Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(CCC1C=CC([C:12]2[C:13]([CH3:43])([CH3:42])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:41])([C@@:18]4([CH3:40])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)=CC=1)(O)=O.[N:44]1[NH:45][N:46]=[N:47][C:48]=1[C:49]1[CH:50]=[C:51](B(O)O)[CH:52]=[CH:53][CH:54]=1.B(O)O>>[N:44]1[NH:45][N:46]=[N:47][C:48]=1[C:49]1[CH:50]=[C:51]([C:12]2[C:13]([CH3:43])([CH3:42])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:41])([C@@:18]4([CH3:40])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:52]=[CH:53][CH:54]=1
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(CCC(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: OB(O)c1cccc(-c2nn[nH]n2)c1
Agent: OBO
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6cccc(-c7nn[nH]n7)c6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following the method described above for compound (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(2-carboxyethyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (example 4a) using 3-(2H-tetrazol-5-yl)phenylboronic acid as the reactant boronic acid. The product was isolated as a white solid (4.56 mg, 26%). LCMS: m/e 581.53 (M−H)−, 4.12 min (method 3). 1H NMR (400 MHz, <DMSOmix>) δ ppm 0.95 (d, J=4.10 Hz, 6H), 0.99 (s, 3H), 1.01 (s, 6H), 1.03-1.76 (m, 17H), 1.69 (s, 3H), 1.81-1.93 (m, 2H), 2.07-2.23 (m, 2H), 2.34 (dd, J=13.47, 2.34 Hz, 1H), 2.95-3.06 (m, 1H), 4.58 (s, 1H), 4.72 (s, 1H), 5.32 (d, J=4.39 Hz, 1H), 7.22 (d, J=6.44 Hz, 1H), 7.38-7.51 (m, 1H), 7.81 (s, 1H), 7.92 (d, J=7.32 Hz, 1H).
Reaction SMILES: [CH3:1][N:2]1[C:9](=[O:10])[CH2:8][C:6](=[O:7])[N:5]([CH3:11])[C:3]1=[S:4].N1C=CC=CC=1.Cl[C:19]([O:21][CH2:22][CH3:23])=[O:20]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:11][N:5]1[C:6](=[O:7])[CH:8]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:9](=[O:10])[N:2]([CH3:1])[C:3]1=[S:4]
Reactant: CN1C(=O)CC(=O)N(C)C1=S
Reactant: CCOC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)C1C(=O)N(C)C(=S)N(C)C1=O
Temperature: 0 °C
Reaction time: 12 h

Procedure:
155 g (0.9 mol) of 1,3-dimethyl-2-thiobarbituric acid, 88,3 g (1.12 mol) of pyridine and 9 g of 4-dimethylaminopyridine are dissolved in 660 ml of dichloromethane and the solution is cooled to 0° C. Then 102 g (0.94 mol) of ethyl chloroformate are added dropwise over 1 hour. The mixture is subsequently stirred for 12 hours at 0° C., then allowed to warm to room temperature and worked up after a further 7 hours as follows. 600 ml of dichloromethane are added and the solution is washed with three 1000 ml portions of water, dried over Na2SO4 and the solvent is evaporated off. The crude product is recrystallised from ethanol. Melting point 90°-93° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[N+:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1B(O)O)([O-:11])=[O:10]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccccc1B(O)O
Reactant: Oc1ccc(Br)cc1
Solvent: ClCCl
Product: O=[N+]([O-])c1ccccc1Oc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Into a 100 mL round bottom flask was added 4-bromophenol (2.07 g, 12.0 mmol), 2-nitrophenylboronic acid (1.00 g, 5.99 mmol), cupric acetate (1.4 g, 7.70 mmol) and DCM (50 mL). TEA (4.0 mL, 29.0 mmol) was then added followed by 4 A° molecular sieves and the reaction mixture was stirred at rt for 48 h. Reaction mixture was then filtered through celite. The filtrate was concentrated in vacuo to give a residue which was purified by silica gel chromatography, eluting with 5% EtOAc in hexane.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[F:18])=[N:9][CH:10]=2)[N:7]=1.C(N(CC)CC)C.[H][H]>[Pd].C(OCC)(=O)C>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][C:8]1[N:6]2[N:7]=[CH:2][CH:3]=[CH:4][C:5]2=[CH:10][N:9]=1
Reactant: [H][H]
Reactant: Fc1ccccc1Cc1ncc2ccc(Cl)nn12
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: Fc1ccccc1Cc1ncc2cccnn12

