Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([NH:8][CH:9]([CH2:21][O:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)[CH2:10][O:11][C:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][N:13]=1)=O)(C)(C)C.O1CCOCC1.[ClH:35]>CO>[ClH:35].[ClH:35].[NH2:8][CH:9]([CH2:21][O:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)[CH2:10][O:11][C:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][N:13]=1
Reactant: CC(C)(C)OC(=O)NC(COc1cccnc1)COc1noc2ccccc12
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: NC(COc1cccnc1)COc1noc2ccccc12

Procedure:
To a solution of 0.30 g of 3-[2-tert-butoxycarbonylamino-3-(3-pyridyloxy)propoxy]-1,2-benzoisoxazole in 5 ml of methanol is added 1 ml of a dioxane solution (3.2N) of hydrogen chloride at room temperature, and they are subjected to reaction at the same temperature for two hours, after which the crystals precipitated are collected by filtration, to obtain 0.24 g of colorless, crystalline 3-[2-amino-3-(3-pyridyloxy)propoxy]-1,2-benzoisoxazole dihydrochloride having a melting point of 216.8°-218.9° C. (decomp.).
Reaction SMILES: [I:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:11]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>CC(C)=O>[I-:1].[C:5]1([CH2:4][CH2:3][CH2:2][N+:26]2[CH:27]=[CH:28][C:23]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:24][CH:25]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: ICCCc1ccccc1
Reactant: CCCCCCCCCCCCc1ccncc1
Solvent: CC(C)=O
Product: CCCCCCCCCCCCc1cc[n+](CCCc2ccccc2)cc1
Product: [I-]

Procedure:
The compound was synthesized by boiling a mixture of 2.26 g (9.2 mmol) 1-iodo-3-phenyl propane and 2,57 g (10.0 mmol) 4-n-dodecylpyridine in 35 ml of dry acetone for 16 hours. The solvent was evaporated and the yellow solid substance was recrystallized from THF/ether. The yield is 3.06 g (6.2 mmol), melting point 79.0°-80.0° C.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].[CH3:22][CH2:23]CCCCCCC=CCCCCCCCC.CC=CCCCCCCCCCCCCC.CC=CCCCCCCCCCCC>>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCCCC=CCCCCCCCCCCC
Reactant: CCCCCCCCC=CCCCCCCCC
Agent: CC=CCCCCCCCCCCC
Agent: CC=CCCCCCCCCCCCCC
Product: C=CCCCCCCCCCCCCCCCCCCC
Product: C=CCCCCCCCCCCCCCCCCCCCCC

Procedure:
A mixture of 9-triscosene and 9-heneicosene was prepared by following the process described in Example 8, namely by conducting, over 39 g. of the aforedescribed rehenium-containing catalyst, at 60° C., a mixture of 196 g. (0.79 mole) of 9-octadecene, 58 g. (0.26 mole) of 2-hexadecene, and 16 g. (0.08 mole) of 2-tetradecene. After a reaction time of 5 hours and with a throughput of 200 ml. of olefin mixture per hour, 3.2% by weight of tricosene and 1.4% by weight of heneicosene were obtained. The content of the cis-isomer was 24%.
Reaction SMILES: C(O[C:4]([C:6]1[S:7][C:8](Br)=[C:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][C:10]=12)=[O:5])C.[CH3:18][O-:19].[Na+].[CH3:21][Li]>CO.CCOCC>[CH3:18][O:19][C:8]1[S:7][C:6]([C:4](=[O:5])[CH3:21])=[C:10]2[CH2:11][CH2:12][C:13]([CH3:15])([CH3:16])[CH2:14][C:9]=12
Reactant: CCOC(=O)c1sc(Br)c2c1CCC(C)(C)C2
Reactant: C[O-]
Reactant: [Li]C
Agent: [Na+]
Solvent: CO
Solvent: CCOCC
Product: COc1sc(C(C)=O)c2c1CC(C)(C)CC2
Reaction time: 0.25 h

