Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH2:11][CH:10]([N:12]2[CH2:17][CH2:16][C:15]([OH:19])([CH3:18])[CH2:14][CH2:13]2)[CH2:9]1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH:8]1[CH2:11][CH:10]([N:12]2[CH2:17][CH2:16][C:15]([CH3:18])([OH:19])[CH2:14][CH2:13]2)[CH2:9]1
Reactant: CC1(O)CCN(C2CN(C(=O)OC(C)(C)C)C2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1(O)CCN(C2CNC2)CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 84.9 %

Procedure:
A 25 mL round-bottomed flask was charged with a solution of 3-(4-hydroxy-4-methylpiperidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester (0.2 g, 0.74 mmol) in DCM/TFA (3 mL/3 mL). The reaction mixture was stirred for 4 h at room temperature. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH to give 1-Azetidin-3-yl-4-methylpiperidin-4-ol as a colourless oil (0.107 g, 85%). 1H NMR (CDCl3, 400 MHz) δ 3.61 (t, J=7.3 Hz, 2H); 3.54 (t, J=7.3 Hz, 2H); 3.29-3.15 (m, 1H); 3.04 (s, 2H); 2.40 (d, J=10.8 Hz, 2H); 2.30-2.18 (m, 2H); 1.67-1.56 (m, 4H); 1.23 (s, 3H).
Reaction SMILES: [OH:1][C@@H:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([O:5][CH3:6])=[O:4].N1C=CC=CC=1.[C:20](Cl)(=[O:28])[O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl>[O:21]([C:20]([O:1][C@@H:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([O:5][CH3:6])=[O:4])=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: COC(=O)[C@@H](O)Cc1ccccc1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)[C@H](Cc1ccccc1)OC(=O)Oc1ccccc1
Yield: 114.1 %

Procedure:
To methyl 2(S)-hydroxy-3-phenylpropionate (5.0 g) and pyridine (8.78 g) in methylene chloride (50 ml) was dropwise added phenyl chlorocarbonate (4.78 g) under cooling at 0°-10° C. over 30 minutes. After the dropwise addition, the mixture was stirred at said temperature for 60 minutes, washed with 10% hydrochloric acid and water, dried over magnesium sulfate, and concentrated to dryness under reduced pressure. As a result, 9.51 g of methyl 2(S)-phenoxycarbonyloxy-3-phenylpropionate was obtained as a pale yellow, oily substance.
Reaction SMILES: [NH2:1][C:2]1[N:6]=[C:5]([C:7]([NH2:9])=[O:8])[NH:4][N:3]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:24]([CH2:29][CH3:30])([CH2:27][CH3:28])[CH2:25][CH3:26])(=O)=O>ClCCCl.C(OCC)(=O)C>[NH2:1][C:2]1[N:6]=[C:5]([C:7]([NH:9][Si:24]([CH2:29][CH3:30])([CH2:27][CH3:28])[CH2:25][CH3:26])=[O:8])[NH:4][N:3]=1
Reactant: NC(=O)c1nc(N)n[nH]1
Reactant: CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: ClCCCl
Solvent: Cc1cccc(C)n1
Product: CC[Si](CC)(CC)NC(=O)c1nc(N)n[nH]1
Temperature: 50 °C
Yield: 26.5 %

