Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][C:13]([O:15]C2C=CC=CC=2)=O)[CH:3]=1.[C:22]([C:25]1[CH:30]=[CH:29][C:28]([S:31]([NH2:34])(=[O:33])=[O:32])=[CH:27][CH:26]=1)(=[O:24])[CH3:23]>>[C:22]([C:25]1[CH:26]=[CH:27][C:28]([S:31]([NH:34][C:13]([NH:12][C:4]2[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:5]=2[C:6]([O:8][CH3:9])=[O:7])=[O:15])(=[O:32])=[O:33])=[CH:29][CH:30]=1)(=[O:24])[CH3:23]
Reactant: COC(=O)c1ccc(Cl)cc1NC(=O)Oc1ccccc1
Reactant: CC(=O)c1ccc(S(N)(=O)=O)cc1
Product: COC(=O)c1ccc(Cl)cc1NC(=O)NS(=O)(=O)c1ccc(C(C)=O)cc1

Procedure:
As the starting substances, methyl 4-chloro-2-phenoxycarbonylaminobenzoate and 4-acetylbenzenesulfonamide were used and the same method was applied as in Example 36 to obtain N-(4-acetylbenzenesulfonyl)-N'-(2-methoxycarbonyl-5-chlorophenyl)urea and further to obtain from 300 mg (0.76 mmol) of N-(4-acetylbenzenesulfonyl)-N'-(2-carboxyl-5-chlorophenyl)urea 170 mg of the above-identified compound (yield 59.1%). Properties: colorless crystal, Melting point: >250° C. (decomposition), PMR (δppm, DMSO-d6):2.64 (3H,s), 7.10 (1H,s), 7.24 (1H,q), 7.85 (1H,d), 8.17 (2H,d), 8.27 (2H,d).
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[N:15]([CH3:26])[N:16]=[N:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3([C:47]([O:49][CH3:50])=[O:48])[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:50][O:49][C:47]([C:44]1([C:41]2[CH:42]=[CH:43][C:38]([C:22]3[CH:23]=[CH:24][C:19]([C:18]4[N:17]=[N:16][N:15]([CH3:26])[C:14]=4[NH:13][C:12]([O:11][CH:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:29])([F:28])[F:1])[CH:4]=4)[CH3:10])=[O:27])=[CH:20][CH:21]=3)=[CH:39][CH:40]=2)[CH2:46][CH2:45]1)=[O:48]
Reactant: COC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: CC(OC(=O)Nc1c(-c2ccc(Br)cc2)nnn1C)c1cccc(C(F)(F)F)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)C1(c2ccc(-c3ccc(-c4nnn(C)c4NC(=O)OC(C)c4cccc(C(F)(F)F)c4)cc3)cc2)CC1
Temperature: 95 °C
Reaction time: 5 h
Yield: 53.3 %

