Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[Sn]Cl.Cl.[CH2:5]([C:7]1[C:15]2[S:14][CH:13]=[N:12][C:11]=2[CH:10]=[C:9]([N+:16]([O-])=O)[CH:8]=1)[CH3:6].[OH-].[Na+]>>[CH2:5]([C:7]1[C:15]2[S:14][CH:13]=[N:12][C:11]=2[CH:10]=[C:9]([NH2:16])[CH:8]=1)[CH3:6]
Reactant: CCc1cc([N+](=O)[O-])cc2ncsc12
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Product: CCc1cc(N)cc2ncsc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.4 %

Procedure:
To a solution of SnCl2 (1.5 g, 1.9 mmol) and 5.0 mL of HCl was added 7-ethyl-5-nitrobenzothiazole (0.12 g, 0.57 mmol) in a portion and resulting reaction mixture was stirred for 1 h at 25° C. The reaction mixture was basified with aqueous NaOH and extracted with EtOAc and CHCl3. Combined organic layers were dried over Na2SO4 and concentrated in vacuo, yielding an oil (0.10 g, >95%) which was identified as the desired amine (>95% pure) and subjected to a following reaction without further purification.
Reaction SMILES: [CH2:1]([C:3]1[C:4](=[O:26])[N:5]=[C:6]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[N:7]([CH2:9][C:10]([O:12]C(C)(C)C)=[O:11])[CH:8]=1)[CH3:2]>FC(F)(F)C(O)=O>[CH2:1]([C:3]1[C:4](=[O:26])[N:5]=[C:6]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[N:7]([CH2:9][C:10]([OH:12])=[O:11])[CH:8]=1)[CH3:2]
Reactant: CCc1cn(CC(=O)OC(C)(C)C)c(CCc2ccc(F)cc2)nc1=O
Solvent: O=C(O)C(F)(F)F
Product: CCc1cn(CC(=O)O)c(CCc2ccc(F)cc2)nc1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 92.7 %

Procedure:
t-Butyl 2-(5-ethyl-2-[2-(4-fluorophenyl)ethyl]-4-oxo-4H-pyrimidin-1-yl)acetate (Int B51) (1 g) was dissolved in trifluoroacetic acid (10 ml) and stirred for 3 h at room temperature. The solution was concentrated under vacuum to a foam. Trituration with ether afforded the title compound as a colourless solid, (0.783 g, 93%), 1H-NMR (DMSO) δ 1.05 (3H, t, J=7.5Hz), 2.24 (2H, q, J=7.5 Hz), 2.79 (2H, m), 2.93 (2H, m), 4.79 (2H, s), 7.11 (2H, m), 7.30 (2H, m), 7.53 (1H, s) and 12.48 (1H, br. s). (APCI−) Found (M−1)=303, C16H17FN2O3 requires 304.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.[C:17]1(=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C([BH3-])#N.[Na+]>CO>[CH2:10]([O:9][C:7]([N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:3]1)=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C1CCCCC1
Reactant: N[C@H]1CCN(C(=O)OCc2ccccc2)C1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: O=C(OCc1ccccc1)N1CC[C@H](NC2CCCCC2)C1
Reaction time: 3 h
Yield: 73 %

Procedure:
To a stirred solution of (3S)-3-amino-pyrrolidine-1-carboxylic acid, benzyl ester (4.40 g, 20 mmol) in methanol (120 mL) was added cyclohexanone (2.75 g, 28 mmol) followed by sodium cyanoborohydride (1.50 g, 24 mmol) at room temprerature. After 3 h, the reaction mixture was concentrated, diluted with dichloromethane (200 mL), washed with aqueous sodium bicarbonate (100 mL), 1 N sodium hydroxide (50 mL), brine (50 mL) and dried (Na2SO4). The crude was purified by flash chromatography using 5% methanol in dichloromethane to give (3S)-3-cyclohexylamino-pyrrolidine-1-carboxylic acid benzyl ester in 73% yield. 1H NMR (300 MHz, CDCl3): in δ 7.36–7.26 (m, 5H), 5.11 (s, 2H), 3.65–3.35 (m, 4H), 3.1–2.95 (m, 1H), 2.5–2.38 (m, 1H), 2.11–1.98 (m, 1H), 1.92–1.54 (m, 5H), 1.31–0.95 (m, 6H); 13C NMR (300 MHz, CDCl3): in δ 154.9, 137.1, 128.4, 127.8, 66.7, 55.0, 54.6, 53.8, 52.6, 44.7, 44.3, 34.1, 32.8, 32.0, 26.1, 25.1; MS (ESI+), 303 (M+H); Rf=1.16.
Reaction SMILES: CS(O[CH2:6][C@@H:7]([NH:14]C(OC(C)(C)C)=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=O)=O.[N-:22]=[N+:23]=[N-:24].[Na+].O>CN(C=O)C>[N:22]([CH2:6][C@@H:7]([NH2:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[N+:23]=[N-:24]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N[C@H](COS(C)(=O)=O)c1ccccc1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: [N-]=[N+]=NC[C@@H](N)c1ccccc1
Temperature: 65 °C
Yield: 135.7 %

