Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([Br:19])[C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([O:16]C)=[CH:12][CH:11]=3)=[CH:7][C:6]=2[CH:18]=1.Cl.N1C=CC=CC=1>O>[Br:1][C:2]1[CH:3]=[C:4]([Br:19])[C:5]2[O:9][C:8]([C:10]3[CH:11]=[CH:12][C:13]([OH:16])=[CH:14][CH:15]=3)=[CH:7][C:6]=2[CH:18]=1
Reactant: COc1ccc(-c2cc3cc(Br)cc(Br)c3o2)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: Oc1ccc(-c2cc3cc(Br)cc(Br)c3o2)cc1
Temperature: 200 °C
Reaction time: 1 h
Yield: 18 %

Procedure:
Compound 87 was treated with Pyridine HCl (5 g) and heated to 200° C. After 1 hr, the reaction was cooled and diluted with water. The aqueous layer was extracted with EtOAc, dried over. MgSO4, and the product was purified by column chromatography (eluant 25% EtOAc/hexanes) to give a solid (0.12 g, 18%); Mp=203–205° C.; 1H NMR (DMSO-d6) δ 10.04 (br s, 1 H), 7.83 (d, 1 H, J=1.5 Hz), 7.75 (d, 2 H, J=8.3 Hz), 7.68 (d, 1 H, J=2.0 Hz), 7.28 (s, 1H), 6.91 (d, 2 H, J=8.3 Hz); MS 365/367/369 [M−H]−
Reaction SMILES: [N:1](=[C:3]1[S:7][C:6]([CH3:9])([CH3:8])[N:5]=[C:4]1[CH3:10])[OH:2].[H-].[Na+].[CH3:13][N:14]([CH3:18])[C:15](Cl)=[O:16]>O1CCCC1.C(OCC)C>[CH3:13][N:14]([CH3:18])[C:15]([O:2][N:1]=[C:3]1[S:7][C:6]([CH3:9])([CH3:8])[N:5]=[C:4]1[CH3:10])=[O:16]
Reactant: CC1=NC(C)(C)SC1=NO
Reactant: CN(C)C(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC1=NC(C)(C)SC1=NOC(=O)N(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3.0 g (0.019 mol) of 5-oxo-2,2,4-trimethyl-3-thiazoline oxime are added portionwise to a suspension of 0.9 g of sodium hydride in 20 ml of tetrahydrofuran. The sodium hydride was liberated shortly before its use from a 55% suspension in oil by two-fold extraction with a small amount of absolute pentane. After completion of the hydrogen evolution, the mixture is stirred at room temperature for an additional 1 hour. 2.05 g (0.019 mol) of dimethylcarbamoyl chloride are added dropwise, and the reaction mixture is stirred at room temperature for 16 hours. The residue is then taken up in diethyl ether, and the organic phase is washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is subsequently distilled off, and the residue is recrystallized from diethyl ether/n-hexane to yield 5-oxo-2,2,4-trimethyl-3-thiazoline O-(dimethylcarbamoyl)oxime, m.p. 92°-95° C.
Reaction SMILES: Cl.[S:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3]1.[C-:11]#[N:12].[Na+].[Cl:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]=O.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>O.CO>[Cl:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]([N:7]1[CH2:8][CH2:9][C:10]2[S:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[C:11]#[N:12]
Reactant: O=Cc1ccccc1Cl
Reactant: c1cc2c(s1)CCNC2
Reactant: [C-]#N
Agent: Cl
Agent: O=S([O-])S(=O)(=O)[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: N#CC(c1ccccc1Cl)N1CCc2sccc2C1
Temperature: 45 °C

