Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][C@:3]12[CH:16]3[CH2:17][CH:14]([C:15]3([CH3:19])[CH3:18])[CH2:13][C@H:4]1[O:5][B:6]([C@@H:8]1[CH2:12][CH2:11][CH2:10][NH:9]1)[O:7]2.[N:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([C:30]([NH:32][CH2:33][C:34](O)=[O:35])=[O:31])=[CH:22][CH:21]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl>[O:35]=[C:34]([N:9]1[CH2:10][CH2:11][CH2:12][C@H:8]1[B:6]1[O:5][C@@H:4]2[CH2:13][CH:14]3[CH2:17][CH:16]([C@:3]2([CH3:2])[O:7]1)[C:15]3([CH3:19])[CH3:18])[CH2:33][NH:32][C:30]([C:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:20]=[CH:21][CH:22]=1)=[O:31]
Reactant: O=C(O)CNC(=O)c1ccnc2ccccc12
Reactant: CC1(C)C2CC1[C@]1(C)OB([C@@H]3CCCN3)O[C@@H]1C2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC1(C)C2CC1[C@]1(C)OB([C@@H]3CCCN3C(=O)CNC(=O)c3ccnc4ccccc34)O[C@@H]1C2
Reaction time: 3 h

Procedure:
(2R)-2-((3aS,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)pyrrolidine hydrochloride (0.190 g, 0.665 mmol) was added to a mixture of 2-(quinoline-4-carboxamido)acetic acid (0.153 g, 0.665 mmol), HATU (0.253 g, 0.665 mmol) and DIPEA (0.360 ml, 2.062 mmol) in dichloromethane (5 mL). The mixture was stirred for 3 h and washed with 0.5N citric acid, saturated sodium bicarbonate and brine, followed by filtration and evaporation. Purification was done using column chromatography DCM-MeOH 0-6% MeOH.
Reaction SMILES: [C:1]([CH2:4][C:5]1[CH:41]=[CH:40][C:8]([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([O:21][CH3:22])=[CH:15][C:14]=2[C@@H:23]2[CH2:32][CH2:31][C:30]3[CH:29]=[C:28]([O:33]C(=O)C(C)(C)C)[CH:27]=[CH:26][C:25]=3[CH2:24]2)=[CH:7][CH:6]=1)(O)=O.[CH2:42]([CH2:45][NH2:46])[CH:43]=[CH2:44]>>[CH2:42]([CH2:45][NH:46][CH2:1][CH2:4][C:5]1[CH:41]=[CH:40][C:8]([CH2:9][CH2:10][CH2:11][NH:12][C:13]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([O:21][CH3:22])=[CH:15][C:14]=2[C@@H:23]2[CH2:32][CH2:31][C:30]3[CH:29]=[C:28]([OH:33])[CH:27]=[CH:26][C:25]=3[CH2:24]2)=[CH:7][CH:6]=1)[CH:43]=[CH2:44]
Reactant: C=CCCN
Reactant: COc1cc(NCCCc2ccc(CC(=O)O)cc2)c([C@@H]2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)cc1OC
Product: C=CCCNCCc1ccc(CCCNc2cc(OC)c(OC)cc2[C@@H]2CCc3cc(O)ccc3C2)cc1
Yield: 17.7 %

Procedure:
Synthesized from pivalic acid (R)-6-{2-[(4-carboxymethylbenzyl)ethylamino]-4,5-dimethoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (19 mg) and allylmethylamine (13 mg) according to an analogous synthetic method to Example 715 and purified by LC-MS, the title compound (3.1 mg) was obtained.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]([C:14]1[C:15]([O:32][CH3:33])=[C:16]([C:20]([CH3:31])([CH3:30])[CH2:21][C:22]([C:26]([F:29])([F:28])[F:27])([OH:25])[CH2:23][OH:24])[CH:17]=[CH:18][CH:19]=1)([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl.O>[OH:25][C:22]([C:26]([F:27])([F:28])[F:29])([CH2:21][C:20]([C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([CH:11]([CH3:13])[CH3:12])[C:15]=1[O:32][CH3:33])([CH3:31])[CH3:30])[CH:23]=[O:24]
Reactant: COc1c(C(C)C)cccc1C(C)(C)CC(O)(CO)C(F)(F)F
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: CS(C)=O
Product: COc1c(C(C)C)cccc1C(C)(C)CC(O)(C=O)C(F)(F)F
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 83.5 %