Procedure:
2.004 g of palladium on carbon (5%) were initially charged under argon, and 20.04 g (76.58 mmol) of the compound obtained in Example 3A in ethyl acetate (750 ml) were then added. 21.348 ml (153.159 mmol) of triethylamine were then added, and the reaction mixture was hydrogenated at standard hydrogen pressure and 20° C. for 16 hours. The same amount of catalyst as indicated above was then added, and the reaction mixture was hydrogenated at standard hydrogen pressure and 20° C. for another night. The mixture was then filtered through Celite, the filter cake was washed with ethanol and the filtrate was concentrated and dried under high vacuum. This gave 22.79 g of the target compound (about 100% of theory, contaminated with triethylamine).
Reaction SMILES: [OH:1][C:2]1([CH2:20][OH:21])[CH2:11][C:10]2[C:5](=[C:6]([O:14][CH3:15])[CH:7]=[CH:8][C:9]=2[O:12][CH3:13])[C:4]2([S:19][CH2:18][CH2:17][S:16]2)[CH2:3]1.[C:22](OC(=O)C)(=[O:24])[CH3:23]>N1C=CC=CC=1>[C:22]([O:21][CH2:20][C:2]1([OH:1])[CH2:11][C:10]2[C:5](=[C:6]([O:14][CH3:15])[CH:7]=[CH:8][C:9]=2[O:12][CH3:13])[C:4]2([S:16][CH2:17][CH2:18][S:19]2)[CH2:3]1)(=[O:24])[CH3:23]
Reactant: COc1ccc(OC)c2c1CC(O)(CO)CC21SCCS1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: COc1ccc(OC)c2c1CC(O)(COC(C)=O)CC21SCCS1
Temperature: 0 °C
Reaction time: 20 h
Yield: 99.7 %

Procedure:
1.6 g of rac-1',2',3',4'-tetrahydro-3'-hydroxy-3'-hydroxymethyl-5',8'-dimethoxyspiro[1,3-dithiolane-2,1'-naphthalene] were dissolved in 30 ml of dry pyridine and 1.5 g of acetic anhydride were added to the solution. The mixture was left to stand at room temperature for 20 hours and then poured into ice-cold 5-M sulphuric acid. The resulting mixture was extracted with ethyl acetate, the extracts were washed with water and sodium hydrogen carbonate solution, dried and evaporated to give 1.8 g of rac-3'-acetoxymethyl-1',2',3',4'-tetrahydro-3'-hydroxy-5',8'-dimethoxyspiro[1,3-dithiolane-2,1'-naphthalene] in the form of a colourless oil which was used directly in the next step.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[CH3:9][N:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:11](Cl)=[O:12]>>[CH3:8][C:5]1[N:4]=[CH:3][C:2]([O:1][C:11](=[O:12])[N:10]([CH3:9])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:7][CH:6]=1
Reactant: Cc1ccc(O)cn1
Reactant: CN(C(=O)Cl)c1ccccc1
Product: Cc1ccc(OC(=O)N(C)c2ccccc2)cn1

Procedure:
The title product was prepared from 3-hydroxy-6-methyl-pyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (79%, colourless oil). HPLC-MS: m/z=243.1 (M+1); Rt: 2.24 min.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([NH:12][C:13]1[C:14](=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:15]([OH:17])=O)=O.[CH2:22]([N:24]([CH2:28][CH3:29])[CH2:25][CH2:26][NH2:27])[CH3:23]>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]1[N:27]([CH2:26][CH2:25][N:24]([CH2:28][CH3:29])[CH2:22][CH3:23])[C:15](=[O:17])[C:14]2[C:13](=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]=1
Reactant: CCN(CC)CCN
Reactant: COc1ccccc1CC(=O)Nc1ccccc1C(=O)O
Solvent: CCO
Product: CCN(CC)CCn1c(Cc2ccccc2OC)nc2ccccc2c1=O
Yield: 34 %