Procedure:
To a solution of (2S)-2-[(tert-Butoxycabonyl)amino]-2-phenylethyl methanesulfonate (ref. Org. Syn. 2008, 85, 219) (5.0 g, 15.9 mmol) in DMF (40 mL) was added solid sodium azide (2.2 g, 33 mmol). The reaction was heated to 65° C. for 48 h. The reaction was cooled to room temperature and water was added to provide a white precipitate. The precipitate was filtered and dried under vacuum to afford the desired compound (3.5 g, 85%). To a solution of azide (0.75 g, 2.86 mmol) in THF (14 mL) was added HCl (as a 4M solution in dioxane, 7 mL, 28 mmol). The reaction was stirred at RT for 16 hours, then solvents were removed under reduced pressure to give the amine hydrochloride, which was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[C:3]1[CH:4]=[C:5]([CH:23]=[CH:24][CH:25]=1)[CH2:6][O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]/[CH:16]=[CH:17]/[C:18]([O:20]CC)=[O:19].[OH-].[K+]>O.C(O)C>[F:1][C:2]([F:26])([F:27])[C:3]1[CH:4]=[C:5]([CH:23]=[CH:24][CH:25]=1)[CH2:6][O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]/[CH:16]=[CH:17]/[C:18]([OH:20])=[O:19]
Reactant: CCOC(=O)/C=C/C=C/CCCCCCOCc1cccc(C(F)(F)F)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)/C=C/C=C/CCCCCCOCc1cccc(C(F)(F)F)c1
Yield: 62.4 %

Procedure:
The product of step (c) (1.74 g, 4.5 mmol) was hydrolysed with potassium hydroxide (0.88 g) in water (20 mL) and ethanol (60 mL) at room temperature over 18 hours to give 1.0 g (63% of theory) of 11-(3'trifluoromethylbenzyloxy)-(2E,4E)-undecadienoic acid.
Reaction SMILES: FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:30]3[C:25](=[CH:26][C:27]([O:31][C@H:32]([C:36]4[CH:37]=[N:38][C:39]5[C:44]([CH:45]=4)=[CH:43][CH:42]=[CH:41][CH:40]=5)[C@@H:33]([NH2:35])[CH3:34])=[CH:28][CH:29]=3)[CH:24]=[N:23]2)=[CH:18][CH:17]=1.C(N(CC)CC)C.[CH:53]1([S:56](Cl)(=[O:58])=[O:57])[CH2:55][CH2:54]1>C1COCC1>[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:30]3[C:25](=[CH:26][C:27]([O:31][C@H:32]([C:36]4[CH:37]=[N:38][C:39]5[C:44]([CH:45]=4)=[CH:43][CH:42]=[CH:41][CH:40]=5)[C@@H:33]([NH:35][S:56]([CH:53]4[CH2:55][CH2:54]4)(=[O:58])=[O:57])[CH3:34])=[CH:28][CH:29]=3)[CH:24]=[N:23]2)=[CH:18][CH:17]=1
Reactant: O=S(=O)(Cl)C1CC1
Reactant: C[C@H](N)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1cnc2ccccc2c1
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Product: C[C@H](NS(=O)(=O)C1CC1)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1cnc2ccccc2c1

Procedure:
(1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(quinolin-3-yl)propan-2-amine bis(2,2,2-trifluoroacetate) (42a, 65 mg, 0.10 mmol) was dissolved in THF (1.5 mL), triethylamine (75 μl, 0.54 mmol) was added followed by cyclopropanesulfonyl chloride (15 μl, 0.15 mmol). The reaction mixture was stirred at room temperature, after 1.5 hours another portion of triethylamine (75 μl, 0.54 mmol) and excess of cyclopropanesulfonyl chloride (50 μl, 0.49 mmol) was added. The reaction mixture was left over night at room temperature. Solvent was removed by evaporation and the residual material was purified by HPLC. Yield 18 mg (34%).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][CH:3]=1.C1C(=O)N([Br:16])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][Br:16])[CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc(Br)n1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1cccc(Br)n1
Temperature: 50 °C