Procedure:
A stirred mixture of 3-amino-1H-1,2,4-triazole-5-carboxamide (103 mg, 0.810 mol) in 1,2-dichloroethane (1.62 mL) treated at room temperature with 2,6-lutidine (283 μL, 2.43 mmol) and triethylsilyl trifluoromethanesulfonate (458 μL, 2.03 mmol). After 22 hours the reaction was heated at 50° C. and after 1.5 hours of heating the reaction was allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (25 mL), dried over magnesium sulfate, filtered, and evaporated to an oil which was flash chromatographed (silica gel, 0-10% ethyl acetate:hexane) to give the title compound as a white solid (130 mg).
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17]([O:19][CH:20]3[CH2:38][CH:37]4[N:22]([C:23](=[O:52])[N:24]([CH2:43][C:44]5[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=5)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH:30]=[CH:31][CH:32]5[C:34]([C:40]([OH:42])=O)([NH:35][C:36]4=[O:39])[CH2:33]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:55])[C:13]([O:53][CH3:54])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].C(Cl)CCl.O1CCNC1=O.C1(C[S:70]([NH2:73])(=[O:72])=[O:71])CC1.[CH2:74]1[CH2:84][CH2:83]N2C(=NCCC2)C[CH2:75]1>ClCCl>[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17]([O:19][CH:20]3[CH2:38][CH:37]4[N:22]([C:23](=[O:52])[N:24]([CH2:43][C:44]5[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=5)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH:30]=[CH:31][CH:32]5[C:34]([C:40]([NH:73][S:70]([C:74]6([CH3:75])[CH2:83][CH2:84]6)(=[O:72])=[O:71])=[O:42])([NH:35][C:36]4=[O:39])[CH2:33]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:55])[C:13]([O:53][CH3:54])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:2])[CH3:3]
Reactant: COc1ccc(CN2CCCCCC=CC3CC3(C(=O)O)NC(=O)C3CC(Oc4cc(-c5nc(C(C)C)cs5)nc5c(C)c(OC)ccc45)CN3C2=O)cc1
Reactant: C1CCC2=NCCCN2CC1
Reactant: NS(=O)(=O)CC1CC1
Agent: O=C1NCCO1
Solvent: ClCCCl
Solvent: ClCCl
Product: COc1ccc(CN2CCCCCC=CC3CC3(C(=O)NS(=O)(=O)C3(C)CC3)NC(=O)C3CC(Oc4cc(-c5nc(C(C)C)cs5)nc5c(C)c(OC)ccc45)CN3C2=O)cc1
Temperature: 25 °C
Reaction time: 7 h
Yield: 44.2 %

Procedure:
To acid 138 (212 mg, 0.276 mmol) dissolved in dichloromethane (7 mL) was added EDC (69 mg, 0.359 mmol) and the reaction mixture was stirred at room temperature. After 7 hours TLC and LC-MS indicated complete conversion of the starting material into the corresponding oxazolidinone. The reaction mixture was diluted with dichloro-methane (20 mL) and the organic phase was washed twice with water after which the organic phase was dried, filtered, and concentrated. The residue was dissolved in dichloromethane (5 mL) and cyclopropylmethyl sulfonamide (53 mg, 0.394 mmol) and DBU (78 μL, 0.525 mmol) were added and the reaction mixture was stirred at room temperature for 20 hours. The mixture was diluted with dichloromethane (30 mL) and the organic phase was washed twice with 10% citric acid and once with brine. The organic phase was dried, filtered and concentrated and the crude product was purified by flash column chromatography (toluene/ethyl acetate 1:1, 1:2, ethyl acetate, ethyl acetate/methanol 9:1) to give the title compound (108 mg, 44%) as a colorless solid. LC-MS purity: >95%. (M+H)+ calcd: 885.4. found: 885.7.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:29]=[C:28]([O:30][CH2:31][CH:32]([CH3:34])[CH3:33])[CH:27]=[CH:26][C:7]=1[C:8]([C:10]1[CH:11]=[CH:12][C:13]([O:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[C:14]([CH2:16][C:17]([O:19]C)=[O:18])[CH:15]=1)=[O:9])[CH:2]([CH3:4])[CH3:3].[OH-].[Na+].C(Cl)(Cl)Cl.Cl>CO.O>[CH2:1]([O:5][C:6]1[CH:29]=[C:28]([O:30][CH2:31][CH:32]([CH3:34])[CH3:33])[CH:27]=[CH:26][C:7]=1[C:8]([C:10]1[CH:11]=[CH:12][C:13]([O:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[C:14]([CH2:16][C:17]([OH:19])=[O:18])[CH:15]=1)=[O:9])[CH:2]([CH3:4])[CH3:3]
Reactant: COC(=O)Cc1cc(C(=O)c2ccc(OCC(C)C)cc2OCC(C)C)ccc1OCC(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(C)COc1ccc(C(=O)c2ccc(OCC(C)C)c(CC(=O)O)c2)c(OCC(C)C)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81.4 %