Procedure:
A mixture of crude 3-bromo-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid ethyl ester (774 mg, 2.44 mmol), CuO (99 mg, 1.25 mmol) and NaOMe (540 mg, 10 mmol) in methanol (3 mL) is refluxed for 76 h. The mixture is diluted with ether (75 mL) and extracted with 1 N aq. NaOH (2×30 mL). The aq. extracts are acidified with 2 N aq. HCl (75 mL) and extracted with DCM (3×50 mL). The organic extracts are dried (Na2SO4), filtered and evaporated to provide crude 3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (262 mg). This material is dissolved in dry diethyl ether (10 mL) and methyllithium (0.7 mL, 1.6 N in diethyl ether) is added slowly at room temperature. After 15 min, the mixture is diluted with diethyl ether (50 mL), extracted with 1 N aq. NaOH (2×5 mL), dried (Na2SO4), filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane/EA to provide 1-(3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-ethanone (44 mg) as a yellow oil; LC-MS: tR=1.03 min, [M+1]=239.30; 1H NMR (CDCl3): δ 3.96 (s, 3H), 2.98 (t, J=6.4 Hz, 2H), 2.41 (s, 3H), 2.26 (s, 2H), 1.53 (t, J=6.4 Hz, 2H), 0.95 (s, 6H).
Reaction SMILES: N(C(C)(C)C#N)=NC(C)(C)C#N.[Br:13]N1C(=O)CCC1=O.[CH3:21][C:22]1[C:31](=[O:32])[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:23]=1[C:39]1[O:40][CH:41]=[CH:42][N:43]=1>C(Cl)(Cl)(Cl)Cl.O>[Br:13][CH2:21][C:22]1[C:31](=[O:32])[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:23]=1[C:39]1[O:40][CH:41]=[CH:42][N:43]=1
Reactant: Cc1c(-c2ncco2)n(-c2ccccc2)c2ncccc2c1=O
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: O=c1c(CBr)c(-c2ncco2)n(-c2ccccc2)c2ncccc12
Temperature: 90 °C
Reaction time: 8 h
Yield: 47.8 %

Procedure:
A mixture of 2,2′-azobis(2-methylpropionitrile) (AIBN, 43.4 mg, 0.265 mmol), N-bromosuccinimide (345 mg, 1.94 mmol) and 3-methyl-2-oxazol-2-yl-1-phenyl-1H-[1,8]naphthyridin-4-one (535 mg, 1.76 mmol) in carbon tetrachloride (22.0 mL) was heated at 90° C. for 2 hr. The reaction was cooled to 25° C. and sat overnight. The reaction was diluted with water (30 mL) and extracted into methylene chloride (2×50 mL). The combined organics were then washed with a saturated aqueous solution of sodium bicarbonate (2×50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in methylene chloride and methanol, treated with silica gel, re-concentrated and dried in vacuo. Flash chromatography (40 g, 15%-40% ethyl acetate-hexanes) gave 3-bromomethyl-2-oxazol-2-yl-1-phenyl-1H-[1,8]naphthyridin-4-one (321.7 mg, 47.7%).
Reaction SMILES: [C:1]12([NH:11][C:12]#[N:13])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[ClH:14].[CH:15]1([NH2:21])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>>[ClH:14].[C:1]12([NH:11][C:12]([NH:21][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[NH:13])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: NC1CCCCC1
Reactant: N#CNC12CC3CC(CC(C3)C1)C2
Agent: Cl
Product: N=C(NC1CCCCC1)NC12CC3CC(CC(C3)C1)C2
Temperature: 200 °C