Procedure:
To a mixture of 6-bromo-2-methylpyridine (46.5 g, 0.27 mol) in CCl4 (800 mL) was added NBS (53 g, 0.297 mol) and benzoylperoxide (4.7 g) and refluxed for 2 h in presence of light. The reaction mixture was cooled to 50° C. and filtered off the solid succinimide. The filtrate was concentrated and the crude 6-bromo-2-bromomethylpyridine (71 g) was used for next reaction.
Reaction SMILES: [Cl-].[NH4+].[Br:3][C:4]1[CH:5]=[C:6]([N+:11]([O-])=O)[CH:7]=[CH:8][C:9]=1[CH3:10]>O.CO.[Fe]>[Br:3][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[CH3:10])[NH2:11]
Reactant: Cc1ccc([N+](=O)[O-])cc1Br
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Product: Cc1ccc(N)cc1Br

Procedure:
To a suspension of iron (1.5 g, 27.6 mmol) and ammonium chloride (2.46 g, 46 mmol) in water (50 mL) was slowly added a solution of 3-bromo-4-methyl-1-nitrobenzene (1.0 g, 4.6 mmol) in methanol (25 mL). The resulting mixture was refluxed for 2 hours. The solids formed were filtered through celite while the reaction mixture was still hot, the solvent of the clear filtrate was then removed. The crude residue was redissolved in water, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The crude oil was adsorbed on silica gel and purified by flash chromatography on silica gel (hexanes/EtOAc from 95:5 to 50:50). The product, 3-bromo-4-methylaniline, was isolated as pale red oil (462 mg). HPLC Rt 3.425 minutes.
Reaction SMILES: [OH-].[Na+].C([O:5][C:6]([CH:8]1[CH2:13][N:12]([CH3:14])[CH2:11][CH2:10][NH:9]1)=[O:7])C.[N+:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1F)([O-:17])=[O:16]>O.C(O)C>[CH3:14][N:12]1[CH2:11][CH2:10][N:9]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N+:15]([O-:17])=[O:16])[CH:8]([C:6]([OH:5])=[O:7])[CH2:13]1
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: CCOC(=O)C1CN(C)CCN1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CN1CCN(c2ccccc2[N+](=O)[O-])C(C(=O)O)C1

Procedure:
A solution of 6.6 g. (0.164 mole) of sodium hydroxide, 28.2 g. (0.165 mole) of ethyl-4-methylpiperazine-2-carboxylate, 20 ml. of water and 200 ml. of ethanol is refluxed for 3 hours. This solution is then added under nitrogen to a hot stirred solution of o-nitrofluorobenzene in 300 ml. of ethanol and 30 ml. of water. The resultant solution is refluxed for 48 hours, cooled and filtered to give 12.8 g. of yellow product, m.p. 222°-225°. Concentration of the mother liquors to ~100 ml. and adjusting the pH to 6 yields an additional 6.6 g. of product. Further concentration of mother liquors gives yet another 3 g. of product. Total yield is 22.4 g., 51.5%. The analytical sample had m.p. 234° dec.
Reaction SMILES: [CH3:1][N+:2]([O-:4])=[O:3].CO[Na].[CH3:8][N:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1>CCO>[CH3:8][N:9]1[CH2:14][CH2:13][C:12]([CH2:1][N+:2]([O-:4])=[O:3])([OH:15])[CH2:11][CH2:10]1
Reactant: C[N+](=O)[O-]
Reactant: CN1CCC(=O)CC1
Agent: CO[Na]
Solvent: CCO
Product: CN1CCC(O)(C[N+](=O)[O-])CC1
Yield: 40.2 %

Procedure:
CH3NO2 (6.6 mL, 122 mmol) and MeONa (221 mg, 4.1 mmol) was added to a solution of compound 1-methylpiperidin-4-one (10 mL, 81.3 mmol) in EtOH (10 mL). After 30 min more ethanol (15 mL) was added to facilitate stirring. The reaction mixture was stirred at room temperature for 2 days and then filtered through celite. The isolated solid was washed with ether to give the product 1-methyl-4-(nitromethyl)piperidin-4-ol (5.7 g, yield 40.4%). 1H-NMR (DMSO-d6/400 MHz): δ 5.01 (s, 1H), 4.47 (s, 2H), 2.41-2.40 (m, 2H), 2.21-2.15 (m, 2H), 2.12 (s, 3H), 1.64-1.53 (m, 4H).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1
Reactant: OB(O)c1ccccc1Br
Reactant: Brc1cncnc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: Brc1ccccc1-c1cncnc1
Temperature: 100 °C
Yield: 54.2 %

Procedure:
A mixture of 5-bromopyrimidine (500 mg, 3.14 mmol, Aldrich), (2-bromophenyl)boronic acid (947 mg, 4.71 mmol, Aldrich), Pd(PPh3)4 (363 mg, 0.314 mmol, GLR) and potassium carbonate (2.17 g, 15.7 mmol, Qualigens) in 1,4-dioxane:water (5.8 mL:2.9 mL) was degassed for 10 min. The reaction mixture was subjected to microwave heating for 30 minutes at 100° C. After completion, the reaction mixture was diluted with water (10 mL) and ethyl acetate (25 mL). The layers were separated. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 15% ethyl acetate in hexane) to get 5-(2-bromophenyl)pyrimidine (400 mg, 30.5%) as yellow solid. 1H NMR (400 MHz, CDCl3) δ 9.24 (s, 1H), 8.83 (s, 2H), 7.73 (d, J=7.9 Hz, 1H), 7.48-7.42 (m, 1H), 7.33 (d, J=7.4 Hz, 2H); MS (ESI, positive ion) m/z: 234.98 (M+1).
Reaction SMILES: [NH:1]([CH2:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:31](Cl)(=[O:33])[CH3:32].O>CN(C)C=O>[C:31]([N:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)=[O:10])(=[O:33])[CH3:32]
Reactant: O=C(CNc1ccccc1)Nc1ccc(-c2ccncc2)cc1
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)N(CC(=O)Nc1ccc(-c2ccncc2)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-anilino-N-[4-(4-pyridinyl)phenyl]acetamide (50 mg) in N,N-dimethylformamide (1.0 mL) were added triethylamine (0.092 mL) and acetyl chloride (0.0352 mL) at ambient temperature and the mixture was stirred at ambient temperature overnight. Water (3 mL) was added to the mixture and the resulting mixture was extracted with ethyl acetate (5 mL). The organic layer was washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was purified by preparative thin-layer chromatography (10% methanol in chloroform) to afford 2-[acetyl(phenyl)amino]-N-[4-(4-pyridinyl)phenyl]acetamide (46.9 mg) as a white amorphous.
Reaction SMILES: Br[C:2]1[C:3]([CH3:13])=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[O:7][CH2:6][CH2:5]2.[CH2:14]([Sn](CCCC)(CCCC)CCCC)[CH:15]=[CH2:16].[Cl-].[Li+].C1(C)C=CC=CC=1>CCOC(C)=O.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>[CH3:13][C:3]1[C:2]([CH2:16][CH:15]=[CH2:14])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][O:7][C:8]2=[O:12]
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Reactant: Cc1c(Br)ccc2c1CCOC2=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: C=CCc1ccc2c(c1C)CCOC2=O

Procedure:
To a flask charged with 6-Bromo-5-methyl-3,4-dihydro-1H-isochromen-1-one (100 mg, 0.42 mmol), Allyl Tri-n-butyltin (165 mg, 0.50 mmol), Palladium Tetrakis (48 mg, 0.041 mmol), and Lithium Chloride (35 mg, 0.83 mmol) was added Toluene (5 ml). The mixture was sealed with a condenser and purged three times with N2. The mixture was then heated to reflux for 6 hours. TLC and LC showed complete reaction. The reaction was diluted with EtOAc (50 mL), washed with brine, dried over sodium sulfate, adsorbed onto silica, and purified by MPLC (Hex/EtOAc gradient) to furnish the product. LC-MS (IE, m/z): 203 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[S:6][C:5]([C@H:7]2[CH2:12][CH2:11][CH2:10][C@H:9]([C:13]3[S:17][C:16]([NH:18][C:19](=[O:27])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)=[N:15][N:14]=3)[CH2:8]2)=[N:4][N:3]=1.[CH3:28][O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH2:36][C:37](O)=[O:38].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>CN(C)C=O.O>[CH3:28][O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH2:36][C:37]([NH:1][C:2]1[S:6][C:5]([C@H:7]2[CH2:12][CH2:11][CH2:10][C@H:9]([C:13]3[S:17][C:16]([NH:18][C:19](=[O:27])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)=[N:15][N:14]=3)[CH2:8]2)=[N:4][N:3]=1)=[O:38]
Reactant: COc1ccccc1CC(=O)O
Reactant: Nc1nnc([C@H]2CCC[C@H](c3nnc(NC(=O)Cc4ccccn4)s3)C2)s1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1ccccc1CC(=O)Nc1nnc([C@H]2CCC[C@H](c3nnc(NC(=O)Cc4ccccn4)s3)C2)s1

Procedure:
A solution of N-(5-((1S,3S)-3-(5-amino-1,3,4-thiadiazol-2-yl)cyclohexyl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide (50 mg, 0.12 mmol), 2-(2-methoxyphenyl)acetic acid (31.0 mg, 0.19 mmol), HATU (71.0 mg, 0.19 mmol), and N-ethyl-N-isopropylpropan-2-amine (29.0 mg, 0.22 mmol) in N,N-dimethylformamide (5 ml) was stirred at 50 degree overnight. The mixture was poured into water (10 ml), the precipitate was filtered to give the crude product. The crude product was purified by a standard method to give the desired product.
Reaction SMILES: [Br-].[C:2]([NH:10][C:11]1[CH:12]=[N+:13]([CH2:17][CH2:18][C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[CH:14]=[CH:15][CH:16]=1)(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[BH4-].[Na+]>C(O)(C)C>[C:2]([NH:10][CH:11]1[CH2:16][CH2:15][CH2:14][N:13]([CH2:17][CH2:18][C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[CH2:12]1)(=[O:9])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=C(Nc1ccc[n+](CCc2c[nH]c3ccccc23)c1)c1ccccc1
Agent: [BH4-]
Agent: [Br-]
Agent: [Na+]
Solvent: CC(C)O
Product: O=C(NC1CCCN(CCc2c[nH]c3ccccc23)C1)c1ccccc1

Procedure:
Following the procedure of Example 1 above 3-benzamido-1-[2-(3-indolyl)ethyl]-pyridinium bromide upon reduction with sodium borohydride in isopropanol gives the title compound.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]([NH:12][CH:13]2[C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][C:16]=3[CH2:15][CH2:14]2)[N:23]=[C:22]([CH3:26])[N:21]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C:20]4=[O:35])[CH:9]=[CH:8][C:3]=1[CH:4]=[C:5]([CH3:7])[CH3:6].[CH2:36](Br)[C:37]#[CH:38].C(=O)([O-])[O-].[Ca+2]>CC(N(C)C)=O>[F:1][C:2]1[CH:11]=[C:10]([N:12]([CH:13]2[C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][C:16]=3[CH2:15][CH2:14]2)[N:23]=[C:22]([CH3:26])[N:21]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C:20]4=[O:35])[CH2:38][C:37]#[CH:36])[CH:9]=[CH:8][C:3]=1[CH:4]=[C:5]([CH3:7])[CH3:6]
Reactant: CC(C)=Cc1ccc(NC2CCc3cc4nc(C)n(COC(=O)C(C)(C)C)c(=O)c4cc32)cc1F
Reactant: C#CCBr
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CC(=O)N(C)C
Product: C#CCN(c1ccc(C=C(C)C)c(F)c1)C1CCc2cc3nc(C)n(COC(=O)C(C)(C)C)c(=O)c3cc21
Temperature: 80 °C

Procedure:
A mixture of o-fluoro-p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-β,β-dimethylstyrene (1.4 g), propargyl bromide (6.1 g), calcium carbonate (0.88 g) and DMA (20 ml) was stirred and heated to 80° C. for 6 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with water and with brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography using initially increasingly polar mixtures of hexane and ethyl acetate and then increasingly polar mixtures of methylene chloride and ethyl acetate as eluant. There was thus obtained o-fluoro-p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino]-β,β-dimethylstyrene (1.04 g);
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][CH2:10][CH2:11][N:12]1[CH2:18][C@H:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:16][CH2:15][C@@H:14]([NH:25]C(=O)OC(C)(C)C)[C:13]1=[O:33]>ClCCl>[NH2:25][CH:14]1[CH2:15][CH2:16][CH:17]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:18][N:12]([CH2:11][CH2:10][O:9][CH3:8])[C:13]1=[O:33]
Reactant: COCCN1C[C@H](c2ccccc2)CC[C@@H](NC(=O)OC(C)(C)C)C1=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCN1CC(c2ccccc2)CCC(N)C1=O
Reaction time: 1 h

Procedure:
Trifluoroacetic acid (2.5 mL) was added to a solution of tert-butyl (3R,6S)-1-(2-methoxyethyl)-2-oxo-6-phenylazepan-3-ylcarbamate (41 mg, 0.113 mmol) in dichloromethane (5 mL). After 1 h, the solution was concentrated. Saturated aqueous sodium bicarbonate solution was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. MS 263 (M+1). 1H NMR (500 MHz, CDCl3) δ 7.32 (t, J=7.3 Hz, 2H), 7.25-7.22 (m, 1H), 7.18 (d, J=8.3 Hz, 2H), 3.83-3.76 (m, 3H), 3.56-3.49 (m, 3H), 3.35 (s, 3H), 3.34-3.30 (m, 1H), 2.77-2.72 (m, 1H), 2.13-2.10 (m, 1H), 2.03-1.94 (m, 2H), 1.74-1.68 (m, 1H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](OS(C(F)(F)F)(=O)=O)[C:5]([CH3:16])=[C:4]([C:17]2[O:18][CH:19]=[CH:20][CH:21]=2)[N:3]=1.[ClH:22].Cl.NCC1C=CC2C(=CC=CC=2)N=1>COCCOC>[Cl:22][C:6]1[C:5]([CH3:16])=[C:4]([C:17]2[O:18][CH:19]=[CH:20][CH:21]=2)[N:3]=[C:2]([NH2:1])[N:7]=1
Reactant: Cc1c(OS(=O)(=O)C(F)(F)F)nc(N)nc1-c1ccco1
Reactant: Cl
Agent: NCc1ccc2ccccc2n1
Solvent: COCCOC
Product: Cc1c(Cl)nc(N)nc1-c1ccco1
Temperature: 80 °C
Yield: 49.6 %

Procedure:
To a stirred solution of 250 mg (0.77 mmol) trifluoromethanesulfonic acid 2-amino-6-furan-2-yl-5-methyl-pyrimidin-4-yl ester in 10 ml DME was added 489 mg (2.12 mmol) 2-(aminomethyl)quinoline dihydrochloride and the mixture heated at 80° C. for 16 hours. The reaction mixture was then concentrated in vacuo. Chromatography (ethyl acetate/hexane 4/1) followed by trituration in ether/hexane afforded 80 mg (50%) 4-chloro-6-furan-2-yl-5-methyl-pyrimidin-2-ylamine as a white crystalline solid. ES-MS m/e (%): 212 (M{37Cl}+H+, 50), 210 (M{35Cl}+H+, 100).
Reaction SMILES: OC1C=C(CCC[N:11]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])C=CC=1.COCCCCO>>[C:12]1(=[O:21])[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19](=[O:20])[NH:11]1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1cccc(O)c1
Agent: COCCCCO
Product: O=C1NC(=O)c2ccccc21

Procedure:
Mitsunobu reaction of phenol 58 with 4-methoxybutanol gave 2434344-methoxybutoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.840 g, 66%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.85 (m, 2H), 7.68-7.72 (m, 2H), 7.11-7.17 (m, 1H), 6.72-6.79 (m, 2H), 6.65 (dd, J=8.2, 2.4 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 3.75 (t, J=6.8 Hz, 2H), 3.44 (t, J=6.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J=7.2 Hz, 2H), 1.98-2.06 (m, 2H), 1.70-1.86 (m, 4H).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:27][CH3:28].O>CN(C=O)C>[CH2:27]([O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:4][CH:3]=1)[CH3:28]
Reactant: CC(C)(C)OC(=O)Nc1cccc2ccc(O)cc12
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOc1ccc2cccc(NC(=O)OC(C)(C)C)c2c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 67.5 %

Procedure:
Next, to a mixture of tert-butyl (7-hydroxy-1-naphthyl)carbamate (64.0 g, 247 mmol) and Cesium carbonate (161 g, 493 mmol) in 300 ml of anhydrous DMF was added iodoethane (42.3 g, 272 mmol) at room temperature. The mixture was stirred at 60° C. for 2 hours. Water was added to the mixture, and the product was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. To the obtained residue was added diisopropyl ether and the precipitate was collected and dried to afford tert-butyl (7-ethoxy-1-naphthyl)carbamate (47.9 g, 67.5% yield).