Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([OH:49])=O)[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][CH:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15][C:16](=[O:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].O.O[N:52]1[C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][C:55]=2N=N1.C1(N)CCCCC1>C1COCC1>[CH:56]1([NH:52][C:47]([C:3]2[C:4]([CH3:46])=[CH:5][C:6]3[CH2:23][C@@H:22]([OH:24])[C@:21]4([O:25][CH3:26])[C@@:8]([OH:45])([C:9](=[O:44])[C:10]5[C:19]([C:20]4=[O:27])=[C:18]([OH:28])[C:17]4[C:16](=[O:29])[CH:15]=[C:14]([NH:30][CH:31]6[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]6)[C:13](=[O:43])[C:12]=4[CH:11]=5)[C:7]=3[C:2]=2[OH:1])=[O:49])[CH2:57][CH2:58][CH2:59][CH2:60][CH2:55]1
Reactant: CO[C@@H]1[C@@H](O)[C@@H](OC)C(NC2=CC(=O)c3c(cc4c(c3O)C(=O)[C@]3(OC)[C@H](O)Cc5cc(C)c(C(=O)O)c(O)c5[C@]3(O)C4=O)C2=O)O[C@H]1C
Reactant: On1nnc2ccccc21
Solvent: O
Solvent: NC1CCCCC1
Solvent: C1CCOC1
Product: CO[C@@H]1[C@@H](O)[C@@H](OC)C(NC2=CC(=O)c3c(cc4c(c3O)C(=O)[C@]3(OC)[C@H](O)Cc5cc(C)c(C(=O)NC6CCCCC6)c(O)c5[C@]3(O)C4=O)C2=O)O[C@H]1C
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of (6R,6aS,14aR)-1,6,8,14a-tetrahydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylic acid (60 mg, 0.09 mmol) in THF (2 mL) was added polystyrene-carbodiimide (156 mg, 0.18 mmol), 1-hydroxybenzotriazole hydrate (24 mg, 0.18 mmol) and cyclohexylamine (10 mg, 0.13 mmol). The reaction mixture was stirred at room temperature under nitrogen for 4 h. The reaction was filtered through a micro filter and concentrated. The crude material was purified by preparative HPLC (10:90 acetonitrile/water to 60:40 acetonitrile/water with 0.05% TFA over 10 min, then isocratic) to afford (6R,6aS,14aR)—N-cyclohexyl-1,6,8,14a-tetrahydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxamide as a mixture of diastereomers (14 mg, 20%) and as a dark red solid: 1H NMR (500 MHz, CD3OD) δ 8.10 (s, 1H), 6.59 (s, 1H), 6.15 (s, 0.3H), 6.00 (s, 0.7H), 5.19 (s, 0.3H), 4.95 (s, 0.7H), 4.89 (br s, 1H), 3.95-3.90 (m, 1H), 3.75 (s, 3H), 3.74-3.71 (m, 0.7H), 3.70-3.68 (m, 0.3H), 3.67-3.64 (m, 1H), 3.58 (s, 3H), 3.53 (s, 1H), 3.50 (s, 2H), 3.48-3.35 (m, 5H), 3.27-3.20 (m, 1H), 3.09-3.02 (m, 1H), 2.22 (s, 3H), 1.93-1.81 (m, 2H), 1.80-1.69 (m, 2H), 1.66-1.57 (m, 1H), 1.40-1.33 (m, 2H), 1.27 (d, J=6.5 Hz, 2H), 1.22 (d, J=6.5 Hz, 1H), 1.19-1.15 (m, 2H); MS (ESI+) m/z 765 (M+H); HPLC 95.4% (AUC), tR 13.79 min.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:10])[CH3:9])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:13]I>CN(C)C=O>[CH3:2][CH2:3][CH2:4][CH:5]([CH3:8])[CH3:6].[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:10][CH3:13])[CH3:9])=[CH:4][CH:3]=1
Reactant: CC(O)c1ccc(Br)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCC(C)C
Product: COC(C)c1ccc(Br)cc1
Yield: 195.2 %

