Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[CH2:6][N:7]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=1)[S:8]([C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[C:12]=1[OH:19])(=[O:10])=[O:9].[F:34][C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=1[N:42]=[C:43]=[O:44]>CN(C=O)C>[Cl:18][C:13]1[C:12]([OH:19])=[C:11]([S:8]([N:7]([CH2:6][C:5]2[CH:31]=[CH:32][CH:33]=[C:3]([CH2:2][NH:1][C:43]([NH:42][C:36]3[CH:37]=[CH:38][C:39]([F:41])=[CH:40][C:35]=3[F:34])=[O:44])[CH:4]=2)[CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]([F:29])([F:28])[F:30])=[CH:25][CH:26]=2)(=[O:9])=[O:10])[CH:16]=[C:15]([Cl:17])[CH:14]=1
Reactant: O=C=Nc1ccc(F)cc1F
Reactant: NCc1cccc(CN(Cc2ccc(C(F)(F)F)cc2)S(=O)(=O)c2cc(Cl)cc(Cl)c2O)c1
Solvent: CN(C)C=O
Product: O=C(NCc1cccc(CN(Cc2ccc(C(F)(F)F)cc2)S(=O)(=O)c2cc(Cl)cc(Cl)c2O)c1)Nc1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 3 h
Yield: 55.6 %

Procedure:
To a solution of N-(3-(aminomethyl)benzyl)-3,5-dichloro-2-hydroxy-N-(4-(trifluoromethyl)benzyl)benzenesulfonamide (40 mg, 0.08 mmol) in DMF (2 mL) was added 2,4-difluorophenyl isocyanate (10.0 μL, 0.09 mmol). The resulting mixture was stirred at rt for 3 h under nitrogen. The mixture was concentrated and purified by preparative HPLC. Fractions containing the desired product were combined, concentrated and lyophilized to give a white solid (30 mg, 57%). 1H NMR (CD3OD): δ 7.59 (d, J=2.8 Hz, 1H), 7.52 (d, J=2.2 Hz, 1H), 7.48 (d, J=7.7 Hz, 2H), 7.44 (d, J=8.8 Hz, 2H), 7.39-7.37 (m, 4H), 7.31 (t, 7.7 Hz, 2H), 7.24 (d, J=7.7 Hz, 2H), 7.19 (t, J=7.1 Hz, 2H), 7.09 (m, 2H), 7.02 (s, 1H), 6.89 (d, J=6.6 Hz, 1H), 4.48 (s, 2H), 4.40 (s, 2H), 4.23 (s, 2H); MS (ESI): (M+H)+=714.2.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[O:3][C:4]1[CH:14]=[CH:13][C:7]([CH2:8][NH:9][C:10](=O)[CH3:11])=[CH:6][CH:5]=1.B>C1COCC1.C(OCC)C>[CH2:10]([NH:9][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:15])[F:16])=[CH:14][CH:13]=1)[CH3:11]
Reactant: CC(=O)NCc1ccc(OC(F)(F)F)cc1
Agent: B
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCNCc1ccc(OC(F)(F)F)cc1
Temperature: -10 °C
Yield: 19.4 %

