Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl.[F:3][C:4]1[CH:31]=[C:30]([NH:32][C:33]([NH:35][C:36](=[O:44])[CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[S:34])[CH:29]=[CH:28][C:5]=1[O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:26][CH3:27])=[C:14]([C:17]([NH:19][CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[O:18])[CH:15]=2)[N:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.[CH2:52]([N:54]=[C:55]=[O:56])[CH3:53]>O1CCCC1>[CH2:52]([NH:54][C:55]([N:23]1[CH2:22][CH2:21][CH:20]([NH:19][C:17]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][C:13]=2[O:26][CH3:27])[N:10]=[CH:9][CH:8]=[C:7]3[O:6][C:5]2[CH:28]=[CH:29][C:30]([NH:32][C:33]([NH:35][C:36](=[O:44])[CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[S:34])=[CH:31][C:4]=2[F:3])=[O:18])[CH2:25][CH2:24]1)=[O:56])[CH3:53]
Reactant: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)Cc4ccccc4)cc3F)c2cc1C(=O)NC1CCNCC1
Reactant: CCN=C=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCNC(=O)N1CCC(NC(=O)c2cc3c(Oc4ccc(NC(=S)NC(=O)Cc5ccccc5)cc4F)ccnc3cc2OC)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 81 %

Procedure:
Compound 14 (335 mg) was suspended in tetrahydrofuran (5 mL), and triethylamine (212 μL) and ethyl isocyanate (71.2 μL) were added to the suspension, followed by stirring at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and the formed solid was filtrated, to thereby yield titled compound 15 (271 mg, yield: 81%).
Reaction SMILES: I[C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C@@H:10]([O:15][CH2:16][C:17]2[C:18](=[O:32])[NH:19][C:20](=[O:31])[N:21]([CH:30]=2)[C@@H:22]2[O:29][C@H:26]([CH2:27][OH:28])[C@@H:24]([OH:25])[CH2:23]2)[C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([N+:33]([O-:35])=[O:34])[CH:3]=1.[CH2:36]([N-:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])[C:37]#[CH:38].CCN(CC)CC>CN(C=O)C.[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.[Cu]I>[CH3:9][O:8][C:7]1[C:2]([C:38]#[C:37][CH2:36][NH:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])=[CH:3][C:4]([N+:33]([O-:35])=[O:34])=[C:5]([C@@H:10]([O:15][CH2:16][C:17]2[C:18](=[O:32])[NH:19][C:20](=[O:31])[N:21]([CH:30]=2)[C@@H:22]2[O:29][C@H:26]([CH2:27][OH:28])[C@@H:24]([OH:25])[CH2:23]2)[C:11]([CH3:14])([CH3:12])[CH3:13])[CH:6]=1
Reactant: COc1cc([C@@H](OCc2cn([C@H]3C[C@H](O)[C@@H](CO)O3)c(=O)[nH]c2=O)C(C)(C)C)c([N+](=O)[O-])cc1I
Reactant: C#CC[N-]C(=O)C(F)(F)F
Agent: [Cu]I
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc([C@@H](OCc2cn([C@H]3C[C@H](O)[C@@H](CO)O3)c(=O)[nH]c2=O)C(C)(C)C)c([N+](=O)[O-])cc1C#CCNC(=O)C(F)(F)F
Yield: 91.8 %