Procedure:
A solution of 3.0 g (10 mmol) of methyl ester of N-(2-methoxyphenyl-acetyl)-anthranilic acid and 5.1 g (50 mmol) of 2-diethylaminoethylamine in ethanol (20 ml) was heated at 180° C. for 7 hours in a seald tube. After cooling, the thus obtained reaction mixture was purified by silica gel column chromatography (eluent; chloroform : ethanol=98:2) to obtain 1.24 g (yield 34 %) of 2-(2-methoxyphenylmethyl)-3-(2-diethylaminoethyl)-4(3H)-quinazolinone as an oily substance. 1.2 g of the oily substance were dissolved in ethanol (5 ml) and a 7% HCl-ethanol solution (1.5 ml) were added thereto. The resulting solution was allowed to cool overnight. The resulting colorless precipitates were collected by filtration to obtain 1.0 g of the captioned hydrochloride which is the desired compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])=[C:4]([CH:16]=O)[CH:3]=1.Cl.[Cl:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:23][O:24][NH2:25].CC([O-])=O.[Na+]>CCO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]([F:13])([F:14])[F:15])(=[O:10])=[O:11])=[C:4]([CH:16]=[N:25][O:24][CH2:23][C:22]2[CH:26]=[CH:27][C:28]([Cl:29])=[C:20]([Cl:19])[CH:21]=2)[CH:3]=1
Reactant: O=Cc1cc(Cl)ccc1NS(=O)(=O)C(F)(F)F
Reactant: NOCc1ccc(Cl)c(Cl)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: O=S(=O)(Nc1ccc(Cl)cc1C=NOCc1ccc(Cl)c(Cl)c1)C(F)(F)F
Yield: 65.4 %

Procedure:
A solution of N-(4-chloro-2-formylphenyl)trifluoromethanesulfonamide 24 (163 mg, 0.57 mmol), O-(3,4-dichlorobenzyl)hydroxylamine hydrochloride (130 mg, 0.57 mmol) and anhydrous NaOAc (77 mg, 0.94 mmol) in EtOH (10 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CHCl3). Purification by radial thin layer chromatography (eluting with CH2Cl2/PE, 1:9) afforded N-{4-chloro-2-[(3,4-dichlorobenzyloxyimino)methyl]phenyl}trifluoromethanesulfonamide 97 (172 mg, 66%), as a colorless oil. 1H n.m.r. (200 MHz, CDCl3) δ 10.65, br s, 1H; 8.14, s, 1H; 7.66, d, J=8.8 Hz, 1H; 7.51-7.45, m, 2H; 7.35, dd, J=2.4 and 8.8 Hz, 1H; 7.27-7.22, m, 2H; 5.12, s, 2H. HRMS (M+) 459.9422.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:9]([Br:17])[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.C1(C)C(S(O[CH2:28][C@@H:29]2[CH2:33][CH2:32][CH2:31][O:30]2)(=O)=O)=CC=CC=1.[OH-].[Na+]>CN(C)C=O>[O:30]1[CH2:31][CH2:32][CH2:33][C@H:29]1[CH2:28][NH:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:9]([Br:17])[O:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Nc1ncnc2oc(Br)c(-c3ccccc3)c12
Reactant: Cc1ccccc1S(=O)(=O)OC[C@@H]1CCCO1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: Brc1oc2ncnc(NC[C@@H]3CCCO3)c2c1-c1ccccc1
Temperature: 120 °C
Reaction time: 2 h
Yield: 37.7 %