Procedure:
To a mixture of methanol (2.50 l) and water (250 ml) was charged 4,5,6,7 -tetrahydro-thieno[3,2-c]pyridine hydrochloride (500 g; 2.85 mol) with stirring. After stirring for 10 minutes, sodium cyanide (153.0 g; 3.12 mol) was added and stirred further for 40 minutes. 2-Chlorobenzaldehyde (392.1 g; 2.79 mol) was added slowly to this reaction mixture between 23-28° C. over a period of 1.5 hours. After the addition was over, the flask was heated in an oil bath between 40-50° C. and maintained at this temperature for 4.5 hours. After cooling the reaction mixture to 25-30° C., 5% sodium metabisulfite solution (250 ml) was added and stirred for 1 hour at this temperature range. To the resulting slurry, water (7.5 l) was added and stirred for 1 hour at 25-30° C. The off-white solid thus formed was filtered, washed with a 1:1 mixture of methanol: water (2.5 l) and the wet cake was dried at 75° C. under vacuum (pressure: −0.8 kg/cm2) for 10 hours to obtain the product as an off-white solid. Yield: 719.0 g (87.4%). mp: 124-126.5° C. The product was identified by IR spectrum, 1H and 13C NMR investigation.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10](C(=O)C)[CH:11]=2)[CH2:6]1.ClC1C=CC=[C:21]([C:25]([O:27]O)=[O:26])C=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:17])[CH2:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:27][C:25](=[O:26])[CH3:21])[CH:11]=2)[CH2:6]1
Reactant: COC(=O)CC1Cc2ccc(C(C)=O)cc2C1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COC(=O)CC1Cc2ccc(OC(C)=O)cc2C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 96.8 %

Procedure:
11.0 g (47.0 mmol) of methyl(5-acetylindan-2-yl)acetate was dissolved in 200 ml of methylene chloride, to which was added 14.6 g (67 mmol) of m-chloroperbenzoic acid and stirred for 4 hours at room temperature, followed by refluxing for 17 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate and water in this order, dried and then the solvent was removed. The residue was purified by silica gel column chromatography (chloroform) to obtain 11.3 g of an oily product. Yield: 97%
Reaction SMILES: F[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][C@H:32]([CH2:37][CH3:38])[CH:33]([OH:36])[CH2:34][CH3:35]>CCCCO.CS(C)=O>[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH:31][C@H:32]([CH2:37][CH3:38])[CH:33]([OH:36])[CH2:34][CH3:35])=[N:3][C:4]=2[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)([CH3:13])[CH3:12]
Reactant: CC(C)n1cnc2c(NCc3ccccn3)nc(F)nc21
Reactant: CCC(O)[C@H](N)CC
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: CCC(O)[C@@H](CC)Nc1nc(NCc2ccccn2)c2ncn(C(C)C)c2n1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-2-ylmethyl-amine (20 mg, 1 eq, 0.07 mmol) in n-BuOH/DMSO (3.75 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.18 mL, 15 eq, 1.03 mmol) followed by (3RS,4R)-4-amino-hexan-3-ol (110 mg, 13 eq, 0.94 mmol). The reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 72 h. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. The residue was partitioned between EtOAc (50 mL) and brine/water (1:1, 100 mL), the aqueous phase was extracted with more EtOAc (2×25 mL), and the combined organic phase was washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient column chromatography on silica gel eluted with CHCl3:MeOH (100:0→98:2), to afford the title compound as a white solid. Yield: 11 mg (41%). (57% de 4R,3S: 43% de 4R,3R). 1H-NMR (d-CDCl3, 250 MHz): δ 0.85-1.06 (m, 6H, —NHCH(CH2CH3)CH(CH2CH3)OH), 1.57 (d, 6H, J=6.79 Hz, & —CH(CH3)2), 1.42-1.65 (m, 4H, —NHCH(CH2CH3)CH(CH2CH3)OH), 3.45 (d, 1H, J=6.31 Hz, OH), 3.57-3.70 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 3.91-4.03 (m, 1H, —NHCH(CH2CH3) CH(CH2CH3) OH), 4.57-4.76 (m, 1H, —CH(CH3)2), 4.86-4.98 (m, 2H, —HNCH2-Pyr), 5.18-5.29 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 6.73-6.89 (m, 1H, —HNCH2-Pyr), 7.15-7.25 (m, 1H, Pyr-H), 7.38 (d, 1H, J=7.90 Hz, Pyr-H), 7.56 (s, 1H, —N═CH—N—), 7.63-7.70 (m, 1H, Pyr-H), 8.60 (d, 1H, J=4.42 Hz, Pyr-H). FABMS m/z (relative intensity): 384 ([M+H]+, 100), 324 (35), 307 (37), 297 (25), 289 (20). Accurate Mass (M+H): Actual: 384.2512 Measured: 384.2523.
Reaction SMILES: C=O.[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[C:9]([C:11]1[CH:20]=[CH:19][C:18]2[NH:17][C:16](=[O:21])[C:15]3[NH:22][CH:23]=[CH:24][C:14]=3[C:13]=2[CH:12]=1)#[CH:10].[CH2:25]([C:27]([O-:29])=[O:28])[CH3:26].C(O)(=O)C>O1CCOCC1.[Cu](I)I>[N:3]1([CH2:25][C:10]#[C:9][C:11]2[CH:20]=[CH:19][C:18]3[NH:17][C:16](=[O:21])[C:15]4[NH:22][CH:23]=[CH:24][C:14]=4[C:13]=3[CH:12]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[CH2:25]([C:27]([O-:29])=[O:28])[CH3:26]
Reactant: C1COCCN1
Reactant: C#Cc1ccc2[nH]c(=O)c3[nH]ccc3c2c1
Agent: I[Cu]I
Agent: C=O
Agent: CCC(=O)[O-]
Solvent: CC(=O)O
Solvent: C1COCCO1
Product: O=c1[nH]c2ccc(C#CCN3CCOCC3)cc2c2cc[nH]c12
Temperature: 85 °C
Yield: 12.4 %