Procedure:
A solution of compound 61 (80 mg, 0.13 mmol), N-propargyltrifluoroacetylamide (196 mg, 1.30 mmol), tetrakis(triphenylphosphine)-palladium(0) (30 mg, 0.026 mmol), CuI (9.9 mg, 0.052 mmol), and Et3N (80 μL) in anhydrous DMF (3.0 mL) was stirred at 50° C. for 12 hours. The mixture was concentrated in vacuo and the residue was purified by silica gel column chromatography to yield 5-{(S)-1-[5-methoxy-4-(3-trifluoroacetamido-1-propynyl)-2-nitrophenyl]-2,2-dimethyl-propyloxy}methyl-2′-deoxyuridine 62 (75 mg, 90%). 1H NMR (400 MHz, MeOD-d4): δ 8.11 (s, 1H, H-6), 8.08 (s, 1H, Ph-H), 7.36 (s, 1H, Ph-H), 6.27 (t, 1H, J=6.4 Hz, H-1′), 5.33 (s, 1H, Ph-CH), 4.47 (m, 1H, H-3′), 4.44 (s, 2H, 5-CH2), 4.32 (d, 2H, J=2.0 Hz, CH2), 4.08 (s, 3H, OCH3), 3.99 (m, 1H, H-4′), 3.87 (m, 1H, H-5′a), 3.79 (m, 1H, H-5′b), 2.30 (m, 2H, H-2), 0.93 (s, 9H, C(CH3)3).
Reaction SMILES: [C:1]([NH:5][NH:6][C:7](=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=1.C(N(CC)CC)C>C(Cl)Cl>[C:1]([N:5]([C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=1)[NH:6][C:7](=[O:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NNC(=O)c1ccccc1
Reactant: O=C(Cl)c1cccnc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)N(NC(=O)c1ccccc1)C(=O)c1cccnc1
Temperature: 23 °C
Reaction time: 0.5 h

Procedure:
A solution of N'-t-butyl-N-benzoylhydrazine (2.0 g) and nicotinoyl chloride hydrochloride in 20 ml of methylene chloride at 23° C. was treated dropwise with triethylamine (4 ml). The reaction mixture was stirred at 23° C. for 0.5 hours. Solids were removed by filtration. The filtrate was diluted with N/10 HCl and ether. The layers were separated and the organic layer was washed with N/10 HCl. The aqueous layer was neutralized with solid sodium bicarbonate and extracted with ether. The ether extracts were treated with charcoal and then dried with magnesium sulfate. Evaporation of solvents afforded a yellow oil which was chromatographed on silica gel using 10% CH3OH, 40% CH2Cl2, 50% Et2O as eluant to afford N'-t-butyl-N-benzoyl-N'-nicotinoylhydrazine as a yellow foam. m.p. 60°-63° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:33])[NH:7][C:8]1([C:14]2[CH:19]=[CH:18][C:17]([C:20](=O)[C:21]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:22]N(C)C)=[CH:16][CH:15]=2)[CH2:11][C:10]([OH:13])([CH3:12])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:34]1([C:40]2[CH:41]=[C:42]([NH2:45])[NH:43][N:44]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(O)(=O)C.C(O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[O:33])[NH:7][C:8]1([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:22][N:43]4[N:44]=[C:40]([C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=5)[CH:41]=[C:42]4[N:45]=3)=[CH:18][CH:19]=2)[CH2:9][C:10]([OH:13])([CH3:12])[CH2:11]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CN(C)C=C(C(=O)c1ccc(C2(NC(=O)OC(C)(C)C)CC(C)(O)C2)cc1)c1ccccc1
Reactant: Nc1cc(-c2ccccc2)n[nH]1
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: CCO
Product: CC1(O)CC(NC(=O)OC(C)(C)C)(c2ccc(-c3nc4cc(-c5ccccc5)nn4cc3-c3ccccc3)cc2)C1

Procedure:
A mixture of 2 (450 mg, 1 mmol) and 5-Phenyl-2H-pyrazol-3-ylamine (160 mg, 1 mmol) in acetic acid (2 mL) and ethanol (4 mL) was heated under reflux for 4 hours. After cooling, the mixture was diluted with 30 mL of DCM, the combined organic phase was washed with NaHCO3 aq. and brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromoatography to give 10-1.
Reaction SMILES: [BH4-].[Li+].[CH3:3][C:4]1[C:9]([C:10]2C=CN=CC=2)=[C:8]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[N:31]=[N:32][N:33]([C:35]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[N:34]=3)=[CH:20][CH:19]=2)[CH:7]=[C:6]([CH3:54])[N:5]=1.[OH2:55]>O1CCCC1>[OH:55][CH2:10][C:9]1[C:4]([CH3:3])=[N:5][C:6]([CH3:54])=[CH:7][C:8]=1[O:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]2[N:31]=[N:32][N:33]([C:35]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)([C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:34]=2)=[CH:22][CH:23]=1
Reactant: Cc1cc(OCc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c(-c2ccncc2)c(C)n1
Reactant: O
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1cc(OCc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c(CO)c(C)n1
Temperature: 0 °C

