Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([P:10](=[O:17])([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13])P(=O)(OCC)OCC.[H-].[Na+].[CH:20]([C:22]1[C:23]([NH:33][C:34](=[O:56])[C:35]2[CH:40]=[CH:39][C:38]([O:41][CH2:42][C:43]3[N:44]=[C:45]([C:49]4[O:50][CH:51]=[CH:52][CH:53]=4)[O:46][C:47]=3[CH3:48])=[C:37]([O:54][CH3:55])[CH:36]=2)=[N:24][N:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:26]=1)=O.O>CN(C)C=O>[O:50]1[CH:51]=[CH:52][CH:53]=[C:49]1[C:45]1[O:46][C:47]([CH3:48])=[C:43]([CH2:42][O:41][C:38]2[CH:39]=[CH:40][C:35]([C:34]([NH:33][C:23]3[C:22](/[CH:20]=[CH:1]/[P:10](=[O:17])([O:11][CH2:12][CH3:13])[O:14][CH2:15][CH3:16])=[CH:26][N:25]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:24]=3)=[O:56])=[CH:36][C:37]=2[O:54][CH3:55])[N:44]=1
Reactant: COc1cc(C(=O)Nc2nn(-c3ccccc3)cc2C=O)ccc1OCc1nc(-c2ccco2)oc1C
Reactant: CCOP(=O)(CP(=O)(OCC)OCC)OCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOP(=O)(/C=C/c1cn(-c2ccccc2)nc1NC(=O)c1ccc(OCc2nc(-c3ccco3)oc2C)c(OC)c1)OCC
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 75 %

Procedure:
To a solution of tetraethyl methylenediphosphonate (277 mg) in N,N-dimethylformamide (5 mL) was added sodium hydride (60% in oil, 38 mg), and the mixture was stirred at room temperature for 20 min. To the reaction mixture was added a solution of N-(4-formyl-1-phenyl-1H-pyrazol-3-yl)-4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzamide (400 mg) in N,N-dimethylformamide (5 mL), and the mixture was stirred at room temperature for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with distilled water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:1 to 1:0, v/v), then methanol-ethyl acetate (0:1 to 0.5:9.5, v/v) to give diethyl (E)-2-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzoyl)amino]-1-phenyl-1H-pyrazol-4-yl}ethenylphosphonate as colorless amorphous form (380 mg, yield 75%).
Reaction SMILES: [C:1]([CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=[O:5])#[N:2].[Cl:13][C:14]1[C:19](O)=[C:18]([Cl:21])[C:17]([Cl:22])=[C:16]([Cl:23])[C:15]=1[Cl:24].O=P(Cl)(Cl)Cl.Cl>C(Cl)(Cl)(Cl)Cl>[Cl:13][C:14]1[C:19]([O:5][C:4](=[O:6])[CH:3]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:1]#[N:2])=[C:18]([Cl:21])[C:17]([Cl:22])=[C:16]([Cl:23])[C:15]=1[Cl:24]
Reactant: N#CC(C(=O)O)c1ccccc1
Reactant: Oc1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl
Agent: Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: N#CC(C(=O)Oc1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl)c1ccccc1
Temperature: 25 °C

Procedure:
8 g. (0.05 moles) of α-cyanophenylacetic acid, 13 g. (0.05 moles) of pentachlorophenol are mixed together. 4.3 g. (0.05 moles) of phosphoroxychloride are added dropwise. The obtained mixture is heated slowly to 85°-90° C. on an oil-bath and the mixture is kept at this temperature until the HCl evolution ceases. When the reaction is completed, the mixture is cooled to room temperature, and the melt is taken up in 100 ml. of carbon tetrachloride. The solution is washed three times with 30 ml. of water, treated with decolorizing charcoal, dried and evaporated. The product is recrystalized from diisopropyl ether, and crystalline pentachlorophenyl ester is precipitated.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH:8]=O)[C:5]2[C:10]([O:32][CH3:33])=[N:11][N:12]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:4]=2[CH:3]=1.C([O-])(=O)C.[Na+].[NH2:39][OH:40]>C(O)C>[Cl:1][C:2]1[N:7]=[C:6](/[CH:8]=[N:39]/[OH:40])[C:5]2[C:10]([O:32][CH3:33])=[N:11][N:12]([C:13]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:4]=2[CH:3]=1
Reactant: NO
Reactant: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(Cl)nc(C=O)c12
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(Cl)nc(/C=N/O)c12
Temperature: 70 °C
Reaction time: 1 h