Procedure:
3.17 g (25.04 mmol) of oxalyl chloride is introduced into 83 ml of dichloromethane and cooled to −78° C. At this temperature, 3.9 g (50.08 mmol) of dimethyl sulfoxide, dissolved in 10 ml of dichloromethane, is added in drops. After five minutes of stirring, 7.15 g (21.38 mmol) of 4-(3-isopropyl-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)pentane-1,2-diol, dissolved in 21.4 ml of dichloromethane, is added. Then, the reaction mixture is stirred for two hours at this low temperature. 10.8 g (106.9 mmol) of triethylamine is carefully added in drops, and the batch is then stirred vigorously at room temperature for one hour. After water is added and after stirring is done for another ten minutes, it is extracted twice with dichloromethane. The combined organic extracts are washed with 1% sulfuric acid, saturated sodium bicarbonate solution and brine. After drying, and after the solvent is spun off, the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). Finally, 5.93 g (83.44%) of the desired aldehyde is obtained.
Reaction SMILES: [N:1]([C:4]1[CH:5]=[C:6]([CH:27]=[CH:28][C:29]=1[CH3:30])[C:7]([NH:9][C:10]1[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=[C:12]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:11]=1[O:25][CH3:26])=[O:8])=[N+:2]=[N-:3].[C:31]([C:33]1[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[N:37][CH:38]=1)#[CH:32]>>[C:16]([C:14]1[CH:13]=[C:12]([NH:20][S:21]([CH3:24])(=[O:22])=[O:23])[C:11]([O:25][CH3:26])=[C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:27]=[CH:28][C:29]([CH3:30])=[C:4]([N:1]3[CH:32]=[C:31]([C:33]4[CH:38]=[N:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)[N:3]=[N:2]3)[CH:5]=2)[CH:15]=1)([CH3:18])([CH3:19])[CH3:17]
Reactant: COc1c(NC(=O)c2ccc(C)c(N=[N+]=[N-])c2)cc(C(C)(C)C)cc1NS(C)(=O)=O
Reactant: C#Cc1ccc(OC)nc1
Product: COc1ccc(-c2cn(-c3cc(C(=O)Nc4cc(C(C)(C)C)cc(NS(C)(=O)=O)c4OC)ccc3C)nn2)cn1

Procedure:
Example 22 was prepared from 3-azido-N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4-methyl-benzamide and 5-ethynyl-2-methoxy-pyridine in the same manner as Example 15. ESI MS m/z 565 [C28H32N6O5S+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]3[CH2:25][CH2:24][CH:23]([OH:26])[CH:22]3[OH:27])[C:11](=[O:28])[C@:10]([CH2:30][C:31]([OH:33])=[O:32])([CH3:29])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.I([O-])(=O)(=O)=O.[Na+]>C1COCC1.O.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([CH:21]([CH2:25][CH2:24][CH:23]=[O:26])[CH:22]=[O:27])[C:11](=[O:28])[C@:10]([CH2:30][C:31]([OH:33])=[O:32])([CH3:29])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: C[C@]1(CC(=O)O)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N(C2CCC(O)C2O)C1=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C[C@]1(CC(=O)O)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N(C(C=O)CCC=O)C1=O
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(2,3-dihydroxycyclopentyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 102, Step F) (110 mg, 0.223 mmol) in THF (3 mL) and water (3 mL) was added sodium periodate (134 mg, 0.626 mmol) at room temperature. The reaction mixture was stirred at room temperature for 45 min and was diluted with EtOAc and the layers were separated. The organic layer was washed with sat. aq. Na2S2O3 solution, sat. aq. NaCl solution, dried over Na2SO4 and concentrated under reduced pressure to provide the title compound.
Reaction SMILES: [NH3:1].CC(O)C.Cl[C:7]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)([C:28]1[N:32]([CH3:33])[CH:31]=[N:30][CH:29]=1)[C:8]1[CH:9]=[CH:10][C:11]2[N:17]([CH3:18])[C:16](=[O:19])[CH2:15][S:14][CH:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:12]=2[CH:27]=1>C1COCC1>[NH2:1][C:7]([C:34]1[CH:35]=[CH:36][C:37]([Cl:40])=[CH:38][CH:39]=1)([C:28]1[N:32]([CH3:33])[CH:31]=[N:30][CH:29]=1)[C:8]1[CH:9]=[CH:10][C:11]2[N:17]([CH3:18])[C:16](=[O:19])[CH2:15][S:14][CH:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:12]=2[CH:27]=1
Reactant: CN1C(=O)CSC(c2cccc(Cl)c2)c2cc(C(Cl)(c3ccc(Cl)cc3)c3cncn3C)ccc21
Reactant: N
Solvent: CC(C)O
Solvent: C1CCOC1
Product: CN1C(=O)CSC(c2cccc(Cl)c2)c2cc(C(N)(c3ccc(Cl)cc3)c3cncn3C)ccc21
Temperature: 5 °C
Reaction time: 2 h
Yield: 22 %