Procedure:
15 mg (0.17 mmol) of para-formaldehyde, 15 mg (0.17 mmol) of morpholine and 3 mg (0.02 mmol) of copper iodide are added to a suspension of 47 mg (0.17 mmol) of 8-ethynyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in 5 ml of anhydrous dioxan, then a drop of acetic acid is added and the mixture is heated at 85° C. for 48 hours. The raw reaction product is then filtered, the filtrate is evaporated and the residue is purified by preparative LCMS to give 4 mg (6%) of 8-(3-morpholin-4-yl-prop-1-ynyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in the form of a white solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[CH:9]3O[CH:8]3[C:7]=2[CH:15]=1)#[N:2].[C:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1)#[N:17].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]([C:8]2[C:7]3[CH:15]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=3[O:11][C:10]([CH3:13])([CH3:12])[CH:9]=2)[CH:19]=1)#[N:17]
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Reactant: N#Cc1c[nH]c2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC1(C)C=C(n2cc(C#N)c3ccccc32)c2cc(C#N)ccc2O1
Temperature: 100 °C
Yield: 59.4 %

Procedure:
The reaction mixture containing 6-cyano-3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-benzopyran (1.5 g, 7.5 mmol) (prepared according to Evans et al., J. Med. Chem., 1983, 26, 1582 and J. Med. Chem., 1986, 29, 2194), 3-cyanoindole (1.46 g, 9.75 mmol) and finely ground potassium carbonate (2.6 g, 18.75 mmol) in dimethylformamide (5.0 mL) was heated at 100° C. for three hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and filtered. The filtrate was washed with water, 1N hydrochloric acid, sodium bicarbonate solution and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to yield a colorless solid. This material was purified by flash chromatography (20% ethyl acetate in hexanes) to yield 4-(3-cyano-1H-indol-1-yl)-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (1.45 g) as a colorless solid, m.p. 192°-193° C. (dichloromethaneisopropyl ether): 1H NMR (CDCl3) δ 7.72 (m, 1 H), 7.6 (s, 1 H), 7.40 (dd, J=8.2 and 1.8 Hz, 1 H), 7.25 (m, 2 H), 7.1 (m, 1 H), 6.90 (d, J=8.7 Hz, 1 H), 6.70 (d, J=2.3 Hz, 1 H), 5.88 (s, 1 H), 1.55 (s, 6 H); 13C NMR (CDCl3) 156.8, 135.6, 135.3, 134.9, 134.4, 129.9, 129.5, 127.3, 126.6, 124.8, 123.0, 120.1, 119.0, 118.2, 114.8, 111.3, 104.5, 88.7, 78.6, 27.9 ppm.
