Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(C(C)C)CC)(C)C.Cl[S:22]([C:25]1[N:26]=[CH:27][N:28]2[CH:32]=[CH:31][S:30][C:29]=12)(=[O:24])=[O:23].C(OCC)(=O)C>CN(C=O)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][S:22]([C:25]2[N:26]=[CH:27][N:28]3[CH:32]=[CH:31][S:30][C:29]=23)(=[O:23])=[O:24])=[CH:10][CH:11]=1)([O-:3])=[O:2]
Reactant: NCc1ccc([N+](=O)[O-])cc1
Reactant: O=S(=O)(Cl)c1ncn2ccsc12
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=[N+]([O-])c1ccc(CNS(=O)(=O)c2ncn3ccsc23)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 74.1 %

Procedure:
4-Nitrobenzylamine (1.24 g) and 2 ml of diisopropylethylamine were added to a solution of 0.95 g of 7-chlorosulfonylimidazo[5,1-b]thiazole in 20 ml of DMF. The mixture was stirred at room temperature for 12 hr. Ethyl acetate was added to the reaction mixture. The mixture was washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resultant powder was collected by filtration to give 1.07 g of 7-(4-nitrobenzylsulfamoyl)imidazo[5,1-b]thiazole.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:10]([C:11](O)=[O:12])[C:9]=1[C:17](O)=[O:18].[OH-].[Na+].O>C1COCC1>[F:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:10]([CH2:11][OH:12])[C:9]=1[CH2:17][OH:18]
Reactant: O=C(O)c1cccc(F)c1C(=O)O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: OCc1cccc(F)c1CO
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.7 %

Procedure:
To a solution of LiAlH4 (1M in tetrahydrofuran) (54 ml, 54.0 mmol, 2.0 molar equivalents), cooled to −78° C., was added dropwise a solution of 3-fluorophtalic acid (5.0 g, 27.2 mmol, 1 molar equivalent) in THF (25 ml). The reaction mixture was allowed to warm up to room temperature and then stirred at 70° C. for 2 hours. To this resulting solution, cooled at 0° C. was added a 2M sodium hydroxide solution (25 ml) followed by cold water (25 ml) and THF (50 ml). The reaction mixture was then further extracted with THF (3×50 ml). The organic fractions were combined, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuum to give a light yellow solid. Purification by recrystallisation from acetone/hexane gave the title compound as white needles (3.3 g, 79%). 1H NMR (300.13 MHz, DMSO) δ(ppm) 4.53 (dd, J1=5.50, J2=2.00 Hz, 2H) 4.67 (d, J=5.50 Hz, 2H) 4.98 (t, J=5.50 Hz, 1H) 5.22 (t, J=5.50 Hz, 1H) 7.00-7.10 (m, 1H) 7.25-7.35 (m, 2H). 19F NMR (282.38 MHz, DMSO) δ(ppm) −119.92 (s). 13C NMR (75.48 MHz, CDCl3) δ (ppm) 52.63, 60.07, 113.26, 122.81, 128.69, 144.02, 158.64, 161.87.
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6](=[O:17])[CH2:7][CH2:8][NH:9]C(=O)OC(C)(C)C)(=[O:4])=[O:3].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:9][CH2:8][CH2:7][C:6]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:17]
Reactant: CC(C)(C)OC(=O)NCCC(=O)NS(C)(=O)=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)NC(=O)CCN
Temperature: 0 °C
Reaction time: 2 h
Yield: 71.7 %

