Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]([CH3:10])=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.Cl[CH2:19][C:20]1[CH:32]=[CH:31][C:30]([CH2:33][CH3:34])=[CH:29][C:21]=1[O:22][CH:23]([CH3:28])[C:24]([O:26][CH3:27])=[O:25].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:33]([C:30]1[CH:31]=[CH:32][C:20]([CH2:19][O:17][C:14]2[CH:13]=[CH:12][C:11]([C:3]3[N:4]=[C:5]([CH3:10])[N:6]([CH:7]([CH3:9])[CH3:8])[C:2]=3[Cl:1])=[CH:16][CH:15]=2)=[C:21]([CH:29]=1)[O:22][CH:23]([CH3:28])[C:24]([O:26][CH3:27])=[O:25])[CH3:34]
Reactant: CCc1ccc(CCl)c(OC(C)C(=O)OC)c1
Reactant: Cc1nc(-c2ccc(O)cc2)c(Cl)n1C(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCc1ccc(COc2ccc(-c3nc(C)n(C(C)C)c3Cl)cc2)c(OC(C)C(=O)OC)c1

Procedure:
This compound is prepared in a manner analogous to that of Step I of Example 1, using 0.75 gram (0.0030 mole) of 4-[5-chloro-1-(1-methylethyl)-2-methylimidazol-4-yl]phenol, 0.84 gram (0.0036 mole) of methyl 2-(2-chlormethyl-5-ethylphenoxy)propanoate (prepared in Steps A through C of Example 1), and 0.62 gram (0.0045 mole) of potassium carbonate in N,N-dimethylformamide, yielding the title compound.
Reaction SMILES: C[O-].[Na+:3].[SH:4][CH:5]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:6]([OH:8])=[O:7].C[O-].Cl.[N:18]1[CH:23]=[CH:22][C:21]([CH2:24]Cl)=[CH:20][CH:19]=1>C(O)C>[C:9]1([CH:5]([S:4][CH2:24][C:21]2[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=2)[C:6]([O-:8])=[O:7])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Na+:3]
Reactant: O=C(O)C(S)c1ccccc1
Reactant: ClCc1ccncc1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: O=C([O-])C(SCc1ccncc1)c1ccccc1
Reaction time: 0.08 h
Yield: 99.9 %

Procedure:
Sodium methoxide (6.8 g., 0.124 mole) was dissolved in 150 ml. of ethanol and cooled to 0° C. A solution of alpha-mercaptophenylacetic acid (7.0 g., 0.042 moles) in 50 ml. of ethanol was added over a period of 5 minutes to the cold methoxide solution. After 5 minutes, a slurry of 4-picolylchloride hydrochloride (6.83 g., 0.042 moles) slurried in 50 ml. of ethanol was then added over 5 minutes. The reaction was removed from the ice bath and left to stir for approximately 60 hours. The reaction mixture was filtered and evaporated to yield sodium phenyl(4-picolylthio)acetate (11.8 g.; waxy solid; ir: 3.0, 6.1, 6.25, 7.3, 13.6μ) used directly in the next step.
Reaction SMILES: [CH3:1][C:2]1[C:3]([S:8]([N:11]([CH2:19][C:20](O)=[O:21])[C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[N:28]=1)[CH3:24]>>[CH2:23]([N:25]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[N:28]=1)[C:20](=[O:21])[CH2:19][N:11]([S:8]([C:3]1[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=1)(=[O:9])=[O:10])[C:12]1[CH:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=1)[CH3:24]
Reactant: Cc1ccc(N(CC(=O)O)S(=O)(=O)c2ncccc2C)cc1
Reactant: CCNCc1cccc(C)n1
Product: CCN(Cc1cccc(C)n1)C(=O)CN(c1ccc(C)cc1)S(=O)(=O)c1ncccc1C