Procedure:
N-[4-(Trifluoromethoxy)benzyl]acetamide (10.4 g, 44.6 mmol) was dissolved in THF (100 mL) and cooled to −10° C. Borane (56 mL of a 2 M solution of the dimethylsulfide complex in diethyl ether) was added and the reaction mixture was stirred at −10° C. for 15 minuters and was then allowed to warm to room temperature. The reaction mixture was refluxed overnight and was then allowed to cool to room temperature. The reaction was quenched by careful addition of 10% HCl (30 mL) at 0° C. and the mixture was stirred at room temperature overnight and then concentrated in, vacuo. The residue was taken up in water (200 mL) and diethyl ether (200 mL) and the phases were separated. Concentration in vacuo of the diethyl ether phase afforded 1.9 g (21%) of the title compound as a colourless oil.
Reaction SMILES: CN1CC[O:5]CC1.[F:8][C:9]1[CH:10]=[C:11]([N:22]2[CH2:26][C@H:25]([CH2:27][NH:28][C:29](=[O:31])[CH3:30])[O:24][C:23]2=[O:32])[CH:12]=[CH:13][C:14]=1[N:15]1[CH2:20][CH2:19][S:18](=[O:21])[CH2:17][CH2:16]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[O:21]=[S:18]1(=[O:5])[CH:17]=[CH:16][N:15]([C:14]2[CH:13]=[CH:12][C:11]([N:22]3[CH2:26][C@H:25]([CH2:27][NH:28][C:29](=[O:31])[CH3:30])[O:24][C:23]3=[O:32])=[CH:10][C:9]=2[F:8])[CH2:20][CH2:19]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCS(=O)CC3)c(F)c2)C(=O)O1
Reactant: CN1CCOCC1
Solvent: ClCCl
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CC(=O)NC[C@H]1CN(c2ccc(N3C=CS(=O)(=O)CC3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
4-Methylmorpholine (1.2 mL, 11.1 mmol) is added to a solution of N-[[(5S)-3-[3-fluoro-4-(1-oxido-4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (0.690 g, 1.87 mmol; prepared as described in U.S. Pat. No. 5,688,792) in DCM (40 mL), followed by trifluoroacetic anhydride (1.06 mL, 7.5 mmol). The solution is stirred at r.t. for about 20 h, and is concentrated under vacuum, then dissolved in 100 mL of EtOAc—2.5% aq. NaHCO3 (1:1). Aqueous phase is extracted with EtOAc (2×50 mL). The combined organic layers are washed with brine, and dried (MgSO4). Solvent is removed under vacuum to afford the title compound that is used directly without further purification. Step 2: Preparation of N-[[(5S)-3-[4-[2,3-dihydro-1,1-dioxido-6-(trifluoroacetyl)-4H-1,4-thiazin-4-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:17]=[CH:18][C:19]=1[N+:20]([O-])=O)[O:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]2[NH:14][CH:15]=[CH:16][C:9]=12)([O-])=O>[Pd].CCO.CCOC(C)=O>[NH:14]1[C:10]2=[N:11][CH:12]=[CH:13][C:8]([O:7][C:6]3[CH:5]=[C:4]([NH2:1])[C:19]([NH2:20])=[CH:18][CH:17]=3)=[C:9]2[CH:16]=[CH:15]1
Reactant: O=[N+]([O-])c1ccc(Oc2ccnc3[nH]ccc23)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1ccc(Oc2ccnc3[nH]ccc23)cc1N

Procedure:
A solution of 4-(3,4-dinitro-phenoxy)-1H-pyrrolo[2,3-b]pyridine (Step C, 0.284 g, 0.95 mmol) in a 2/1 EtOH/EtOAc (30 mL) mixture with a catalytic amount of 10% Pd/C was stirred under H2 at RT and atmospheric pressure. The catalyst was removed by filtration and the solvents were removed under vacuum. The crude material was purified on silica gel using a CH2Cl2/EtOH/NH4OH gradient (100/0/0 to 90/10/1) to give 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-benzene-1,2-diamine.
Reaction SMILES: N[C@H](C(O)=O)C([SH:6])(C)C.C[Si](C)(C)S[Si](C)(C)C.C[O-].[Na+].[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:48]=[CH:47][C:32]3[N:33]=[C:34]([C:39]4[CH:40]=[C:41]([CH:44]=[CH:45][CH:46]=4)[C:42]#[N:43])[CH2:35][C:36](=[O:38])[NH:37][C:31]=3[CH:30]=2)=[CH:25][CH:24]=1>CN1CCN(C)C1=O.O>[F:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]2[CH:48]=[CH:47][C:32]3[N:33]=[C:34]([C:39]4[CH:40]=[C:41]([CH:44]=[CH:45][CH:46]=4)[C:42]([NH2:43])=[S:6])[CH2:35][C:36](=[O:38])[NH:37][C:31]=3[CH:30]=2)=[CH:27][CH:28]=1
Reactant: CC(C)(S)[C@H](N)C(=O)O
Reactant: N#Cc1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1
Agent: C[O-]
Agent: C[Si](C)(C)S[Si](C)(C)C
Agent: [Na+]
Solvent: O
Solvent: CN1CCN(C)C1=O
Product: NC(=S)c1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1
Reaction time: 0.08 h