Procedure:
tert-butyl 3-(methylsulfonamido)-3-oxopropylcarbamate (3.6 g, 15.1 mmol) was dissolved in DCM (60 mL). Then CF3COOH (1.1 mL, 0.3 mmol, 20 equiv) was added to the mixture at 0° C. and stirred for 2 h at 0° C. The reaction mixture was concentrated. The residue was purified by flash chromatography to give 3-amino-N-(methylsulfonyl)propanamide as a transparent solid (1.8 g, 80%), (mobile phase: CH3OH/H2O=0˜5%). ESI-MS (M+1)+: 167.0. 1H NMR (400 MHz, CD3OD) δ: 3.21˜3.11 (m, 2H), 3.07 (s, 3H), 2.60˜2.54 (m, 2H).
Reaction SMILES: [C:1]([C@@H:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:4])#[N:2].C(N(CC)CC)C.[NH2:20][OH:21]>C(O)C>[NH2:2]/[C:1](=[N:20]\[OH:21])/[C@@H:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:4]
Reactant: C[C@@H](C#N)NC(=O)OC(C)(C)C
Reactant: NO
Solvent: CCO
Solvent: CCN(CC)CC
Product: C[C@H](NC(=O)OC(C)(C)C)/C(N)=N/O
Temperature: 50 °C
Reaction time: 8 h
Yield: 98.4 %

Procedure:
To a mixture of tert-butyl [(1S)-1-cyanoethyl]carbamate (Step 2, 250 mg, 1.5 mmol) in ethanol (3 mL) were added triethylamine (0.41 mL, 2.9 mmol) and hydroxylamine (58 mg, 1.8 mmol). The mixture was stirred at 50° C. overnight. The reaction mixture was concentrated to afford the desired crude product (300 mg) which was directly used in the next step reaction without further purification. 1H-NMR (300 MHz, DMSO-d6): 8.94 (s, 1H), 6.80 (d, J=8.5 Hz, 1H), 5.24 (s, 2H), 4.01 (m, 1H), 1.36 (s, 9H), 1.15 (d, J=7.0 Hz, 3H).
Reaction SMILES: [NH2:1][C@H:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[CH3:3].[CH3:14][S:15](Cl)(=[O:17])=[O:16]>>[CH3:14][S:15]([NH:1][C@H:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[CH3:3])(=[O:17])=[O:16]
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1ccc([C@H](C)N)cc1
Product: COC(=O)c1ccc([C@H](C)NS(C)(=O)=O)cc1

Procedure:
Using methyl (S)-4-(1-aminoethyl)benzoate (0.61 g) and methanesulfonyl chloride (0.29 mL) and by the reaction and treatment in the same manner as in Preparation Example 71, the title compound (0.81 g) was obtained.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[C:8]([Cl:15])[C:9]([Cl:14])=[C:10]([Cl:13])[C:11]([Cl:12])=[C:4]2[C:3]1=[O:16].[CH3:17][S:18](Cl)(=[O:20])=[O:19].C(N(CC)CC)C>C(Cl)Cl>[CH3:17][S:18]([O:1][N:2]1[C:3](=[O:16])[C:4]2=[C:11]([Cl:12])[C:10]([Cl:13])=[C:9]([Cl:14])[C:8]([Cl:15])=[C:5]2[C:6]1=[O:7])(=[O:20])=[O:19]
Reactant: CS(=O)(=O)Cl
Reactant: O=C1c2c(Cl)c(Cl)c(Cl)c(Cl)c2C(=O)N1O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)ON1C(=O)c2c(Cl)c(Cl)c(Cl)c(Cl)c2C1=O
Yield: 87 %