Procedure:
prepared by reaction of [(3-methyl-pyridine-2-sulfonyl)-p-tolyl-amino]-acetic acid with ethyl-(6-methyl-pyridin-2-ylmethyl)-amine
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:15](=[N:16][CH:17]=2)[N:14]([C:18]([NH2:20])=[O:19])[CH2:13][CH2:12][CH2:11]3)[CH:5]=[N:6][CH:7]=1.[Br:21]C1C=CN=CC=1I>>[Br:21][C:3]1[CH:2]=[CH:7][N:6]=[CH:5][C:4]=1[C:8]1[CH:9]=[C:10]2[C:15](=[N:16][CH:17]=1)[N:14]([C:18]([NH2:20])=[O:19])[CH2:13][CH2:12][CH2:11]2
Reactant: Brc1ccncc1I
Reactant: NC(=O)N1CCCc2cc(-c3cncc(Br)c3)cnc21
Product: NC(=O)N1CCCc2cc(-c3cnccc3Br)cnc21

Procedure:
6-(4-Bromo-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide is synthesized using the same procedures for preparing 6-(5-bromo-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide in Example 15, replacing 3,5-dibromo-pyridine with 4-bromo-3-iodo-pyridine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1.[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C@H:11]1[CH2:16][CH2:15][C@H:14]([NH:25][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:13][CH2:12]1
Reactant: NCc1ccccc1
Reactant: O=C1CCC(c2c[nH]c3ccc(F)cc23)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: Fc1ccc2[nH]cc([C@H]3CC[C@H](NCc4ccccc4)CC3)c2c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 4-(5-fluoro-1H-indol-3-yl)-cyclohexanone (2.31 g, mmol), benzylamine (1.1 g, 10 mmol), sodium triacetoxyborohydride (3.1 g, 14 mmol) and acetic acid (0.57 ml) in 1,2-dichloroethane (30 ml) was allowed to stir at room temperature for 4 hours. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3×60 ml) and washed with brine (3×60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (ethyl acetate-hexanes-methanol-ammonium hydroxide: 50:50:5:0.5) afforded 0.51 g (16%) of product as a white solid: mp 131-133° C. MS EI m/e 322 (M+)
Reaction SMILES: [CH2:1]([O:3][P:4]([CH2:9][C:10]([O-:12])=[O:11])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[H-].[Na+].[CH2:15](Br)[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[C:17]([O:11][C:10](=[O:12])[CH:9]([P:4]([O:3][CH2:1][CH3:2])([O:6][CH2:7][CH3:8])=[O:5])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:22])([CH3:18])[CH3:16]
Reactant: BrCCc1ccccc1
Reactant: CCOP(=O)(CC(=O)[O-])OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOP(=O)(OCC)C(CCc1ccccc1)C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
Diethylphosphonoacetate (1.00 g, 3.96 mmol) was added drop wise at 0° C. to a stirring suspension of sodium hydride (0.095 g, 3.96 mmol) in anhydrous THF (50 mL). The mixture was then allowed to stir for 10 minutes at 0° C. and then for 1 hour at room temperature before it was cooled again to 0° C. followed by the addition of phenethyl bromide (0.73 g, 3.96 mmol). The mixture was then allowed to proceed for 24 hours at room temperature. The solvent was evaporated and the residue was taken-up in water and extracted 4 times with ethyl acetate. The organic extracts were combined, washed with water and brine, dried using magnesium sulfate, filtered and evaporated. The crude residue was purified by flash chromatography (ethyl acetate in hexanes, 10%–50%) to afford the desired compound as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.18 (m, 2H), 7.09 (m, 2H), 4.07–3.99 (m, 4H), 2.82–2.72 (m, 1H), 2.69–2.60 (m, 1H), 2.54–2.45 (m, 1H), 2.25–2.12 (m, 1H), 2.08–1.94 (m, 1H), 1.41 (s, 9H), 1.24–1.18 (m, 6H); 13C (CDCl3, 400 MHz) δ 167.7, 140.4, 128.3, 128.2, 125.9, 81.5, 62.2, 46.3, 45.0, 34.1, 28.5, 27.7, 16.1; 31P (CDCl3, 400 MHz) δ 23.7. HRMS calcd. for C18H29O5P 356.1753. found 356.1757.
Reaction SMILES: [OH-].[Li+].[CH3:3][C:4]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][N:18]=2)[C:12]([O:14]C)=[O:13])[O:6][N:5]=1>C(O)C>[CH3:3][C:4]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][N:18]=2)[C:12]([OH:14])=[O:13])[O:6][N:5]=1
Reactant: COC(=O)c1ccnc(-c2nc(C)no2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Product: Cc1noc(-c2cc(C(=O)O)ccn2)n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 89 %