Procedure:
Adamantan-1-ylcyanamide (514 mg, 2.92 mmol), and cyclohexylamine hydrochloride (398 mg, 2.93 mmol) were finely ground together, and heated at 200° C. for 10 min. The resultant glassy solid was pulverized, and extracted twice with 50 ml boiling 5% HCl. The insoluble material was filtered, and dried. 346 mg, mp 264°-270° (p.h.b. 240° C.). On cooling the combined aqueous extracts to 25°, a white ppt. formed, and was filtered off, 56 mg. Combined crude yield: 44%. Crystallization of a 50 mg sample of the crude product from EtOH/Et2O afforded white needles (25 mg, mp 269°-271° C. (p.h.b. 240°), lit. 268°-269° C.). 1H (CD3OD) 1.208-1.474 (m, 5H), 1.744 (s, 9H), 1.967 (s, H), 2.119 (5, 3H), 3.434 (m, 1H), 13C (CD3OD) (broad band decoupled) 5.55, 26.26, 30.96, 33.74, 36.74, 42.73.
Reaction SMILES: [C:1]1([C:7]2[C:19]3[C:18]4[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][C:13]=4[CH:12]=[N:11][C:10]=3[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:27].O1CCOCC1>ClCCl>[Cl-:27].[C:1]1([C:7]2[C:19]3[C:18]4[CH2:17][CH2:16][NH2+:15][CH2:14][C:13]=4[CH:12]=[N:11][C:10]=3[NH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cl
Reactant: CC(C)(C)OC(=O)N1CCc2c(cnc3[nH]nc(-c4ccccc4)c23)C1
Solvent: C1COCCO1
Solvent: ClCCl
Product: [Cl-]
Product: c1ccc(-c2n[nH]c3ncc4c(c23)CC[NH2+]C4)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 95 %

Procedure:
To a solution of tert-butyl 1-phenyl-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylate (0.21 g, 0.60 mmol) in dichloromethane (5 mL) was added 4 M solution of HCl gas in 1,4-dioxane (1.5 mL, 6.0 mmol). The reaction was shaken at room temperature for 16 hours. A yellow solid precipitated out in the reaction mixture, which was filtered to give the pure desired product, 1-phenyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7-ium chloride (0.184 g, 95%) as a yellow solid; M.p.=265° C. decomposition; 400 MHz 1H NMR (DMSO-d6) δ: 13.91 (s, 1H), 9.39 (s, 2H), 8.43 (s, 1H), 7.62-7.46 (m, 5H), 4.44-3.38 (m, 2H), 3.38-3.2 (m, 2H), 3.01 (t, J=6.4 Hz, 2H); LCMS [M+H]: 251.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]([OH:35])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][C:15]([C:17]3([C:20]4[CH:30]=[CH:29][C:23]5[O:24][C:25]([F:28])([F:27])[O:26][C:22]=5[CH:21]=4)[CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[C:31]([CH3:34])([CH3:33])[CH3:32]>CO.C(N(CC)CC)C>[C:31]([C:6]1[N:5]([CH2:4][C@@H:3]([OH:35])[CH2:2][NH:1][C:25](=[O:26])[O:24][CH3:23])[C:13]2[C:8]([CH:7]=1)=[CH:9][C:10]([NH:14][C:15]([C:17]1([C:20]3[CH:30]=[CH:29][C:23]4[O:24][C:25]([F:28])([F:27])[O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]1)=[O:16])=[CH:11][CH:12]=2)([CH3:32])([CH3:34])[CH3:33]
Reactant: CC(C)(C)c1cc2cc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)ccc2n1C[C@H](O)CN
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)NC[C@H](O)Cn1c(C(C)(C)C)cc2cc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)ccc21
Reaction time: 0.5 h