Procedure:
N-Methanesulfonyloxytetrachlorophthalimide was prepared by the following procedure. To a flask equipped with a stirrer and addition funnel were added N-hydroxytetrachlorophthalimide (9.00 g, 0.030 mol), methanesulfonyl chloride (3.60 g, 0.032 mol), and 200 mL of methylene chloride. The mixture was cooled in ice and a solution of triethylamine (5.0 mL, 0.036 mol) in 25 mL of methylene chloride was added slowly. Upon completion of this addition the reaction mixture was diluted with 200 mL of methylene chloride and washed successively with water (250 mL), 5% aqueous sodium bicarbonate (250 mL), and water (250 mL). The organic layer which contained a substantial amount of precipitated product was evaporated, and the resulting solid was dried by addition of toluene and evaporation to give 9.89 g (87.0%) of pale yellow crystalline N-methanesulfonyloxytetrachlorophthalimide: mp 240°-241°; uv (CH3CN) 240 (51,400), 329 (2736), 340 nm (2937); ir (KBr) 3040 (w), 3020 (w), 2940 (w), 1800 (m), 1700 (vs), 1375 (s), 1330 (m), 1310 (m), 1180 (s), 1120 (m), 1030 (s), 965 (m), 790 (m), 725 (s); nmr (CDCl3) 3.53 (s); mass spectrum 376.8472 (calcd for C9H3NO5Cl4S: 376.8783). Anal. Calcd for C9H3NO5Cl4S: C, 28.52; H, 0.80; N, 3.70; O, 21.11; Cl, 37.42; S, 8.46. Found: C, 28.52, 28.94, 28.92; H, 0.80, 1.07, 1.05; N, 3.70, 3.84, 3.82; Cl, 37.42, 37.08.
Reaction SMILES: [CH2:1]([O:4][C:5](=[O:16])[C@@H:6]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[NH2:7])[CH:2]=[CH2:3].C(N(CC)CC)C.[CH2:24]([O:31][C:32]([NH:34][C:35]([CH3:42])([CH3:41])[CH2:36][CH2:37][C:38](O)=[O:39])=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH2:1]([O:4][C:5](=[O:16])[C@H:6]([NH:7][C:38](=[O:39])[CH2:37][CH2:36][C:35]([NH:34][C:32]([O:31][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:33])([CH3:42])[CH3:41])[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH:2]=[CH2:3]
Reactant: CC(C)(CCC(=O)O)NC(=O)OCc1ccccc1
Reactant: C=CCOC(=O)[C@H](N)CCc1ccccc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCOC(=O)[C@@H](CCc1ccccc1)NC(=O)CCC(C)(C)NC(=O)OCc1ccccc1
Temperature: 25 °C

Procedure:
D-Homophenylalanine allyl ester (175 mg; 0.80 mmol) (see Example 9, Step B), triethylamine (222 μl; 1.59 mmol) were dissolved in dry methylene chloride (2 ml) and 4-(benzyloxycarbonylamino)-4-methyl-pentanoic acid (211 mg; 0.80 mmol) added. The solution was stirred at room temperature and BOP (353 mg; 0.80 mmol) was added over 5 minutes, and this reaction mixture stirred at room temperature for 17 h. The reaction was quenched by adding brine and then the products of the reaction isolated by extraction with methylene chloride (3×15 ml). The methylene chloride layers were combined and dried with anhydrous magnesium sulfate powder, filtered and evaporated under reduced pressure. A thick golden yellow gum was obtained which was purified by column chromatography on silica gel using ethyl acetate and hexanes 1:2 v/v. The product (182 mg; 48.9%) was isolated as a pale yellow gum. FAB-MS:- calculated for C27H34 N2O5 466.3; found 467.7 (M+1).
Reaction SMILES: [CH:1]([NH:4][C@@H:5]([CH3:11])[C:6]([O:8][CH2:9][CH3:10])=[O:7])([CH3:3])[CH3:2].Cl[C:13]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1>CCOC(C)=O>[CH2:9]([O:8][C:6](=[O:7])[C@@H:5]([N:4]([CH:1]([CH3:3])[CH3:2])[C:13]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1)[CH3:11])[CH3:10]
Reactant: COC(=O)c1cnc(Cl)c([N+](=O)[O-])c1
Reactant: CCOC(=O)[C@H](C)NC(C)C
Solvent: CCOC(C)=O
Product: CCOC(=O)[C@H](C)N(c1ncc(C(=O)OC)cc1[N+](=O)[O-])C(C)C
Temperature: 90 °C
Reaction time: 20 h
Yield: 41.6 %