Procedure:
Preparation of 4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamides (according to Pen-Yuan Lin et al. Synthesis 1992, 1219]: To a solution of hexamethyldisilthiane (1.45 g, 8.0 mmol) in 1,3-dimethyl-2-imidazolidinone (8 mL) was added at 23° C. sodium methoxide (0.31 g, 6.8 mmol). The mixture was stirred for 5 min. and the blue solution formed was then added to a solution of 3-[7-(4-fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile (Example 57) (1.42 g, 4 mmol) in 1,3-dimethyl-2-imidazolidinone (12 mL). The mixture was stirred for 3 h at 23° C. and then poured into water (100 mL). Stirring was continued for 0.5 h and the precipitate was isolated by filtration and triturated with ethyl acetate (50 mL) to give the title compound as light yellow solid (1.38 g).
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][C:8]2[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]3[N:19]=[CH:20][CH:21]=[CH:22][C:5]=3[C:4]=2[C:3]=1[F:23].[CH3:24][N:25](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:23][C:3]1[C:4]2[C:5]3[CH:22]=[CH:21][CH:20]=[N:19][C:6]=3[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:8]=2[CH:9]=[N:10][C:2]=1[C:24]#[N:25]
Reactant: C[Si](C)(C)CCOCn1c2cnc(Cl)c(F)c2c2cccnc21
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: C[Si](C)(C)CCOCn1c2cnc(C#N)c(F)c2c2cccnc21
Temperature: 130 °C
Reaction time: 3 h
Yield: 68 %

Procedure:
A solution of 6-chloro-5-fluoro-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′3′-d]pyrrole (12.2 g, 34.7 mmol) in DMF (120 mL) was treated with zinc cyanide (4.88 g, 41.7 mmol) and tetrakis(triphenylphosphine)palladium(0) (6 g, 5.2 mmol). The mixture was degassed and stirred under a nitrogen atmosphere at 130° C. for 3 hours. After cooling to ambient temperature the mixture was filtered through Celite© and the filter cake washed with DMF (10 mL). The filtrate was partitioned between ethyl acetate and water and the aqueous phase further extracted with ethyl acetate. The combined organic layer was washed with water (×2) and brine, dried (Na2SO4), filtered and evaporated. The resultant residue was dissolved in dichloromethane, stirred with flash silica gel, filtered to remove the solid and the solid washed well with dichloromethane. The filtrate was evaporated and the resultant residue triturated with pentane:diethyl ether (ca. 4:1) to afford the title compound as a white solid (8.15 g, 68%). The trituration liquors were evaporated and the resultant residue purified by flash chromatography to afford a second crop of title compound (0.92 g, 8%). Total yield=9.07 g, 76%. 1H NMR (400 MHz, CDCl3): 8.99 (d, J=2.1 Hz, 1H), 8.75 (dd, J=4.8, 1.7 Hz, 1H), 8.57 (dd, J=7.9, 1.7 Hz, 1H), 7.44 (dd, J=7.9, 4.8 Hz, 1H), 6.02 (s, 2H), 3.63-3.56 (m, 2H), 0.93 (t, J=8.2 Hz, 2H), −0.08 (d, J=0.6 Hz, 9H).
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[NH2:15])[CH2:5][CH2:4]1.C(OC([NH:23][C:24]1[S:28][C:27]([CH:29]2[CH2:32][CH2:31][CH2:30]2)=[N:26][C:25]=1[C:33](O)=[O:34])=O)(C)(C)C>>[NH2:23][C:24]1[S:28][C:27]([CH:29]2[CH2:32][CH2:31][CH2:30]2)=[N:26][C:25]=1[C:33]([NH:15][C:10]1[CH:11]=[N:12][N:13]([CH3:14])[C:9]=1[N:6]1[CH2:7][CH2:8][CH:3]([CH2:2][NH2:1])[CH2:4][CH2:5]1)=[O:34]
Reactant: Cn1ncc(N)c1N1CCC(CN)CC1
Reactant: CC(C)(C)OC(=O)Nc1sc(C2CCC2)nc1C(=O)O
Product: Cn1ncc(NC(=O)c2nc(C3CCC3)sc2N)c1N1CCC(CN)CC1
Yield: 37 %