Procedure:
Lithium borohydride (66 mg) was added over a period of 10 minutes to a solution of compound A (800 mg) in tetrahydrofuran (THF) (25 ml) stirred at 0° C. under an atmosphere of argon. The solution was then stirred at ambient temperature for 16 hours, cooled to 0° C. and water (100 ml) was added. The mixture was extracted with dichloromethane (2×50 ml) and the extracts were washed with saturated sodium chloride solution (50 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue purified by flash chromatography, eluting with methanol/dichloromethane (1:19 v/v, to give 3-hydroxymethyl-2,6-dimethyl-4-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl)methoxy]pyridine (B) (246 mg), as a foam; NMR (d6 -DMSO/d4 -acetic acid): 2.55(s,3H), 2.65(s,3H), 4.7(s,2H), 5.4(s,2H), 6.9-7.0(m,6H), 7.2(d,2H), 7.25-7.45(complex m,12H), 7.45-7.8(complex m,3H), 7.9(dd,1H).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](O)([C:17]1[C:25]([OH:26])=[CH:24][C:20]3[O:21][CH2:22][O:23][C:19]=3[CH:18]=1)[C:5](=[O:16])[N:6]2[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([C:17]1[C:25]([OH:26])=[CH:24][C:20]3[O:21][CH2:22][O:23][C:19]=3[CH:18]=1)[C:5](=[O:16])[N:6]2[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCN1C(=O)C(O)(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCCN1C(=O)C(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 49.1 %

Procedure:
To a solution of 4-bromo-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one (34.9 g, 80.4 mmol) in dichloromethane (100 mL) was added trifluoroacetic acid (18.7 g, 161 mmol) and triethylsilane (18.3 g, 161 mmol). The brown solution was stirred at ambient temperature for 3 h and concentrated in vacuo to dryness. The residue was diluted with dichloromethane (200 mL), washed with saturated ammonium chloride solution (50.0 mL), brine (3×50.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was crystallized from ether to give the title compound (16.5 g, 49%) as a brown solid: 1H NMR (300 MHz, CDCl3) δ 7.29-7.21 (m, 2H), 7.14 (dd, 1H), 6.58 (s, 1H), 6.10 (s, 1H), 5.85 (dd, 2H), 5.01 (s, 1H), 3.75-3.55 (m, 2H), 1.69-1.56 (m, 2H), 1.35-1.21 (m, 4H), 0.86 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 177.9, 150.9, 147.6, 145.4, 141.6, 130.3 127.1 126.8, 120.8, 113.3 108.0, 106.7, 101.5, 101.2, 59.9, 48.6, 40.7, 28.9, 26.9, 22.3 13.9; MS (ES+) m/z 418.3 (M+1), 420.3 (M+1).
Reaction SMILES: C[O:2][C:3](=[O:32])[C@@H:4]([NH:8][C:9]([C:11]1[O:15][N:14]=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:24])=[CH:18][CH:17]=2)[CH:12]=1)=[O:10])[CH:5]([CH3:7])[CH3:6].[K+].[Br-]>>[CH3:6][CH:5]([CH3:7])[C@H:4]([NH:8][C:9]([C:11]1[O:15][N:14]=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:24])=[CH:18][CH:17]=2)[CH:12]=1)=[O:10])[C:3]([OH:32])=[O:2]
Reactant: COC(=O)[C@@H](NC(=O)c1cc(-c2ccc(NC(=O)Nc3ccccc3)cc2)no1)C(C)C
Agent: [Br-]
Agent: [K+]
Product: CC(C)[C@H](NC(=O)c1cc(-c2ccc(NC(=O)Nc3ccccc3)cc2)no1)C(=O)O
Yield: 83 %