Procedure:
(S)-ethyl 2-(isopropylamino)propanoate (2.83 g, 17.8 mmol) was added to methyl 6-chloro-5-nitronicotinate (1.72 g, 7.94 mmol) and the reaction mixture was stirred in a closed vial at 90° C. for 20 h. It was cooled and diluted with EtOAc (25 mL). The resulting precipitate was filtered off, the filtrate was concentrated in vacuo and purified using flash column chromatography on silica gel (220 g SiO2, hexanes:ethyl acetate 4:1) to afford the title compound as yellow oil (1.12 g, 42%). 1H NMR (400 MHz, CHLOROFORM-d) δ (ppm): 1.18 (t, J=7.07 Hz, 3 H) 1.30 (d, J=6.32 Hz, 3 H) 1.36 (d, J=6.57 Hz, 3 H) 1.66 (d, J=6.82 Hz, 3 H) 3.48-3.62 (m, 1 H) 3.90 (s, 3 H) 4.03 (q, J=6.65 Hz, 1 H) 4.06-4.21 (m, 2 H) 8.54 (d, J=2.02 Hz, 1 H) 8.70 (d, J=2.02 Hz, 1 H); [M+H] calc'd for C15H21N3O6, 340; found, 340.
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([N:8]2[CH:12]=[C:11]([C:13]3[CH:36]=[CH:35][C:16]4[N:17]([C:20]5[CH:21]=[C:22]([NH:26][C:27]([NH:29][CH2:30][C:31]([F:34])([F:33])[F:32])=[O:28])[CH:23]=[CH:24][CH:25]=5)[CH:18]=[N:19][C:15]=4[CH:14]=3)[CH:10]=[N:9]2)[CH2:4][CH2:3]1.[CH3:37][N:38]1[CH:42]=[CH:41][C:40]([S:43](Cl)(=[O:45])=[O:44])=[N:39]1.C(N(CC)CC)C>C(#N)C.CO>[CH3:37][N:38]1[CH:42]=[CH:41][C:40]([S:43]([N:2]2[CH2:3][CH2:4][CH:5]([N:8]3[CH:12]=[C:11]([C:13]4[CH:36]=[CH:35][C:16]5[N:17]([C:20]6[CH:21]=[C:22]([NH:26][C:27]([NH:29][CH2:30][C:31]([F:33])([F:32])[F:34])=[O:28])[CH:23]=[CH:24][CH:25]=6)[CH:18]=[N:19][C:15]=5[CH:14]=4)[CH:10]=[N:9]3)[CH2:6][CH2:7]2)(=[O:45])=[O:44])=[N:39]1
Reactant: Cn1ccc(S(=O)(=O)Cl)n1
Reactant: O=C(NCC(F)(F)F)Nc1cccc(-n2cnc3cc(-c4cnn(C5CCNCC5)c4)ccc32)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: CO
Product: Cn1ccc(S(=O)(=O)N2CCC(n3cc(-c4ccc5c(c4)ncn5-c4cccc(NC(=O)NCC(F)(F)F)c4)cn3)CC2)n1

Procedure:
To a solution of N-{3-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea HCl salt (20.0 mg, 0.0385 mmol) in acetonitrile (1 mL) was added 1-methyl-1H-pyrazole-3-sulfonyl chloride (10. mg, 0.058 mmol, Maybridge, Cat. No. CC48303) and triethylamine (16 μL, 0.12 mmol), the solution was stirred at r.t. overnight. The reaction solution was diluted with MeOH and then purified by RP-HPLC (pH=10) to afford the desired compound. LCMS (M+H)+: m/z=628.2.
Reaction SMILES: CB1OB(C)OB(C)O1.[NH2:10][C:11]1[C:20](I)=[CH:19][C:18]([Br:22])=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14].Cl[CH2:24]Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:10][C:11]1[C:20]([CH3:24])=[CH:19][C:18]([Br:22])=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)c1cc(Br)cc(I)c1N
Reactant: ClCCl
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CB1OB(C)OB(C)O1
Solvent: C1COCCO1
Product: COC(=O)c1cc(Br)cc(C)c1N
Yield: 1179.1 %