Procedure:
In 6 ml of methanol is dissolved 0.57 g of methyl 2-[5-(2,4-diisobutoxybenzoyl)-2-isobutoxyphenyl]acetate. After adding 0.72 ml of 5 mol/L solution of sodium hydroxide, the mixture thus obtained is stirred at ambient temperature for one hour and thereafter at 50-60° C. for one hour. Chloroform and water are added to the reaction mixture, pH is adjusted to 2.0 with 2 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is successively washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. Thus, 0.45 g of 2-[5-(2,4-diisobutoxybenzoyl)-2-isobutoxyphenyl]acetic acid is obtained as a colorless crystalline product.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH3:10][S:11]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)(=[O:13])=[O:12].C(=O)([O-])[O-].[K+].[K+].Cl>O.CN(C=O)C>[CH3:10][S:11]([N:14]1[CH2:19][CH2:18][N:17]([C:2]2[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=2)[CH2:16][CH2:15]1)(=[O:13])=[O:12]
Reactant: O=Cc1cccc(Br)n1
Reactant: CS(=O)(=O)N1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CS(=O)(=O)N1CCN(c2cccc(C=O)n2)CC1
Temperature: 120 °C
Yield: 20.2 %

Procedure:
A suspension of 6-bromopicolinaldehyde (1.50 g, 8.10 mmol), 1-(methylsulfonyl)piperazine (9, 5.30 g, 32.2 mmol), potassium carbonate (4.45 g, 32.2 mmol) and anhydrous DMF (10 mL) was placed in a sealed vessel and the mixture was heated at 120° C. for 20 h. The mixture was diluted with water (50 mL) and brought to pH 7 using 2 N aq. HCl (15 mL). The resulting solution was extracted with CH2Cl2 (3×50 mL) and the combined extracts were washed with brine (200 mL). The solution was dried (MgSO4), filtered, concentrated, and purified by silica gel chromatography eluting with 0-3% CH3OH in CH2Cl2 to afford the title compound (0.441 g, 20%) as an orange oil: 1H NMR (500 MHz, CDCl3) δ 9.90 (s, 1H), 7.67 (t, J=8.0 Hz, 1H), 7.34 (d, J=7.0 Hz, 1H), 6.89 (d, J=8.5 Hz, 1H), 3.80-3.78 (m, 4H), 3.37-3.33 (m, 4H), 2.81 (s, 3H).
Reaction SMILES: [C:1]([NH2:6])(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[CH2:7](Cl)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CN(C)C=O>[CH2:7]([NH:6][C:1](=[O:5])/[CH:2]=[CH:3]/[CH3:4])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: ClCc1ccccc1
Reactant: C/C=C/C(N)=O
Solvent: CN(C)C=O
Product: C/C=C/C(=O)NCc1ccccc1
Yield: 71 %

Procedure:
To 200 ml of N,N-dimethylformamide, were added 17 g of crotonamide, 105 g of LEVATIT MP-500, which was also used in Example 68, and 32 g of benzylchloride. They were reacted at 50° C. for 4 hours with stirring. After the reaction, the reaction solution was treated in the same manner as in Example 69, the resulting distillation residue was recrystallized from benzine, and 25 of N-benzylcrotonamide having a melting point of 112.5°-113.6° C. was obtained (yield: 71%).
Reaction SMILES: Cl[C:2]1[N:22]=[C:5]2[C:6]([C:10]3[CH:11]=[N:12][N:13]([C:15]4[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=4)[CH:14]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:31]=[C:32]([CH:34]=[CH:35][CH:36]=2)[NH2:33])[CH2:26][CH2:25]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[F:21][C:18]1[CH:19]=[CH:20][C:15]([N:13]2[CH:14]=[C:10]([C:6]3[C:5]4[N:4]([N:3]=[C:2]([NH:33][C:32]5[CH:34]=[CH:35][CH:36]=[C:30]([N:27]6[CH2:26][CH2:25][N:24]([CH3:23])[CH2:29][CH2:28]6)[CH:31]=5)[N:22]=4)[CH:9]=[CH:8][CH:7]=3)[CH:11]=[N:12]2)=[CH:16][CH:17]=1
Reactant: CN1CCN(c2cccc(N)c2)CC1
Reactant: Fc1ccc(-n2cc(-c3cccn4nc(Cl)nc34)cn2)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCN(c2cccc(Nc3nc4c(-c5cnn(-c6ccc(F)cc6)c5)cccn4n3)c2)CC1