Procedure:
To a stirred solution (R)—N-(1-(3-amino-2-hydroxypropyl)-2-tert-butyl-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (0.10 g, 0.20 mmol) in methanol (1 mL) was added 2 drops of triethylamine and methylchloroformyl chloride (0.020 mL, 0.25 mmol). After 30 min, the reaction mixture was filtered and purified using reverse phase HPLC providing (S)-methyl 3-(2-tert-butyl-5-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indol-1-yl)-2-hydroxypropylcarbamate. The retention time on a three minute run is 1.40 min. LC/MS (M+1)=544.3. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, 1H, J=2 Hz), 7.30 (dd, 1H, J=2, 8 Hz), 7.28 (m, 1H), 7.22 (d, 1H, J=8 Hz), 7.14 (d, 1H, J=8 Hz), 7.04 (br s, 1H), 6.97 (dd, 1H, J=2, 8 Hz), 6.24 (s, 1H), 5.19 (1H, br s), 4.31 (dd, 1H, J=6, 15 Hz), 4.28 (dd, 1H, J=11, 15 Hz), 4.18 (m, 1H), 3.70 (s, 3H), 3.40 (dd, 1H, J=3, 6 Hz), 3.36 (dd, 1H, J=3, 6 Hz), 3.26 (m, 1H), 1.74 (m, 2H), 1.40 (s, 9H), 1.11 (m, 2H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4](=[N:7][O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:3][CH2:2]1.Cl[C:22]1[C:23]([F:32])=[CH:24][C:25]([N+:29]([O-:31])=[O:30])=[C:26]([NH2:28])[CH:27]=1.C(N(C(C)C)CC)(C)C>CS(C)=O.C([O-])(O)=O.[Na+]>[CH:18]([O:17][C:15]([N:12]1[CH2:11][CH2:10][CH:9]([O:8][N:7]=[C:4]2[CH2:3][CH2:2][N:1]([C:22]3[CH:27]=[C:26]([NH2:28])[C:25]([N+:29]([O-:31])=[O:30])=[CH:24][C:23]=3[F:32])[CH2:6][CH2:5]2)[CH2:14][CH2:13]1)=[O:16])([CH3:20])[CH3:19]
Reactant: CC(C)OC(=O)N1CCC(ON=C2CCNCC2)CC1
Reactant: Nc1cc(Cl)c(F)cc1[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(C)OC(=O)N1CCC(ON=C2CCN(c3cc(N)c([N+](=O)[O-])cc3F)CC2)CC1
Temperature: 110 °C
Reaction time: 72 h

Procedure:
2d (0.12 g), 5-chloro-4-fluoro-2-nitro-phenylamine (0.1 g) and diisopropylethylamine (0.1 mL) were combined in 1.2 mL of DMSO and stirred at 110° C. for 3 days. The mixture was cooled to room temperature, diluted with aqueous NaHCO3 (5 mL) and extracted with EtOAc (5 mL). The organic layer was concentrated under vacuum and purified on column chromatography (eluent: 10 to 50% EtOAc in hexane+0.1% triethylamine) to yield 60a.
Reaction SMILES: [C:1]([O:5][C:6]1[CH:11]=[N:10][CH:9]=[C:8]([CH:12]=[CH2:13])[N:7]=1)([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]1[CH:28]=[CH:27][CH:26]=[CH:25][C:16]=1[O:17][CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>C(O)C>[C:1]([O:5][C:6]1[CH:11]=[N:10][CH:9]=[C:8]([CH2:12][CH2:13][N:22]2[CH2:21][CH2:20][CH:19]([CH2:18][O:17][C:16]3[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=3[F:14])[CH2:24][CH2:23]2)[N:7]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Fc1ccccc1OCC1CCNCC1
Reactant: C=Cc1cncc(OC(C)(C)C)n1
Solvent: CCO
Product: CC(C)(C)Oc1cncc(CCN2CCC(COc3ccccc3F)CC2)n1
Yield: 11.8 %

Procedure:
After dissolving 262 mg of 2-tert-butoxy-6-vinylpyrazine and 401 mg of 4-(2-fluorophenoxymethyl)piperidine [CAS No. 63608-34-4] in 3 ml of ethanol, the mixture was stirred for 2 days at 80° C. The reaction solution was concentrated under reduced pressure, and the residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (67 mg, 12% yield).
Reaction SMILES: BrBr.[CH3:3][O:4][C:5]([N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH2:8]1)=[O:6].[NH2:13][C:14]([NH2:16])=[O:15].CC#N>CN(C=O)C>[CH3:3][O:4][C:5]([N:7]1[CH2:8][CH:9]=[CH:10][C@H:11]2[O:15][C:14]([NH2:16])=[N:13][C@@H:12]12)=[O:6]
Reactant: NC(N)=O
Reactant: COC(=O)N1C=CC=CC1
Agent: BrBr
Solvent: CC#N
Solvent: CN(C)C=O
Product: COC(=O)N1CC=C[C@H]2OC(N)=N[C@H]21
Yield: 49.9 %