Procedure:
2,4,6-Trimethyl-cyclotriboroxane (6.99 ml, 50.0 mmol) was added to a stirred suspension of methyl 2-amino-5-bromo-3-iodo-benzoate (Preparation #11a, 15.5 g, 43.6 mmol), [1,1′-bis(diphenylphosphino)-ferrocene)dichloropalladium(II) 1:1 complexed with dichloromethane (1.67 g, 2.05 mmol) and cesium carbonate (42.9 g, 132 mmol) in 1,4-dioxane (200 mL) under N2. After about 4 hours at about 90° C. additional 2,4,6-trimethyl-cyclotriboroxane (1.00 ml, 7.15 mmol) was added and the reaction was continued with heating for about 2 more hours. The reaction was cooled, filtered through a short pad of silica gel and concentrated to afford an oil. The crude product was purified by flash chromatography over silica gel using heptane:EtOAc (92:8) as the eluent to yield methyl 2-amino-5-bromo-3-methyl-benzoate (5.9 g, 55%) as a pale yellow solid; RP HPLC (Table 1, Method e) Rt=2.72, m/z: (MH)+ 244/246.
Reaction SMILES: [CH2:1]1[O:7][P:5]2([O:8][CH2:9][C:2]1([CH2:10][OH:11])[CH2:3][O:4]2)=[O:6].P(Cl)(Cl)([Cl:14])=O.OCC(CO)(CO)CO>>[CH2:3]1[O:4][P:5]2([O:7][CH2:1][C:2]1([CH2:10][OH:11])[CH2:9][O:8]2)=[O:6].[ClH:14]
Reactant: O=P(Cl)(Cl)Cl
Agent: O=P12OCC(CO)(CO1)CO2
Agent: OCC(CO)(CO)CO
Product: Cl

Procedure:
A process for the production of pentaerythritol phosphate alcohol (PEPA) comprising reacting in the liquid phase phosphorus oxychloride (POCl3) with pentaerythritol (PE) at a molar ratio of no more than about 1.20 mole of POCl3 per mole of PE and at a reaction temperature of at least about 100° C. in the presence of a solvent which is an alkane substituted with at least one halogen atom and having an atmospheric boiling point of 40 to about 150° C., the reaction pressure being sufficiently high to maintain the solvent in the liquid phase, the reaction resulting in the production of PEPA and HCl by-product.
Reaction SMILES: [C:1]1([C:7]2[N:8]([C:16]3[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=3)[C:9]3[C:14]([CH:15]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:44]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[C:38]3[C:33]2=[CH:34][CH:35]=[CH:36][CH:37]=3)=[CH:28][CH:27]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)C>[C:1]1([C:7]2[N:8]([C:16]3[CH:21]=[CH:20][C:19]([C:26]4[CH:31]=[CH:30][C:29]([N:32]5[C:33]6[CH:34]=[CH:35][CH:36]=[CH:37][C:38]=6[C:39]6[C:44]5=[CH:43][CH:42]=[CH:41][CH:40]=6)=[CH:28][CH:27]=4)=[CH:18][CH:17]=3)[C:9]3[C:14]([CH:15]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Brc1ccc(-n2c3ccccc3c3ccccc32)cc1
Reactant: OB(O)c1ccc(-n2c(-c3ccccc3)cc3ccccc32)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: c1ccc(-c2cc3ccccc3n2-c2ccc(-c3ccc(-n4c5ccccc5c5ccccc54)cc3)cc2)cc1
Temperature: 25 °C
Yield: 38.6 %