Procedure:
Following the procedure for Example 304 starting with 5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-amine and 5-(tert-butoxycarbonylamino)-2-cyclobutylthiazole-4-carboxylic acid gave 305 as a white solid (44 mg, 37% over two steps). 1H NMR (400 MHz, d4-MeOD) δ 7.45 (s, 1H), 3.75-3.62 (m, 4H), 3.23-3.07 (m, 4H), 2.60 (d, J=6.5 Hz, 2H), 2.47-2.29 (m, 4H), 2.17-2.01 (m, 1H), 2.00-1.90 (m, 1H), 1.84 (d, J=12.5 Hz, 2H), 1.56-1.43 (m, 1H), 1.36 (qd, J=11.9, 4.4 Hz, 2H). LCMS (ES+) m/z 390 (M+1)
Reaction SMILES: [O:1]=[S:2]1(=[O:28])[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:4]([C:12]2[C:17](=[O:18])[N:16]([N:19]=[CH:20][CH:21]([CH3:23])[CH3:22])[C:15]3[CH:24]=[CH:25][S:26][C:14]=3[C:13]=2[OH:27])=[N:3]1.CO.[BH4-].[Li+].Cl.O1C[CH2:37][CH2:36][CH2:35]1>O>[CH2:20]([NH:19][N:16]1[C:17](=[O:18])[C:12]([C:4]2[NH:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[S:2](=[O:1])(=[O:28])[N:3]=2)=[C:13]([OH:27])[C:14]2[S:26][CH:25]=[CH:24][C:15]1=2)[C:21]1[CH:22]=[CH:37][CH:36]=[CH:35][CH:23]=1
Reactant: CC(C)C=Nn1c(=O)c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2sccc21
Reactant: C1CCOC1
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: CO
Product: O=c1c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2sccc2n1NCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The product of Example 269A (0.116 g, 0.257 mmol) in tetrahydrofuran (5 mL) and methanol (0.021 mL, 0.514 mmol) at 0° C. was treated dropwise with a 2.0M solution of lithium borohydride in tetrahydrofuran (0.19 mL, 0.386 mmol). The reaction was stirred at 25° C. for 2 hour, acidified with 1M hydrochloric acid a pH of approximately 2-4, diluted with water (20 mL), and the resulting precipitate was collected by filtration and dried to give the title compound. The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.97 (d, J=5.54 Hz, 2 H) 6.17 (t, J=6.43 Hz, 1 H) 7.08 (d, J=5.52 Hz, 1 H) 7.21 (d, J=8.09 Hz, 1 H) 7.33 (m, 4 H) 7.47 (d, J=6.62 Hz, 2 H) 7.55 (t, J=6.99 Hz, 1 H) 7.66 (d, J=7.35 Hz, 1 H) 7.73 (d, J=5.52 Hz, 1 H) 15.92 (s, 1 H). MS (ESI−) m/z 451 (M−H)−.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:4]=1[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27].O>N1C=CC=CC=1>[C:26]([N:6]([CH2:5][C:4]1[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:3]=1[O:2][CH3:1])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:28])[CH3:27]
Reactant: COc1ccc(CNc2ccccc2Oc2ccccc2)c(OC)c1
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: COc1ccc(CN(C(C)=O)c2ccccc2Oc2ccccc2)c(OC)c1
Temperature: 25 °C
Yield: 96.9 %