Procedure:
6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine-4-carbaldehyde (11B, 100 mg, 0.220 mmol), sodium acetate (54.2 mg, 0.661 mmol), and hydroxylamine (21.8 mg, 0.331 mmol) were taken up in Ethanol (2.2 ml). The reaction was allowed to stir at 70° C. for 1 hour. Room temperature was attained and the reaction mixture was concentrated in vacuo. The mixture was partitioned between EtOAc and saturated NaHCO3. The combined orgniac layers were washed with brine, dried over MgSO4, and concentrated in vacuo to give (E)-6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine-4-carbaldehyde oxime. The products were carried forward without purification. MS: [M+H]+ m/z 469.
Reaction SMILES: [C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[C:7]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[N:16]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl.[CH3:57][S:58]([C:61]1[CH:62]=[C:63]([CH:65]=[CH:66][CH:67]=1)[NH2:64])(=[O:60])=[O:59]>CN(C=O)C>[C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:64][C:63]2[CH:65]=[CH:66][CH:67]=[C:61]([S:58]([CH3:57])(=[O:60])=[O:59])[CH:62]=2)=[O:10])=[C:7]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:24])[F:23])[N:16]=2)[CH:6]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)c1ccc(C(=O)O)c(Oc2cccc(C(F)(F)F)n2)c1
Reactant: CS(=O)(=O)c1cccc(N)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(C(=O)Nc2cccc(S(C)(=O)=O)c2)c(Oc2cccc(C(F)(F)F)n2)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A solution of 4-tert-butyl-2-(6-(trifluoromethyl)pyridin-2-yloxy)benzoic acid (17 mg, 50 μmol), HATU (19 mg, 50 μmol), and triethylamine (20 μL, 0.15 mmol) in DMF (0.5 mL) was stirred for five minutes, then 3-(methylsulfonyl)aniline hydrochloride (11 mg, 55 μmol) was added. The reaction was stirred at room temperature for 20 hours and was purified by reverse phase HPLC (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)) to give 4-tert-butyl-N-(3-(methylsulfonyl)phenyl)-2-(6-(trifluoromethyl)pyridin-2-yloxy)benzamide. LC/MS: m/z 493.3 (M+H)+ at 1.97 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:21]3[C:20]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[N+:14]([O-])=[CH:13][C:12]=3[N:11]=[CH:10]2)=[CH:5][CH:4]=1.C(OC(=O)C)(=[O:25])C>>[OH:25][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:21]=2[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N:14]=1
Reactant: COc1ccc(-n2cnc3c[n+]([O-])c4ccccc4c32)cc1
Reactant: CC(=O)OC(C)=O
Product: COc1ccc(-n2cnc3c(O)nc4ccccc4c32)cc1

Procedure:
Using the method of Example 133, 1-(4-methoxyphenyl)-1H-imidazo[4,5-c]quinolin-5-oxide (from Exmaple 86) was reacted with acetic anhydride to provide 4-hydroxy-1-(4-methoxyphenyl)-1H-imidazo[4,5-c]quinoline m.p. >300° C. after recrystallization from N,N-dimethylformamide. Analysis: Calculated for C17H13N3O2 : %C, 70.1; %H, 4.5; %N, 14.4; Found: %C, 70.0; %H, 4.4; %N, 14.5.
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:20]=[CH:21][CH:22]=2)[O:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]([NH:18][NH2:19])=[S:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:23][N:24]=[C:25]=[O:26].CCOCC>C1COCC1>[CH3:23][NH:24][C:25]([NH:19][NH:18][C:16]([NH:15][CH2:14][CH2:13][CH2:12][O:11][C:10]1[CH:20]=[CH:21][CH:22]=[C:8]([CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:9]=1)=[S:17])=[O:26]
Reactant: CN=C=O
Reactant: NNC(=S)NCCCOc1cccc(CN2CCCCC2)c1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CNC(=O)NNC(=S)NCCCOc1cccc(CN2CCCCC2)c1
Reaction time: 8 h