Procedure:
The title compound was prepared from (S)-3-methyl-2-({3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-butyric acid methyl ester as set forth in Example 8 and was obtained in 83% yield. Mass (ES+): 423 (M++1); IR (KBr): 3347, 3317, 1708, 1671 (br), 1599, 1547 (br); 1H NMR (DMSO-d6) δ: 0.95 (2×d, 6H), 2.20 (m, 1H), 4.27 (q, 2H), 6.97 (t, 1H), 7.28 (t, 2H), 7.45 (d, 2H), 7.60 (d, 2H), 7.68 (s, 1H), 7.82 (d, 2H), 8.75 (s, 1H), 8.94 (d, 1H), 8.96 (d, 1H).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:21])[CH2:18][C:19]#[N:20])[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].[N-:22]=[N+:23]=[N-:24].[Na+].Cl>O.[Br-].[Zn+2].[Br-]>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:12][CH2:13][N:14]([C:17](=[O:21])[CH2:18][C:19]2[NH:24][N:23]=[N:22][N:20]=2)[CH2:15][CH2:16]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)c1ccccc1N1CCN(C(=O)CC#N)CC1
Agent: Cl
Agent: [Br-]
Agent: [Na+]
Solvent: O
Product: CC(C)(C)c1ccccc1N1CCN(C(=O)Cc2nnn[nH]2)CC1
Temperature: 150 °C
Yield: 26.1 %

Procedure:
A stirred suspension of 3-(4-(2-tert-butylphenyl)piperazin-1-yl)-3-oxopropanenitrile (0.060 g, 0.21 mmol), sodium azide (0.015 g, 0.23 mmol) and zinc bromide (0.055 g, 0.21 mmol) in water (1.0 mL) was heated at 150° C. for 24 h. After this time, the reaction mixture was cooled to room temperature, acidified with 1.0 M hydrochloric acid to pH 1-2 and extracted with ethyl acetate (3×15 mL). The combined organics were washed with water, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was triturated with acetonitrile to provide 1-(4-(2-tert-butylphenyl)piperazin-1-yl)-2-(1H-tetrazol-5-yl)ethanone (0.018 g, 27%) as an off-white solid, mp 236-237° C.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[C@@H:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[C@H:14]([CH:20]=[C:21]([CH2:25][CH2:26][O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[C:22](O)=[O:23])[O:13][C:12]1([CH3:35])[CH3:34])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[NH-].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[CH2:55]([N:57](CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[CH3:55][NH:57][C:22](=[O:23])[C:21]([CH2:25][CH2:26][O:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][O:29]1)=[CH:20][C@@H:14]1[O:13][C:12]([CH3:35])([CH3:34])[N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[C@H:15]1[CH2:16][CH:17]([CH3:19])[CH3:18]
Reactant: CCN(CC)CC
Reactant: CC(C)C[C@H]1[C@H](C=C(CCOC2CCCCO2)C(=O)O)OC(C)(C)N1C(=O)OCc1ccccc1
Agent: C[NH-]
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CNC(=O)C(=C[C@@H]1OC(C)(C)N(C(=O)OCc2ccccc2)[C@H]1CC(C)C)CCOC1CCCCO1
Temperature: -10 °C
Yield: 37.9 %