Procedure:
To a solution of 1.00 g of N-(2,4-dimethoxy benzyl)-2-phenoxyaniline in 1.18 g of pyridine was added 0.76 g of acetic anhydride, followed by stirring at room temperature for a day. The reaction mixture was poured into water and extracted with ethyl acetate, and the extract was washed with 0.5 N hydrochloric acid, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate-hexane=1:3) to give 1.09 g of N-acetyl-N-(2,4-dimethoxybenzyl)-2-phenoxyaniline as an oil.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[OH:12][C@@H:13]([C@H:15]1[C:21](=[O:22])[N:20]2[C@@H:16]1[CH2:17][C:18]([CH2:36][S:37][CH2:38][CH2:39][NH:40][C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([N+:51]([O-:53])=[O:52])=[CH:47][CH:46]=1)=[O:42])=[C:19]2[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])[CH3:14]>C(Cl)Cl.CS(C)=O>[OH:12][C@@H:13]([C@H:15]1[C:21](=[O:22])[N:20]2[C@@H:16]1[CH2:17][C:18]([CH2:36][S:37]([CH2:38][CH2:39][NH:40][C:41]([O:43][CH2:44][C:45]1[CH:46]=[CH:47][C:48]([N+:51]([O-:53])=[O:52])=[CH:49][CH:50]=1)=[O:42])=[O:9])=[C:19]2[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])[CH3:14]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(CSCCNC(=O)OCc3ccc([N+](=O)[O-])cc3)C[C@H]12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CS(C)=O
Solvent: ClCCl
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(CS(=O)CCNC(=O)OCc3ccc([N+](=O)[O-])cc3)C[C@H]12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 89.3 %

Procedure:
A solution of 22 mg of m-chloroperbenzoic acid in 2 ml of methylene chloride was added dropwise to 60 mg of p-nitrobenzyl (5R,6S)-6-[1-(R)-hydroxyethyl]-3-(2-p-nitrobenzyloxycarbonylaminoethyl)thiomethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (53), prepared as described in step (g) of Example 6, in 3 ml of methylene chloride, whilst cooling with ice-water. When the addition was complete, the reaction mixture was stirred at 0°-5° C. for 30 minutes. The resulting mixture containing precipitated material was diluted with 100 ml of ethyl acetate and then the solution was washed successively with a 5% w/v aqueous solution of sodium hydrogen sulphite (once), a saturated aqueous solution of sodium bicarbonate (twice) and a saturated aqueous solution of sodium chloride (three times). The solution was then dried over sodium sulphate, after which the solvents were evaporated under reduced pressure at room temperature, to give a solid substance. This crude substance was dissolved in dimethyl sulphoxide and then reprecipitated by the addition of benzene, to give 55 mg of the title compound as an amorphous powder.
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].[CH2:14]([O:21][P:22]([O:32][CH2:33][CH2:34][OH:35])([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>ClCCl>[C:2](=[O:3])([O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:11]([O-:13])=[O:12])=[CH:9][CH:10]=1)[O:35][CH2:34][CH2:33][O:32][P:22]([O:21][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]
Reactant: O=P(OCCO)(OCc1ccccc1)OCc1ccccc1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCCOP(=O)(OCc1ccccc1)OCc1ccccc1)Oc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 45 %