Procedure:
1.62 g (5 mmol) of N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]hydrazine carbothioamide are dissolved in 30 ml of THF, 0.40 g (6 mmol) of methylisocyanate are added and the reaction mixture is left to stand overnight at room temperature. Ether is added to complete the precipitation, and the precipitate is suction filtered, washed with ether and recrystallised from ethanol. The analytical values are summarized in Table I.
Reaction SMILES: [CH3:1][C:2]1[C:3](S(C)(=O)=O)=[N:4][C:5]([N:8]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[N:9]2)=[N:6][CH:7]=1.[F:21][C:22]([F:31])([F:30])[C:23]1[CH:24]=[C:25]([OH:29])[CH:26]=[CH:27][CH:28]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:1][C:2]1[C:3]([O:29][C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([C:22]([F:21])([F:30])[F:31])[CH:24]=2)=[N:4][C:5]([N:8]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[N:9]2)=[N:6][CH:7]=1
Reactant: Oc1cccc(C(F)(F)F)c1
Reactant: Cc1cnc(-n2cc(C(F)(F)F)cn2)nc1S(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cnc(-n2cc(C(F)(F)F)cn2)nc1Oc1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 72.2 %

Procedure:
A mixture of 11.2 g (36.4 mmol) of 5-methyl-4-methylsulfonyl-2-(4-trifluoromethyl-1H -1-pyrazolyl)pyrimidine, 7.7 g (47.4 mmol) of 3-trifluoromethylphenol and 10.1 g (72.9 mmol) of K2CO3 in 200 ml of DMF is stirred at RT for 24 h. It is then poured into 200 ml of water and extracted with four times 100 ml of CH2Cl2. The combined organic phase is dried over Na2SO4, filtered and concentrated. Chromatographic purification on silica gel with heptane/ethyl acetate (1:1) as eluent gives 10.2 g (72%) of 5-methyl-4-(3-trifluoromethylphenoxy)-2-(4-trifluoromethyl-1H-1-pyrazolyl)pyrimidine as colourless crystals having a melting point of 103-105° C.
Reaction SMILES: CS([C:4]1[S:5][C:6]2[CH:12]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:15]=3)[CH:10]=[CH:9][C:7]=2[N:8]=1)=O.[C@@H:27]1(N)[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]1[NH2:33].CCN(C(C)C)C(C)C.CN1C(=[O:50])CCC1>>[OH:50][C@@H:27]1[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]1[NH:33][C:4]1[S:5][C:6]2[CH:12]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH:15]=3)[CH:10]=[CH:9][C:7]=2[N:8]=1
Reactant: CN1CCCC1=O
Reactant: N[C@@H]1CCCC[C@H]1N
Reactant: CS(=O)c1nc2ccc(Oc3ccnc(C(=O)OC(C)(C)C)c3)cc2s1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)c1cc(Oc2ccc3nc(N[C@@H]4CCCC[C@H]4O)sc3c2)ccn1
Temperature: 100 °C
Reaction time: 72 h

Procedure:
To the solution of tert-butyl 4-(2-(methylsulfinyl)benzo[d]thiazol-6-yloxy)picolinate (500 mg, 1.25 mmol) in 10 ml of NMP was added (1R,2R)-cyclohexane-1,2-diamine (581 mg, 3.84 mmol) and DIPEA (0.995 ml, 5.76 mmol). The reaction solution was stirred at 100° C. for 3 days. The crude reaction solution was purified on prep HPLC and evaporated in vacuo to give tert-butyl 4-(2-((1R,2R)-2-hydroxycyclohexylamino)benzo[d]thiazol-6-yloxy)picolinate (240 mg, 0.544 mmol) as white powder. ES/MS m/z 442.5 (MH+).
Reaction SMILES: Br[C:2]1[S:3][C:4]2[CH2:5][C:6]3[C:12]([C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=4)=[N:11][N:10]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:7]=3[C:8]=2[CH:9]=1.[F:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:33]=[CH:34][C:35]=1[F:36].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:29][C:30]1[CH:31]=[C:32]([C:2]2[S:3][C:4]3[CH2:5][C:6]4[C:12]([C:13]5[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=5)=[N:11][N:10]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:7]=4[C:8]=3[CH:9]=2)[CH:33]=[CH:34][C:35]=1[F:36]
Reactant: COc1ccc(-c2nn(COCC[Si](C)(C)C)c3c2Cc2sc(Br)cc2-3)cc1
Reactant: CC1(C)OB(c2ccc(F)c(F)c2)OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1ccc(-c2nn(COCC[Si](C)(C)C)c3c2Cc2sc(-c4ccc(F)c(F)c4)cc2-3)cc1
Temperature: 100 °C
Yield: 65 %