Procedure:
A solution of Br2 (1 ml, 19.3 mmol, 1 equiv.) in DMF (5 ml) is added over 20 min to a solution of N-methoxycarbonyl-1,2-dihydropyridine 1 (2.68 g, 19.3 mmol, 1 equiv.) and of urea (2.3 g, 38.6 mmol, 3 equiv.) in a mixture of DMF (19 ml) and of CH3CN (6 ml) at ambient temperature and under argon. The reaction being complete from the end of the addition of the bromine, the reaction mixture is concentrated to dryness. The residue is dissolved in methanol (30 ml), poured onto ice-cold water (150 ml) and then filtered through a Buchner funnel. The filtrate is basified (5% Na2CO3) until a pH of greater than 10 is obtained. After extracting with dichloromethane (4×100 ml), the aqueous phase is saturated with NaCl and then reextracted with dichloromethane (4×100 ml). After drying over MgSO4 and evaporating the solvent, the solid obtained (5.94 g) is chromatographed on silica gel using dichloromethane (DCM) saturated with ammonia and then DCM saturated with NH3:MeOH, 98:2. The product is obtained in the form of a beige solid (1.9 g, 50%).
Reaction SMILES: [S:1]([C:4]1[CH:24]=[CH:23][C:7]2[N:8]=[C:9]([NH:11][C:12](=[O:22])[O:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[S:10][C:6]=2[CH:5]=1)C#N.SCC(C(CS)O)O>P([O-])(O)(O)=O.[K+]>[SH:1][C:4]1[CH:24]=[CH:23][C:7]2[N:8]=[C:9]([NH:11][C:12](=[O:22])[O:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[S:10][C:6]=2[CH:5]=1
Reactant: N#CSc1ccc2nc(NC(=O)OCCN3CCOCC3)sc2c1
Agent: O=P([O-])(O)O
Agent: OC(CS)C(O)CS
Agent: [K+]
Product: O=C(Nc1nc2ccc(S)cc2s1)OCCN1CCOCC1
Yield: 173.7 %

Procedure:
The 2-morpholin-4-ylethyl (6-sulphanyl-1,3-benzothiazol-2-yl)carbamate was prepared according to the method described in Example 1b, but using 547 mg of 2-morpholin-4-ylethyl (6-thiocyanato-1,3-benzothiazol-2-yl)carbamate, 12 mg of potassium dihydrogen phosphate and 1.16 g of DL-dithiothreitol. 885 mg of 2-morpholin-4-ylethyl (6-sulphanyl-1,3-benzothiazol-2-yl)carbamate are thus obtained in the form of a white solid, the characteristics of which are as follows:
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[C:3](=O)[C:2]2=O.COP([CH2:16][C:17]([C:19]1[CH:20]=[N:21][N:22]([CH3:27])[C:23]=1[CH:24]1[CH2:26][CH2:25]1)=O)(=O)OC.O.[NH2:29][NH2:30]>>[CH:24]1([C:23]2[N:22]([CH3:27])[N:21]=[CH:20][C:19]=2[C:17]2[CH:16]=[C:3]3[C:2]([CH:1]4[CH2:7][CH:4]3[CH2:5][CH2:6]4)=[N:30][N:29]=2)[CH2:26][CH2:25]1
Reactant: COP(=O)(CC(=O)c1cnn(C)c1C1CC1)OC
Reactant: NN
Reactant: O=C1C(=O)C2CCC1C2
Solvent: O
Product: Cn1ncc(-c2cc3c(nn2)C2CCC3C2)c1C1CC1

Procedure:
yellow foam. MS (ESI): 267.1 (MH+). Prepared from bicyclo[2.2.1]heptane-2,3-dione, [2-(5-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)-2-oxo-ethyl]-phosphonic acid dimethyl ester, hydrazine monohydrate.
Reaction SMILES: S(C1C=CC(C)=CC=1)(O[CH2:5][CH:6]1[O:8][CH2:7]1)(=O)=O.[NH2:16][C:17]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][C:18]=1[OH:26].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[NH2:16][C:17]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][C:18]=1[O:26][CH2:5][CH:6]1[O:8][CH2:7]1
Reactant: Cc1ccc(S(=O)(=O)OCC2CO2)cc1
Reactant: Nc1c(O)cccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Nc1c(OCC2CO2)cccc1[N+](=O)[O-]