Procedure:
Dissolve 1-(4-bromo-phenyl)-ethanol (0.79 mL, 6.62 mmol) in dry N,N-dimethylformamide (7 mL) at ambient temperature under nitrogen atmosphere. Add sodium hydride (60% dispersion in oil, 397 mg, 9.93 mmol), stir the reaction for 30 min., then add methyl iodide (0.50 mL, 7.94 mmol) and stir the reaction for a further 23 hr. under nitrogen. Quench with water (30 mL), extract with DCM (3×30 mL), pass through an IST Phase Separator Frit® and concentrate. Purify using silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate: isohexane to give 1-bromo-4-(1-methoxy-ethyl)-benzene as a clear oil (1.39 g, 98%). 1H-NMR (400 MHz, CDCl3) δ 7.47 (d, 2H), 7.20 (d, 2H), 4.25 (q, 1H), 3.21 (s, 3H), 1.40 (d, 3H).
Reaction SMILES: P(Br)(Br)[Br:2].O[CH:6]([C:8]1[O:9][C:10](=[O:26])[C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:7]>C(Cl)Cl>[Br:2][CH:6]([C:8]1[O:9][C:10](=[O:26])[C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:7]
Reactant: COc1ccc(-c2c(C(C)O)oc(=O)c3ccccc23)cn1
Reactant: BrP(Br)Br
Solvent: ClCCl
Product: COc1ccc(-c2c(C(C)Br)oc(=O)c3ccccc23)cn1
Yield: 38.5 %

Procedure:
1M PBr3 in DCM (1.80 mL, 1.80 mmol) was added 3-(1-hydroxyethyl)-4-(6-methoxypyridin-3-yl)-1H-isochromen-1-one (intermediate B17, 225 mg, 0.76 mmol) in DCM (9 ml) at RT. The reaction mixture was straightforward purified on Biotage SNAP 25 g silica cartridge with a gradient of hexane and EtOAc to give the title compound (105 mg, 38.5%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N+:10]([O-:12])=[O:11])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:19]([N:22]([CH3:24])[CH3:23])[C:20]#[CH:21]>CN(C=O)C.CC#N.CC#N.Cl[Pd]Cl>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([C:21]#[C:20][CH2:19][N:22]([CH3:24])[CH3:23])=[CH:3][C:4]=1[N+:10]([O-:12])=[O:11]
Reactant: C#CCN(C)C
Reactant: COc1ncc(Br)cc1[N+](=O)[O-]
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CC#N
Product: COc1ncc(C#CCN(C)C)cc1[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 4 h
Yield: 27.1 %

Procedure:
To a solution of 5-bromo-2-methoxy-3-nitropyridine (1.50 g, 6.44 mmol) in DMF (30 mL) were added bis(acetonitrile)palladium(II)chloride (83.5 mg, 0.322 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1-1′-biphenyl (399 mg, 0.837 mmol), cesium carbonate (4.19 g, 12.9 mmol) and propargyl(dimethylamine) (0.832 mL, 7.72 mmol). The reaction mixture was flushed with nitrogen gas and allowed to stir for 4 h at 50° C. The reaction mixture was diluted with EtOAc and washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 3-(6-methoxy-5-nitropyridin-3-yl)-N,N-dimethylprop-2-yn-1-amine (0.41 g, 27%) as a white solid. LCMS (FA): Rt=0.85 min, m/z=236.2 (M+H).
Reaction SMILES: Cl[C:2]1[O:3][C:4]2[C:5](=[C:7]([C:19]#[N:20])[C:8]([CH3:18])=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10]=2[F:11])[N:6]=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:31][NH:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>ClCCl>[C:19]([C:7]1[C:5]2[N:6]=[C:2]([CH2:31][NH:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[O:3][C:4]=2[C:10]([F:11])=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]=1[CH3:18])#[N:20]
Reactant: Cc1c(-c2ccccc2)c(F)c2oc(Cl)nc2c1C#N
Reactant: CCOC(=O)CCNC
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOC(=O)CCNCc1nc2c(C#N)c(C)c(-c3ccccc3)c(F)c2o1
Yield: 81 %

