Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1B(O)O.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.CCOC(C)=O.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]>[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(F)cc1F
Reactant: Nc1ccc(Br)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: Nc1ccc(-c2ccc(F)cc2F)cc1
Temperature: 25 °C

Procedure:
4-Bromoaniline (2.0 g, 11.6 mmol), (2,4-difluorophenyl)boronic acid (2.1 g, 13.4 mmol), Pd(dppf)Cl2 (952 mg, 1.2 mmol), and K2CO3 (3.2 g, 23.3 mmol) were dissolved in 1,4-dioxane (80 mL) and water (20 mL) and the resulting mixture was heated to 80° C. After 16 h the resulting mixture was cooled to room temperature, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and dry packed onto silica gel. Column chromatography yielded the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]([OH:12])[CH2:10]Cl)[CH:5]=[CH:6][CH:7]=1.[N-:13]=[N+:14]=[N-:15].[Na+].[Na+].[I-]>CN(C=O)C.CCOCC>[N:13]([CH2:10][CH:9]([OH:12])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)=[N+:14]=[N-:15]
Reactant: [N-]=[N+]=[N-]
Reactant: OC(CCl)Cc1cccc(Br)c1
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: [N-]=[N+]=NCC(O)Cc1cccc(Br)c1
Temperature: 75 °C

Procedure:
To a solution of 1-(3-bromophenyl)-3-chloropropan-2-ol (8.49 g, 34.0 mmol) in anhydrous DMF (100 mL) under N2 was added NaN3 (11.05 g, 170.0 mmol) and NaI (cat., 0.75 g, 5.0 mmol). The mixture was heated at 75° C. overnight. After cooling to room temperature, the mixture was diluted with ether and washed with water and brine. The solution was dried over Na2SO4 and concentrated under reduced pressure. The product was dried in a vacuum oven at 40° C. for 2 h to give 1-azido-3-(3-bromophenyl)propan-2-ol as a yellow oil which was used without purification. Yield (8.6 g, 98% crude).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl[C:15]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25]C)=[O:24])=[O:16].O[Li].O>C1COCC1.N1C=CC=CC=1>[C:8]1([C:4]2[CH:3]=[C:2]([NH:1][C:15]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:16])[CH:7]=[CH:6][CH:5]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: COC(=O)CCCCCCC(=O)Cl
Reactant: Nc1cccc(-c2ccccc2)c1
Agent: [Li]O
Solvent: c1ccncc1
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CCCCCCC(=O)Nc1cccc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 3-amino-biphenyl (315, 536 mg, 3.17 mmol) in THF/pyridine (2:1, 6 mL) was added methyl 7-(chlorocarbonyl)heptanoate (0.49 mL, 3.48 mmol), and the resulting solution was stirred at room temperature for 16 h. After dilution with saturated NaCl solution (15 mL) and extraction with ethyl acetate, the organic layer was dried over Na2SO4, filtered and concentrated. The residue was then dissolved in THF/methanol/H2O (1:1:2, 8 mL), followed by the treatment of LiOH—H2O (665 mg, 15.85 mmol). The reaction mixture was stirred at room temperature for 1 h prior to acidification (pH=1), and extraction with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated. After purification by flash chromatography (eluent 0-100% EtOAc in hexanes), the title compound 316 was obtained as a white solid (889 mg, 86% yield). 1H NMR: (DMSO) δ (ppm): 1.30-1.40 (m, 4H), 1.50-1.59 (m, 2H), 1.60-1.68 (m, 2H), 2.24 (t, J=7.4 Hz, 2H), 2.37 (t, J=7.4 Hz, 2H), 7.32 (dt, J=7.8, 1.6 Hz, 1H), 7.36-7.42 (m, 2H), 7.46-7.52 (m, 2H), 7.58-7.64 (m, 3H), 7.96 (s, 1H), 10.07 (br s, 1H). MS: (calc.) 325.4; (obt.) 326.1 (MH)+.
Reaction SMILES: [F:1][CH2:2][C:3]([CH3:8])([CH3:7])[C:4](=[O:6])[CH3:5].[Br:9]Br.N1C=NC=N1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CC(C)=O>[F:1][CH2:2][C:3]([CH3:8])([CH3:7])[C:4](=[O:6])[CH2:5][Br:9]
Reactant: BrBr
Reactant: CC(=O)C(C)(C)CF
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: c1nc[nH]n1
Solvent: CC(C)=O
Solvent: ClCCl
Product: CC(C)(CF)C(=O)CBr
Yield: 99.9 %