Procedure:
[5-(4-Bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester (680 mg, 1.45 mmol), methyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (525 mg, 1.74 mmol), X-Phos (138 mg, 0.29 mmol), palladium acetate (33 mg, 0.14 mmol) and potassium phosphate tribasic (923 mg, 4.35 mmol) were mixed in toluene (10 mL). Degassed water (2 mL) was added and the mixture was degassed with argon and then sealed. The mixture was stirred at 95° C. for 5 hrs until all starting material was consumed. The mixture was extracted with ethyl acetate and water. The organic layer was washed with brine and dried. Solvents were evaporated and the residue was purified by flash column chromatography (ethyl acetate in hexanes 5% to 70% in 15 minutes, 40 g silica gel) to give an amorphous white fluffy material as 1-(4′-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester (436 mg, 53.3% yield). LC/MS calcd for C30H27F3N4O4 (m/e) 564.0, obsd 565.0 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.35 (m, 2.6H), 1.48-1.55 (m, 2H), 1.60 (br d, J=3.8 Hz, 2.4H), 3.57 (s, 3H), 3.86 (s, 3H), 5.80-5.90 (br m, 1H), 7.44 (d, J=8.3 Hz, 2.5H), 7.63 (d, J=8.1 Hz, 2.5H), 7.69 (br d, J=7.3 Hz, 3.5H), 7.80 (d, J=7.3 Hz, 3.5H), 9.65 and 10.06 (br s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]([C@@H:17]3[CH2:21][CH2:20][C@H:19]([NH:22]C(=O)OC(C)(C)C)[CH2:18]3)=[O:16])[CH:9]=2)=[C:4]([O:30][CH3:31])[CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:22][C@H:19]1[CH2:20][CH2:21][C@@H:17]([C:15]([NH:14][C:10]2[CH:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=3[O:30][CH3:31])[CH:13]=[CH:12][N:11]=2)=[O:16])[CH2:18]1
Reactant: COc1cc(F)ccc1-c1ccnc(NC(=O)[C@@H]2CC[C@H](NC(=O)OC(C)(C)C)C2)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(F)ccc1-c1ccnc(NC(=O)[C@@H]2CC[C@H](N)C2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(1R,3S)-3-Amino-N-(4-(4-fluoro-2-methoxyphenyl)pyridin-2-yl)cyclopentanecarboxamide was prepared according to Method C using tert-Butyl (1S,3R)-3-(4-(4-fluoro-2-methoxyphenyl)pyridin-2-ylcarbamoyl)cyclopentylcarbamate (1.00 g, 2.33 mmol), TFA (2 ml) in DCM (6 ml) starting at 0° C. which was allowed to warm up to room temperature and stirred for 2 h.
Reaction SMILES: [OH:1][C:2]([C:19]([F:22])([F:21])[F:20])([CH2:16][C:17]#[CH:18])[CH2:3][C:4]([C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10])([CH3:6])[CH3:5].N1C=CN=C1.Cl[Si:29]([CH3:32])([CH3:31])[CH3:30]>CN(C=O)C.C(OCC)C>[CH3:6][C:4]([C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10])([CH3:5])[CH2:3][C:2]([C:19]([F:20])([F:21])[F:22])([O:1][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH2:16][C:17]#[CH:18]
Reactant: C#CCC(O)(CC(C)(C)c1ccccc1C(=O)O)C(F)(F)F
Reactant: C[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOCC
Product: C#CCC(CC(C)(C)c1ccccc1C(=O)O)(O[Si](C)(C)C)C(F)(F)F
Reaction time: 2 h
Yield: 99.7 %

Procedure:
To a solution of 2-(3-hydroxy-1,1-dimethyl-3-trifluoromethylhex-5-ynyl)benzoic acid (345 mg, 1.10 mmol) and imidazole (374 mg, 5.49 mmol) in 1 mL of DMF was added chlorotrimethylsilane (0.42 mL, 3.29 mmol). The reaction mixture was stirred for 2 hours then diluted with 75 mL of diethyl ether, washed with two 50 mL portions of 1M aqueous HCl, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 2-(1,1-dimethyl-3-trifluoromethyl-3-trimethylsilanyloxy-hex-5-ynyl)benzoic acid (424 mg, 100%). MS (ES+) m/z 387 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)[CH:21]=4)=[CH:19][C:14]3=[N:13][CH:12]=2)[CH:10]=1)[C:5]([NH2:7])=[O:6].[CH3:33][C:34](O)=[O:35].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[C:34]([NH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][N:27]5[CH2:28][CH2:29][O:30][CH2:31][CH2:32]5)[CH:21]=4)=[CH:19][C:14]3=[N:13][CH:12]=2)[CH:10]=1)[C:5]([NH2:7])=[O:6])(=[O:35])[CH3:33]
Reactant: CC(=O)O
Reactant: NC(=O)c1cc(N)cc(-c2cnc3cc(-c4cccc(CN5CCOCC5)c4)ccn23)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(=O)Nc1cc(C(N)=O)cc(-c2cnc3cc(-c4cccc(CN5CCOCC5)c4)ccn23)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 40.5 %