Procedure:
NH3/2-propanol (10 ml) was added dropwise at 5° C. under N2 flow to a mixture of 7-[chloro(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-5-(3-chlorophenyl)-1,5-dihydro-1-methyl-4,1-benzothiazepin-2(3H)-one (described in Example B11a) (0.00247 mol) in THF (15 ml). The mixture was stirred at 5° C. for 1 hour and at room temperature for 2 hours, then poured out into ice water and extracted with CH2Cl2. The organic layer was separated, washed with water, dried (MgSO4), filtered and the solvent was evaporated. The residue (1.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.5; 15–40 μm). The pure fractions were collected and the solvent was evaporated. The residue (0.35 g, 27%). was crystallized from acetonitrile and diethyl ether. The precipitate was filtered off and dried in vacuo, yielding 0.28 g (22%) of 7-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-5-(3-chlorophenyl)-1,5-dihydro-1-methyl-4,1-benzothiazepin-2(3H)-one, mp. 218° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[C:9]([C:10]([O:12]C)=[O:11])=[CH:8][CH:7]=[CH:6][N:5]2[CH:14]=1.[OH-].[Na+]>C(O)C.O>[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=[CH:6][N:5]2[CH:14]=1
Reactant: COC(=O)c1cccn2cc(C)nc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1cn2cccc(C(=O)O)c2n1
Temperature: 25 °C
Yield: 62.1 %

Procedure:
Methyl 2-methylimidazo[1,2-a]pyridine-8-carboxylate (4 g, 21 m moles) was dissolved in a mixture of ethanol (45 ml) and water (20 ml), and sodium hydroxide (2.5 g, 63 m moles) was added thereto and refluxed under heating for 30 minutes. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Water (40 ml) was added to the concentrate, and the mixture was adjusted to pH 4 with conc. hydrochloric acid. The precipitating crystals were collected by filtration to give the object compound (2.3 g, yield 64%).
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:31])=[C:7]2[C:12](=[C:13]([C:15]#[N:16])[N:14]=1)[N:11]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:10](=[O:24])[C:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:8]2)=[O:4].[NH2:32][C@H:33]([C:41]([OH:43])=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C[O-].[Na+]>COCCO>[CH2:17]([N:11]1[C:12]2[C:7](=[C:6]([OH:31])[C:5]([C:3]([NH:32][C@@H:33]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:41]([OH:43])=[O:42])=[O:4])=[N:14][C:13]=2[C:15]#[N:16])[CH:8]=[C:9]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:10]1=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: COC(=O)c1nc(C#N)c2c(cc(-c3ccccc3)c(=O)n2Cc2ccccc2)c1O
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Agent: C[O-]
Agent: [Na+]
Solvent: COCCO
Product: N#Cc1nc(C(=O)N[C@@H](Cc2ccccc2)C(=O)O)c(O)c2cc(-c3ccccc3)c(=O)n(Cc3ccccc3)c12
Temperature: 25 °C
Yield: 93.1 %