Procedure:
{8-[1-(4-Fluoro-phenyl)-1H-pyrazol-4-yl]-[1,2,4]triazolo[1,5-a]pyridine-2-yl}-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 2-chloro-8-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[1,2,4]triazolo[1,5-a]pyridine (Example 280a) and 3-(4-methylpiperazine-1-yl)aniline with 2,2′-bis-dicyclohexylphosphanyl-biphenyl as the ligand in a manner analogous to Example 2d (0.055 g, 20%). MP=216-218° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.53 (s, 1H), 9.25 (s, 1H), 8.67 (d, 2H), 7.92 (m, 3H), 7.43 (m, 3H), 7.12 (m, 3H), 6.50 (m, 1H), 3.12 (m, 4H), 2.43 (m, 4H), 2.21 (s, 3H). MS=469 (MH)+.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([S:9](Cl)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)#[N:2].CCN(C(C)C)C(C)C.[CH2:22]([NH:24][C:25]([N:27]1[N:31]=[CH:30][C:29]2([CH2:35][CH2:34][CH2:33][CH2:32]2)[CH2:28]1)=[NH:26])[CH3:23]>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([S:9]([N:26]=[C:25]([N:27]2[N:31]=[CH:30][C:29]3([CH2:35][CH2:34][CH2:33][CH2:32]3)[CH2:28]2)[NH:24][CH2:22][CH3:23])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)#[N:2]
Reactant: N#Cc1cccc(S(=O)(=O)Cl)c1
Reactant: CCNC(=N)N1CC2(C=N1)CCCC2
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCNC(=NS(=O)(=O)c1cccc(C#N)c1)N1CC2(C=N1)CCCC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.7 %

Procedure:
To a solution of 3.50 g 3-cyanobenzenesulfonyl chloride in 150 mL DCM were added 17.69 mL (6.0 equiv.) DiPEA and 4.00 g (1.0 equiv.) N-ethyl-2,3-diaza-spiro[4.4]non-3-ene-2-carboxamidine. The reaction mixture was stirred overnight at room temperature and extracted with water. The organic phase was dried over Na2SO4 and evaporated, and the residue was purified by automated flash chromatography (EtOAc/PA 1:1) to give 3.54 g (57%) of a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.17 (t, J=8 Hz, 3H), 1.65-1.86 (m, 8H), 3.41-3.50 (m, 2H), 3.87 (br.s., 2H), 6.70-6.80 (br.s., 1H), 6.87 (s, 1H), 7.60 (t, J=8 Hz, 1H), 7.77 (d, J=8 Hz, 1H), 8.17 (d, J=8 Hz, 1H), 8.23 (br.s., 1H).
Reaction SMILES: [OH-].[Na+].CO.[CH2:5]([O:7][C:8]1[CH:13]=[C:12]([CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[CH2:30][CH2:29][C:28]4[N:27]=[C:26]([CH2:31][CH2:32][CH3:33])[C:25]([C:34]([O:36]C)=[O:35])=[CH:24][C:23]=4[C:22]3=[O:38])[CH2:17][CH2:16]2)[CH:11]=[C:10]([O:39][CH2:40][CH3:41])[C:9]=1[C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH3:6].Cl>C(OCC)(=O)C.C1COCC1>[CH2:40]([O:39][C:10]1[CH:11]=[C:12]([CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[CH2:30][CH2:29][C:28]4[N:27]=[C:26]([CH2:31][CH2:32][CH3:33])[C:25]([C:34]([OH:36])=[O:35])=[CH:24][C:23]=4[C:22]3=[O:38])[CH2:17][CH2:16]2)[CH:13]=[C:8]([O:7][CH2:5][CH3:6])[C:9]=1[C:42]1[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=1)[CH3:41]
Reactant: CCCc1nc2c(cc1C(=O)OC)C(=O)N(C1CCN(Cc3cc(OCC)c(-c4ccc(F)cc4)c(OCC)c3)CC1)CC2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCc1nc2c(cc1C(=O)O)C(=O)N(C1CCN(Cc3cc(OCC)c(-c4ccc(F)cc4)c(OCC)c3)CC1)CC2
Temperature: 50 °C
Reaction time: 1 h
Yield: 25.8 %