Procedure:
A mixture of lithium hydroxide (15 g, 0.35 mol), ethanol (500 mL) and methyl 2-(3-methyl-1,2,4-oxadiazol-5-yl)isonicotinate (52 g, 0.23 mol) were stirred at room temperature for 5 hours, then mixture was concentrated in vacuo. Water was added then extracted with ethyl acetate. The water layer was brought to pH 1.5 with aqueous 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was concentrated in vacuo to afford the title compound as a white solid (42 g). 1H NMR (300 MHz, DMSO-d6) δ ppm 14.08 (br s, 1H) 9.00-8.98 (m, 1 H) 8.50 (s, 1H) 8.09-8.07 (m, 1H), 2.46 (s, 3H).
Reaction SMILES: [C:1](Cl)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[NH2:15][CH2:16][CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][OH:27])[CH2:21][CH2:20]1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[OH:27][CH2:26][CH2:25][N:22]1[CH2:23][CH2:24][N:19]([CH2:18][CH2:17][CH2:16][NH:15][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:20][CH2:21]1
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: NCCCN1CCN(CCO)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCC(=O)NCCCN1CCN(CCO)CC1
Temperature: 0 °C

Procedure:
A 50 mL chloroform solution of 2.45 g. (0.0112 mol) of dodecanoyl chloride was added dropwise under argon to an ice cold 50 mL chloroform solution of 2.12 g. (0.0113 mol) of N-(3-aminopropyl)-N'-(2-hydroxyethyl) piperazine and stirred for one hour maintaining the temperature between 2°-4° C. This reaction mixture was then treated with 100 mL of aqueous sodium bicarbonate and extracted with chloroform (2×50 mL). The combined chloroform layers were washed with aqueous sodium bicarbonate (2×50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The remaining solid was crystallized in ethyl acetate/hexane to yield 1.69 g. (40.8%)of the subject product.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]2[O:11][CH2:12][O:13][C:5]=2[CH:4]=1.II.C[O:17][B:18](OC)[O:19]C.Cl>O1CCCC1>[CH3:10][O:9][C:7]1[C:6]2[O:11][CH2:12][O:13][C:5]=2[CH:4]=[C:3]([B:18]([OH:19])[OH:17])[CH:8]=1
Reactant: COc1cc(Br)cc2c1OCO2
Reactant: COB(OC)OC
Agent: Cl
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Product: COc1cc(B(O)O)cc2c1OCO2
Temperature: -78 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
To tetrahydrofuran (40 mL) was added magnesium turnings (2.33 g, 95.8 mmol), 1-bromo-3,4-methylenedioxy-5-methoxybenzene (21.7 g, 93.9 mmol) and a catalytic amount of iodine. Following vigorous reaction, the metal was consumed, and the solution was added to a solution of trimethylborate (38 mL, 334 mmol) in tetrahydrofuran (100 mL) at −78° C. over 45 minutes. The mixture was stirred at −78° C. for an additional 2 hours, then at 25° C. overnight. To the mixture was added 1N HCl (200 mL) followed by stirring at 25° C. for 3 days. The solvent was removed in vacuo, and the suspension was extracted with ethyl ether. The ether phase was washed with brine, and the product was extracted into 0.5N NaOH. The NaOH solution was washed with ethyl ether and acidified to pH 1 with 2N HCl. The acidified aqueous phase was extracted with ethyl ether, washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to a brown solid, 7.43 g, 40% yield. The material was of sufficient purity to be used in subsequent preparations.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][CH2:26][F:27])[C@H:9]1[CH2:13][CH2:12][N:11](C(OCC2C=CC=CC=2)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+].[H][H]>CO.[Pd]>[F:27][CH2:26][CH2:25][CH2:24][N:8]([C@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N(CCCF)[C@H]1CCN(C(=O)OCc2ccccc2)C1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: CC(C)(C)OC(=O)N(CCCF)[C@H]1CCNC1