Procedure:
4.18 kg (35.4 mol) of 1-fluoro-2,2-dimethyl-butan-3-one were dissolved in 30 liters of methylene chloride, and 5.67 kg of bromine were added dropwise at 20° C. in the course of 2 hours such that continuous decolorisation occurred. The solvent was distilled off under a waterpump vacuum, a further 15 liters of methylene chloride were added to the residue and the solvent was again distilled off under a waterpump vacuum. The crude 1-fluoro-4-bromo-2,2-dimethyl-butan-3-one (6.97 kg, quantitative yield) was added dropwise to 2.45 kg of 1,2,4-triazole and 4.89 kg of potassium carbonate in 21.4 liters of acetone at 30° to 35° C. in the course of 2 hours, whilst cooling. The mixture was subsequently stirred at room temperature for 15 hours, the insoluble material was filtered off and the solvent was distilled off from the filtrate under a waterpump vacuum. 6.12 kg (93% of theory) of 1-fluoro-2,2-dimethyl-4-(1,2,4-triazol-1-yl)-butan-3-one, which could be further reacted directly, were obtained.
Reaction SMILES: [CH3:1][C:2]1([CH3:34])[CH2:9][C:8](=O)[CH2:7][CH2:6][CH2:5][C:4]([CH3:12])([CH3:11])[P:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[C:24]([CH:25]([CH3:27])[CH3:26])=[CH:23][C:22]([CH:28]([CH3:30])[CH3:29])=[CH:21][C:20]=1[CH:31]([CH3:33])[CH3:32].C(O)COCCO.O.NN.[OH-].[K+]>>[CH3:34][C:2]1([CH3:1])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]([CH3:11])([CH3:12])[P:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[C:20]([CH:31]([CH3:32])[CH3:33])=[CH:21][C:22]([CH:28]([CH3:30])[CH3:29])=[CH:23][C:24]=1[CH:25]([CH3:27])[CH3:26]
Reactant: CC(C)c1cc(C(C)C)c(-c2ccccc2P2C(C)(C)CCCC(=O)CC2(C)C)c(C(C)C)c1
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: OCCOCCO
Solvent: O
Product: CC(C)c1cc(C(C)C)c(-c2ccccc2P2C(C)(C)CCCCCC2(C)C)c(C(C)C)c1
Temperature: 210 °C
Reaction time: 7 h
Yield: 41.1 %

