction SMILES: [NH2:1][C:2]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:3]=1[CH2:4][N:5]([CH2:8][CH3:9])[CH2:6][CH3:7].[Br:16]Br>C(Cl)Cl>[NH2:1][C:2]1[C:13]([Br:16])=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:3]=1[CH2:4][N:5]([CH2:8][CH3:9])[CH2:6][CH3:7]
Reactant: BrBr
Reactant: CCN(CC)Cc1cc(OC)ccc1N
Solvent: ClCCl
Product: CCN(CC)Cc1cc(OC)cc(Br)c1N

Procedure:
2-Amino-3-bromo-N,N-diethyl-5-methoxy-benzylamine was prepared from 2-amino-N,N-diethyl-5-methoxy-benzylamine and bromine analogous to Example 9. Proof of structure by IR-, UV- and NMR-spectra. IR-spectrum (methylenechloride): 3250 cm-1NH2 ; 3410 cm-1NH2 ; 2830 cm-1OCH3 ; 2800 cm-1N-ethyl; 1480 cm-1C=C; 1590 cm-1C=C.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.Cl[C:12](Cl)([O:14]C(=O)OC(Cl)(Cl)Cl)Cl>C1(C)C=CC=CC=1>[N:1]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2)=[C:12]=[O:14]
Reactant: Nc1cccc2[nH]ccc12
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: O=C=Nc1cccc2[nH]ccc12
Temperature: 25 °C
Yield: 187.3 %

Procedure:
4-Aminoindole (0.5 g, 3.78 mmol) in toluene (50 mL) was treated with triphosgene (0.4 g, 1.35 mmol) and heated at reflux for 5 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was taken up in diethyl ether, filtered, and the filtrate was concentrated under reduced pressure to provide title compound as yellow oil (0.4 g). 1H NMR (300 MHz, CDCl3-d6) δ 6.62 (m, 1H), 6.84 (d, 1H), 7.1 (t, 1H), 7.23 (m, 2H), 8.3 (s, 1H).