Procedure:
A 2 M aqueous sodium hydroxide solution (1.50 mL) was added at room temperature to a methanol (2 mL)-THF (2 mL) solution of methyl 6-(1-((2,6-diethoxy-4′-fluorobiphenyl-4-yl)methyl)piperidin-4-yl)-5-oxo-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate (560 mg), and the mixture was stirred at 50° C. for 1 hour. The reaction mixture was neutralized with 6 M hydrochloric acid at room temperature. Then, ethyl acetate was added thereto, and the mixture was concentrated. The deposited solid was collected by filtration and washed with diethyl ether. The obtained solid was recrystallized (DMSO/ethanol/hexane) to obtain the title compound (141 mg).
Reaction SMILES: COC1C=CC(C[S:10][C:11]2[N:12]([C:32]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)=[O:33])[CH:13]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=3)[C:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:15]([CH3:17])[N:16]=2)=CC=1.FC(F)(F)C(O)=O.C(S)C>ClCCl>[CH3:17][C:15]1[NH:16][C:11](=[S:10])[N:12]([C:32]([C:34]2[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=2)=[O:33])[CH:13]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=2)[C:14]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]
Reactant: CCOC(=O)C1=C(C)N=C(SCc2ccc(OC)cc2)N(C(=O)c2ccc(OC)cc2)C1c1cccc([N+](=O)[O-])c1
Solvent: CCS
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)C1=C(C)NC(=S)N(C(=O)c2ccc(OC)cc2)C1c1cccc([N+](=O)[O-])c1
Reaction time: 48 h

Procedure:
A solution of 1.5 g. (0.0026 mole) of 1,6-dihydro-2-[[(4-methoxyphenyl)methyl]thio]-4-methyl-6-(3-nitrophenyl)-1-[(4-methoxyphenyl)carbonyl]-5-pyrimidinecarboxylic acid, ethyl ester in 15 ml. of dichloromethane is treated with 0.88 ml. (0.0113 mole) of trifluoroacetic acid and 0.38 g. (0.0059 mole) of ethanethiol. After stirring for 48 hours, the solvent is evaporated and the oil residue is triturated with isopropyl ether to form 0.91 g. of the title compound as a yellow solid, m. p. 130°-132°. TLC(silica gel; ethyl acetate hexane, 1:1) Rf =0.50.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:17][C:18]([F:32])([F:31])[C:19]([F:30])([F:29])[C:20]([F:28])([F:27])[O:21][C:22]([F:26])=[C:23]([F:25])[F:24].C(C1C=CC=C(OC(F)(F)C(F)OC(F)(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F)C=1)#C>O1CCCC1>[F:25][C:23]([F:24])([O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1)[CH:22]([F:26])[O:21][C:20]([F:27])([F:28])[C:19]([F:29])([F:30])[C:18]([F:17])([F:31])[F:32]
Reactant: CC(=O)c1ccc(O)cc1
Reactant: FC(F)=C(F)OC(F)(F)C(F)(F)C(F)(F)F
Agent: C#Cc1cccc(OC(F)(F)C(F)OC(F)(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(=O)c1ccc(OC(F)(F)C(F)OC(F)(F)C(F)(F)C(F)(F)F)cc1