Reaction SMILES: [CH3:1][C:2]1[N:10]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:12])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[C:19]([OH:21])=O.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[NH2:55][CH2:56][C:57]1[C:58]([OH:65])=[N:59][C:60]([CH3:64])=[CH:61][C:62]=1[CH3:63].C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[OH:65][C:58]1[C:57]([CH2:56][NH:55][C:19]([C:3]2[C:4]3=[N:5][CH:6]=[CH:7][CH:8]=[C:9]3[N:10]([CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH3:12])[C:2]=2[CH3:1])=[O:21])=[C:62]([CH3:63])[CH:61]=[C:60]([CH3:64])[N:59]=1
Reactant: Cc1c(C(=O)O)c2ncccc2n1C(C)c1ccccc1
Reactant: Cc1cc(C)c(CN)c(O)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: C[NH3+]
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: Cc1cc(C)c(CNC(=O)c2c(C)n(C(C)c3ccccc3)c3cccnc23)c(O)n1
Reaction time: 12 h
Yield: 32.9 %

Procedure:
The mixture of 2-methyl-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (20 mg, 0.11 mmol), 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium (50 mg, 0.13 mmol), 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (19 mg, 0.12 mmol) and triethylamine (23 mg, 0.22 mmol) in N,N-dimethylformamide (5 mL) was stirred for 12 hours. After the reaction was completed, the reaction was diluted with ethyl acetate (100 mL), and washed with water (20 mL×3) and brine (20 mL), dried over anhydrous sodium sulfate and concentrated to give the residue, which was purified by column chromatography (silica gel, dichloromethane/methanol=30:1) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-methyl-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (15 mg, 33%). LRMS (M+H+) m/z: calcd 415.20. found 415. HPLC Purity (214 nm): 99%. 1H NMR (300 MHz, d6-DMSO) δ 11.46 (s, 1H), 9.49 (t, J1=4.2 Hz, J2=8.1 Hz, 1H), 8.28 (d, J=3.6 Hz, 1H), 7.50 (d, J=6.3 Hz, 1H), 7.36-7.27 (m, 3H), 7.16 (d, J=5.7 Hz, 1H), 7.03-7.00 (m, 1H), 6.03 (m, 1H), 5.85 (s, 1H), 4.37 (s, 2H), 2.89 (s, 3H), 2.50 (s, 3H), 2.10 (s, 3H), 1.89 (d, J=5.4 Hz, 3H).
Reaction SMILES: [CH:1]([N-:4]C(C)C)(C)C.[Li+].[CH2:9]([CH:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20][C:21]2([C:36]#[CH:37])[CH2:26][CH2:25][CH:24]([CH:27]3[CH2:32][CH2:31][CH:30]([CH2:33][CH2:34][CH3:35])[CH2:29][CH2:28]3)[CH2:23][CH2:22]2)=[O:19])[CH2:14][CH2:13]1)[CH2:10][CH3:11].C1(C)C=CC(S(C#N)(=O)=O)=CC=1>C1COCC1>[CH2:9]([CH:12]1[CH2:13][CH2:14][CH:15]([C:18]([O:20][C:21]2([C:36]#[C:37][C:1]#[N:4])[CH2:26][CH2:25][CH:24]([CH:27]3[CH2:28][CH2:29][CH:30]([CH2:33][CH2:34][CH3:35])[CH2:31][CH2:32]3)[CH2:23][CH2:22]2)=[O:19])[CH2:16][CH2:17]1)[CH2:10][CH3:11]
Reactant: CC(C)[N-]C(C)C
Reactant: C#CC1(OC(=O)C2CCC(CCC)CC2)CCC(C2CCC(CCC)CC2)CC1
Agent: Cc1ccc(S(=O)(=O)C#N)cc1
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCC1CCC(C(=O)OC2(C#CC#N)CCC(C3CCC(CCC)CC3)CC2)CC1
Reaction time: 0.25 h