Procedure:
A mixture of 3-Amino-5-[7-(3-morpholin-4-ylmethyl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-benzamide (90 mg), AcOH (29 μL, 0.5 mmol), 1-hydroxybenzotriazole (68 mg, 0.5 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (96 mg, 0.5 mmol) in dry DMF (2 ml) was stirred at RT under N2 for 24 h. The mixture was partitioned between CH2Cl2/H2O. The layers were separated and the aqueous layer was loaded on to a SCX cartridge. This was washed with MeOH, then 2M NH3-MeOH. The NH3-MeOH fraction was evaporated and the residue was purified by preparative HPLC to give the title compound (40 mg, solid). 1H NMR (400 MHz, DMSO-d6): 10.26 (1H, s), 8.68 (1H, d), 8.12 (1H, s), 8.07 (2H, brs), 7.99 (1H, s), 7.87 (1H, s), 7.83 (1H, s), 7.81-7.72 (2H, m), 7.54-7.43 (2H, m), 7.43-7.34 (2H, m), 3.66-3.54 (6H, m), 2.47-2.36 (4H, m), 2.11 (3H, s).
Reaction SMILES: CCCCCCCCCCCC.C([O:32][C:33]1[C:34]([O:42][CH3:43])=[CH:35][C:36]([CH2:39][CH:40]=[CH2:41])=[CH:37][CH:38]=1)(=O)CCCCCCC/C=C\CCCCCCCC.[C:44]1([O:54][CH3:55])[C:45](=[CH:47][CH:48]=[C:49]([CH:53]=1)[CH2:50][CH:51]=[CH2:52])[OH:46]>>[CH3:43][O:42][C:34]1[CH:35]=[C:36](/[CH:39]=[CH:40]/[CH:41]=[O:46])[CH:37]=[CH:38][C:33]=1[OH:32].[C:44]1([O:54][CH3:55])[C:45](=[CH:47][CH:48]=[C:49]([CH:53]=1)[CH2:50][CH:51]=[CH2:52])[OH:46]
Reactant: C=CCc1ccc(OC(=O)CCCCCCC/C=C\CCCCCCCC)c(OC)c1
Agent: C=CCc1ccc(O)c(OC)c1
Solvent: CCCCCCCCCCCC
Product: COc1cc(/C=C/C=O)ccc1O
Reaction time: 72 h
Yield: 10.4 %

Procedure:
Diplodia gossypina ATCC 10936 is used for inoculating 800 ml of the abovementioned medium with n-dodecane as carbon source and, during inoculation, induced using 400 mg of eugenol oleate. The culture is allowed to grow for 3 days, after which 400 mg of eugenol are added. After a contact time of 143 hours, 45 mg of coniferyl aldehyde (10.4% of theory) as well as 100 mg of unmetabolised eugenol are isolated.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]([OH:13])=[O:12])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH2:14](O)[CH3:15]>>[CH2:14]([O:12][C:11](=[O:13])[CH2:10][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Br:1])[CH:3]=1)[CH3:15]
Reactant: CCO
Reactant: COc1ccc(CC(=O)O)cc1Br
Product: CCOC(=O)Cc1ccc(OC)c(Br)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 1, using the following starting materials: 3-bromo-4-methoxyphenylacetic acid and ethanol.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[N:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)[CH:2]=1.F[P-](F)(F)(F)(F)F.[N:24]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:28]2C=CC=[CH:32][C:27]=2N=N1.CCN(C(C)C)C(C)C.C(N)CC>CN(C)C=O>[CH2:28]([NH:24][C:10](=[O:12])[C:9]1[CH:13]=[CH:14][CH:15]=[N:16][C:8]=1[O:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[CH2:27][CH3:32]
Reactant: O=C(O)c1cccnc1Oc1cccnc1
Reactant: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCN
Product: CCCNC(=O)c1cccnc1Oc1cccnc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 57.2 %