Procedure:
A mixture of 1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.073 mmol), L-phenylalanine (241 mg, 1.46 mmol), and NaOMe (59 mg, 1.09 mmol) in 2-methoxyethanol (10 mL) was refluxed for 3 h. After the mixture was cooled to r.t., solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 2. The organic layer was dried over MgSO4 and concentrated. The residue was chromatographed (5-40% EtOAc/hexanes+2% AcOH) to give 37 mg of the title compound. MS: (+) m/z 544.99 (M+1).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[N:11]([CH3:12])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[N:7]=1.[H-].[Na+].[F:15][C:16]([F:34])([F:33])[C:17]1[CH:18]=[CH:19][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][OH:32])=[CH:26][CH:25]=2)=[N:21][CH:22]=1>CN(C=O)C>[CH3:12][N:11]1[C:4]2[N:5]([C:6](=[O:8])[N:7]=[C:2]([O:32][CH2:31][CH2:30][C:27]3[CH:26]=[CH:25][C:24]([O:23][C:20]4[CH:19]=[CH:18][C:17]([C:16]([F:34])([F:15])[F:33])=[CH:22][N:21]=4)=[CH:29][CH:28]=3)[CH:3]=2)[CH2:9][CH2:10]1
Reactant: OCCc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
Reactant: CN1CCn2c1cc(Cl)nc2=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1CCn2c1cc(OCCc1ccc(Oc3ccc(C(F)(F)F)cn3)cc1)nc2=O

Procedure:
Prepared in a manner similar to that described for E1 using 7-chloro-1-methyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one (50 mg, 0.269 mmol), sodium hydride (21.55 mg, 0.539 mmol) and 2-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)ethanol (76 mg, 0.269 mmol) in DMF (1 mL).
Reaction SMILES: C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[I-].[CH:12]1([CH2:17][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:16][CH2:15][CH2:14][CH2:13]1.[CH3:37][O:38][C:39]1[N:44]=[C:43]([C:45]([C:47]2[CH:52]=[CH:51][C:50]([S:53][CH3:54])=[CH:49][CH:48]=2)=O)[CH:42]=[CH:41][C:40]=1[CH3:55].O>O1CCCC1>[CH:12]1(/[CH:17]=[C:45](\[C:43]2[N:44]=[C:39]([O:38][CH3:37])[C:40]([CH3:55])=[CH:41][CH:42]=2)/[C:47]2[CH:52]=[CH:51][C:50]([S:53][CH3:54])=[CH:49][CH:48]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: COc1nc(C(=O)c2ccc(SC)cc2)ccc1C
Reactant: c1ccc([P+](CC2CCCC2)(c2ccccc2)c2ccccc2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [I-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: COc1nc(/C(=C\C2CCCC2)c2ccc(SC)cc2)ccc1C
Yield: 40 %

Procedure:
A solution of lithiumhexamethyldisilazide in tetrahydrofuran (1 M, 5.5 mL) was added to a solution of (cyclopentylmethyl)triphenylphosphonium iodide (1.73 g, 3.66 mmol) in tetrahydrofuran (5 mL) in a nitrogen atmosphere under ice-cooling, and the mixture was stirred under ice-cooling for one hour. A solution of (6-methoxy-5-methylpyridin-2-yl)[4-(methylsulfanyl)phenyl]methanone obtained in Reference Example 1-36 (1.0 g) in tetrahydrofuran (2.5 mL) was added to the reaction solution under ice-cooling, and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:hexane=1:9→1:2) to give (Z)-6-{2-cyclopentyl-1-[4-(methylsulfanyl)phenyl]ethenyl}-2-methoxy-3-methylpyridine (493 mg, 40%) as a more polar product.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:18]=[CH:19][C:20]=2[S:21][CH3:22])[C:10]([O:12]C2CCCC2)=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].C(O)(=O)C>O.CO>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:18]=[CH:19][C:20]=2[S:21][CH3:22])[C:10]([OH:12])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CSc1ccc(C(=O)OC2CCCC2)cc1OC1CCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Solvent: CO
Product: CSc1ccc(C(=O)O)cc1OC1CCCC1
Yield: 92.5 %