Procedure:
To a solution of (S)-benzyl 3-(tert-butoxycarbonyl(3-fluoropropyl)amino)pyrrolidine-1-carboxylate (611 mg, 1.6 mmol) in methanol (6.5 mL) was added ammonium formate (1.1 g, 18 mmol) followed palladium on carbon (10% w/w, 479 mg, 0.22 mmol). The reaction mixture was stirred at ambient temperature under a balloon of hydrogen for 1 hour, then degassed and filtered over a pad of celite. The filtrate was concentrated in vacuo to afford a residue, which was used in the next step without any further purification.
Reaction SMILES: [CH3:1][N:2]1[C:10]([CH:11]=O)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:19]1[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]1[CH3:28])=[N:6][C:7]=2[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[CH3:29][S:30]([CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)(=[O:32])=[O:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][N:2]1[C:10]([CH2:11][N:38]2[CH2:37][CH2:36][N:35]([CH2:34][CH2:33][S:30]([CH3:29])(=[O:31])=[O:32])[CH2:40][CH2:39]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:19]1[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]1[CH3:28])=[N:6][C:7]=2[N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1
Reactant: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C=O)n(C)c2n1
Reactant: CS(=O)(=O)CCN1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCN(CCS(C)(=O)=O)CC3)n(C)c2n1
Reaction time: 64 h

Procedure:
A mixture of 9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (60 mg, 0.16 mmol), 1-(2-methanesulfonylethyl)piperazine (37 mg, 0.19 mmol) and 4 Å powdered molecular sieves (100 mg) in DCE (4 mL) was stirred at room temperature for 4 h before the addition of sodium triacetoxyborohydride (67 mg, 0.32 mmol). The reaction mixture was stirred for 64 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 329 as a cream solid (55 mg, 62%). LCMS (Method G): RT 5.54 min [M+H]+ 554.3. 1H NMR (CDCl3, 400 MHz): δ 8.11-8.06 (m, 1 H); 7.74-7.70 (m, 1 H); 7.30-7.25 (m, 2 H); 4.35 (m, 4 H); 3.90-3.82 (m, 7 H); 3.76 (s, 2 H); 3.15 (t, J=6.4 Hz, 2 H); 3.04 (s, 3 H); 2.95 (s, 3 H); 2.90 (t, J=6.4 Hz, 2 H) and 2.57 (m, 8 H)
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[CH2:5][NH:6][CH2:7][CH2:8][NH:9][S:10]([C:13]1[S:14][C:15]([C:18]2[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=2[Cl:25])=[N:16][N:17]=1)(=[O:12])=[O:11])[CH3:2].[N:27]1([CH2:36][C:37](O)=[O:38])[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]1=[O:29]>>[CH2:1]([O:3][C:4](=[O:26])[CH2:5][N:6]([CH2:7][CH2:8][NH:9][S:10]([C:13]1[S:14][C:15]([C:18]2[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=2[Cl:25])=[N:16][N:17]=1)(=[O:12])=[O:11])[C:37](=[O:38])[CH2:36][N:27]1[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]1=[O:29])[CH3:2]
Reactant: CCOC(=O)CNCCNS(=O)(=O)c1nnc(-c2cc(Cl)ccc2Cl)s1
Reactant: Cc1cn(CC(=O)O)c(=O)[nH]c1=O
Product: CCOC(=O)CN(CCNS(=O)(=O)c1nnc(-c2cc(Cl)ccc2Cl)s1)C(=O)Cn1cc(C)c(=O)[nH]c1=O