Procedure:
A mixture of the corresponding 2-Bromo-6-(4-methoxy-phenyl)-4-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalene (0.5 g, 0.1 mmol), 2-(3,4-Difluoro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.24 g, 0.1 mmol), Na2CO3 (2 M, 2.45 mL), and Pd(PPh3)2Cl2 (9.7 mg, 0.084 mmol) in toluene/ethanol (1:1, 8.0 mL) was heated at 100° C. for 8 hr. The solution was cooled to room temperature and extracted with ethyl acetate. The target product was purified by gravity column chromatography (20% EtOAc in hexane) to give 2-(3,4-Difluoro-phenyl)-6-(4-methoxy-phenyl)-4-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalene as orange solid in 65% yield.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[CH:21][C:22]([C:26]([OH:28])=O)=[CH:23]2)=[CH:18][CH:17]=1.CCN(CC)CC.[Cl:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1>CN(C=O)C.C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[CH:21][C:22]([C:26]([NH:41][C:40]3[CH:42]=[CH:43][C:37]([Cl:36])=[CH:38][CH:39]=3)=[O:28])=[CH:23]2)=[CH:18][CH:17]=1
Reactant: COc1cc2nccc(Oc3ccc4ccc(C(=O)O)cc4c3)c2cc1OC
Reactant: Nc1ccc(Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3ccc4ccc(C(=O)Nc5ccc(Cl)cc5)cc4c3)c2cc1OC
Reaction time: 2 h

Procedure:
A slurry of 7-(6,7-dimethoxyquinolin-4-yloxy)-2-naphthoic acid (0.54 g, 1.44 mmol) in 10 mL of C2O2Cl2 and 2 drops of DMF was stirred at RT. After 2 h, the solution was concentrated to dryness and placed under high vacuum overnight. A portion of the crude residue (0.075 g, 0.191 mmol) was dissolved in 1 mL of CH2Cl2. To the resulting solution was added Et3N (0.106 mL, 0.76 mmol), 4-chloroaniline (0.036 g, 0.286 mmol) and a catalytic amount of DMAP. The reaction was stirred under a nitrogen atmosphere for 16 h. The reaction was diluted with CH2Cl2, washed with saturated aqueous NaHCO3, and brine. The organic layer was dried (MgSO4), filtered and concentrated. The residue was passed through a medium-pressure silica gel column (solvent gradient: 95:5 CH2Cl2:MeOH; 90:10 CH2Cl2:MeOH) to afford the desired crude compound. The fractions were concentrated to dryness to afford a solid residue. The residue was triturated with Et2O/Hexanes to afford the desired compound as a pale yellow solid. MS (ESI, pos. ion) m/z: 485.0 (M+1). Mass Calc'd for C28H21ClN2O4: 484.937.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:35][C:36]1[CH:49]=[CH:48][C:39]([C:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:41])=[CH:38][CH:37]=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:24]([NH:35][C:36]2[CH:37]=[CH:38][C:39]([C:40]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[O:41])=[CH:48][CH:49]=2)=[O:26])=[CH:20][CH:21]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1ccc(C(=O)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccc(C(=O)c5ccccc5)cc4)cc3)c2cc1OC
Yield: 20.5 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (54 mg) was suspended in toluene (5 ml), triphosgene (53 mg) was added, and the admixture was refluxed with heat for 20 minutes. 4-Aminobenzophenone (85 mg) was added to the reaction mixture, and the admixture was refluxed for 1 hour with heat. After the addition of aqueous sodium hydrogen carbonate, the reaction mixture was extracted 2 times with ethyl acetate, and the organic layer was then washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by reduced-pressure distillation and the resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 19 mg of the title compound (yield: 21%).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH2:13]([C:15]1[N:16]=[C:17]([CH2:48][CH2:49][CH3:50])[N:18]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[C:40]([C:45]#[N:46])=[CH:41][CH:42]=[CH:43][CH:44]=3)=[CH:35][C:34]=2[F:47])[C:19](=[O:31])[C:20]=1[C:21]1[CH:22]=[N:23][C:24]([O:27][CH:28]([CH3:30])[CH3:29])=[CH:25][CH:26]=1)[CH3:14]>O>[CH2:13]([C:15]1[N:16]=[C:17]([CH2:48][CH2:49][CH3:50])[N:18]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[C:45]3[NH:3][C:4](=[O:7])[O:5][N:46]=3)=[CH:35][C:34]=2[F:47])[C:19](=[O:31])[C:20]=1[C:21]1[CH:22]=[N:23][C:24]([O:27][CH:28]([CH3:29])[CH3:30])=[CH:25][CH:26]=1)[CH3:14]
Reactant: O=C([O-])O
Reactant: CCCc1nc(CC)c(-c2ccc(OC(C)C)nc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1F
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCCc1nc(CC)c(-c2ccc(OC(C)C)nc2)c(=O)n1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1F
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 52.9 %