Procedure:
4-Nitrophenyl chloroformate (1.01 g; 5.04 mmol) was added at 0° C. under argon atmosphere to a solution of 2-[di (benzyloxy)phosphoryloxy]ethanol (1.62 g; 5.09 mmol) and triethylamine (0.7 ml; 5 mmol) in dichloromethane (20 ml). The mixture was stirred at ambient temperature for 30 minutes, evaporated and purified by flash chromatography, eluting with petroleum ether/ethyl acetate (40/60) to give 2-[di(benzyloxy)phosphoryloxy]ethyl 4-nitrophenyl carbonate.
Reaction SMILES: [CH:1]([O:3][CH2:4][CH2:5]Cl)=[CH2:2].[C:7]1(=[O:17])[NH:11][C:10](=[O:12])[C:9]2=[CH:13][CH:14]=[CH:15][CH:16]=[C:8]12.[K].CN(C=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH:1]([O:3][CH2:4][CH2:5][C:16]1[CH:15]=[CH:14][CH:13]=[C:9]2[C:10]([NH:11][C:7](=[O:17])[C:8]=12)=[O:12])=[CH2:2]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: C=COCCCl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: C=COCCc1cccc2c1C(=O)NC2=O

Procedure:
2-Vinyloxy Ethyl Phthalimide was prepared via reacting 2-chloroethyl vinyl ether (25 g, 0.24 mol) and potassium phthalimide (25 g, 0.135 mol) in 100° C. DMF (75 ml) using tetra n-butyl ammonium bromide (0.5 g) as the phase transfer catalyst. This solution was heated for 6 h and then crashed out in water and filtered. This solid was then recrystallized twice from methanol to give white crystals.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:9]=[C:8]([CH2:10]I)[N:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[C:19](=[O:27])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])[N:6]=1)=[O:4].[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>CO>[CH3:1][O:2][C:3]([C:5]1[N:9]=[C:8]([CH2:10][N:32]2[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]2)[N:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[C:19](=[O:27])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])[N:6]=1)=[O:4]
Reactant: COC(=O)c1nc(CI)n(-c2ccc(Cl)cc2C(=O)c2ccccc2Cl)n1
Reactant: CN1CCNCC1
Solvent: CO
Product: COC(=O)c1nc(CN2CCN(C)CC2)n(-c2ccc(Cl)cc2C(=O)c2ccccc2Cl)n1
Reaction time: 16 h

Procedure:
A mixture of 8.0 g (0.015 mole) of 1-[2-(o-chlorobenzoyl)-4-chlorophenyl]-5-(iodomethyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester [see Example 13 b)] and 3.3 ml of 1-methyl-piperazine in 160 ml of methanol is stirred for 16 hours at 40°. The reaction solution is then concentrated in vacuo; water is added to the residue and extraction is performed twice with methylene chloride. The organic phase is washed twice with icewater, and extraction is then performed twice with 2N hydrochloric acid solution. To the aqueous acidified extracts there are added ice and sufficient 5N sodium hydroxide solution to bring the pH-value to 10. The base that has precipitated is taken up in ether. The organic phase is washed twice with saturated sodium chloride solution; it is afterwards dried over sodium sulphate and concentrated in vacuo to dryness. There is obtained 1-[2-(o-chlorobenzoyl)-4-chlorophenyl]-5-[(4-methyl-1-piperazinyl)-methyl]-1H-1,2,4-triazole-3-carboxylic acid methyl ester as solidified foam.
Reaction SMILES: ClC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)[C:8]([F:17])([F:16])[C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[I:11].[Cl:30]C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I.ICl.FC1(F)C(F)(F)C1(F)F>>[Cl:30][C:8]([F:17])([F:16])[C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[I:11]
Reactant: FC(F)(Cl)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Reactant: FC(F)(Cl)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Agent: ClI
Agent: FC1(F)C(F)(F)C1(F)F
Product: FC(F)(Cl)C(F)(F)C(F)(F)I