Procedure:
5.10 ml of a 26% solution of lithium diisopropylamide in THF are added dropwise at −70° C. to 4.00 g of 4-ethynyl-4′-propylbicyclohexyl-4-yl 4-propylcyclohexanecarboxylate in 30 ml of THF, and the mixture is stirred for 15 minutes. A solution of 1.89 g of p-toluenesulfonyl cyanide in 10 ml of THF is subsequently added dropwise to the reaction solution at this temperature, and the cooling is removed. Conventional work-up gives 4-cyanoethynyl-4′-propylbicyclohexyl-4-yl 4-propylcyclohexanecarboxylate (C 89 N (58) I, Δε−10.18, Δn 0.02).
Reaction SMILES: COCCOC.O1CCCC1.[NH:12]1[CH2:17][CH2:16][CH:15]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:27]([O:29][CH3:30])=[O:28])[CH:25]=3)[CH:20]=[CH:19]2)[CH2:14][CH2:13]1.[CH3:31][O:32][C:33]1[C:42]([CH2:43][CH:44]=O)=[C:41]2[C:36]([C:37](=[O:48])[CH2:38][C:39]([CH3:47])([CH3:46])[O:40]2)=[CH:35][CH:34]=1>C(O)(=O)C>[CH3:31][O:32][C:33]1[C:42]([CH2:43][CH2:44][N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:27]([O:29][CH3:30])=[O:28])[CH:25]=4)[CH:20]=[CH:19]3)[CH2:16][CH2:17]2)=[C:41]2[C:36]([C:37](=[O:48])[CH2:38][C:39]([CH3:47])([CH3:46])[O:40]2)=[CH:35][CH:34]=1
Reactant: COC(=O)c1ccc2ccn(C3CCNCC3)c2c1
Reactant: COc1ccc2c(c1CC=O)OC(C)(C)CC2=O
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: COCCOC
Product: COC(=O)c1ccc2ccn(C3CCN(CCc4c(OC)ccc5c4OC(C)(C)CC5=O)CC3)c2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 105.7 %

Procedure:
28 mL of DME, 14 mL of tetrahydrofuran and 1.24 mL of acetic acid were added to 2.80 g of methyl 1-piperidin-4-yl-1H-indole-6-carboxylate and 3.16 g of (7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)acetaldehyde. Although crystals precipitated, the reaction mixture was stirred for one hour as it was. The reaction mixture was cooled with an ice-water bath, and 2.75 g of sodium triacetoxyborohydride was added portionwise divided into three to the reaction mixture. The reaction mixture was warmed to room temperature and added with 3 mL of tetrahydrofuran and about 1.5 hours later, progress of the reaction was confirmed. The reaction mixture cooled with an ice-water bath again and added with 68 mL of toluene and 29 mL of water and, after clarification and filtration, added with 30 mL of toluene and the aqueous layer was discarded. The organic layer was washed with 29 mL of 1 N aqueous sodium hydroxide, 29 mL×2 of 5% sodium chloride solution and 29 mL of water. The solvent was evaporated and 5.62 g of the crude title compound was obtained.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[CH:14]([CH2:15][C:16](=[O:24])[CH:17]=[CH:18]1)[CH2:13][CH2:12]3)(=[O:3])[CH3:2].[CH3:25][Al](C)C.O>C(OCC)(=O)C.C1(C)C=CC=CC=1.[Cu]Br>[C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[C@H:14]([CH2:15][C:16](=[O:24])[CH2:17][C@@H:18]1[CH3:25])[CH2:13][CH2:12]3)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@H]2[C@@H]3CCC4CC(=O)C=C[C@]4(C)[C@H]3CC[C@]12C
Reactant: C[Al](C)C
Agent: [Cu]Br
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: O
Product: CC(=O)O[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)C[C@H](C)[C@]4(C)[C@H]3CC[C@]12C
Reaction time: 0.5 h