Procedure:
0.78 g (2.49 mmole) of 4-(2-phenylindole-1-yl)phenyl boronic acid and 0.80 g (2.48 mmole) of 9-(4-bromophenyl)carbazole were put in a 20 ml three-necked flask, and 2.5 ml of toluene, 1.5 ml of ethanol, and 2.5 ml of 2M-sodium carbonate solution were put therein, and 0.09 g (0.08 mmole) of tetrakis-(triphenylphosphine) palladium (0) was added under stirring at room temperature under nitrogen flow. Then, the mixture was refluxed with stirring for 5 hours under nitrogen flow. After the reaction was completed, the reaction mixture was cooled to room temperature and deposited crystal was separated by filtration. The crystal was washed with acetone and recrystallized with a mixed solvent of toluene/ethanol. The obtained crystal was refined by alumina column chromatography (eluent:toluene) and crystallize with methanol to give 0.49 g of a white crystal of 4-(2-phenylindole-1-yl)-4′-(carbazole-9-yl)biphenyl (Exemplary Compound No. 34)(yield: 38.6%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:17][NH2:18])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[C:7]([CH3:16])[CH:6]=2.[O:19]1[CH2:24][CH2:23][CH:22]([C:25](O)=[O:26])[CH2:21][CH2:20]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[C:3]([NH:17][NH:18][C:25]([CH:22]2[CH2:23][CH2:24][O:19][CH2:20][CH2:21]2)=[O:26])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[C:7]([CH3:16])[CH:6]=2
Reactant: COC(=O)c1cc2nc(Cl)c(NN)nc2cc1C
Reactant: O=C(O)C1CCOCC1
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: COC(=O)c1cc2nc(Cl)c(NNC(=O)C3CCOCC3)nc2cc1C
Temperature: 25 °C
Reaction time: 9 h
Yield: 64.1 %

Procedure:
To a mixture of 10 g of methyl 3-chloro-2-hydrazino-7-methylquinoxaline-6-carboxylate, 5.9 g of tetrahydro-2H-pyran-4-carboxylic acid, 16 mL of triethylamine, and 100 mL of dichloromethane was added 21 g of bromo(tripyrrolidin-1-yl)phosphonium hexafluorophosphate, followed by stirring at room temperature for 9 hours. To the reaction mixture were added saturated aqueous sodium hydrogen carbonate solution and chloroform. The solid was collected by filtration and washed with ethyl acetate to obtain 9.1 g of methyl 3-chloro-7-methyl-2-[2-(tetrahydro-2H-pyran-4-ylcarbonyl)hydrazino]quinoxaline-6-carboxylate as a pink solid. Further, to the filtrate obtained above was added chloroform, and then the aqueous layer was separated. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was washed with ethyl acetate to obtain 3.58 g of methyl 3-chloro-7-methyl-2-[2-(tetrahydro-2H-pyran-4-ylcarbonyl)hydrazino]quinoxaline-6-carboxylate as a colorless solid.
Reaction SMILES: B.CSC.[C:5]([O:9][C:10]([N:12]([CH2:16][C:17]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=1)[CH:13]([CH3:15])[CH3:14])=[O:11])([CH3:8])([CH3:7])[CH3:6].OS([O-])(=O)=O.[K+].[OH-].[Na+]>C1COCC1.CO>[C:5]([O:9][C:10]([N:12]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:21][NH2:22])=[CH:23][CH:24]=1)[CH:13]([CH3:15])[CH3:14])=[O:11])([CH3:7])([CH3:8])[CH3:6]
Reactant: CC(C)N(Cc1ccc(C#N)cc1)C(=O)OC(C)(C)C
Agent: B
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: C1CCOC1
Solvent: CO
Solvent: CSC
Product: CC(C)N(Cc1ccc(CN)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.9 %

Procedure:
Under a nitrogen atmosphere add borane-dimethylsulfide complex (13.7 mL, 27.4 mmol, 2M solution in THF) to 4-[N-(tert-butoxycarbonyl)-N-(iso-propyl)-aminomethyl]-benzonitrile (1.5 g, 5.5 mmol) in THF (20 mL) at 0° C. Warm to room temperature and stir overnight. Heat the mixture under reflux for 2 h. Cool the mixture in an ice-bath and add methanol (20 mL). Warm to room temperature and add KHSO4 (7 g in 50 mL of water). Stir for 2 h at room temperature and basify with 3N aqueous NaOH. Extract with DCM, dry the organic phase over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel (150 g) eluting with a gradient of DCM to 4:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) to obtain the title compound as an oil (1.3 g, 85%). MS (APCI+) m/z: 279 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+:12]([O-:14])=[O:13])[C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH2:7]Br.P(OCC)(OCC)OCC.[H-].[Na+].O=[C:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.[Cl-].[NH4+]>O1CCCC1.CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([N+:12]([O-:14])=[O:13])[C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH:7]=[C:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: COc1c(CBr)cc(Br)cc1[N+](=O)[O-]
Agent: CCOP(OCC)OCC
Agent: [Cl-]
Agent: [H-]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: COc1c(C=C2CCN(C(=O)OC(C)(C)C)CC2)cc(Br)cc1[N+](=O)[O-]
Temperature: 160 °C
Reaction time: 1 h
Yield: 35.1 %