Procedure:
A mixture of hydroxylammonium chloride (0.89 g), sodium hydrogen carbonate (1.3 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[4-ethyl-5-(6-isopropoxypyridin-3-yl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}-3′-fluorobiphenyl-2-carbonitrile (0.39 g) was added, and the mixture was stirred at 90° C. for 24 hr. The reaction mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.18 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.17 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.23 g, 54%).
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([O:8][CH2:9][C@H:10]2[O:15][CH:13]([OH:14])[C@H:12]([OH:16])[C@:11]2([C:18]#[CH:19])[OH:17])=[O:7])=[CH:4][CH:3]=1.C(N([CH2:27][CH3:28])CC)C.[C:29](Cl)(=[O:33])[O:30][CH2:31][CH3:32]>ClCCl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][C@H:10]2[O:15][CH:13]([O:14][C:29]([O:30][CH2:31][CH3:32])=[O:33])[C@H:12]([O:16][C:6]([O:8][CH2:9][CH3:10])=[O:7])[C@:11]2([C:18]#[CH:19])[O:17][C:13]([O:15][CH2:27][CH3:28])=[O:14])=[O:7])=[CH:20][CH:21]=1
Reactant: CCOC(=O)Cl
Reactant: CCN(CC)CC
Reactant: C#C[C@@]1(O)[C@@H](COC(=O)c2ccc(Cl)cc2)OC(O)[C@@H]1O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: C#C[C@@]1(OC(=O)OCC)[C@@H](COC(=O)c2ccc(Cl)cc2)OC(OC(=O)OCC)[C@@H]1OC(=O)OCC
Reaction time: 1 h
Yield: 167.8 %