Procedure:
45 mg of 3-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl-2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid was dissolved in 0.3 ml of dry dimethylformamide, and 3.71 mg of methylamide, 32.9 mg of diphenylphosphorylazide and 12.1 mg of triethylamine were added thereto at -10° C. under stirring. Then, the mixture was stirred at -10° C. for one hour and at room temperature overnight. To the reaction solution, 20 ml of ethyl acetate was added. The ethyl acetate layer was washed sequentially with a 10% citric acid aqueous solution, water, a 4% sodium hydrogencarbonate aqueous solution, water and a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (Kieselgel 60) by using a mixture of chloroform/methanol (5/1) to obtain 17.5 mg of 3-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl- 2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid methylamide as a colorless oily substance.
Reaction SMILES: OC1C=CC=C2C=1N=CC=C2.[CH:12]1[CH:17]=[C:16]([NH:18]/[N:19]=[C:20]2\[CH:21]=[CH:22][CH:23]=[CH:24][C:25]\2=O)[C:15](O)=[CH:14][CH:13]=1.[Al+3].[Cl-].[Cl-].[Cl-].N1CCCCC1.[Al](Cl)(Cl)Cl.O.O.O.O.O.O>C(O)C.O>[N:18]([C:16]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:17]=1)=[N:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C1C=CC=C/C1=N\Nc1ccccc1O
Agent: Cl[Al](Cl)Cl
Agent: Oc1cccc2cccnc12
Agent: [Al+3]
Solvent: CCO
Solvent: O
Solvent: C1CCNCC1
Product: c1ccc(N=Nc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Complex 12 was synthesized through a reaction in the ethanol solution of 8-hydroxyquinoline, o,o′-dihydroxyazobenzene (L1) and AlCl3. First, a solution of 8-hydroxyquinoline (0.05M) and piperidine (0.05M) in 100 ml ethanol was added to a solution of AlCl3.6H2O (0.5M) in 10 ml ethanol very slowly with an intensive stirring. Then, a solution of L1 (0.01M) and piperidine (0.02M) in 500 ml ethanol was introduced slowly. The mixture was stirred for about 1 hour and cooled to room temperature and kept in dark for about 10 hours. A scarlet precipitate was formed when equivalent amount water was poured into the solution. The product was collected by filtration and washed with ethanol rapidly, then dried under an infrared lamp. The obtained product power showed strong red fluorescence under an ultraviolet lamp. The materials were further purified by an improved train sublimation method. The L1 ligand was obtained by typical synthesis method of azobenzene. The molecular structure of Complex 12 was supported by high-resolution mass spectrum (MS) shown in FIG. 5 and element analysis. High-resolution MS found: 383.0845240. Calc. for C21H14O3N3Al: 383.0845062 (shown in FIG. 6); Element analysis found: C, 65.9; H, 3.89; N, 10.68, Calc. For Complex 12: C, 65.80, H, 3.66; N, 10.97.
Reaction SMILES: C[Si](C)(C)C1C=C(Br)C=C([Si](C)(C)C)C=1.[C:16]([C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([OH:30])=O)=[CH:22][CH:21]=1)([CH3:19])([CH3:18])[CH3:17].S(Cl)([Cl:33])=O>CN(C)C=O.C(Cl)Cl.C(C1C=CC(CCC(O)=O)=CC=1)(C)(C)C>[C:16]([C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([Cl:33])=[O:30])=[CH:22][CH:21]=1)([CH3:19])([CH3:18])[CH3:17]
Reactant: CC(C)(C)c1ccc(CCC(=O)O)cc1
Reactant: O=S(Cl)Cl
Agent: C[Si](C)(C)c1cc(Br)cc([Si](C)(C)C)c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)c1ccc(CCC(=O)Cl)cc1
Reaction time: 8 h
Yield: 76.5 %

Procedure:
A 2 L 3 neck round bottom flask fit with a condenser, thermometer, nitrogen inlet, and overhead stirrer was charged with 3-(4-t-butylphenyl)propionic acid (118.7 g, 0.576 mol),thionyl chloride (210 mL, 2.88 mol), dimethylformamide (3 drops), and methylene chloride solvent. The reaction was refluxed for 3 hours and additional 3-(4-t-butylphenyl)propionic acid (8.17 g, 0.040 mol) was added to the reactor and refluxed for an additional hour. After allowing to stand overnight, the reaction was stripped of volatiles to yield the crude 3-(4-t-butylphenyl)propionyl chloride (99.0 g). 1HNMR (CDCl3, 500 MHz) δ7.33 (d, JAB=8 Hz, 2H); 7.12 (d, JAB=8 Hz, 2H); 3.20 (t, J=7.5 Hz, 2H); 2.98 (t, J=7.5, 2H); 1.31 (s, 9H).
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[CH3:13][C@H:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH2:15]O.[C:22]1(=[O:32])[NH:26][C:25](=[O:27])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(OCC)C.O1CCCC1>[CH3:13][C@H:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH2:15][N:26]1[C:22](=[O:32])[C:23]2[C:24](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:25]1=[O:27]
Reactant: C[C@@H](CO)CC(F)(F)F
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: C[C@@H](CN1C(=O)c2ccccc2C1=O)CC(F)(F)F
Reaction time: 8 h
Yield: 74.7 %

Procedure:
Diethyl azodicarboxylate (15.4 mL) was added to a 0° C., stirred slurry of (R)-2-methyl-4,4,4-trifluorobutan-1-ol (about 12.0 g), phthalimide (13.4 g), and triphenylphosphine (23.7 g) in diethyl ether (about 6.5 g, see above) and dry tetrahydrofuran (110 mL), warmed to rook temperature overnight, and stirred an additional 8 h. The mixture was evaporated, methylene chloride was added to the residue, and the slurry was filtered. The filtrate was purified by flash chromatography, eluting with 1:1 methylene chloride:hexanes, to give (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindol-1,3(2H)-dione (17.1 g, 75%) as a white solid; mp 45°-47 ° C.; partial NMR (400 MHz, CDCl3): 1.08 (d, 3H, CH3), 1.94-2.07 (m, 1H, CF3CH2), 2.14-2.31 (m, 1H, CF3CH2), 2.36-2.50 (m, 1H, CHCH3), 3.58 (dd, 1H, CH2N), 3.64 (dd, 1H, CH2N).
Reaction SMILES: [H-].[Na+].CN(C)C=O.[CH2:8]1[C:20]2[NH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:10][CH2:9]1.[C:31]1([CH3:40])[CH:36]=[CH:35][C:34]([C:37](Cl)=[O:38])=[CH:33][CH:32]=1>CCOCC.O.C(O)(=O)C>[C:31]1([CH3:40])[CH:36]=[CH:35][C:34]([C:37]([N:19]2[C:20]3[CH2:8][CH2:9][CH2:10][CH:11]([C:21]([O:23][CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[O:22])[C:12]=3[C:13]3[C:18]2=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:38])=[CH:33][CH:32]=1
Reactant: Cc1ccc(C(=O)Cl)cc1
Reactant: O=C(OCc1ccccc1)C1CCCc2[nH]c3ccccc3c21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Solvent: O
Product: Cc1ccc(C(=O)n2c3c(c4ccccc42)C(C(=O)OCc2ccccc2)CCC3)cc1
Reaction time: 2 h

Procedure:
To a steam bath warmed mixture of 1.5 g sodium hydride in 25 ml. of dry dimethylformamide was added, dropwise and with stirring, 9.15 g. of benzyl 1,2,3,4-tetrahydrocarbazole-4-carboxylate in 25 ml. dry dimethylformamide followed by 5.4 g. of 4-toluoyl chloride in 15 ml. dry dimethylformamide, and heating was continued for two hours. The mixture was cooled and diluted with ether and 1.5 ml. glacial acetic acid. Water was added, the layers were separated and the ether extract was washed with water, 5% potassium bicarbonate solution, 1% aqueous hydrochloric acid and water, and dried over magnesium sulfate. The ether was evaporated to give the title compound which was used without purification in the next step.
Reaction SMILES: Br[C:2]1[N:9]2[C:5](=[N:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)[S:4][N:3]=1.[CH3:14][NH:15][CH3:16]>ClCCl>[CH3:14][N:15]([CH3:16])[C:2]1[N:9]2[C:5](=[N:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)[S:4][N:3]=1
Reactant: Brc1nsc2nc3ccccc3n12
Reactant: CNC
Solvent: ClCCl
Product: CN(C)c1nsc2nc3ccccc3n12
Temperature: 25 °C
Reaction time: 16 h
Yield: 79.5 %

Procedure:
To a cooled mixture of 3-bromo-1,2,4-thiadiazolo[4,5-a]benzimidazole (15.44 g, 0.0603 mole) in 100 mL dichloromethane, dimethylamine (40% solution in water) (5.44 g, 0.121 mole) was added dropwise. The reaction mixture was allowed to stir for 16 h at room temperature. It was then diluted with dichloromethane, washed with water, dried with sodium sulfate and evaporated under vacuum to give 10.47 g (80%) of 3-(dimethylamino)-1,2,4-thiadiazolo[4,5-a]benzimidazole as colourless crystals: mp 102°-104° C.; 1H NMR (CDCl3) δ7.74 (t, 2H), 7.41 (t, 1H), 7.27 (t, 1H), 3.06 (s, 6H) ppm. Anal. Calcd for C10H10N4S: C, 55.03; H, 4.62; N, 25.69. Found: C, 54.53; H, 4.90; N, 25.50.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH:8]([CH2:14]/[CH:15]=[CH:16]/[CH:17]=O)[CH2:7][CH2:6]2.[C:19]1([CH3:33])[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][NH:26][C:27]([CH3:32])=[CH:28][C:29](=[O:31])[CH3:30]>>[C:29]([C:28]1[CH:15]([CH2:14][CH:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]2=[O:13])[CH:16]=[CH:17][N:26]([CH2:25][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH3:33])[C:27]=1[CH3:32])(=[O:31])[CH3:30]
Reactant: COc1ccc2c(c1)CCC(C/C=C/C=O)C2=O
Reactant: CC(=O)C=C(C)NCc1ccccc1C
Product: COc1ccc2c(c1)CCC(CC1C=CN(Cc3ccccc3C)C(C)=C1C(C)=O)C2=O

Procedure:
The title compound 71 is prepared according to the procedure reported in step D of Example 8 with aldehyde 54 (60 mg, 0.24 mmol) and enamine 72 (45 mg, 0.22 mmol) as reactants. Purification by column chromatography on SiO2 (Petroleum Ether/EtOAc=2:1) afford the title compound 71 as a yellow solid. (Yield 36 mg, 34%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:22]([C:24]2[CH:39]=[CH:38][CH:37]=[CH:36][C:25]=2[C:26]([O:28][CH2:29]C2C=CC=CC=2)=[O:27])=[O:23])[CH:7]=[CH:8][C:9]=1[NH:10][CH2:11][C:12](=[O:21])OCC1C=CC=CC=1)([O-])=O.C[Si](C=[N+]=[N-])(C)C.CCCCCC>O1CCCC1.C(OCC)(=O)C.C1(CO)C=CC=CC=1>[O:21]=[C:12]1[NH:1][C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:22]([C:24]3[CH:39]=[CH:38][CH:37]=[CH:36][C:25]=3[C:26]([O:28][CH3:29])=[O:27])=[O:23])[CH:5]=2)[NH:10][CH2:11]1
Reactant: O=C(CNc1ccc(C(=O)c2ccccc2C(=O)OCc2ccccc2)cc1[N+](=O)[O-])OCc1ccccc1
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: OCc1ccccc1
Product: COC(=O)c1ccccc1C(=O)c1ccc2c(c1)NC(=O)CN2
Yield: 65.5 %

Procedure:
A solution of phenylmethyl 2-{[3-nitro-4-({2-oxo-2-[(phenylmethyl)oxy]ethyl}amino)phenyl]carbonyl}benzoate (0.31 g, 0.59 mmol) in a mixture of tetrahydrofurane-ethyl acetate (1:1, 50 mL) was hydrogenated in the presence of 10% Pd/C (0.15 g) in a Parr shaker at 40 psi, until the consumption of hydrogen ceased. The catalyst was filtered off and the solvent was evaporated. The resulting crude product was converted into its methyl ester in a mixture of benzene-methanol (9:1, 5.0 mL) by the addition of 2.0 M trimethylsilyldiazomethane solution in hexane (0.3 mL, 0.60 mmol). The reaction was quenched by the addition of a few drops of acetic acid and the solvent was evaporated. The resulting crude product was purified by silica gel flash chromatography (hexane:ethyl acetate 4:1 to 1:1 eluent) to give methyl 2-[(3-oxo-1,2,3,4-tetrahydroquinoxalin-6-yl)carbonyl]benzoate (0.12 g, 67% yield). 1H NMR (400 MHz, DMSO-d6): 8.06 (s, 1H), 7.83 (dd, 1H), 7.64 (d, 1H), 7.52 (t, 1H), 7.38 (d, 1H), 7.09 (7.03 (d, 1H), 4.41 (s, 2H), 3.77 (s, 3H); MS (EI) for C17H14N2O4: 311 (MH+).