Procedure:
To a solution of 2-(pyridin-3-yloxy)-nicotinic acid (0.100 g 0.462 mmole), BOP (0.205 grams, 0.463 mmole) and DIEA (0.242 μl) in dimethylformamide (5 ml) was added n-propyl amine (40 μl, 0.486 mmole) and stirred for 4 hours at room temperature. The reaction was quenched with 10 μl water and extracted with ethyl acetate. The combined organics were washed with alternating portions of 5% citric acid and sat'd bicarb, dried over Na2SO4, filtered and concentrated to a product which was purified by chromatography on silica gel eluting with diethyl ether to give a white crystalline solid (0.068 g). M.P. 55-56° C.; 1H H NMR (400 mhz, CDCl3) d 0.98 (t, J=7.3 Hz, 3H), 1.61-1.70 (m, 2H), 3.45-3.50 (m, 2H), 7.19 (dd, J=7.5 Hz, 4.8 Hz, 1H), 7.38-7.41 (m, 1H), 7.52-7.55 (m, 1H), 7.72 (bs, 1H), 8.16 (dd, J=4.8 hz, 2.1 Hz, 1H), 8.52-8.63 (m, 3H).
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][N:28]=[C:4]2[NH:3]1.[C:29]([O:32][CH2:33][C:34]([CH3:46])([CH3:45])[O:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)(=[O:31])[CH3:30].N1C=CC=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(OCC)(=O)C.O1CCCC1>[C:29]([O:32][CH2:33][C:34]([O:35][C:36]1[CH:37]=[CH:38][C:39]([N:3]2[C:2](=[O:1])[C:7]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[C:21]#[N:22])=[CH:13][CH:14]=3)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]3[N:26]=[CH:27][N:28]=[C:4]23)=[CH:40][CH:41]=1)([CH3:46])[CH3:45])(=[O:31])[CH3:30]
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)[nH]c2ncnn12
Reactant: CC(=O)OCC(C)(C)Oc1ccc(B(O)O)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(-c2ccc(OC(C)(C)COC(C)=O)cc2)c2ncnn12
Temperature: 25 °C
Reaction time: 24 h
Yield: 80.2 %

Procedure:
A mixture of 4′-[(5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.68 g), {4-[2-(acetyloxy)-1,1-dimethylethoxy]phenyl}boronic acid (0.94 g), copper(II) acetate (0.68 g), pyridine (2.0 mL), triethylamine (1.0 mL), molecular sieves 4A (2.00 g) and tetrahydrofuran (20 mL) was stirred at room temperature for 1 day. To the reaction mixture was added ethyl acetate (100 mL), and the mixture was stirred at room temperature for 1 hr, and the insoluble material was filtered off. The filtrate was concentrated, and the residue was purified by silica gel column chromatography to give 2-(4-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}phenoxy)-2-methylpropyl acetate as a colorless oil (0.85 g, 80%). A mixture of hydroxylammonium chloride (1.55 g), sodium hydrogen carbonate (2.50 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 2-(4-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}phenoxy)-2-methylpropyl acetate (0.85 g) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.36 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.33 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.25 g, 28%).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([CH2:11][CH2:12][C:13]([OH:15])=[S:14])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.S(Cl)(Cl)=O.[CH3:27]O>C(Cl)(Cl)Cl>[CH3:27][O:15][C:13](=[S:14])[CH2:12][CH2:11][C:9]1[N:8]=[C:7]2[C:3]([N:4]=[CH:5][N:6]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:2]([NH2:1])[N:10]=1
Reactant: CO
Reactant: Nc1nc(CCC(O)=S)nc2c1ncn2Cc1ccccc1
Solvent: ClC(Cl)Cl
Solvent: O=S(Cl)Cl
Product: COC(=S)CCc1nc(N)c2ncn(Cc3ccccc3)c2n1
Yield: 68 %

Procedure:
To 3-(6-amino-9-benzyl-2-purinyl) thiopropionic acid (100 mg, 0.30 mmol) suspended in 10 ml of chloroform was added thionylchloride (0.14 ml, 2 mmol). After refluxing under heating for 1 hour methanol was dropped to the mixture under ice cooling. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (1% methanol/chloroform) to give the subject compound (70 mg, yield 68%).
Reaction SMILES: C[O:2][C:3]1[C:8]2=[CH:9][CH:10]=[C:11]3[C:16]([O:15][CH2:14][C:13]4[CH:17]=[C:18]([O:21]C)[CH:19]=[CH:20][C:12]3=4)=[C:7]2[CH:6]=[CH:5][CH:4]=1.Cl.N1C=CC=CC=1>>[C:3]1([OH:2])[CH:4]=[CH:5][CH:6]=[C:7]2[C:16]3[O:15][CH2:14][C:13]4[CH:17]=[C:18]([OH:21])[CH:19]=[CH:20][C:12]=4[C:11]=3[CH:10]=[CH:9][C:8]=12
Reactant: COc1ccc2c(c1)COc1c-2ccc2c(OC)cccc12
Agent: Cl
Solvent: c1ccncc1
Product: Oc1ccc2c(c1)COc1c-2ccc2c(O)cccc12