Procedure:
A round bottom flask was charged with 2,2,8,8-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphocan-4-one (1.25 g, 2.61 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Nitrogen-sparged diethylene glycol (13.7 mL, 144 mmol, 55 equiv) was added, and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The mixture was charged with hydrazine hydrate (1.16 mL, 13.1 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (733 mg, 13.1 mmol, 5 equiv). The mixture was immersed in an oil bath at 160° C. under a nitrogen atmosphere. The temperature of the bath was gradually increased to 210° C. over 30 minutes and kept at that temperature for 7 hours. The reaction mixture was cooled to room temperature under a positive pressure of nitrogen overnight. The Claisen adapter was washed with ethyl acetate (30 mL). The phases were partitioned, and the organic layer was collected. The aqueous layer was washed with ethyl acetate (3×20 mL), and the combined organic fractions were washed once with water (50 mL) and aqueous saturated sodium chloride (50 mL), dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The purified product was triturated from hot methanol and collected by filtration to afford the title compound as a white solid (499 mg, 92 area % by HPLC, 41% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.96-7.87 (m, 1H), 7.33-7.26 (m, 2H), 7.23-7.17 (m, 1H), 6.97 (s, 2H), 3.00-2.85 (m, 1H), 2.61-2.44 (m, 2H), 1.91-1.61 (m, 5H), 1.61-1.41 (m, 5H), 1.39 (d, J=2.5 Hz, 6H), 1.31 (d, J=6.9 Hz, 6H), 1.23 (d, J=6.8 Hz, 6H), 0.98 (d, J=6.7 Hz, 6H), 0.74 (d, J=15.0 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 148.2 (d, J=35 Hz), 147.1, 145.8, 137.3, 136.8 (d, J=8 Hz), 136.6 (d, J=21 Hz), 132.0 (d, J=7 Hz), 126.9, 124.6, 119.8, 43.8 (d, J=18 Hz), 36.3 (d, J=30 Hz), 34.3, 31.1, 31.0 (d, J=18 Hz), 28.3 (d, J=4 Hz), 26.8 (d, J=11 Hz), 26.7, 24.4, 23.1 (d, J=2 Hz), 22.4 (d, J=6 Hz). 31P NMR (CDCl3, 202 MHz) δ ppm 10.5 (s). HRMS (TOF-ESI+) calcd for [M, C32H49P]+ 464.3572, found 464.3584.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C@H:13]([NH:18][C:19]([C@@H:21](/[CH:31]=[CH:32]/[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C:39]([F:48])([F:47])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[C@@:22]([OH:30])([CH2:26][CH2:27][O:28][CH3:29])[C:23]([OH:25])=[O:24])=[O:20])[C:14]([O:16][CH3:17])=[O:15])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[I-].[Na+].C(=O)(O)[O-].[Na+].Cl[CH2:57][C:58]1[O:59][C:60](=[O:64])[O:61][C:62]=1[CH3:63]>CN(C=O)C>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][C@H:13]([NH:18][C:19]([C@@H:21](/[CH:31]=[CH:32]/[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C:39]([F:47])([F:48])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[C@@:22]([OH:30])([CH2:26][CH2:27][O:28][CH3:29])[C:23]([O:25][CH2:57][C:58]2[O:59][C:60](=[O:64])[O:61][C:62]=2[CH3:63])=[O:24])=[O:20])[C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCCCCC(F)(F)CCCCCC/C=C/[C@H](C(=O)N[C@@H](Cc1ccc(OCCCC)cc1)C(=O)OC)[C@@](O)(CCOC)C(=O)O
Reactant: Cc1oc(=O)oc1CCl
Agent: O=C([O-])O
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCC(F)(F)CCCCCC/C=C/[C@H](C(=O)N[C@@H](Cc1ccc(OCCCC)cc1)C(=O)OC)[C@@](O)(CCOC)C(=O)OCc1oc(=O)oc1C
Reaction time: 22 h
Yield: 83 %