Procedure:
2-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (0.49 g, 1.71 mmol), diisopropylethylamine (0.70 ml, 4.12 mmol) and ethyl 3-(methylamino)propionate hydrochloride (I-159) (0.32 g, 1.91 mmol) were dissolved in dichloromethane (15 ml). After heated under reflux for 3 hours, this was diluted with dichloromethane. After washed with water and drying over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by silica gel column chromatography (dichloromethane to dichloromethane:methanol=70; 1), then again purified by silica gel column chromatography (hexane:ethyl acetate=4:1 to 2:1) to obtain the entitled compound (0.53 g, 81%) as a brown oil.
Reaction SMILES: [CH2:1]([O:8][CH2:9][C:10]([CH3:32])([CH3:31])[C:11]([O:13][C:14]1[C:15]([F:30])=[C:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:17]([CH3:23])=[C:18]([C:21]#[N:22])[C:19]=1[NH2:20])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH2:1]([O:8][CH2:9][C:10]([C:11]1[O:13][C:14]2[C:19](=[C:18]([C:21]#[N:22])[C:17]([CH3:23])=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:15]=2[F:30])[N:20]=1)([CH3:32])[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(C#N)c(N)c(OC(=O)C(C)(C)COCc2ccccc2)c(F)c1-c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: Cc1c(-c2ccccc2)c(F)c2oc(C(C)(C)COCc3ccccc3)nc2c1C#N
Yield: 90.1 %

Procedure:
A mixture of 4-amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 3-benzyloxy-2,2-dimethylpropionate (I-64) (390 mg, 0.902 mmol), p-toluenesulfonic acid monohydrate (17 mg, 0.09 mmol) and toluene (16 ml) was heated under reflux for 3 hours. After cooling, the reaction liquid was diluted with ethyl acetate, successively washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine, dried on anhydrous magnesium sulfate, then the solvent was evaporated away to obtain a pale brown residue. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1→10:1) to obtain the entitled compound (337 mg, 90%) as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8]3[C:9](=[O:23])[NH:10][C:11]([NH:16]C(=O)C(C)(C)C)=[N:12][C:13]=3[CH:14]=[CH:15][C:6]=2[CH:5]=[CH:4][C:3]=1[Br:24].[OH-].[Na+].NC1NC(=O)C2C3C=C(Br)C=CC=3C=CC=2N=1>>[NH2:16][C:11]1[NH:10][C:9](=[O:23])[C:8]2[C:7]3[C:2]([NH2:1])=[C:3]([Br:24])[CH:4]=[CH:5][C:6]=3[CH:15]=[CH:14][C:13]=2[N:12]=1
Reactant: CC(C)(C)C(=O)Nc1nc2ccc3ccc(Br)c(N)c3c2c(=O)[nH]1
Agent: Nc1nc2ccc3ccc(Br)cc3c2c(=O)[nH]1
Agent: [Na+]
Agent: [OH-]
Product: Nc1nc2ccc3ccc(Br)c(N)c3c2c(=O)[nH]1

Procedure:
N-(10-Amino-9-bromo-1,2-dihydro-1-oxobenzo[f]quinazolin-3-yl)pivalamide (0.58 g, 1.5 mmoles) was reacted with aqueous sodium hydroxide as described for the analogous 9-bromo compound (example 2). The product was precipitated from the reaction mixture with acetic acid, filtered and washed with water to give 3,10-diamino-9-bromobenzo[f]quinazolin-1(2H)-one as a yellow solid. (0.36 g, 80%) 1H NMR (DMSO-d6, 200 MHz) δ: 6.49(br s, 2H, NH2); 6.69(br s, 1H, NH2); 7.09(d, J=8.4 Hz, 1H, Ar); 7.22(d, J=8.9 Hz, 1H, Ar); 7.56(d, J=8.4 Hz, 1H, Ar); 7.90(d, J=8.9 Hz, 1H, Ar); 11.47(br s, 1H, NH).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@:12]2([F:20])[CH3:19])=[C:4]([N:21]2[CH2:24][CH2:23][CH2:22]2)[N:3]=1.N1C=NN=N1.[C:30](#N)C.C(N([CH:40]([O:48][P:49](N)[O-])N(C(C)C)C(C)C)C(C)C)(C)C>N1C=CC=CC=1>[CH2:24]([N:21]([CH2:22][CH3:30])[C:4]1[N:3]=[C:2]([NH2:1])[N:10]=[C:9]2[C:5]=1[N:6]=[CH:7][N:8]2[C@@H:11]1[O:15][C@H:14]2[C@@H:13]([O:18][P:49]([O:48][CH3:40])[O:17][CH2:16]2)[C@:12]1([F:20])[CH3:19])[CH3:23]
Reactant: CC(C)N(C(C)C)C(OP(N)[O-])N(C(C)C)C(C)C
Reactant: CC#N
Reactant: C[C@@]1(F)[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(N3CCC3)nc(N)nc21
Agent: c1nnn[nH]1
Solvent: c1ccncc1
Product: CCN(CC)c1nc(N)nc2c1ncn2[C@@H]1O[C@@H]2COP(OC)O[C@H]2[C@@]1(C)F
Temperature: 25 °C
Reaction time: 17 h
Yield: 12 %