Procedure:
The title compound was prepared by reacting 1,8-dimethoxy-6H dibenzo[c,h]chromene (1.0 g, 3.42 mmol) with pyridine hydrochloride (5.0 g, 43.3 mmol) according to method D to yield 0.93 g (99%) white foam. mp 213-214° C.; 1H NMR (300 MHz, DMSO-d6) δ 5.21 (2H, s), 6.72 (1H, d, J=1.9 Hz), 6.82 (2H, m), 7.27 (1H, t, J=7.9 Hz), 7.54 (1H, d, J=8.3 Hz), 7.68 (1H, d, J=8.4 Hz), 7.78 (2H, brs), 9.72 (1H, s), 10.09 (1H, s); MS m/z263 (M−H+);
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:25])/[CH:7]=[CH:8]/[C@@H:9]1[C@@H:13]([CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C@@H:12]([OH:23])[CH2:11][C@H:10]1[OH:24]>C(O)C>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:25])/[CH:7]=[CH:8]/[C@@H:9]1[C@H:13]([CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C@@H:12]([OH:23])[CH2:11][C@H:10]1[OH:24]
Reactant: CCCCC[C@H](O)/C=C/[C@@H]1[C@@H](C/C=C\CCCC(=O)O)[C@@H](O)C[C@H]1O
Solvent: CCO
Product: CCCCC[C@H](O)/C=C/[C@@H]1[C@H](C/C=C\CCCC(=O)O)[C@@H](O)C[C@H]1O
Reaction time: 0.01 h

Procedure:
All isomers of PGF2α were dissolved or diluted in adequate amount of ethanol and after aliquot, stored at −70° C. As an internal standard, 10 ng of 8-iso-PGF2α-d4 was mixed with 0.5 ml of plasma in a glass tube and was then purified by a C18 Solid-Phase Extraction column (J. T. Baker, M A, USA). Sample eluants were evaporated under a stream of nitrogen and re-dissolved in 50 μl acetonitrile:water (15:85 v/v) solution followed by vortex for 30 seconds and 10 μl extract was further analyzed with a LC/MS/MS system.
Reaction SMILES: [OH:1][CH2:2][CH2:3][S:4][C:5]1[N:10]2[CH:11]=[CH:12][N:13]=[C:9]2[CH:8]=[CH:7][CH:6]=1.N1C=CC=CC=1.Cl[C:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22]>C(Cl)Cl>[O:23]([C:21]([O:1][CH2:2][CH2:3][S:4][C:5]1[N:10]2[CH:11]=[CH:12][N:13]=[C:9]2[CH:8]=[CH:7][CH:6]=1)=[O:22])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: OCCSc1cccc2nccn12
Reactant: O=C(Cl)Oc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(OCCSc1cccc2nccn12)Oc1ccccc1
Yield: 91.3 %

Procedure:
To a solution of 5-[2-(hydroxy)ethylthio]imidazo[1,2-a]pyridine (5.83 g, 30 mmoles) and pyridine (4.36 ml, 60 mmoles) in methylene chloride (120 ml) was added phenyl chloroformate (7.53 ml, 60 mmoles) with stirring under ice-cooling and the mixture was stirred under ice-cooling for 30 minutes. The reaction solution was washed in turn with an aqueous 5% sodium bicarbonate solution and saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain 8.61 g of the desired product (91.3%, oily product).
Reaction SMILES: C(O)(C(F)(F)F)=O.[Si]([O:15][CH2:16][CH2:17][CH2:18][C:19]([NH:35][S:36]([C:38]([CH3:41])([CH3:40])[CH3:39])=[O:37])([C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([F:34])[CH:27]=1)[C:20]1[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=1)(C(C)(C)C)(C)C.O.C([O-])(O)=O.[Na+]>CC#N>[C:32]([C:29]1[CH:30]=[CH:31][C:26]([C:19]([NH:35][S:36]([C:38]([CH3:40])([CH3:39])[CH3:41])=[O:37])([C:20]2[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=2)[CH2:18][CH2:17][CH2:16][OH:15])=[CH:27][C:28]=1[F:34])#[N:33]
Reactant: Cn1cncc1C(CCCO[Si](C)(C)C(C)(C)C)(NS(=O)C(C)(C)C)c1ccc(C#N)c(F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: CC#N
Product: Cn1cncc1C(CCCO)(NS(=O)C(C)(C)C)c1ccc(C#N)c(F)c1
Temperature: 25 °C