Procedure:
In the dry box, tetrahydrofuran (50 mL) and 1-(4-hydroxyphenyl)ethanone (0.68 g, 0.005 mol) were added to a round bottom flask equipped with a stirrer. Potassium carbonate (0.175 g, 0.00126 mol) was then added to the flask. 1,1,1,2,2,3,3-heptafluoro-3-((1,2,2-trifluorovinyl)oxy)propane (1.99 g, 0.0075 mol) was then added via the addition funnel and the reaction was placed in an oil bath and heated to a gentle reflux for 5.5 hours. The content was analyzed by proton NMR and shown to be 1-ethynyl-3-(1,1,2-trifluoro-2-(1,1,2,3,3,3-hexafluoro-2-(perfluoropropoxy)propoxy)ethoxy)benzene.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]([NH:25][C@@H:26]1[C:32](=[O:33])[N:31]([CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:30]2[CH:42]=[CH:43][CH:44]=[CH:45][C:29]=2[O:28][CH2:27]1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][N:14]1C(=O)C2=CC=CC=C2[C:15]1=[O:24])=[O:5])[CH3:2].[OH2:46].NN>C(O)C>[C:38]([O:46][C:15]([NH:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]([NH:25][C@@H:26]1[C:32](=[O:33])[N:31]([CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:30]2[CH:42]=[CH:43][CH:44]=[CH:45][C:29]=2[O:28][CH2:27]1)[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:24])([CH3:41])([CH3:40])[CH3:39]
Reactant: O
Reactant: CCOC(=O)[C@H](CCCCCCCN1C(=O)c2ccccc2C1=O)N[C@H]1COc2ccccc2N(CC(=O)OC(C)(C)C)C1=O
Agent: NN
Solvent: CCO
Product: CCOC(=O)[C@H](CCCCCCCNC(=O)OC(C)(C)C)N[C@H]1COc2ccccc2N(CC(=O)OC(C)(C)C)C1=O
Reaction time: 8 h
Yield: 183.4 %

Procedure:
A mixture of tert-butyl 3(S)-[1(S)-ethoxycarbonyl-8-phthalimidooctyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.55 g), hydrazine hydrate (0.22 g) and ethanol (10 ml) is allowed to stand overnight at room temperature. After evaporation of ethanol, the residue is dissolved in water (50 ml) and extracted with ethyl acetate (50 ml×4). Water (50 ml) and sodium bicarbonate (0.6 g) are added to the organic extract, and to the resulting mixture is added dropwise di-tert-butyl dicarbonate (0.29 g) with stirring. After stirring for 30 minutes at room temperature, the ethyl acetate layer is separated, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue is purified by silica gel column chromatography using hexane:ethyl acetate (2:1-1:1) as an eluent to give tert-butyl 3(S)-[8-tert-butoxycarbonylamino-1(S)-ethoxycarbonyloctyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.48 g) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[N:6]([C@@H:7]2[O:27][C@H:26]([CH2:28][O:29]CC3C=CC=CC=3)[C@@H:17]([O:18]CC3C=CC=CC=3)[C@H:8]2[O:9]CC2C=CC=CC=2)[C:5]2[CH:37]=[C:38]([N+:44]([O-:46])=[O:45])[C:39]([N+:41]([O-:43])=[O:42])=[CH:40][C:4]=2[N:3]=1.B(Cl)(Cl)Cl.CO>C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[N:6]([C@@H:7]2[O:27][C@H:26]([CH2:28][OH:29])[C@@H:17]([OH:18])[C@H:8]2[OH:9])[C:5]2[CH:37]=[C:38]([N+:44]([O-:46])=[O:45])[C:39]([N+:41]([O-:43])=[O:42])=[CH:40][C:4]=2[N:3]=1
Reactant: O=[N+]([O-])c1cc2nc(Cl)n([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c2cc1[N+](=O)[O-]
Agent: ClB(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CO
Solvent: ClCCl
Product: O=[N+]([O-])c1cc2nc(Cl)n([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2cc1[N+](=O)[O-]
Temperature: -78 °C
Reaction time: 2 h
Yield: 77.6 %