Procedure:
The 5-O-(4-chlorobenzoyl)-3-C-ethynyl-D-ribofuranose (1.0 g; 3.20 mmol) obtained in Example 6 was suspended in dichloromethane (12 ml). To the resultant suspension were added 4-dimethylaminopyridine (12 mg; 0.098 mmol) and triethylamine (1.56 ml; 11.2 mmol). The mixture was cooled on ice. Ethyl chlorocarbonate (1.07 ml; 11.2 mmol) was added thereto and the liquid temperature was returned to room temperature. The mixture was stirred for one hour. The solvent was evaporated under reduced pressure. Ethyl acetate (40 ml) and water (40 ml) were added to the residue, then phases were separated. The ethyl acetate phase was washed once with saturated aqueous sodium hydrogencarbonate solution, then dried over magnesium sulfate. After filtration, the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:3), yielding 1.42 g (yield: 84.0%) of the title compound as a colorless oily substance.
Reaction SMILES: C([N:8]([CH2:54][C@@H:55]([C:64]1[CH:73]=[CH:72][C:71]([O:74]CC2C=CC=CC=2)=[C:70]2[C:65]=1[CH:66]=[CH:67][C:68](=[O:82])[NH:69]2)[O:56][Si:57]([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[CH:21]=[C:22]([CH2:26][NH:27][C:28]([CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH:35]([O:38][C:39](=[O:53])[NH:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH2:34][CH2:33]3)=[O:29])[CH:23]=[CH:24][CH:25]=2)=[O:19])=[CH:13][CH:12]=1)C1C=CC=CC=1>CCO.CC(O)=O.[Pd]>[Si:57]([O:56][C@H:55]([C:64]1[CH:73]=[CH:72][C:71]([OH:74])=[C:70]2[C:65]=1[CH:66]=[CH:67][C:68](=[O:82])[NH:69]2)[CH2:54][NH:8][CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18]([C:20]2[CH:21]=[C:22]([CH2:26][NH:27][C:28]([CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH:35]([O:38][C:39](=[O:53])[NH:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH2:34][CH2:33]3)=[O:29])[CH:23]=[CH:24][CH:25]=2)=[O:19])=[CH:15][CH:16]=1)([C:60]([CH3:63])([CH3:61])[CH3:62])([CH3:59])[CH3:58]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CN(CCc1ccc(NC(=O)c2cccc(CNC(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)c2)cc1)Cc1ccccc1)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: CC(C)(C)[Si](C)(C)O[C@@H](CNCCc1ccc(NC(=O)c2cccc(CNC(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)c2)cc1)c1ccc(O)c2[nH]c(=O)ccc12
Reaction time: 8 h
Yield: 75.9 %

Procedure:
A solution of biphenyl-2-ylcarbamic acid 1-[2-({3-[4-(2-{benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]phenyl}methylcarbamoyl)ethyl]piperidin-4-yl ester (1.74 g, 1.56 mmol) in EtOH (12.2 mL) and AcOH (0.122 mL) was flushed with nitrogen for 3 min. Palladium on carbon (10%, ˜50% water, 0.18 g) was added and the reaction mixture was flushed with hydrogen for 4 min. The mixture was stirred under a hydrogen atmosphere (balloon) overnight and then filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-15% MeOH in DCM) to give the title compound (1.11 g, 76% yield) as a thick brownish liquid.
Reaction SMILES: C(C1[CH:5]=[C:6]([F:11])[C:7]([Cl:10])=[N:8][CH:9]=1)C=C.C[N+]1([O-])CC[O:16]CC1.[CH2:20]1[CH2:24][O:23][CH2:22][CH2:21]1>O.[Os](=O)(=O)(=O)=O>[Cl:10][C:7]1[N:8]=[CH:9][C:22]([CH2:21][CH:20]([OH:16])[CH2:24][OH:23])=[CH:5][C:6]=1[F:11]
Reactant: C1CCOC1
Reactant: C=CCc1cnc(Cl)c(F)c1
Reactant: C[N+]1([O-])CCOCC1
Agent: O=[Os](=O)(=O)=O
Solvent: O
Product: OCC(O)Cc1cnc(Cl)c(F)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 55 %

Procedure:
In a flask containing a solution of 2 (1.0 g, 5.81 mmol) in THF (7.2 mL) was added H2O (3.5 mL). The mixture was cooled with an ice bath and then N-methylmorpholine N-oxide (1.0 g, 8.71 mmol) was added followed by osmium tetroxide (0.074 g, 0.291 mmol) and the mixture stirred at 0° C. for 1 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL×2). The organic layer was separated, washed with brine, concentrated, and chromatographed on silica gel eluted with ethyl acetate/hexanes (0-20%) to afford 0.66 g (55%) of 41 as an oil. 1HNMR (CDCl3) δ 1.92 (1 H, t, J=5.0 Hz), 2.36 (1 H, d, J=5.0 Hz), 2.80 (2 H, m), 3.52 (1 H, m), 3.73 (1 H, m), 3.93 (1 H, m), 7.46 (1 H, d, J=11.0 Hz), 8.10 (1 H, s); LC/MS (M+1) 207.