Procedure:
As for a compound in which n is 9 or 11 in formula (22), 1-chloro-9-iodoperfluorononane (22-4) or 1-chloro-11-iodoperfluoroundecane (22-5) can be obtained by allowing iodine monochloride to react with commercially available perfluorocyclopropane (53) at a high temperature to obtain 1-chloro-3-iodoperfluoropropane (54), and then allowing 1-chloro-3-iodoperfluoropropane (54) to react with tetrafluoroethylene (51) under high temperature and pressurized conditions.
Reaction SMILES: [CH2:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH2:3][N:2]1[C:14]1[N:19]=[CH:18][C:17]([C:20]([O:22]C)=[O:21])=[CH:16][N:15]=1.[OH-].[Li+].Cl>C1COCC1.O>[CH2:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH2:3][N:2]1[C:14]1[N:19]=[CH:18][C:17]([C:20]([OH:22])=[O:21])=[CH:16][N:15]=1
Reactant: COC(=O)c1cnc(N2CCc3c([nH]c4ccccc34)C2)nc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cnc(N2CCc3c([nH]c4ccccc34)C2)nc1
Reaction time: 4.5 h
Yield: 83.8 %

Procedure:
To a stirred solution of Example 8 (500 mg, mmol) in THF and water (10 mL, 1:1) was added lithium hydroxide (205 mg, mmol) at room temperature and the mixture was stirred for 4-5 hours. After completion, the reaction mixture was acidified using 1N hydrochloric acid. The mixture was extracted with EtOAc, washed with brine, the organics dried over sodium sulfate and concentrated to give 2-(1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxylic acid (400 mg, 83% yield).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[Li]CCCC.[OH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=O)[CH3:19])=[CH:14][CH:13]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1C=CC=CC=1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:18]([C:15]1[CH:16]=[CH:17][C:12]([OH:11])=[CH:13][CH:14]=1)=[CH2:19]
Reactant: CC(=O)c1ccc(O)cc1
Reactant: c1ccsc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Li]CCCC
Solvent: c1ccccc1
Solvent: C1CCOC1
Product: C=C(c1ccc(O)cc1)c1cccs1
Temperature: -78 °C
Reaction time: 2 h
Yield: 11.5 %

Procedure:
A solution of thiophene (0.60 mL, 7.5 mmol) in THF (15 mL) was cooled to −78° C., BuLi solution (2.5 M in hexanes, 3.0 mL, 7.5 mmol) was added dropwise, after 1 h at −78° C., a solution of 1-(4-hydroxy-phenyl)-ethanone (1.0 g, 7.34 mmol) was added. The slurry mixture was stirred at −78° C. for 2 h, then slowly warmed to rt. The reaction was quenched with saturated aqueous NH4Cl, extracted with ethyl acetate, the extract was washed with brine, dried over MgSO4 and concentrated to give yellow oil residue. To the above oil residue was added benzene (10 mL) and catalytic amount of TsOH. The mixture was heated with Dean-Stark trap for 15 min, then concentrated 4-(1-Thiophen-2-yl-vinyl)-phenol (170 mg, 11.5%) was obtained after flash column chromatography (20%–40% ethyl acetate-hexanes). MS Found: (M+H)+=203.
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([N+:12]([O-])=O)[CH:9]=[CH:10][CH:11]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[H][H]>C(O)(=O)C.[Pd]>[N:1]1([C:6]2[CH:7]=[C:8]([CH:9]=[CH:10][CH:11]=2)[NH2:12])[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=[N+]([O-])c1cccc(-n2ccnc2)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(=O)O
Product: Nc1cccc(-n2ccnc2)c1

Procedure:
To 3-(1-imidazolyl)nitrobenzene (51.6 g, 0.27 mol) in acetic acid (500 ml) is added palladium catalyst (5 g 5% Pd on activated carbon) and the mixture is hydrogenated under pressure (Pstart : 4 bar) until the hydrogen uptake has ceased. The mixture is filtered through celite and the filtrate is evaporated to dryness to leave 2d as a light-brown oil. Yield: 40.4 g (93%).