Procedure:
Variant 2 (in ethyl acetate : 66.1 g (0.2 mol) of 17β-acetoxy-androst-1-en-3-one is dissolved in 350 ml of dry ethyl acetate and mixed with 1.43 g (10 mmol) of copper(I) bromide. 188 ml (0.22 mol) of a 10% solution of trimethyl aluminum in toluene is added over 15 minutes to the reaction under nitrogen atmosphere, so that the temperature does not rise above 25° C. Then it is stirred for 30 minutes more. For hydrolysis, 15 ml of water is added to the reaction and stirred for 40 minutes more. The solid is suctioned off and absorptively precipitated three times, each with 200 ml of dioxane. After concentration by evaporation of the combined organic phases, 65.6 g of 17β-acetoxy-1α-methyl-androstan-3-one (95% of theory) of a melting point of 181° C. is obtained.
Reaction SMILES: Cl[C:2]1[C:3]2[S:18][C:17]([NH2:19])=[N:16][C:4]=2[N:5]=[C:6]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]=1.[NH2:20][C@H:21]([CH3:31])[CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[NH2:19][C:17]1[S:18][C:3]2[C:2]([NH:20][C@H:21]([CH3:31])[CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[N:7][C:6]([S:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[N:5][C:4]=2[N:16]=1
Reactant: C[C@@H](N)CNC(=O)OC(C)(C)C
Reactant: Nc1nc2nc(SCc3ccccc3)nc(Cl)c2s1
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](CNC(=O)OC(C)(C)C)Nc1nc(SCc2ccccc2)nc2nc(N)sc12
Temperature: 110 °C

Procedure:
The product from example 1 step c) (2.0 g) and the product from example 25 step d) (1.3 g) in a solvent of NMP (10 ml) containing Hunigs base (3 ml) was heated at 110° C. for 10 hours. The mixture was evaporated to dryness and purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant) to give the subtitle compound (1.9 g).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH:4]1[NH:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[CH2:7][C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]1=2.[C:19]([Br:21])#[N:20].CCOCC>C(O)C.O1CCCC1>[BrH:21].[CH3:1][N:2]1[CH2:3][CH:4]2[C:5]3[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=3[CH2:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[N:10]2[C:19]1=[NH:20]
Reactant: CNCC1Nc2ccccc2Cc2ccccc21
Reactant: N#CBr
Solvent: CCO
Solvent: C1CCOC1
Solvent: CCOCC
Product: Br
Product: CN1CC2c3ccccc3Cc3ccccc3N2C1=N

Procedure:
A suspension of 7.15 gm (0.03 mol) of 6-methylaminomethyl-6,11-dihydro-5H-dibenz-[b,e]-azepine [formula II; R1 to R4 =H; R6 =--CH3 ; X=--CH2 --; broken line=single bond] in 70 ml of absolute ethanol was mixed with a solution of 3.2 gum (0.03 mol) of bromocyanogen in 8 ml of absolute tetrahydrofuran, while stirring. Accompanied by a slightly exothermic reaction, a solution was formed which was stirred after four hours of standing at ambient temperature. The reaction solution was then mixed with ether. The crystals thus obtained were suction-filtered off and dried.
Reaction SMILES: C(N(CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[O:25]=[C:26]1[NH:30][CH2:29][C@@H:28]([C:31]([OH:33])=O)[O:27]1.[N+]([O-])(O)=O.[N+:38]([O:41][CH2:42][CH2:43][NH2:44])([O-:40])=[O:39]>O1CCCC1>[N+:38]([O:41][CH2:42][CH2:43][NH:44][C:31]([C@H:28]1[O:27][C:26](=[O:25])[NH:30][CH2:29]1)=[O:33])([O-:40])=[O:39]
Reactant: NCCO[N+](=O)[O-]
Reactant: O=C1NC[C@@H](C(=O)O)O1
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Solvent: O=[N+]([O-])O
Solvent: CCN(CC)CC
Product: O=C1NC[C@@H](C(=O)NCCO[N+](=O)[O-])O1
Temperature: 25 °C
Reaction time: 6 h
Yield: 43.4 %