Procedure:
To the mixture of (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-(2-methoxy-ethyl)-nonadec-4-enoic acid (No. 5514403, 50 mg, 0.0731 mmol), sodium iodide (16.4 mg, 0.110 mmol), sodium bicarbonate (7.4 mg, 0.877 mmol) and the DMF (1 mL) was added commercially available 4-chloromethyl-5-methyl-1,3-dioxol-2-one (15.9 μL, 0.145 mmol) at room temperature, and the mixture was stirred as it was for 22 hours. After confirming the consumption of the starting materials by LCMS, the reaction solution was filtered through a syringe filter, and purified as it was by preparative HPLC. The purified fraction was freeze-dried to obtain the title compound (48 mg, 83% yield) as yellow oil.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:25]([CH3:26])=[CH:24][C:14]2[N:15]=[C:16]([N:18]3[CH2:22][CH:21]=[CH:20][C:19]3=[O:23])[S:17][C:13]=2[C:12]=1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:34][N:35]1[C:43]2[C:38](=[CH:39][C:40](B(O)O)=[CH:41][CH:42]=2)[CH:37]=[N:36]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh]>[C:1]([O:5][C@@H:6]([C:11]1[C:25]([CH3:26])=[CH:24][C:14]2[N:15]=[C:16]([N:18]3[CH2:22][CH:21]([C:40]4[CH:39]=[C:38]5[C:43](=[CH:42][CH:41]=4)[N:35]([CH3:34])[N:36]=[CH:37]5)[CH2:20][C:19]3=[O:23])[S:17][C:13]=2[C:12]=1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(N3CC=CC3=O)sc2c1-c1ccc(Cl)cc1
Reactant: Cn1ncc2cc(B(O)O)ccc21
Agent: [Rh]
Agent: C1=C\CC/C=C\CC/1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Solvent: C1=CCCC=CCC1
Product: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(N3CC(c4ccc5c(cnn5C)c4)CC3=O)sc2c1-c1ccc(Cl)cc1
Temperature: 80 °C

Procedure:
To a solution of (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-oxo-2,5-dihydro-1H-pyrrol-1-yl)benzo[d]thiazol-6-yl)acetate (12 mg, 0.025 mmol) in 1,4-dioxane/water (0.5 mL/50 μL) was added 1-methyl-1H-indazol-5-ylboronic acid (8 mg, 0.050 mmol), followed by chloro(1,5-cyclooctadiene)rhodium (I) dimer (1 mg), BINAP (5 mg), and potassium carbonate solution (2 N, 6 μL). The mixture was purged with nitrogen and heated at 80° C. for 24 hours. The mixture was diluted with EtOAc, and was washed with water and brine, dried with sodium sulfate and filtered. Concentration and purification by flash column chromatography (hexanes/EtOAc) gave (2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate. LCMS-ESI+: calc'd for C33H33ClN4O4S: 617.2 (M+H+); Found: 617.2 (M+H+).
Reaction SMILES: CON(C)[C:4](=[O:19])[CH2:5][CH:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Cl:21][C:22]1[C:23](I)=[CH:24][C:25]([F:28])=[N:26][CH:27]=1>>[Cl:21][C:22]1[C:23]([C:4](=[O:19])[CH2:5][CH:6]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:24][C:25]([F:28])=[N:26][CH:27]=1
Reactant: CON(C)C(=O)CC(c1ccccc1)c1ccccc1
Reactant: Fc1cc(I)c(Cl)cn1
Product: O=C(CC(c1ccccc1)c1ccccc1)c1cc(F)ncc1Cl

Procedure:
In analogy to example 55, step 2, the title compound was prepared from N-methoxy-N-methyl-3,3-diphenyl-propionamide and 5-chloro-2-fluoro-4-iodopyridine as a light yellow liquid, MS (EI): m/z=339 ([M]+, 1Cl).
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C:3](=O)[CH2:4][C:5]#[N:6].[N+:10]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][NH2:20])=[CH:15][CH:14]=1)([O-:12])=[O:11].C(O)(=O)C>CCO>[C:2]([C:3]1[CH:4]=[C:5]([NH2:6])[N:19]([C:16]2[CH:15]=[CH:14][C:13]([N+:10]([O-:12])=[O:11])=[CH:18][CH:17]=2)[N:20]=1)([CH3:9])([CH3:8])[CH3:1]
Reactant: NNc1ccc([N+](=O)[O-])cc1
Reactant: CC(C)(C)C(=O)CC#N
Solvent: CC(=O)O
Solvent: CCO
Product: CC(C)(C)c1cc(N)n(-c2ccc([N+](=O)[O-])cc2)n1
Temperature: 25 °C
Yield: 84.9 %

Procedure:
To a solution of 4,4-dimethyl-3-oxopentanenitrile (20.4 g, 163 mmol) and 4-nitrophenylhydrazine (25.0 g, 163 mmol) in anhydrous EtOH (300 mL) was added acetic acid (3.4 mL, 60 mL) dropwise. The reaction was stirred at reflux under N2 for 18 h. The reaction mixture was cooled to room temperature and concentrated at reduced pressure. The residue was partitioned between EtOAc (500 mL) and aqueous saturated NaHCO3 solution (300 mL). The organic layer was washed with water and brine, dried over Na2SO4, and concentrated at reduced pressure. The crude residue was purified by MPLC (eluting with 80:20 hexanes/EtOAc) to give 36.0 g (85%) of the desired product. 1H-NMR (DMSO-d6) δ 8.28 (d, J=6.9 Hz, 2H), 7.93 (d, J=6.9 Hz, 2H), 5.55 (s, 2H), 5.46 (s, 1H), 1.20 (s, 9H); MS LC-MS [M+H]+=261, RT=2.74 min.
Reaction SMILES: [F:1][C:2]1[C:3]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=2[F:23])=[C:4]([CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[C:10]=1[F:11])[C:5]([OH:7])=[O:6].[C:24](=O)(O)[O-].[Na+].COS(OC)(=O)=O.CCCCCC>CC(C)=O.CCOC(C)=O>[CH3:24][O:6][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[C:10]([F:11])=[C:2]([F:1])[C:3]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[F:23]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(F)c(F)c1Nc1ccc(I)cc1F
Reactant: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Solvent: COS(=O)(=O)OC
Solvent: CCCCCC
Product: COC(=O)c1cc([N+](=O)[O-])c(F)c(F)c1Nc1ccc(I)cc1F
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-nitro-benzoic acid (595.3 g, 1.363 mol) in acetone (9 L) was added sodium bicarbonate (609.0 g, 3.48 mol) and the mixture was stirred for 10 min. To this suspension was added dimethylsulfate (285.6 ml, 3.026 mol) and refluxed for 3 h (completion of reaction was confirmed by TLC-hexane: EtOAc/4:1), cooled to room temperature and evaporated under vacuum. The residue (yellow) was further digested in hot methanol (2 L), filtered, washed with methanol and dried to give the title compound as a solid (yellow). Yield: 405.63g (65.54%).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH:9]([NH:14]C(OC(C)(C)C)=O)[CH2:8]2)(=[O:3])[CH3:2].[ClH:22].O1CCOCC1>C(O)(=O)C>[ClH:22].[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH:9]([NH2:14])[CH2:8]2)(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1ccc2c(c1)CC(NC(=O)OC(C)(C)C)C2
Agent: Cl
Solvent: CC(=O)O
Solvent: C1COCCO1
Product: CC(=O)Oc1ccc2c(c1)CC(N)C2

Procedure:
Using 5-acetoxy-2-(tert-butoxycarbonylamino)indan (120 mg, 0.40 mmol), 4N hydrochloric acid-dioxane (2 ml) and acetic acid (6 ml), a similar procedure to Production Example 213 was carried out to obtain 5-acetoxy-2-aminoindan hydrochloride (86 mg, 0.38 mmol) having the following physical properties:
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[O:17][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH2:4]1)[NH:11][C:10](=[O:16])[CH:9]=[CH:8]3.C(Cl)(Cl)Cl.[C:22](OC(=O)C)(=[O:24])C.C(OC=O)=O>O1CCCC1.CCOCC>[CH:22]([NH:1][CH2:2][CH:3]1[O:17][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH2:4]1)[NH:11][C:10](=[O:16])[CH:9]=[CH:8]3)=[O:24]
Reactant: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CN)C2
Reactant: CC(=O)OC(C)=O
Agent: O=COC=O
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CNC=O)C2
Temperature: 70 °C

Procedure:
(+)-2-Aminomethyl-5-methyl-2,3,6,7-tetrahydrofuro-[2,3-f]quinoline-7-one (1.17 g, 5.08 mmol) was suspended in tetrahydrofuran (30 ml)--chloroform (30 ml). To the suspension, acetic anhydride--formic anhydride (2.24 g, 25.4 mmol) was added, and refluxed with heat in a bath of 70° C. for 3 hours. The resulting reaction mixture was cooled at room temperature, and combined with ether. The insoluble matter, which was collected by filtration, was recrystallized from chloroform--methanol--ether. As a result, 460 mg of the title compound was obtained as colorless powder (35.1%).
Reaction SMILES: [CH2:1]([N:12]1[CH:17]=[C:16]([CH2:18][C:19]2[CH:20]=[N:21][C:22](=[O:29])[N:23]([CH2:25][C:26](O)=[O:27])[CH:24]=2)[C:15](=[O:30])[N:14]=[C:13]1[S:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].Cl.[CH3:41][NH:42][CH3:43].C(N(C(C)C)CC)(C)C.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CO.C(=O)([O-])[O-].[K+].[K+]>[CH2:1]([N:12]1[CH:17]=[C:16]([CH2:18][C:19]2[CH:20]=[N:21][C:22](=[O:29])[N:23]([CH2:25][C:26]([N:42]([CH3:43])[CH3:41])=[O:27])[CH:24]=2)[C:15](=[O:30])[N:14]=[C:13]1[S:31][CH2:32][C:33]1[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CNC
Reactant: CCCCCCCCCCCn1cc(Cc2cnc(=O)n(CC(=O)O)c2)c(=O)nc1SCc1ccc(F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCCCCCCCCCCn1cc(Cc2cnc(=O)n(CC(=O)N(C)C)c2)c(=O)nc1SCc1ccc(F)cc1
Reaction time: 24 h

Procedure:
A mixture of 1-undecyl-2-(4-fluorobenzyl)thio-5-(1-(carboxymethyl)-2-oxopyrimid-5-ylmethyl)pyrimidin-4-one, dimethylamine hydrochloride (0.02 g), diisopropylethylamine (0.045 ml), hydroxybenzotriazole (0.005 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.045 g) in dry methylene chloride were stirred together for 24 h and diluted with 3% methanol in methylene chloride and 5% aqueous potassium carbonate. The organic layer was added directly to a SepPak cartridge (SiO2, 10 g) and eluted with 0-20% methanol in ethyl acetate to give the desired product (0.085 g). 1H-NMR (CDCl3) δ0.8-0.95 (3H,m), 1.15-1.4 (16H,m), 1.6-1.85 (2H,m), 2.98 (3H,s), 3.13 (3H,s), 3.49 (2H,s), 3.77 (2H,t), 4.46 (2H,s), 4.74 (2H,s), 6.9-7.1 (2H,m), 7.14 (1H,s), 7.3-7.45 (2H,m), 7.78 (1H,bd), 8.49 (1H,bd); MS (APCI+) found (M+1)=584; C31H42FN5O3S requires 583.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:14])=[CH:4][CH:5]=[C:6]2[NH:12][C:11](=[O:13])[O:10][C:8](=O)[C:7]=12.[NH:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1C(O)=O.O>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:10])[N:15]3[CH2:22][CH2:21][CH2:20][C@H:16]3[C:11](=[O:13])[NH:12][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14]
Reactant: O=c1[nH]c2ccc(F)c(Cl)c2c(=O)o1
Reactant: O=C(O)[C@@H]1CCCN1
Solvent: CN(C)C=O
Solvent: O
Product: O=C1Nc2ccc(F)c(Cl)c2C(=O)N2CCC[C@@H]12

Procedure:
3.3 g (0.015 mol) of 6-chloro-5-fluoroisatoic acid anhydride and 2 g (0.017 mol) of L-proline in 7.5 ml of dimethylformamide are heated to 120° for 2 hours, cooled, treated with 12 ml of distilled water and the precipitated brown crystals are filtered off. By recrystallization of the crude product from acetone/hexane there is obtained (S)-6-chloro-7-fluoro-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione of melting point 217°-219°.
Reaction SMILES: CCCCCCCCCCCCCCCCCC(N[C@H:21]([C@H:91](O)/[CH:92]=[CH:93]/[CH2:94][CH2:95][CH2:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH2:104][CH2:105][CH3:106])[CH2:22][O:23][C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@H]3NC(C)=O)[C@H](O[C@@]3(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)[C@H]2O)[C@H](O)[C@H]1O)=O.[OH2:108]>>[C:22]([OH:23])(=[O:108])[CH2:21][CH2:91][CH2:92][C:93]#[C:94][C:95]#[C:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH2:104][CH2:105][CH2:106][CH2:22][CH2:21][CH2:91][CH3:92]
Reactant: CCCCCCCCCCCCC/C=C/[C@@H](O)[C@H](CO[C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@H]3NC(C)=O)[C@H](O[C@]3(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O3)[C@H]2O)[C@H](O)[C@H]1O)NC(=O)CCCCCCCCCCCCCCCCC
Reactant: O
Product: CCCCCCCCCCCCCCC#CC#CCCCC(=O)O

Procedure:
Ganglioside GM1, cholera toxin from Vibrio Cholerae, human serum albumin, and wheat germ agglutinin were purchased from Sigma. 5,7-docosadiynoic acid was synthesized. Deionized water was obtained by passing distilled water through a Millipore μF ultrapurification train. Solvents used were reagent grade. The ganglioside GM1 was mixed at 5 mol % with the diacetylene “matrix lipid” monomers. Liposomes were prepared using the probe sonication method and polymerized by UV irradiation (254 nm). The conjugated ene-yne backbone of polydiacetylene liposomes results in the appearance of a deep blue/purple solution. The visible absorption spectrum of the freshly prepared purple liposomes is shown in FIG. 25.
Reaction SMILES: [Cl:1][C:2](=[CH2:7])[CH2:3][N:4]=[C:5]=[S:6].[CH2:8]([SH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N12CCN(CC1)CC2>C(#N)C.C1(C)C=CC=CC=1>[CH2:8]([S:15][C:5](=[S:6])[NH:4][CH2:3][C:2]([Cl:1])=[CH2:7])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: C=C(Cl)CN=C=S
Reactant: SCc1ccccc1
Agent: C1CN2CCN1CC2
Solvent: CC#N
Solvent: Cc1ccccc1
Product: C=C(Cl)CNC(=S)SCc1ccccc1
Temperature: 75 °C
Reaction time: 1 h

Procedure:
47 g of 2-chloro-allyl isothiocyanate and 40 g of benzyl mercaptan are dissolved in 150 ml of acetonitrile and 150 ml of toluene. Then 1 g of 1,4-diazabicyclo[2.2.2]octane is added and the mixture is heated to 75° C. and stirred for one hour. After cooling to room temperature, the solvent is removed by evaporation and the residue is crystallised from ether/hexane. In that manner the title product having a melting point of 46-48° C. (compound A) is obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[C:9]([C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][N:12]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[CH3:27][S:28]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29]>>[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([S:28]([CH3:27])(=[O:30])=[O:29])[CH:36]=2)=[CH:13][N:12]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NC(C(=O)c1ccc(Br)cn1)c1ccc(Cl)c(Cl)c1
Reactant: CS(=O)(=O)c1cccc(B(O)O)c1
Product: CC(C)(C)OC(=O)NC(C(=O)c1ccc(-c2cccc(S(C)(=O)=O)c2)cn1)c1ccc(Cl)c(Cl)c1

Procedure:
The title compound was prepared from rac-[2-(5-bromo-pyridin-2-yl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester and 3-methylsulfonylphenylboronic acid in analogy to Example 1b): MS (ISP): 535.1 and 536.1 (M+H)+, 479.1 and 481.0 ((M-isobutene)+H)+ (100%).