Procedure:
21.7 g (0.095 mol) of glycidyl tosylate, 10 g (0.0475 mol) of 2-amino-3-nitrophenol and 6.5 g of crushed K2CO3 are mixed in acetone and the mixture is heated at reflux for 18 hours. The mixture is filtered and the solvent is evaporated under reduced pressure. The crude reaction product is purified by flash chromatography, elution being carried out with a 9/1 hexane/ethyl acetate mixture. The title compound is obtained. M.p.: 7°-78° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:13])([CH3:12])[CH:6]=[C:5]2[N:14]1[CH2:18][CH2:17][CH2:16][C:15]1=[O:19].C(C1C=C2C(=CC=1)NC(C)(C)C=C2N1CCCC1=[O:39])#N>>[CH3:13][C:7]1([CH3:12])[C@@H:6]([OH:39])[C@H:5]([N:14]2[CH2:18][CH2:17][CH2:16][C:15]2=[O:19])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=2)[NH:8]1
Reactant: CC1(C)C=C(N2CCCC2=O)c2cc(Br)ccc2N1
Reactant: CC1(C)C=C(N2CCCC2=O)c2cc(C#N)ccc2N1
Product: CC1(C)Nc2ccc(Br)cc2[C@@H](N2CCCC2=O)[C@@H]1O

Procedure:
A method according to claim 11, wherein the compound of formula (I) is 6-bromo-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-1,2-dihydroquinoline or 6-cyano-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-1,2-dihydroquinoline.
Reaction SMILES: [NH:1]([C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[C@H:2]([C:4]([NH:6][C@H:7]([C:15]([O:17]C)=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:3].O[Li].O.N(C(OCC1C=CC=CC=1)=O)[C@H](C(N[C@H](C(NCC(OCC1C=CC=CC=1)=O)=O)CC1C=CC=CC=1)=O)C.C(=O)(O)[O-]>C1COCC1.O>[NH:1]([C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[C@H:2]([C:4]([NH:6][C@H:7]([C:15]([OH:17])=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:3]
Reactant: COC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)OCc1ccccc1
Agent: C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To methyl ester 21 (1.64 g, 4.27 mmol) dissolved in 25 mL of THF and cooled to 0° C. was added LiOH.H2O (0.25 g, 140 mol %) dissolved in 8 mL of water. The resulting solution was cooled to 0° C., added to the THF solution of 27, stirred at 0° C. for 0.5 h, then poured into 50 mL of saturated aqueous bicarbonate. The basic mixture was then extracted with 50 mL of ether which was discarded. The water layer was acidified with 1N HCl to pH 2 and extracted with 2×100 mL of ether. The organic extracts were combined, dried, and evaporated to give a thick white foam, which was crystallized from ether/hexane affording 1.53 g, 97% of 11 as a white powder; mp 126°-127° C.; [α]25D +39.8° (c 2.1, CHCl3); 1H NMR δ 11.5-11.1 (br s, 1H), 7.40-7.10 (m, 10H), 6.80 (d, 1H, J=5), 5.49 (d, 1H, J=4), 5.07 (s, 2H), 4.49-4.46 (m, 1H), 4.25-4.23 (m, 1H), 3.18 (dd, 1H, J=14, 5.5), 3.03 (dd, 1H, J=14, 6.5), 1.28 (d, 3H, J=7). Anal. Calcd for C24H22N3O5 : C, 64.8; H, 6.0,; N, 7.6. Found: C, 64.8; H, 6.0; N, 7.4.
Reaction SMILES: C([O:3][C:4](=[O:19])[C@@H:5]([O:17][CH3:18])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15]Br)=[CH:9][CH:8]=1)C.[CH3:20][C:21]1[S:22][C:23]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][C:24]=2[N:25]=1.CO[C@@H](CC1C=CC(OCCCOC2C=CC=CC=2)=CC=1)C(O)=O>>[CH3:18][O:17][C@@H:5]([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][O:30][C:27]2[CH:28]=[CH:29][C:23]3[S:22][C:21]([CH3:20])=[N:25][C:24]=3[CH:26]=2)=[CH:11][CH:12]=1)[C:4]([OH:3])=[O:19]
Reactant: Cc1nc2cc(O)ccc2s1
Reactant: CCOC(=O)[C@H](Cc1ccc(OCCBr)cc1)OC
Agent: CO[C@@H](Cc1ccc(OCCCOc2ccccc2)cc1)C(=O)O
Product: CO[C@@H](Cc1ccc(OCCOc2ccc3sc(C)nc3c2)cc1)C(=O)O

Procedure:
The title compound was prepared from (2S)-3-[4-(2-bromo-ethoxy)-phenyl]-2-methoxy-propionic acid ethyl ester (Example 283, Step 2) and 2-methyl-benzothiazol-5-ol via the same procedure used for the preparation of (2S)-2-methoxy-3-[4-(3-phenoxy-propoxy)-phenyl]-propionic acid (Example 285, Step 1), to produce a yellow oil.
Reaction SMILES: [C:1]([F:6])(F)=[C:2](Cl)F.N1C=CC=CC=1.F.NC1C=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][C:22]2=[O:25])=[CH:17][CH:16]=1.N([O-])=O.[Na+]>N1C=CC=CC=1>[F:6][C:1]1[CH:2]=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][C:22]2=[O:25])=[CH:17][CH:16]=1
Reactant: FC(F)=C(F)Cl
Reactant: Nc1ccc2c(c1)C(=O)CCC2
Agent: F
Agent: O=N[O-]
Agent: [Na+]
Solvent: c1ccncc1
Product: O=C1CCCc2ccc(F)cc21
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 56 %

Procedure:
In a specially designed Kel-F reactor (cylindrical shape 1.25"od×3"h equipped with a screw cap and N2 inlet-outlet) was placed hydrogen fluoride-pyridine 6:4 solution (10 mL, prepared by diluting commercially available hydrogen fluoride-pyridine 7:3 solution with dry pyridine). 7-amino-tetralone (644 mg, 4.0 mmol), (Example 35, Step A) was added under N2 and the solution was cooled to 0°. Sodium nitrite (304 mg, 4.4 mol, 1.1 eq) was added in portions and the mixture was stirred for 30 minutes. The mixture was then heated at 90° C. for 1 hour with stirring. The reaction mixture was quenched with approx. 60 mL of ice/water and the solid that separated extracted with methylene chloride (3×30 mL). The combined extracts were washed with water and brine, dried over magnesium sulfate, filtered and evaporated to dryness under vacuum at room temperature. Purification by flash chromatography on silica, eluting with ethyl acetate/hexane (5:95), afforded pure 7-fluoro- 1-tetralone (367 mg, 2.2 mmol, 56%). 1H NMR (300 MHz, CDCl3): 2.13 (m,2H), 2.65 (t,7 Hz,2H), 2.94 (t,7 Hz,2H), 7.1-7.3 (m,2H), 7.69 (dd;2,8 Hz;1H). EI-MS: calculated for C10H9FO 164; found 164 (M+,71%).
Reaction SMILES: [CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](O)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].P(Br)(Br)([Br:22])=O.O>C(#N)C>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([Br:22])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)c1nc(O)c2ccccc2c1O
Reactant: O=P(Br)(Br)Br
Solvent: CC#N
Solvent: O
Product: CCCCOC(=O)c1nc(Br)c2ccccc2c1O
Temperature: 80 °C
Reaction time: 64 h
Yield: 3.9 %

Procedure:
2 g (7.7 mmol) of 1,4-Dihydroxy-isoquinoline-3-carboxylic acid butyl ester (from Example D-20b) dissolved in 100 ml of acetonitrile. 15.4 g (53.6 mmol) of phosphorous oxybromide added to solution and mixture stirred at 80° C. for 64 h. 100 ml of water was added to mixture, and mixture was removed from heat. Mixture was partitioned between ethyl acetate and water. Two phases were separated and the aqueous layer was extracted with ethyl acetate. Organic layers were combined, washed with brine, dried over magnesium sulfate, filtered, and evaporated. Residue was purified by silica gel flash chromatography to give 0.1 g (0.3 mmol) of product. 1H NMR (200 MHz, CDCl3) δ 11.89 (s, 1H), 8.41 (m, 1H), 8.25 (m, 1H), 7.84 (m, 2H), 4.49 (t, J=7.0 Hz, 2H), 1.87 (m, 2H), 1.47 (m, 2H), 1.00 (t, J=7.2 Hz, 3H).