Procedure:
0.35 ml of triethylamine and 0.22 ml of diphenylphosphoryl azide were added, whilst ice-cooling and stirring, to a suspension of 110 mg of (5S)-2-oxooxazolidine-5-carboxylic acid (prepared by a procedure similar to that described in Preparation 3) and 170 mg of N-(2-nitrooxyethyl)amine nitrate in 10 ml of dry tetrahydrofuran, and the resulting mixture was stirred at room temperature for 6 hours. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography through silica gel, using ethyl acetate as the eluent. The pale yellow oil thus obtained was triturated with ethyl acetate, and the resulting precipitate was collected by filtration and washed, to give 79.8 mg of the title compound as a colorless powder, melting at 101°-103° C.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][C:5]1[CH:12]=[CH:11][C:9]([OH:10])=[C:7]([OH:8])[CH:6]=1.[C:13]([NH:16][C@H:17]([C:22](O)=[O:23])[CH2:18][CH2:19][S:20][CH3:21])(=[O:15])[CH3:14].C(N(CC)CC)C>CN(C)C=O>[C:13]([NH:16][C@H:17]([C:22]([NH:2][CH2:3][CH2:4][C:5]1[CH:12]=[CH:11][C:9]([OH:10])=[C:7]([OH:8])[CH:6]=1)=[O:23])[CH2:18][CH2:19][S:20][CH3:21])(=[O:15])[CH3:14]
Reactant: NCCc1ccc(O)c(O)c1
Reactant: CSCC[C@H](NC(C)=O)C(=O)O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CSCC[C@H](NC(C)=O)C(=O)NCCc1ccc(O)c(O)c1

Procedure:
2.85 g of dopamine hydrochloride, 4.32 g of N-hydroxysuccinimide ester of N-acetyl-L-methionine, 3.04 g of triethylamine and 15 ml of dimethylformamide are treated in the same manner as described in Example 5. After the reaction, the mixture is condensed under reduced pressure to remove solvent. The residue is dissolve in ethyl acetate, washed with water and dried. The solution is condensed to remove solvent. 3.1 g of N-(N-acetyl-L-methionyl)-dopamine are obtained as caramel.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[NH:11][C:10]3([CH2:15][CH2:14][CH2:13][CH2:12]3)[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=CC(S(O[CH2:33][CH2:34][O:35][CH:36]([CH3:38])[CH3:37])(=O)=O)=CC=1.O>CC#N.C(OCC)(=O)C>[Cl:1][C:2]1[N:3]=[C:4]2[N:11]([CH2:33][CH2:34][O:35][CH:36]([CH3:38])[CH3:37])[C:10]3([CH2:15][CH2:14][CH2:13][CH2:12]3)[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)OCCOC(C)C)cc1
Reactant: O=c1cc(Cl)nc2n1CC1(CCCC1)N2
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)OCCN1c2nc(Cl)cc(=O)n2CC12CCCC2
Temperature: 65 °C
Yield: 61.5 %

Procedure:
0.200 g of 7′-chlorospiro[cyclopentane-1,2′-imidazo[1,2-a]pyrimidin]-5′-one are suspended in 7 mL of CH3CN, 0.70 g of cesium carbonate and 0.55 g of 2-isopropoxyethyl 4-methylbenzenesulfonate are added. The mixture is heated to 65° C. for 36 h. Water, ethyl acetate are added and then after decantation, the organic phase is dried with magnesium sulfate and then evaporated. The crude is purified by flash chromatography on silica gel (CH2Cl2/MeOH, 99/1). 0.17 g (yield=47%) of 7′-chloro-1′-(2-isopropoxyethyl)-spiro[cyclopentane-1,2′-imidazo[1,2-a]pyrimidin]-5′-one are obtained as a brown powder and including the following characteristics: