Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si]([O:8][CH2:9][CH:10]([N:12]1[C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[C:14]([C:21]([C:23]2[CH:24]=[N:25][CH:26]=[C:27]([N:29]=C(C3C=CC=CC=3)C3C=CC=CC=3)[CH:28]=2)=[O:22])=[CH:13]1)[CH3:11])(C(C)(C)C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:29][C:27]1[CH:28]=[C:23]([C:21]([C:14]2[C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[N:12]([CH:10]([CH3:11])[CH2:9][OH:8])[CH:13]=2)=[O:22])[CH:24]=[N:25][CH:26]=1
Reactant: CC(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N=C(c3ccccc3)c3ccccc3)c2)c2cnccc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(CO)n1cc(C(=O)c2cncc(N)c2)c2cnccc21
Temperature: 25 °C
Reaction time: 4 h
Yield: 51.9 %

Procedure:
To a solution of [1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]{5-[(diphenylmethylene)amino]pyridin-3-yl}methanone (Enantiomer 1, Preparation 33, 150 mg, 0.260 mmol) in DCM (5 mL) was added TFA (0.2 mL) and the reaction stirred at room temperature for 4 hours. The reaction was purified directly by preparative HPLC to afford the title compound (40 mg, 52%).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH:22][C@H:23]2[C@@H:27]3[O:28][C:29]([CH3:32])([CH3:31])[O:30][C@@H:26]3[C@@H:25]([CH2:33][OH:34])[CH2:24]2)=[N:12][C:13](S(C)(=O)=O)=[N:14][C:15]=1[O:16]C.[CH:35]1([NH2:39])[CH2:38][CH2:37][CH2:36]1>CC#N>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:15](=[O:16])[NH:14][C:13]([NH:39][CH:35]2[CH2:38][CH2:37][CH2:36]2)=[N:12][C:11]=1[NH:22][C@H:23]1[C@H:27]2[C@H:26]([O:30][C:29]([CH3:31])([CH3:32])[O:28]2)[C@@H:25]([CH2:33][OH:34])[CH2:24]1
Reactant: COc1nc(S(C)(=O)=O)nc(N[C@@H]2C[C@H](CO)[C@H]3OC(C)(C)O[C@H]32)c1-c1nc2ccccc2s1
Reactant: NC1CCC1
Solvent: CC#N
Product: CC1(C)O[C@@H]2[C@@H](CO)C[C@@H](Nc3nc(NC4CCC4)[nH]c(=O)c3-c3nc4ccccc4s3)[C@@H]2O1
Temperature: 80 °C

Procedure:
Compound 8 (100 mg, 0.197 mmol) was dissolved in MeCN (2 mL) and cyclobutylamine (168 μL, 1.97 mmol) was added. The reaction was heated to 80° C. for 1 h. The solvent was evaporated and the residue was purified by column chromatography on silica gel, eluting with EtOAc/hexane to give the title compound as a yellow solid. MS 498 (M+H).
Reaction SMILES: [CH2:1]([SH:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C[O-].[Na+:16]>CO>[CH2:1]([S-:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Na+:16]
Reactant: CCCCCCCCCCCCS
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CCCCCCCCCCCC[S-]

Procedure:
Dodecanethiol (246 g) and sodium methylate in methanol 30% (216 g) are charged to a rotary evaporator. Vacuum is applied and the solvent is abstracted completely using a bath temperature up to 90° C. The remaining sodium dodecanethiolate (272 g) is used without further purification in the subsequent step.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5](OC)[C:4]=1/[CH:11]=[N:12]/[CH:13]([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH3:2].[CH:20]([Li])([CH3:22])[CH3:21]>C1COCC1.CCCCC>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH:20]([CH3:22])[CH3:21])[C:4]=1/[CH:11]=[N:12]/[CH:13]([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH3:2]
Reactant: CCc1cccc(OC)c1/C=N/C(C(C)C)C(C)C
Reactant: [Li]C(C)C
Solvent: CCCCC
Solvent: C1CCOC1
Product: CCc1cccc(C(C)C)c1/C=N/C(C(C)C)C(C)C
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
To a solution of 0.8 g (3.1 mmol) (E)-[1-(2-ethyl-6-methoxy-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine (Example 3 a)) in 3 ml dry THF cooled to −20° C. were added 9.62 ml of a 0.7M solution of isopropyl lithium in pentane drop-wise to keep temperature below 0° C. Then the mixture was stirred at −20° C. for further 30 min and the reaction quenched by addition of water. The aqueous phase was extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. Purification of the crude product by flash chromatography on silica gel with heptane as eluent provided 0.220 g (E)-[1-(2-ethyl-6-isopropyl-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine as colourless liquid: MS (ISP): 274.1 (M+H+.).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]2[CH2:17][CH:16]=[CH:15][O:14]2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH2:18]([O:20][C:21](=[O:29])[C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1)[CH3:19].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([O:20][C:21](=[O:29])[C:22]1[CH:27]=[CH:26][C:25]([CH:15]2[CH:16]=[CH:17][CH:13]([C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[O:14]2)=[CH:24][CH:23]=1)[CH3:19]
Reactant: COc1cc(C2CC=CO2)cc(OC)c1OC
Reactant: CCOC(=O)c1ccc(I)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: CCOC(=O)c1ccc(C2C=CC(c3cc(OC)c(OC)c(OC)c3)O2)cc1
Temperature: 80 °C
Reaction time: 18 h
Yield: 86.1 %

Procedure:
To a solution of 287 (200 mg, 0.846 mmol) and 4-Iodo-benzoic acid ethyl ester (468 mg, 1.69 mmol) in dry acetonitrile (4 mL) were added PPh3 (20 mg, 0.076 mmol), Ag2CO3 (467 m 1.69 mmol) and Pd(OAc)2 (7 mg, 0.03 mmol). The reaction mixture was stirred 18 h at 80° C. The reaction mixture was filtered through celite and washed with AcOEt. Water was added and the phases were separated. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue was then purified by flash chromatography on silica gel (AcOEt/Hexane: 30/70) to afford the title compound 288 (280 mg, 0.728 mmol, 86% yield). 1H NMR (300 MHz, CDCl3) δ (ppm): 8.05 (d, J=7.5 Hz, 2H), 7.45 (d, J=7.5 Hz, 2H), 6.61 (s, 2H), 6.18-5.95 (m, 4H), 4.38 (q, J=7.0 Hz, 2H, 3.88 (s, 6H), 3.84 (s, 3), 1.39 (t, J=7.0 Hz).
Reaction SMILES: Br[C:2]1[N:3]([C:13]2[N:14]=[C:15]([I:21])[N:16]=[C:17]([NH2:20])[C:18]=2[N:19]=1)[C@@H:4]1[O:12][C@H:9]([CH2:10][OH:11])[C@@H:7]([OH:8])[C@H:5]1[OH:6].[CH2:22]([NH2:26])[CH2:23][CH2:24][CH3:25].O.CO>C(Cl)Cl>[I:21][C:15]1[N:16]=[C:17]([NH2:20])[C:18]2[N:19]=[C:2]([NH:26][CH2:22][CH2:23][CH2:24][CH3:25])[N:3]([C:13]=2[N:14]=1)[C@@H:4]1[O:12][C@H:9]([CH2:10][OH:11])[C@@H:7]([OH:8])[C@H:5]1[OH:6]
Reactant: CCCCN
Reactant: Nc1nc(I)nc2c1nc(Br)n2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: CCCCNc1nc2c(N)nc(I)nc2n1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

Procedure:
The reaction was performed with 2-iodo-8-bromoadenosine (5, 1.15 g, 2.44 mmol) and n-butylamine (25 ml). Some drops of water were added to dissolve everything. Yield 0.92 g (1.98 mmol, 81%), mp 142–144÷C, Rƒ 0.23 (10% MeOH in CH2Cl2); 1H NMR (DMSO-d6) δ 6.94–6.86 (m, 3H, NH, NH2), 5.79 (d, 1H, J=7.56 Hz, H-1′), 5.67–5.62 (m, 1H, OH-2′), 5.30–5.16 (m, 2H, OH-3′,5′), 4.54–4.49 (m, 1H, H-2′), 4.07–4.04 (m, 1H, H-3′), 3.95–3.92 (m, 1H, H-4′), 3.64–3.57 (m, 2H, H-5′), 2.49–2.42 (m, 2H, NHCH2), 1.55–1.26 (m, 4H, CH2CH2CH3), 0.88 (t, 3H, J=7.21 Hz, CH3); MS m/z 464 (M+H)+; Anal. (C14H21IN6O4) C, H, N.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]([OH:12])[CH:9]=[C:8]2[C:3]=1[C:4](=[S:14])[CH:5]=[C:6]([CH3:13])[O:7]2.C(=O)([O-])[O-].[K+].[K+].[CH:21](I)([CH3:23])[CH3:22].CN(C=O)C>O>[OH:1][C:2]1[CH:11]=[C:10]([O:12][CH:21]([CH3:23])[CH3:22])[CH:9]=[C:8]2[C:3]=1[C:4](=[S:14])[CH:5]=[C:6]([CH3:13])[O:7]2
Reactant: CC(C)I
Reactant: Cc1cc(=S)c2c(O)cc(O)cc2o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(=S)c2c(O)cc(OC(C)C)cc2o1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 88.3 %

Procedure:
A mixture consisting of 6.88 g (30.35 mmol) 5,7-dihydroxy-2-methylthiochromone, 12.56 g (91.05 mmol) potassium carbonate, 6.07 ml (60.70 mmol) isopropyl iodide, and 150 ml DMF was stirred at 60° C. for 30 min. Subsequently, water was added to the solution. The product was extracted twice with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was distilled out under reduced pressure. The resulting crude product was purified by flash column chromatography (hexane ethyl acetate=4:1), whereby 6.71 g of 5-hydroxy-7-isopropoxy-2-methylthiochromone was obtained (yield: 83%).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[CH3:19][O:20][CH2:21]Cl.O>CN(C=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([O:12][CH2:19][O:20][CH3:21])=[CH:10][N:11]=2)[CH2:2][CH2:3]1
Reactant: COCCl
Reactant: Oc1ccc(OCC2CC2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COCOc1ccc(OCC2CC2)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 6-(cyclopropylmethoxy)pyridin-3-ol (855 mg) and potassium carbonate (1.44 g) in DMF (15 mL) was added chloromethyl methyl ether (0.635 mL), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed twice with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (789 mg) as an oil.
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1)#[N:2].[CH3:11][C:12]1([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:16](=[O:17])[CH:15]=[C:14]([CH3:18])[O:13]1.[OH-].[Na+].[Cl-].[Na+]>C(O)C>[F:25][C:22]1[CH:23]=[CH:24][C:19]([C:12]2([CH3:11])[C:16](=[O:17])[CH:15]=[C:14]([CH:18]=[CH:7][C:6]3[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[O:13]2)=[CH:20][CH:21]=1
Reactant: N#Cc1ccc(C=O)cc1
Reactant: CC1=CC(=O)C(C)(c2ccc(F)cc2)O1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC1(c2ccc(F)cc2)OC(C=Cc2ccc(C#N)cc2)=CC1=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 38.7 %

Procedure:
To a solution of p-cyanobenzaldehyde (1.6 g, 11.8 mM) and 2,5-dimethyl-2-(4-fluorophenyl)-3(2H)-furanone (2.0 g, 9.8 mM) in ethanol (75 mL), was added 1N aqueous sodium hydroxide (1.0 mL, 1 mM). After the reaction solution was stirred at room temperature for two days, saturated aqueous sodium chloride (400 mL) was added. The aqueous layer was extracted with dichloromethane (3×100 mL). The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL), dried over MgSO4, filtered and concentrated to give an orange liquid. The crude product was purified by chromatography (silica gel, pet. ether-ethyl acetate) to give a yellow crystalline solid (1.2 g, 38% yield), m.p. 140°-142° C.
Reaction SMILES: OO.[Br:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([C:13]1([C:18]#[N:19])[CH2:17][CH2:16][CH2:15][CH2:14]1)(=[O:12])=[O:11].C([O-])([O-])=[O:21].[K+].[K+].CS(C)=O>O>[Br:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([C:13]1([C:18]([NH2:19])=[O:21])[CH2:17][CH2:16][CH2:15][CH2:14]1)(=[O:12])=[O:11]
Reactant: N#CC1(S(=O)(=O)c2ccccc2Br)CCCC1
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: NC(=O)C1(S(=O)(=O)c2ccccc2Br)CCCC1
Reaction time: 0.5 h
Yield: 88.5 %

Procedure:
A 30% H2O2 solution (1.6 mL) was added drop-wise at rt to a mixture of 1-(2-bromophenylsulfonyl)cyclopentanecarbonitrile (1.6 g, 5.1 mmol), K2CO3 (2.1 g, 15 mmol), and DMSO (5 mL). The mixture was stirred for 30 min before diluting with water (40 mL) and isolating the precipitate via vacuum filtration. The precipitate was washed with water and air-dried to give the title compound (1.5 g, 89%). MS (ESI): mass calcd. for C12H19NO3S, 330.99; m/z found, 331.9 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 7.99-7.95 (m, 1H), 7.89-7.84 (m, 1H), 7.64-7.51 (m, 4H), 2.41-2.25 (m, 4H), 1.78-1.66 (m, 2H), 1.58-1.45 (m, 2H).
Reaction SMILES: [CH:1](=[N:9]O)[C:2]1[C:3](=[CH:5][CH:6]=CC=1)O.[N+:11]([C:14]1[CH:15]=[N:16][NH:17][CH:18]=1)([O-:13])=[O:12].C(=O)([O-])[O-].[Cs+].[Cs+].BrC1C=NC=CC=1>[Cu]=O.CN(C=O)C.C(OCC)(=O)C>[N+:11]([C:14]1[CH:15]=[N:16][N:17]([C:2]2[CH:1]=[N:9][CH:6]=[CH:5][CH:3]=2)[CH:18]=1)([O-:13])=[O:12]
Reactant: O=[N+]([O-])c1cn[nH]c1
Reactant: ON=Cc1ccccc1O
Agent: O=[Cu]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: Brc1cccnc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cnn(-c2cccnc2)c1
Temperature: 130 °C
Reaction time: 8 h

Procedure:
A flask which had been baked out and filled with argon was initially charged with 8.3 g (56.6 mmol) of copper oxide, 31.9 g (228 mmol) of salicylaldoxime, 200 g (1.71 mol) of 4-nitro-1H-pyrazole and 597 g (1.83 mol) of caesium carbonate. The flask was repeatedly evacuated and filled with argon. 218 g (800 mmol) of 3-bromopyridine and 1 l of DMF which had been degassed on a rotary evaporator were added. The reaction mixture was stirred at 130° C. overnight, cooled and filtered, and the DMF was removed on a rotary evaporator. The substance was dissolved in 1 l of ethyl acetate, and extracted with 2 l of H2O. The water phase was extracted twice with 500 ml of ethyl acetate. Filtration of the aqueous phase gave a green solid. 1 l of ethyl acetate and 100 ml of DMF were added thereto, and the mixture was heated to 50° C. Cooling was followed by filtration through Hyflo and washing with 500 ml of ethyl acetate. The filtrate was washed with 300 ml of water and 300 ml of saturated NaCl solution, dried over Na2SO4, filtered and concentrated. The solid was suspended in 100 ml of ethyl acetate, filtered and washed with ethyl acetate and methyl tert-butyl ether, and the beige solid (45 g) was dried on a rotary evaporator.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[CH:11]=2)[CH:6]=1.C1COCC1.[Cl-].[NH4+].O>CO.[Zn]>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[CH:11]=2)[CH:6]=1
Reactant: COC(=O)Cc1cc2ccc(Cl)cc2c(-c2ccc([N+](=O)[O-])cc2)c1C
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)Cc1cc2ccc(Cl)cc2c(-c2ccc(N)cc2)c1C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 98.1 %

Procedure:
To a suspension of [6-chloro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl ester (133 mg, 0.36 mmol) in methanol (2 mL) was added THF (2 mL). Then, zinc dust (192.1 mg, 2.9 mmol) and ammonium chloride (192.6 mg, 3.6 mmol) were added followed by water (0.9 mL). The reaction mixture was stirred at room temperature for 10 minutes and TLC analysis of the mixture indicated the absence of starting material. The resulting solids were filtered and washed with ethyl acetate (20 mL). The solution was concentrated to remove organic solvent, then diluted with water (20 mL) and the mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (30 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent under vacuum gave [4-(4-amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (120 mg, 97.9%) as a light brown oil which solidified slowly. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.90 (d, J=8.7 Hz, 1 H), 7.79 (s, 1 H), 7.43 (dd, J=8.7, 1.9 Hz, 1 H), 7.27 (d, J=1.9 Hz, 1 H), 6.85 (d, J=8.2 Hz, 2 H), 6.72 (d, J=8.2 Hz, 2 H), 5.26 (s, 2 H), 3.93 (s, 2 H), 3.64 (s, 3 H), 2.09 (s, 3 H). HRMS calcd. for C20H18ClNO2 [(M+H)+] 340.1099, obsd. 340.1097.
Reaction SMILES: [C:1]([OH:20])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH:12]=[CH:13][CH2:14][CH:15]=[CH:16][CH2:17][CH3:18].C(Cl)(=O)C([Cl:24])=O>C(Cl)(Cl)Cl>[C:1]([Cl:24])(=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH:12]=[CH:13][CH2:14][CH:15]=[CH:16][CH2:17][CH3:18]
Reactant: CCC=CCC=CCC=CCCCCCCCC(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClC(Cl)Cl
Product: CCC=CCC=CCC=CCCCCCCCC(=O)Cl

Procedure:
To a solution of 834 mg of 9,12,15-octadecatrienoic acid in 8 ml of dry chloroform was added 0.4 ml of oxalyl chloride under argon at room temperature. The mixture was reacted for 2 hours. From the reaction mixture were removed the chloroform and the remaining oxalyl chloride by distillation under reduced pressure to give 9,12,15-octadecatrienoyl chloride, which was then dissolved in 6 ml of dry chloroform.
Reaction SMILES: [NH2:1][NH2:2].[Br:3][C:4]1[CH:13]=[CH:12][C:7]([C:8](=S)[NH:9][CH3:10])=[C:6](F)[CH:5]=1>CS(C)=O.C(OCC)(=O)C.O>[Br:3][C:4]1[CH:5]=[C:6]2[C:7]([C:8]([NH:9][CH3:10])=[N:1][NH:2]2)=[CH:12][CH:13]=1
Reactant: CNC(=S)c1ccc(Br)cc1F
Reactant: NN
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: CNc1n[nH]c2cc(Br)ccc12
Temperature: 100 °C
Reaction time: 2 h
Yield: 54.2 %

Procedure:
Anhydrous hydrazine (0.25 mL, 8.1 mmol) was added to a solution of 4-bromo-2-fluoro-N-methylbenzothioamide (200 mg, 0.8 mmol) in dimethylsulfoxide (2.5 mL). The reaction was heated to 100° C. and stirred for 2 hours. The reaction was cooled to room temperature and diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate (3×). The combined organics were washed with saturated aqueous sodium carbonate and brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (20-100% ethyl acetate/heptanes) gave the title compound (98 mg, 54%) as a white solid. +ESI (M+H+1) 228.0; 1H NMR (400 MHz, CD3OD, δ): 7.52 (d, J=8.58 Hz, 1H), 7.43 (s, 1H), 7.04 (d, J=8.39 Hz, 1H), 2.94 (s, 3H).
Reaction SMILES: [CH:1]([N:4]1[C@H:8]2[CH2:9][CH2:10][CH2:11][CH2:12][C@@H:7]2[N:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:5]1=[O:19])([CH3:3])[CH3:2].O=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:22]1.C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH:1]([N:4]1[C@H:8]2[CH2:9][CH2:10][CH2:11][CH2:12][C@@H:7]2[N:6]([CH:13]2[CH2:14][CH2:15][N:16]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:22]3)[CH2:17][CH2:18]2)[C:5]1=[O:19])([CH3:3])[CH3:2]
Reactant: CCOC(=O)N1CCC(=O)CC1
Reactant: CC(C)N1C(=O)N(C2CCNCC2)[C@H]2CCCC[C@@H]21
Agent: [BH3-]C#N
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: CCOC(=O)N1CCC(N2CCC(N3C(=O)N(C(C)C)[C@H]4CCCC[C@@H]43)CC2)CC1
Reaction time: 3 h
Yield: 23.8 %

Procedure:
(3aS,7aS)-1-isopropyl-3-piperidin-4-yloctahydro-2H-benzimidazol-2-one (85 mg, 0.3 mmol) was dissolved in MeOH (2 mL) and ethyl 4-oxopiperidine-1-carboxylate (48 μL, 0.32 mmol) was added. A solution of sodium cyanoborohydride (31 mg, 0.45 mmol) and zinc chloride (20 mg, 0.15 mmol) in MeOH (1 mL) was then added drop wise at room temperature. The mixture was then stirred for 3 hours and then more sodium cyanoborohydride (40 mg) was added and the mixture stirred at room temperature over night. The solvent was then removed under reduced pressure and the residue was diluted in dichloromethane (80 mL) and was washed with 1N NaOH (5 mL), brine and then dried and concentrated in vacuo. The residue was purified by high pH prep LCMS to provide the title compound (30 mg). Free Base-1H NMR (400 MHz, METHANOL-D4): δ ppm 1.14 (dd, J=6.84, 5.27 Hz, 6H), 1.20 (t, J=7.23 Hz, 3H), 1.28-1.45 (m, 6H), 1.54 (d, J=12.50 Hz, 1H), 1.61-1.69 (m, 1H), 1.75-1.92 (m, 6H), 2.12-2.32 (m, 4H), 2.38-2.52 (m, 1H), 2.64-2.81 (m, 2H), 2.80-2.92 (m, 2H), 2.92-3.05 (m, 2H), 3.52-3.65 (m, 1H), 3.83-3.98 (m, 1H), 4.05 (q, J=7.03 Hz, 2H), 4.13 (d, J=13.28 Hz, 2H). MS (M+1): 421.4
Reaction SMILES: [N:1]1[C:9]([NH2:10])=[C:8]2[C:4]([N:5]([CH2:11][O:12][CH2:13][CH2:14][P:15](=[O:20])([O-:19])[O:16]CC)[CH:6]=[N:7]2)=[N:3][CH:2]=1.[NH4+].CO.O>CN(C=O)C>[N:1]1[C:9]([NH2:10])=[C:8]2[C:4]([N:5]([CH2:11][O:12][CH2:13][CH2:14][P:15](=[O:16])([OH:19])[OH:20])[CH:6]=[N:7]2)=[N:3][CH:2]=1
Reactant: CCOP(=O)([O-])CCOCn1cnc2c(N)ncnc21
Agent: [NH4+]
Solvent: O
Solvent: CO
Solvent: CN(C)C=O
Product: Nc1ncnc2c1ncn2COCCP(=O)(O)O
Temperature: 40 °C
Reaction time: 6 h
Yield: 43.9 %

Procedure:
To a solution of 12 (0.32 g, 1.0 mmol) in DMF (7.0 mL) was added Me3 SiBr (1.07 g, 7.01 mmol). After the solution was stirred at 40° C. for 6 h, a mixture of MeOH and H2O(5:1, 20 mL) was added and the solvents were evaporated. The crude residue was purified by use of column chromatography (resin XAD-4, H2O) to afford 13 (0.12 g, 45%): mp 296° C. (dec.); TLC Rf 0.32 (MeOH); UV λmax (EtOH): 259 nm (ε13 700); 1H NMR(DMSO-d6 /D2O): δ1.49 (m, 2 H, CH2P), 3.80 (m, 2 H, CH2O), 5.55 (s, 2 H, OCH2 N), 7.90, 8.19 (2 s, 2 H, HC(2)+HC(8)). Anal. (C8H12N5 O4P) C, H, N.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[C:2]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccccc1
Reactant: Clc1ccccc1
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: c1ccc(Nc2ccccc2)cc1
Reaction time: 25 h
Yield: 74.5 %

Procedure:
The above general procedure was followed using chlorobenzene (135 mg, 1.20 mmol) and aniline (93 mg, 1.00 mmol) with 5 mol % Pd(dba)2 and 4 mol % tri-t-butylphosphine in 2.0 mL of toluene. After 25 hours, the reaction mixture was adsorbed onto silica gel and chromatographed with 2.5% ethyl acetate/hexanes to give 126 mg (75%) of diphenylamine as an off-white solid.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([OH:13])=O)[CH:8]=2)[NH:3]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH2:56]([NH2:63])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>C(#N)C.CN(C)C=O>[CH2:56]([NH:63][C:11]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2](=[O:1])[CH2:10]2)=[O:13])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1
Reactant: O=C1Cc2cc(C(=O)O)ccc2N1
Reactant: NCc1ccccc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: O=C1Cc2cc(C(=O)NCc3ccccc3)ccc2N1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 32.3 %

Procedure:
2-Oxoindoline-5-carboxylic acid (0.214 g, 1.21 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.462 g, 1.44 mmol), 1-hydroxybenzotriazole hydrate (0.194 g, 1.44 mmol) and N,N-diisopropylethylamine (0.3 mL, 1.71 mmol) were suspended in a mixture of acetonitrile (4 mL) and N,N-dimethylformamide (1 mL) and stirred at room temperature for 30 min. Benzylamine (0.155 g, 1.45 mmol) was added and stirring was continued for 12 h. The solvent was removed in vacuo and the residue was separated between chloroform and a saturated aqueous sodium hydrogen carbonate solution. The aqueous layer was extracted with chloroform (3×30 mL). The combined organic layers were dried over sodium sulfate. Filtration and removal of the solvent in vacuo yielded the crude product which was purified on a silica gel column using a gradient chloroform/methanol, (100:1 to 1:1), as the eluent to give 0.104 g (30% yield) of the title compound as a solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.60 (s, 1H), 8.85 (m, 1H), 7.77 (m, 2H), 7.29 (m, 4H), 7.21 (m, 1H), 6.85 (d, J=11 Hz, 1H), 4.45 (d, J=6 Hz, 2H), 3.52 (s, 2H); MS (ES) m/z 267 (M++1).