Procedure:
A mixture of 5-bromo-2-methoxy-3-nitrobenzyl bromide (8.4 9, 26 mmol) and triethyl phosphite (4.5 g, 27 mmol) was heated to 160° C. for 2 h and then evaporated in vacuo to give a dark amber oil. This was dissolved in anhydrous tetrahydrofuran (20 mL) and added dropwise to a stirring suspension of sodium hydride (60%) (1.14 g) in anhydrous N,N-dimethylformamide (100 mL) at 0° C. The mixture was left to stir for 1 hour. tert-Butyl 4-oxopiperidine-1-carboxylate (5.17 g, 26 mmol) in anhydrous THF (30 mL) was added to the mixture. Stirring was continued for 4 h at room temperature before the mixture was poured into saturated ammonium chloride (100 mL) and extracted with diethyl ether (2×150 mL). The combined organic layer was evaporated in vacuo to give a crude oil. Silica gel chromatography eluting with diethyl ether in petroleum ether (5–30%) gave the title compound (3.9 g, 35%) as an oil.
Reaction SMILES: C1(P([N:15]=[N+:16]=[N-:17])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2.[S:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH2:34]O>C1(C)C=CC=CC=1>[N:15]([CH2:34][C:30]1[S:29][CH:33]=[CH:32][N:31]=1)=[N+:16]=[N-:17]
Reactant: OCc1nccs1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: [N-]=[N+]=NCc1nccs1
Temperature: 25 °C
Reaction time: 1 h
Yield: 60.4 %

Procedure:
Diphenylphosphoryl azide (3.25 mL, 0.015 mol) and 1,8-diazabicyclo[5.4.0] undec-7-ene (2.25 mL, 0.025 mol) were added to a solution of thiazol-2-yl-methanol (1.44 g, 0.013 mol) in toluene (20 mL) at 0° C. After 1 hour, the reaction was warmed to room temperature and stirred overnight. The mixture was diluted with toluene (20 mL) and washed with H2O (3×) brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to afford the azide as a tan oil (1.1 g, 63%). IR: 2098 cm-1.
Reaction SMILES: [Br:1]Br.[C:3]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)([O:5][CH2:6][CH3:7])=[O:4].Br>O.C1COCC1>[CH2:6]([O:5][C:3]([N:8]1[CH2:9][CH2:10][C:11](=[O:14])[CH:12]([Br:1])[CH2:13]1)=[O:4])[CH3:7]
Reactant: BrBr
Reactant: CCOC(=O)N1CCC(=O)CC1
Agent: Br
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)N1CCC(=O)C(Br)C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 108 %

Procedure:
Bromine (2.83 mL, 55 mmol) was added dropwise to a stirred solution of N-carbethoxy-4-piperidone (7.54 mL, 50 mmol) and a 48% solution of HBr in H2O (1.41 mL) in THF (88 mL) at 0° C. The mixture was stirred at room temperature for 15 minutes and then quenched with a saturated solution of Na2S2O3, basified with a saturated solution of Na2CO3 and extracted with diethyl ether. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo to yield 3-bromo-4-oxo-1-piperidinecarboxylic acid ethyl ester (13.5 g, 54% yield, 50% pure) as a dark brown oil that was used in the next step without further purification. C8H12BrNO3 GCMS (EI): Rt 3.77, MW (theor) 249; m/z [M]+ 249 (using method, GC-MS Method 2).