Procedure:
The title compound was synthesized by the reaction of N-{2-[5-(2,5-dichlorophenyl)-1,3,4-thiadiazole-2-sulfonylamino]-ethyl}-glycine ethyl ester with (thymin-1-yl)-acetic acid as per the procedure of example 13. 1H NMR (500 MHz; DMSO-d6) δ 11.27 (s, 0.6H), 11.25 (s, 0.4H), 9.13 (brs, 1H), 8.26 (d, 0.4H), 8.25 (d, 0.6H), 7.81–7.74 (m, 2H), 7.32 (s, 0.6H), 7.23 (s, 0.4H), 4.63 (s, 1.2H), 4.47 (s, 0.8H), 4.32 (s, 0.8H), 4.16 (q, 0.8H), 4.06 (q, 1.2H), 4.04 (s, 1.2H), 3.55 (t, 1.2H), 3.45–3.38 (m, 2H), 3.25 (t, 0.8H), 1.73 (s, 3H), 1.22 (t, 1.2H), 1.16 (t, 1.8H).
Reaction SMILES: [F:1][C:2]([F:29])([S:25]([NH2:28])(=[O:27])=[O:26])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10].[OH-].[Li+:31]>O>[C:2]([S:25]([NH:28][Li:31])(=[O:27])=[O:26])([C:3]([C:4]([C:5]([C:6]([C:7]([C:8]([C:9]([F:12])([F:11])[F:10])([F:14])[F:13])([F:16])[F:15])([F:18])[F:17])([F:19])[F:20])([F:22])[F:21])([F:23])[F:24])([F:1])[F:29]
Reactant: NS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: [Li+]
Agent: [OH-]
Solvent: O
Product: [Li]NS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
49.4 g (0.099 mol) of perfluorooctane sulphonamide and 2.37 g (0.099 mol) of lithium hydroxide were introduced into 448 g of water and dissolved at ca. about 50° C. with stirring. A 10% solution of C8F17SO2NHLi was obtained.
Reaction SMILES: C([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]([C:26]#[N:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9]1)C1C=CC=CC=1.C(O)(=O)C(O)=O.[H][H]>[C].[Pd].C(O)C>[C:26]([C:13]([C@@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)#[N:27]
Reactant: [H][H]
Reactant: N#CC(c1ccccc1)(c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
Agent: [Pd]
Agent: O=C(O)C(=O)O
Solvent: CCO
Product: N#CC(c1ccccc1)(c1ccccc1)[C@@H]1CCNC1
Temperature: 60 °C
Reaction time: 3.5 h

Procedure:
The procedure of Example 1 was followed except that the autoclave was charged with 3.9 g of 79% pure (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine, 3.1 ml of ethanol, 786 mg of oxalic acid and 158 mg of moist 5% palladium-carbon (water content 52% by weight) and that hydrogen was introduced thereinto and the autoclave was heated to thereby raise the temperature to 60° C. and the pressure to 203 kPa and the reaction was allowed to proceed for 3.5 hours. (S)-3-(1-Cyano-1,1-diphenylmethyl)-pyrrolidine was obtained in a yield of 70 mole percent.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:49]=[CH:50][CH:51]=1)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[N:25]=[CH:24][C:23]([N:26]5[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]5)=[CH:22][CH:21]=4)[CH:18]=3)[N:13]([S:39]([C:42]3[CH:48]=[CH:47][C:45]([CH3:46])=[CH:44][CH:43]=3)(=[O:41])=[O:40])[CH:12]=2)[CH:8]=[N:7]1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:49]=[CH:50][CH:51]=1)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:21]=[CH:22][C:23]([N:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]5)=[CH:24][N:25]=4)[CH:18]=3)[N:13]([S:39]([C:42]3[CH:48]=[CH:47][C:45]([CH3:46])=[CH:44][CH:43]=3)(=[O:41])=[O:40])[CH:12]=2)[CH:8]=[N:7]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3)c3cc(-c4ccc(N5CCN(C(=O)OC(C)(C)C)CC5)cn4)cnc32)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3)c3cc(-c4ccc(N5CCNCC5)cn4)cnc32)cc1
Yield: 87.4 %

Procedure:
Using similar reaction conditions as described in step-ii of example-7, tert-butyl 4-(6-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-3-yl)piperazine-1-carboxylate (800 mg, 1.130 mmol) was deprotected in TFA/DCM (3/10 ml) to afford 600 mg (87.4% yield) of the titled compound. MS: m/z=608.2 (M+1).
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[CH:11](I)([CH3:13])[CH3:12].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:12][CH:11]([N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1)[CH3:13]
Reactant: CC(C)I
Reactant: c1ccc2c(c1)CCCN2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)N1CCCc2ccccc21
Temperature: 60 °C
Yield: 74741.8 %