Procedure:
A solution of cyclopentyl 3-cyclopentyloxy-4-(methylthio)benzoate (0.5 g, 1.5 mmol) in water (30 mL) and methanol (10 mL) containing sodium hydroxide (1 g, 25 mmol) is heated under reflux for 3 hours. The solution is then poured into water (60 mL) and acetic acid is added dropwise with stirring to between pH 5-6. The solid which separates is collected by filtration, washed with water (5×10 mL) and dried giving 3-cyclopentyloxy-4-(methylthio)benzoic acid (0.35 g, 88.6%) as a cream solid m.p. 158°-160° C.
Reaction SMILES: [CH3:1][O:2]CC1NC(=O)C2C(=CC=CC=2)N=1.[N+:15]([C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[N:24]=[C:23]([CH2:28]CC)[N:22]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[C:44]3[N:48]([C:49]([C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[N:47]=[N:46][N:45]=3)=[CH:34][CH:33]=1)[C:21]2=[O:68])([O-:17])=[O:16]>>[CH3:1][O:2][CH2:28][C:23]1[N:22]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[C:44]3[N:48]([C:49]([C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)([C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)[C:56]4[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=4)[N:47]=[N:46][N:45]=3)=[CH:34][CH:33]=2)[C:21](=[O:68])[C:20]2[C:25](=[CH:26][CH:27]=[C:18]([N+:15]([O-:17])=[O:16])[CH:19]=2)[N:24]=1
Reactant: COCc1nc2ccccc2c(=O)[nH]1
Reactant: CCCc1nc2ccc([N+](=O)[O-])cc2c(=O)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: COCc1nc2ccc([N+](=O)[O-])cc2c(=O)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1

Procedure:
2-methoxymethylquinazolin-4(3H)-one was alkylated in the same manner as described above for 6-nitro-2-n-propyl-3-[(2'-(N-triphenylmethyl-tetrazol-5-yl)-biphen-4-yl)-methyl]-quinazolin-4(3H)-one to give the title compound. 200 MHz-1H-NMR (CDCl3): 3.43 (s, 3H), 4.36 (s, 2H), 5.46 (bs, 2H), 6.90 (m, 6H), 7.00 (d, 2H, J=8.2 Hz), 7.12 (d, 2H, J=8.2H), 7.19-7.38 (m, 10H), 7.48 (m, 2H), 7.84(d, 1H, J=8.9 Hz), 7.92 (m, 1H), 8.56 (dd, 1H, J=2.7, 9.01 Hz), 9.20 (d, 1H, J=2.6 Hz).
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6]/[CH:7]=[C:8]1\[CH2:9][C@@H:10]2[C@H:14]([CH2:15]\1)[C@@H:13](/[CH:16]=[CH:17]/[C@@H:18]([OH:25])[CH:19]([CH3:24])[CH2:20][C:21]#[C:22][CH3:23])[C@H:12]([OH:26])[CH2:11]2)(O)=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.[Cl-].[NH4+]>CN(C)C=O>[O:42]1[CH2:43][CH2:44][N:39]([CH2:1][CH2:4][CH2:5][CH2:6]/[CH:7]=[C:8]2\[CH2:9][C@@H:10]3[C@H:14]([CH2:15]\2)[C@@H:13](/[CH:16]=[CH:17]/[C@@H:18]([OH:25])[CH:19]([CH3:24])[CH2:20][C:21]#[C:22][CH3:23])[C@H:12]([OH:26])[CH2:11]3)[CH2:40][CH2:41]1
Reactant: C1COCCN1
Reactant: CC#CCC(C)[C@H](O)/C=C/[C@@H]1[C@H]2C/C(=C/CCCC(=O)O)C[C@H]2C[C@H]1O
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CC#CCC(C)[C@H](O)/C=C/[C@@H]1[C@H]2C/C(=C/CCCCN3CCOCC3)C[C@H]2C[C@H]1O
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 30.4 %