Procedure:
(2R,3R,4R,5R)-5-(2-Amino-6-azetidin-1-yl-purin-9-yl)-4-fluoro-2-hydroxymethyl-4-methyl-tetrahydro-furan-3-ol (8, 340 mg, 1.0 mmol) was dissolved in anhydrous pyridine (6 ml) at ambient temperature. A solution of 0.45 M 1H-tetrazole in acetonitrile (5.5 mL, 2.5 mmol) was added followed by bis(N,N-diisopropylamino)methylphosphoramidite (317 μL, 1.1 mmol). The mixture was stirred at ambient temperature for 17 h. The solvent was concentrated under reduced pressure and the residue was triturated with ethyl acetate (20 mL). The resulting precipitant of salts was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using a gradient of ethyl acetate in hexanes (40-80%). The product containing fractions were combined and concentrated to a white solid, 47 mg (12% yield).
Reaction SMILES: [C:1]([C:3]1([CH2:9][O:10][C:11]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:14]([C:15]([O:17]C(C)(C)C)=[O:16])=[C:13]([F:27])[CH:12]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([C:3]1([CH2:9][O:10][C:11]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:27])[CH:12]=2)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1)#[N:2]
Reactant: CC(C)(C)OC(=O)c1cc(C2CC2)c(OCC2(C#N)CCCCC2)cc1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N#CC1(COc2cc(F)c(C(=O)O)cc2C2CC2)CCCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.8 %

Procedure:
To a solution of tert-butyl 4-((1-cyanocyclohexyl)methoxy)-5-cyclopropyl-2-fluorobenzoate (0.498 g, 1.33 mmol) in dichloromethane (15 mL) was added trifluoroacetic acid (5 mL). The solution was stirred at ambient temperature for 1 hour and the solvent was concentrated in vacuo to dryness. The residue was triturated with diethyl ether (10 mL) to afford the title compound as a colorless solid (0.32 g, 75%): 1H NMR (300 MHz, DMSO-d6) 12.88 (br s, 1H), 7.32 (d, J=8.4 Hz, 1H), 6.93 (d, J=12.8 Hz, 1H), 4.14 (s, 2H), 2.02-1.95 (m, 3H), 1.72-1.65 (m, 3H), 1.51-1.43 (m, 4H), 1.24-1.18 (m, 1H), 0.91-0.85 (m, 2H), 0.61-0.56 (m, 2H); MS (ES−) m/z 316.2 (M−1).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:6][C:7]([NH:9][C:10]1[NH:11][C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH2:25][CH2:26][CH2:27]Cl)=[CH:13][C:14]=1[C:15]([NH2:17])=[O:16])=[O:8]>>[NH2:6][C:7]([NH:9][C:10]1[NH:11][C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH2:25][CH2:26][CH2:27][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:13][C:14]=1[C:15]([NH2:17])=[O:16])=[O:8]
Reactant: NC(=O)Nc1[nH]c(-c2ccccc2OCCCCl)cc1C(N)=O
Reactant: C1CCNC1
Product: NC(=O)Nc1[nH]c(-c2ccccc2OCCCN2CCCC2)cc1C(N)=O
Temperature: 120 °C
Reaction time: 5 h
Yield: 42 %

Procedure:
Pyrrolidine (0.5 mL) was added to 2-aminocarbonylamino-5-[2-(3-chloropropyloxy)phenyl]pyrrole-3-carboxamide (Compound No. 4-29, 30 mg, 0.090 mmol), the whole was sealed and stirred at 120° C. for 5 hours. This mixture was purified by silica gel column chromatography to give the target compound (14 mg) as a brown amorphous Powder (Yield 42%).
Reaction SMILES: [CH3:1][C:2]1[C@@H:19]([OH:20])[CH2:18][C@:14]2([OH:21])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([OH:48])[C:5]([C@@:7]1([CH3:47])[C@H:12]([C@@H:13]2[O:22][C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:24])[C@:11]2([O:33][C:34]([CH3:36])=[O:35])[CH2:31][O:32][C@@H:10]2[CH2:9][C@@H:8]1[O:37][C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O)=[O:6].I([O-])(=O)(=O)=O>>[CH3:1][C:2]1[C@@H:19]([OH:20])[CH2:18][C@:14]2([OH:21])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([OH:48])[C:5]([C@@:7]1([CH3:47])[C@H:12]([C@@H:13]2[O:22][C:23]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:24])[C@:11]2([O:33][C:34]([CH3:36])=[O:35])[CH2:31][O:32][C@@H:10]2[CH2:9][C@@H:8]1[OH:37])=[O:6]
Reactant: CC(=O)O[C@@]12CO[C@@H]1C[C@H](O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O)[C@@]1(C)C(=O)[C@H](O)C3=C(C)[C@@H](O)C[C@@](O)([C@@H](OC(=O)c4ccccc4)[C@H]21)C3(C)C
Agent: [O-][I+3]([O-])([O-])[O-]
Product: CC(=O)O[C@@]12CO[C@@H]1C[C@H](O)[C@@]1(C)C(=O)[C@H](O)C3=C(C)[C@@H](O)C[C@@](O)([C@@H](OC(=O)c4ccccc4)[C@H]21)C3(C)C

Procedure:
by dissolving the taxol analogue of formula 2 in a polar solvent, reacting the resultant solution with a base at a temperature of 20-50° C. for a time period in the range of 20-40 hours, and isolating 7-xyloxyl-10-deacetylbaccatin III, dissolving the 7-xylosyl-10-deacetylbaccatin III in a polar solvent, reacting the resultant solution with a periodate at 20-40° C. for a time period in the range of 20-40 hours to cleave the diol system of the xyloside into dialdehyde, treating the generated dialdehyde in an organic acid medium with salts of amine at 0-40° C. for 12-18 hours and isolating 10-deacetylbaccatin III of formula 1.
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH:4]([O:7][CH:8]([CH3:10])[CH3:9])[NH:3]1.[Li+].CCC[CH2-].[CH:16]([S:24](Cl)(=[O:26])=[O:25])=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCCC1.CCCCCC>[CH:16]([S:24]([N:3]1[CH:4]([O:7][CH:8]([CH3:10])[CH3:9])[CH2:5][CH2:6][C:2]1=[O:1])(=[O:26])=[O:25])=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CC(C)OC1CCC(=O)N1
Reactant: O=S(=O)(Cl)C=Cc1ccccc1
Agent: [CH2-]CCC
Agent: [Li+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)OC1CCC(=O)N1S(=O)(=O)C=Cc1ccccc1
Temperature: -45 °C
Reaction time: 0.5 h
Yield: 40.6 %

Procedure:
To a solution of 3.53 g of 2-oxo-5-isopropyloxy pyrrolidine in 85 cm3 of anhydrous tetrahydrofuran, cooled to -10° C., 15.42 g of a 1.6M solution of N-butyllithium in hexane is added, operating at -10° to -5° C. This is agitated for 30 minutes, while cooling to -45° C., then a solution of 5 g of styrenesulphonyl chloride (CA 47, 3262c, 1953) in 35 cm3 of anhydrous tetrahydrofuran is added slowly, while operating at -45° to -40° C. After allowing a return to ambient temperature, the solvent is evaporated off under reduced pressure and the residue is chromatographed on silica, eluting with a mixture of ethyl ethyl acetate and hexane (1--1). The product obtained is crystallized from ethanol, and 3.1 g of the expected product is obtained. m.p. 92°-94° C.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([O:12][CH3:13])=[CH:7][C:6]=1[CH3:14])=O.[NH2:15][C:16]([NH2:18])=[S:17]>CCO>[CH3:13][O:12][C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([C:3]2[N:15]=[C:16]([NH2:18])[S:17][CH:2]=2)=[C:6]([CH3:14])[CH:7]=1
Reactant: COc1cc(C)c(C(=O)CBr)c(C)c1
Reactant: NC(N)=S
Solvent: CCO
Product: COc1cc(C)c(-c2csc(N)n2)c(C)c1
Yield: 74.9 %

Procedure:
A mixture of 2-bromo-1-(4-methoxy-2,6-dimethylphenyl)ethanone (8.65 g, 33.6 mmol) and thiourea (2.56 g, 33.6 mmol) in 95% EtOH (48 mL) was heated at reflux for 60 min. The solution was concentrated and added with water (50 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene (50 mL). The solids were filtered and dried under vacuum to give 4-(4-methoxy-2,6-dimethylphenyl)thiazol-2-amine (5.9 g) as white solids in 66% yield: 1H NMR (500 MHz, CDCl3) δ 6.61 (s, 2 H), 6.27(s, 1 H), 4.91 (bs, 2 H), 3.79 (s, 3 H), 2.15 (s, 6 H).
Reaction SMILES: CCCCCCCCCO[C:11]1[CH:16]=[CH:15][C:14]([N:17]=[N:18][C:19]2[CH:24]=[CH:23][C:22](OCCCCCCCCCOC(C=C)=O)=[CH:21][CH:20]=2)=[CH:13][CH:12]=1.N#N>O.C(Cl)(Cl)Cl>[N:17]([C:14]1[CH:13]=[CH:12][CH:11]=[CH:16][CH:15]=1)=[N:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: C=CC(=O)OCCCCCCCCCOc1ccc(N=Nc2ccc(OCCCCCCCCC)cc2)cc1
Agent: N#N
Solvent: O
Solvent: ClC(Cl)Cl
Product: c1ccc(N=Nc2ccccc2)cc1
Temperature: 64 °C
Reaction time: 1 h

Procedure:
The polymer precursors A9AB9 and DA9AB along with the surfactant AC10COONa were used, with the structure of each shown in FIG. 3. The azobenzene nanoparticles were synthesized using a mini-emulsion process. Similar processes have been described in documents 12 through 14. To prepare the instant nanoparticle, 15 mg of surfactant AC10COONa was dissolved in 10 ml of water. 20 mol % of A9AB9 and 80 mol % of DA9AB were mixed with 2 w % 2,2′-azoisobutyronitrile (AIBN) in 2 g of chloroform. The solution was added drop by drop to the surfactant solution and stirred for 1 hour. The mixture was then sonicated in an ice bath for 2 minutes at 90% amplitude using an Ultrasonic Processor (ACE Glass, Inc) with a probe (Model LV261). The resulting mini-emulsion was stirred at room temperature with N2 bubbled into it for 15 min to remove oxygen. With continuous stirring and bubbling of N2, the emulsion was then heated in an oil bath at 64° C. for 6 hours to remove chloroform and promote polymerization. A nanocolloid suspension comprising the desired nanoparticles was obtained.
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[CH3:9].[C:10]([O:14][CH3:15])(=[O:13])[CH:11]=[CH2:12].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.O>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[NH2:6][C:5]1[CH:7]=[CH:8][C:2](/[CH:12]=[CH:11]/[C:10]([O:14][CH3:15])=[O:13])=[C:3]([CH3:9])[CH:4]=1
Reactant: Cc1cc(N)ccc1Br
Reactant: C=CC(=O)OC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)/C=C/c1ccc(N)cc1C
Temperature: 90 °C
Reaction time: 18 h

Procedure:
A solution of 4-bromo-3-methylaniline (5 g, TCI) in triethylamine (50 ml) was added with methyl acrylate (3.6 ml, TCI), tris(2-methylphenyl)phosphine (2.5 g, TCI), and palladium acetate (606 mg, WAKO), and stirred at 90° C. for 18 hours. The reaction mixture was added with water (30 ml) and ethyl acetate (30 ml×2) for extraction, and then successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine, the organic layer was dried, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Yamazen, n-hexane:ethyl acetate=3:1), and the solvent was evaporated under reduced pressure by using a rotary evaporator to obtain the title compound (yield: 4.0 g).
Reaction SMILES: [C:1]([N:4]([CH2:8][CH2:9][OH:10])[CH2:5][CH2:6][OH:7])(=[O:3])[CH3:2].C(N(CC)CC)C.Cl[C:19](Cl)([O:21]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[C:1]([N:4]1[CH2:8][CH2:9][O:10][C:19](=[O:21])[O:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N(CCO)CCO
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)N1CCOC(=O)OCC1

Procedure:
The procedure of Example 1 was followed using N-acetyl diethanolamine (12.3 g, 83.9 mmol), triethylamine (24.0 mL, 167.8 mmol), dry THF (600 mL) and triphosgene (8.3 g, 28.8 mmol). The filtrate was concentrated yielding only oligomeric compounds.
Reaction SMILES: [C:1]([CH:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][N:16]([CH3:18])[N:17]=2)=[CH:9][C:8]=1[N+:19]([O-])=O)[C:4]([NH2:6])=[O:5])#[N:2]>CN(C=O)C.O.CO.[Zn]>[NH2:2][C:1]1[NH:19][C:8]2[C:7]([C:3]=1[C:4]([NH2:6])=[O:5])=[CH:12][CH:11]=[C:10]([C:13]1[N:14]=[N:15][N:16]([CH3:18])[N:17]=1)[CH:9]=2
Reactant: Cn1nnc(-c2ccc(C(C#N)C(N)=O)c([N+](=O)[O-])c2)n1
Agent: [Zn]
Solvent: CO
Solvent: CN(C)C=O
Solvent: O
Product: Cn1nnc(-c2ccc3c(C(N)=O)c(N)[nH]c3c2)n1
Temperature: 100 °C
Yield: 39.8 %

Procedure:
Ferric chloride hexahydrate (2.82 g, 10.44 mmol) and zinc (2.276 g, 34.8 mmol) were added portionwise to a mixture of 2-cyano-2-(4-(2-methyl-2H-tetrazol-5-yl)-2-nitrophenyl)acetamide (1 g, 3.48 mmol) in DMF (8.71 mL) and water (8.71 mL) to give a yellow suspension which was heated to 100° C. for 1.25 hour. The mixture was then cooled to 20° C., diluted with MeOH (50.0 mL), filtered over Celite and concentrated under reduced pressure to ca. 20 mL (to remove most of the MeOH). Then the mixture was diluted with water (50 mL) and EtOAc (100 mL), stirred vigorously and filtered. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic layers were washed with sat. NaHCO3 (50 mL) and brine (50 mL). The organic layer was dried over anh. MgSO4, filtered and concentrated to give 489 mg as a purple solid which was purified by flash chromatography to give 2-amino-6-(2-methyl-2H-tetrazol-5-yl)-1H-indole-3-carboxamide (356 mg, 39.7% yield) as a purple solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 4.38 (s, 3H) 6.57 (s, 2H) 7.01 (s, 2H) 7.61-7.69 (m, 2H) 7.81 (s, 1H) 10.77 (s, 1H); MS m/z 258.2 (M+H)+; HPLC ca. 78%, RT=1.34 minutes.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([Cl:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].N1C=CC=CC=1.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>C(Cl)Cl>[Cl:12][C:5]1[CH:4]=[C:3]([F:13])[C:2]([NH:1][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1cc(N)c(F)cc1Cl
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1cc(NS(C)(=O)=O)c(F)cc1Cl
Reaction time: 72 h
Yield: 45.4 %

Procedure:
To a solution of methyl 5-amino-2-chloro-4-fluorobenzoate (152 mg, 0.75 mmol) and pyridine (0.07 mL, 0.82 mmol) in 3 mL CH2Cl2 was added methanesulfonyl chloride (0.06 mL, 0.82 mmol). After 3 days at room temperature, the reaction mixture was washed with saturated aqueous NaHCO3 and filtered through a silica plug to provide methyl 2-chloro-4-fluoro-5-[(methylsulfonyl)amino]benzoate (96 mg, 44%) as a solid (ESI-MS 280 (M−H)), which was hydrolyzed using aqueous NaOH to provide 2-chloro-4-fluoro-5-[(methylsulfonyl)amino]benzoic acid (ESI-MS 266 (M−H)), which was used without further purification.