Procedure:
13.8 g (0.1 mmol) of 1,2,3,4-tetrahydroquinoline was dissolved in 60 ml of N,N-dimethylformamide, followed by the addition of 21.1 g (0.124 mmol) of isopropyl iodide and 20.6 g (0.208 mol) of potassium carbonate. The obtained mixture was stirred under heating at 60° C. for 5 hours. Water was added to the resulting reaction mixture, followed by the extraction with ethyl acetate. The organic phase was washed with a saturated aqueous solution of common salt, dried over anhydrous magnesium sulfate, and concentrated in a vacuum. The obtained residue was purified by silica gel column chromatography (3% ethyl acetate/n-hexane) to give 13.1 g of the title compound as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]2[NH:10][CH:11]=[CH:12][C:3]=12.[H-].[Na+].[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>CN(C)C=O>[Br:1][C:2]1[CH:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]2[N:10]([S:22]([C:19]3[CH:20]=[CH:21][C:16]([CH3:15])=[CH:17][CH:18]=3)(=[O:24])=[O:23])[CH:11]=[CH:12][C:3]=12
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COc1ncc(Br)c2cc[nH]c12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ncc(Br)c2ccn(S(=O)(=O)c3ccc(C)cc3)c12
Reaction time: 0.17 h
Yield: 99.5 %

Procedure:
A solution of Example 1b (7.42 g, 32.7 mmol) in dimethylformamide (235 mL) was stirred at room temperature. To this solution was added sodium hydride (1.18 g, 1.96 g of 60% dispersion in oil, 49.0 mmol), and the reaction mixture was stirred for 10 min. P-toluenesulfonyl chloride (9.35 g, 49.0 mmol) was then added portion-wise, and the mixture was stirred at room temperature under nitrogen for 16 hours. The reaction mixture was quenched carefully with water and the resulting beige solid collected by vacuum filtration on a Buchner funnel, and washed with water. The solid was collected and dried in a vacuum oven at 50° C. to provide 12.4 g (100%) of the title compound.
Reaction SMILES: [CH:1]1([N:6]2[CH2:11][CH2:10][N:9]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][N:19]=3)[C:15]#[N:16])[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H]>CO.C(OCC)(=O)C.N.[Ni]>[CH:1]1([N:6]2[CH2:11][CH2:10][N:9]([C:12]3[CH:13]=[C:14]([CH2:15][NH2:16])[CH:17]=[CH:18][N:19]=3)[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: N#Cc1ccnc(N2CCN(C3CCCC3)CC2)c1
Agent: [Ni]
Agent: N
Solvent: CO
Solvent: CCOC(C)=O
Product: NCc1ccnc(N2CCN(C3CCCC3)CC2)c1

Procedure:
A solution of 2.8 g (11 mmol) 2-(4-cyclopentyl-piperazin-1-yl)-isonicotinonitrile in 10 ml methanol, 15 ml ethyl acetate and 5 ml ammonia was hydrogenated over Raney Nickel with 1 bar hydrogen at 30° C. for 4 h. The mixture was filtered and the residue was washed with 20 ml ethyl acetate three times. After evaporation of the organic phase the residue was purified with preparative HPLC on reversed phase to yield after evaporation of the combined product fractions 1.21 g (42%) of the title compound as yellow solid. (m/e): 261.3 (MH+; 100%).
Reaction SMILES: C([O:3][C:4](=O)[C:5](=[O:21])[CH:6]([C:19]#[N:20])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])C.C([OH:25])C.O>CS(O)(=O)=O>[OH:21][C:5]1[C:4](=[O:3])[NH:20][C:19](=[O:25])[C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCC(C#N)C(=O)C(=O)OCC
Reactant: CCO
Agent: CS(=O)(=O)O
Solvent: O
Product: CCCCCCCCCCCCC1=C(O)C(=O)NC1=O
Reaction time: 8 h

Procedure:
1 G. of the 3-cyano-2-oxopentadecanoic acid ethyl ester is dissolved in 5 ml of methanesulfonic acid and the mixture allowed to stand overnight at room temperature. The reaction mixture is worked up by first pouring into ethanol-water (20 ml ethanol--5 ml water). After standing for several hours, the ethanol is removed by evaporation. The aqueous acidic residue is diluted further with water and then extracted with chloroform. The chloroform solution is then washed well with water, dried and evaporated to give the desired 3-hydroxy-4-(n-dodecyl)-3-pyrroline-2,5-dione. Recrystallization from hexane or cyclohexane provides pure 3-hydroxy-4-(n-dodecyl)-3-pyrroline-2,5-dione, mp 108°-109° C.