Procedure:
20 mg of (1S,2R,3R,5S)-7-[(E)-4-carboxybutylidene]-2-[(3S,1E)-3-hydroxy-4-methyl-6-octyne-1-enyl]-3-hydroxybicyclo[3.3.0]octane was taken and dissolved in 2 mL of dimethylformamide. After addition of 20 mg of 1,1′-carbonyldiimidazole, it was stirred at 50° C. for 1.5 hours. It was then cooled to ambient temperature, and 100 mg of morpholine was added. After stirring at 50° C. for 2 hours, an aqueous solution saturated with ammonium chloride was added and extraction was performed with ethyl acetate. The organic layer was washed with a saturated saline solution, and dried with anhydrous sodium sulfate. After filtration and concentration, 3 mL of tetrahydrofurane was added. While stirring, 100 mg of lithium aluminium hydride was added, and stirring continued at 50° C. for 3 hours. While stirring at ambient temperature, 200 μL of an aqueous solution saturated with sodium sulfate was added, then 1 g of anhydrous sodium sulfate was added, and stirred for 16 hours. A filtration was performed over celite, and after washing the residue with ethyl acetate, the filtrate was concentrated and subjected to a silicagel column chromatography, to obtain 7 mg of the compound presented in the title (40% yield).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=3)[N:12]=[C:11]([C:22]([O:24]CC)=[O:23])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[OH-:27].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:21][C:16]1[CH:15]=[C:14]([N:13]2[C:9]([C:4]3[CH:3]=[C:2]([OH:27])[CH:7]=[C:6]([F:8])[CH:5]=3)=[CH:10][C:11]([C:22]([OH:24])=[O:23])=[N:12]2)[CH:19]=[CH:18][C:17]=1[F:20]
Reactant: CCOC(=O)c1cc(-c2cc(F)cc(Br)c2)n(-c2ccc(F)c(Cl)c2)n1
Reactant: [OH-]
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)c1cc(-c2cc(O)cc(F)c2)n(-c2ccc(F)c(Cl)c2)n1
Temperature: 80 °C

Procedure:
200 mg (0.453 mmol) of the compound of Example 52A are provided in a mixture of 1.5 ml of 1,4-dioxane and 0.9 ml of degassed water under argon, 152 mg (2.72 mmol) of potassium hydroxide, 23.1 mg (0.054 mmol) of 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl and 16.6 mg (0.018 mmol) of tris(dibenzylideneacetone)dipalladium(0) are added, and the mixture is heated at 80° C. overnight. A 1N aqueous hydrogen chloride solution is subsequently added until the pH is acidic, and the reaction mixture is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). 100 mg (63% of theory) of the title compound are obtained.
Reaction SMILES: C([Si](C)(C)[O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][C:29]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:9][CH:8]=1)(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:29]([O:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][O:22][CH2:21][CH2:20][O:19][CH2:18][CH2:17][O:16][CH2:15][CH2:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([OH:6])=[CH:8][CH:9]=1)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(OCCOCCOCCOCCOCCOC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Oc1ccc(OCCOCCOCCOCCOCCOC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 92.4 %

Procedure:
To an ice-cooled solution of Compound 21 (1.88 g, 2.74 mmol) in THF (20 ml), a solution of 1M tetrabutylammonium fluoride in THF (4 ml) was added. After completion of the addition, the ice bath was removed, and this was followed by stirring at room temperature for 10 minutes. This was poured over water to stop the reaction, after which extraction from ethyl acetate was conducted. The organic phases were combined, washed with saturated brine, thereafter dried with anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue obtained was purified by silica gel column chromatography (Yamazen YFLC Gel, eluent (n-hexane:ethyl acetate 2:1-1:1)) to yield Compound 22 (light-yellow oil 1.45 g, 92%).