Procedure:
TFA (1 mL) was added to a solution of N-[4-{[tert-butyl(dimethyl)silyl]oxy}-1-(4-cyano-3-fluorophenyl)-1-(1-methyl-1H-imidazol-5-yl)butyl]-2-methylpropane-2-sulfinamide (0.111 g, 0.219 mmol) in CH3CN ( ): H2O (20 mL) with stirring at ambient temperature. After 0.5 h aqueous saturated NaHCO3 solution was added, the CH3CN was removed in vacuo, and the residue was chromatographed on a Chiralcel AD column eluting with 90/10, hexane/EtOH to give the two diastereomers of the title compound. MS(M+1) 393.
Reaction SMILES: C([O:11][C@@H:12]1[CH2:20][C:19]2[C:14](=[CH:15][C:16]([N+:21]([O-:23])=[O:22])=[CH:17][CH:18]=2)[C@H:13]1[NH2:24])(=O)C(C1C=CC=CC=1)O.[OH-].[Na+].[C:27]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=[CH:31][C:30]([C:33](Cl)=[O:34])=[CH:29][CH:28]=1>C1(C)C=CC=CC=1>[N+:21]([C:16]1[CH:15]=[C:14]2[C:19]([CH2:20][CH:12]([OH:11])[C@@H:13]2[NH:24][C:33]([C:30]2[CH:31]=[CH:32][C:27]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[CH:28][CH:29]=2)=[O:34])=[CH:18][CH:17]=1)([O-:23])=[O:22]
Reactant: N[C@@H]1c2cc([N+](=O)[O-])ccc2C[C@H]1OC(=O)C(O)c1ccccc1
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: O=C(N[C@@H]1c2cc([N+](=O)[O-])ccc2CC1O)c1ccc(-c2ccccc2)cc1
Reaction time: 1 h
Yield: 106.8 %

Procedure:
Add (1R,2R)-1-amino-6-nitroindan-2-ol mandelate (0.64 kg, 1.85 mol) to a mixture of toluene (9.6 L) and aqueous 1 N NaOH (4.8 L, 4.8 mol, 2.6 equiv). After 1 h, add 4-biphenylcarbonyl chloride (0.44 kg, 2.0 mol, 1.1 equiv) in portions over 20–30 min. After 22 hours, filter the solids under vacuum and rinse sequentially with 0.5 L of toluene, 2 L of water, and 2 L of toluene. Dry the cake to afford 0.74 kg of biphenyl-4-carboxylic acid (R)-(6-nitro-2-hydroxyindan-1-yl)amide. Add 38.2 L of ethyl acetate to 1.914 kg of biphenyl-4-carboxylic acid (R)-(6-nitro-2(R)-hydroxyindan-1-yl)amide prepared in a similar manner. Stir the slurry for 18 h, collect the solid by filtration, dry to afford 1.76 kg of biphenyl-4-carboxylic acid (R)-(6-nitro-2(R)-hydroxyindan-1-yl)amide as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])[C:5]([Cl:20])=[CH:4][N:3]=1.[Cl:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]=O.C([O-])(=O)C.[NH4+]>>[Cl:20][C:5]1[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])=[C:7]2[N:8]=[C:25]([C:24]3[CH:27]=[CH:28][CH:29]=[C:22]([Cl:21])[CH:23]=3)[NH:1][C:2]2=[N:3][CH:4]=1
Reactant: NC(=O)[C@@H]1[C@H](Nc2c(Cl)cnc(N)c2N)[C@H]2C=C[C@@H]1C2
Reactant: O=Cc1cccc(Cl)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: NC(=O)[C@@H]1[C@H](Nc2c(Cl)cnc3[nH]c(-c4cccc(Cl)c4)nc23)[C@H]2C=C[C@@H]1C2
Yield: 29.5 %