Procedure:
To a solution of 0.464 g (0.719 mmol) of 60 in 12 mL of CH2Cl2, was added dropwise 8.4 mL of 1M BCl3 at -78° C. The reaction mixture was stirred at -78° C. for 2 hr and then at -40° C. for 2 hr. MeOH (5 mL) was added and stirring was continued at -40° C. for 10 min. The reaction mixture was diluted with EtOAc (75 mL). The EtOAc solution was washed with cold H2O (50 mL), sat. NaHCO3 solution (50 mL), sat. NaCl solution (50 mL), dried (Na2SO4), and evaporated. The residue was coevaporated with MeOH (3×) and then suspended in a small amount of CHCl3 for a few hours. The solid product was filtered to give 0.209 g of 61. This sample was contaminated by a small amount of 2-chloro-5,6-dinitrobenzimidazole. A part of the sample (0.18 g) was purified on a silica column (2.4×10 cm, eluted with pure EtOAc). Evaporation of the appropriate fractions and crystallization by addition of CHCl3 gave 0.084 g of 61 as a white solid. MP: 132°-135° C. MS: (El) m/e 374.0276 (1%, M+ =374.0265). 1H NMR (DMSO-d6): δ9.18 (s, 1, 7-H), 8.60 (s, 1, 4-H), 6.00 (d, 1, 1'-H, J1'-2' =7.5 Hz), 5.59 (d, 1, 2'-OH, J2'-2'OH =6.0 Hz), 5.52 (t, 1, 5'-OH, J5'-5'OH =4.5 Hz), 5.38 (d, 1, 3'-OH, J3'-3'OH =4.5 Hz), 4.01 (m, 1, 2'-H, J2'-3' =5.5 Hz), 4.16 (m, 1, 3'-H, J3'-4' =2.0 Hz), 4.07 (m, 1, 4'-H, J4'-5' =J4'-5" =2.5 Hz), 3.73 (m, 2, 5'-H and 5"-H, J5'-5" =12.0 Hz). 13C NMR (DMSO-d6): δ146.55 (C2), 142.63 (C3a), 138.90, 138.60 (C5 and C6), 134.12 (C7a), 116.67 (C4), 111.62 (C7), 89.98 (C1'), 86.91 (C4'), 72.86 (C2'). 69.84 (C3'), 60.85 (C5'). Anal. Calcd. for C12H11ClN4O8 : C, 38.47; H, 2.96; N, 14.95. Found: C, 38.46; H, 2.98; N, 14.62.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[N:12]1[C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[NH:14][C:13]=1[S:21][C:22]1[O:26][C:25]([CH:27]=O)=[CH:24][CH:23]=1.[C:29]1(=O)[CH2:34][CH2:33][CH2:32][C:31](=[O:35])[CH2:30]1>C(O)CCC>[CH2:10]([O:9][C:7]([C:3]1[NH:4][CH:5]=[C:6]2[CH:27]([C:25]3[O:26][C:22]([S:21][C:13]4[NH:14][C:15]5[CH:16]=[N:17][CH:18]=[CH:19][C:20]=5[N:12]=4)=[CH:23][CH:24]=3)[C:30]3[C:31](=[O:35])[CH2:32][CH2:33][CH2:34][C:29]=3[NH:1][C:2]=12)=[O:8])[CH3:11]
Reactant: O=C1CCCC(=O)C1
Reactant: O=Cc1ccc(Sc2nc3ccncc3[nH]2)o1
Reactant: CCOC(=O)c1[nH]ccc1N
Solvent: CCCCO
Product: CCOC(=O)c1[nH]cc2c1NC1=C(C(=O)CCC1)C2c1ccc(Sc2nc3ccncc3[nH]2)o1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 37.4 %

Procedure:
A suspension of 154.2 mg (1.0 mmol) of 3-amino-2-ethoxycarbonylpyrrole and 245.3 mg (1.0 mmol) of 5-(3H-imidazo[4,5-c]pyridin-2-ylsulfanyl)-furan-2-carbaldehyde (obtained from step 1) in 10 mL of n-butanol under argon is stirred at room temperature for 15 min. 1,3-Cyclohexanedione (112.1 mg, 1.0 mmol) is then added and the reaction mixture is heated at reflux temperature for 2 h. The mixture is then cooled to room temperature and concentrated under reduced pressure. The residue is triturated in ethanol, filtered and washed with diethyl ether. The solid is purified by chromatography on a prepacked 70 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol from 100/0 to 80/20 v/v; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. 178 mg of 9-[5-(3H-imidazo[4,5-c]pyridin-2-ylsulfanyl)-furan-2-yl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester are obtained as a beige powder. LCMS: m/z 476: [M+H]+ (base peak). Anal. Calcd for C24H21N5O4S: C, 60.62; H, 4.45; N, 14.73; O, 13.46; S, 6.74. Found: C, 59.41; H, 4.47; N, 14.33; S, 6.41; H2O, 2.11%.