Procedure:
In a similar fashion to Compound CXXV, (1S,2S,3R,4R)-3-(2,3-Diamino-5-chloro-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (75.00 mg, 0.2553 mmol), 3-Chlorobenzaldehyde (39.5 mg, 0.281 mmol), and Ammonium acetate (39.4 mg, 0.511 mmol) were reacted to produce 31.23 mg (30%) of the title compound. (300 MHz, DMSO-d6) 13.42 (s, 1H), 8.19 (s, 1H), 8.10 (d, J=8 Hz, 1H), 7.98 (s, 1H), 7.78 (s, 1H), 7.62-7.53 (m, 2H), 7.32 (d, J=9 Hz, 1H), 7.25 (s, 1H), 6.39 (s, 2H), 5.18 (t, J=17 Hz, 9 Hz, 1H), 2.87 (s, 1H), 2.91 (s, 1H), 2.81 (d, J=8 Hz, 1H), 2.63 (d, J=8 Hz, 1H), 2.23 (d, J=8 Hz, 1H), 1.38 (d, J=8 Hz, 1H). MS=414 (M+H), HPLC: 2.73 min. (G Method)
Reaction SMILES: Cl.Cl[C:3]1[N:8]=[CH:7][N:6]=[C:5]([N:9]2[C:13](=[O:14])[C:12]([N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)=[CH:11][NH:10]2)[CH:4]=1.[CH2:20]([SH:22])[CH3:21].[H-].[Na+].O>CN(C=O)C>[CH2:20]([S:22][C:3]1[N:8]=[CH:7][N:6]=[C:5]([N:9]2[C:13](=[O:14])[C:12]([N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)=[CH:11][NH:10]2)[CH:4]=1)[CH3:21]
Reactant: O=c1c(-n2ccnn2)c[nH]n1-c1cc(Cl)ncn1
Reactant: CCS
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCSc1cc(-n2[nH]cc(-n3ccnn3)c2=O)ncn1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
200 mg (0.7 mmol) of the compound from Example 52A are suspended in 1.1 ml DMF under argon. 61 mg (1.0 mmol) ethanethiol are added. 35 mg (0.8 mmol, 60% strength in mineral oil) sodium hydride are added cautiously, while cooling with ice. The mixture is stirred at RT for 2.5 h. 1 ml water is subsequently added dropwise and the mixture is subsequently stirred at RT for 15 min. The clear reaction solution obtained is purified directly by means of preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined, the mixture is concentrated and the residue is dried under a high vacuum.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[C:13]([CH3:17])=[CH:12][C:11]=2[O:18][CH3:19])=[O:9])=[CH:6][N:5]=[C:4]([NH:20][CH:21]2[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]2)[N:3]=1.[C:28](Cl)(=[O:30])[CH3:29]>>[NH2:1][C:2]1[C:7]([C:8](=[O:9])[C:10]2[CH:15]=[C:14]([F:16])[C:13]([CH3:17])=[CH:12][C:11]=2[O:18][CH3:19])=[CH:6][N:5]=[C:4]([NH:20][CH:21]2[CH2:26][CH2:25][CH:24]([NH:27][C:28](=[O:30])[CH3:29])[CH2:23][CH2:22]2)[N:3]=1
Reactant: CC(=O)Cl
Reactant: COc1cc(C)c(F)cc1C(=O)c1cnc(NC2CCC(N)CC2)nc1N
Product: COc1cc(C)c(F)cc1C(=O)c1cnc(NC2CCC(NC(C)=O)CC2)nc1N

Procedure:
The similar procedure as described in Example 60 was used, starting from [4-amino-2-(4-amino-cyclohexylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-4-methyl-phenyl)-methanone (Example 345) and acetyl chloride (Aldrich) to give N-[4-[4-amino-5-(5-fluoro-2-methoxy-4-methyl-benzoyl)-pyrimidin-2-ylamino]-cyclohexyl]-acetamide. MS (M+H)+, 416.