Procedure:
To a solution of 4-amino-5-phenyl-6-bromofuro-[2,3-d]pyrimidine (0.99 g, 3.4 mmol) in dimethyl formamide (10 mL) was added 2-(S)-(toluenesulfonyloxymethyl)-tetrahydrofuran (0.88 g, 3.4 mmol) and sodium hydroxide powder (0.15 g, 3.8 mmol). The resulting mixture was stirred at 120° C. for 2 h. The mixture was then partitioned between ethyl acetate and water and the organic layer washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude solid was purified by flash column chromatography (10% ethyl acetate/hexane) to yield the product as a white solid (0.48 g, 38%).
Reaction SMILES: NC(C1C=CC(OCCO[Si](C)(C)C)=CC=1)C(NC(C(C1C=CC=CC=1)C)C([NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:18][CH2:17]2)=[CH:12][C:11]=1[F:19])=O)=O.N1C=CC=CC=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.Cl>ClCCl>[CH:16]1([C:13]2[CH:14]=[CH:15][C:10]([NH2:9])=[C:11]([F:19])[CH:12]=2)[CH2:18][CH2:17]1
Reactant: CC(c1ccccc1)C(NC(=O)C(N)c1ccc(OCCO[Si](C)(C)C)cc1)C(=O)Nc1ccc(C2CC2)cc1F
Agent: Cl
Agent: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: Nc1ccc(C2CC2)cc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.7 %

Procedure:
2-{2-Amino-2-[4-(2-trimethylsilanyloxy-ethoxy)-phenyl]-acetylamino}-N-(4-cyclopropyl-2-fluorophenyl)-3-phenyl-butyramide (680 mg, 1.2 mmol) and pyridine (3 mL) were dissolved in dichloromethane (60 mL) at −78° C. To this mixture was added a solution of triphosgene (296 mg, 1 mmol) in dichloromethane (15 mL) dropwise. The mixture was allowed to slowly warm to room temperature and stirred overnight at room temperature. The mixture was cooled in an ice bath and 3 M HCl (60 mL) was added slowly and stirring was continued at 0° C. for 30 minutes. The organic layer was separated and dried over anhydrous sodium sulfate. Concentration gave 150 mg of a oily solid that was chromatographed over silica gel (65% v/v ethyl acetate in hexanes) to give N-(4-cyclopropyl-2-fluoro-phenyl)-2-{4-[4-(2-hydroxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1yl}-3-phenyl-butyramide as a yellow solid (70 mg, 0.13 mmol, 13%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:28]=[CH:29][N:30]=3)[N:15]=[C:16]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[CH:20][CH:19]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>O1CCOCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:28]=[CH:29][N:30]=3)[N:15]=[C:16]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]
Reactant: COC(=O)c1ccc(-c2cc(Nc3ccc(OC)c(OC)n3)c3nccn3n2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(Nc2cc(-c3ccc(C(=O)O)cc3)nn3ccnc23)nc1OC
Yield: 77.5 %

Procedure:
To a stirred solution of methyl 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (0.135 g, 0.333 mmol) in dioxane (20 mL) and H2O (10 mL) was added NaOH (133 mg, 3.33 mmol) at 25° C. After 2 h the mixture was washed with ether (10 mL) and the aqueous layer was adjusted to pH=4 with concentrated HCl, then it was concentrated and filtered. The solid was washed with ether and dried to afford 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (0.101 g, 77%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.98 (s, 1H), 8.57 (s, 1H), 8.24 (s, 1H), 8.11-8.03 (m, 4 h), 7.69 (s, 1H), 7.43 (d, 1H, J=8.4 Hz), 7.13 (d, 1H, J=8.7 Hz), 4.04 (s, 3H), 3.79 (s, 3H). LC-MS: [M+H]+, 391.9, tR=1.454 min, HPLC: 98.08% at 214 nm, 95.71% at 254 nm, tR=3.628 min.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][C@H:11]2[C@H:13]([NH2:16])[CH2:14][CH2:15][C@H:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]1([C@H:23]([CH2:27]C)[C:24]([OH:26])=O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:1]([N:8]1[CH2:12][C@@H:11]2[C@@H:13]([NH:16][C:24](=[O:26])[C@H:23]([C:17]3[CH:18]=[CH:19][C:20]([CH2:1][CH:2]([CH3:7])[CH3:3])=[CH:21][CH:22]=3)[CH3:27])[CH2:14][CH2:15][C@@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N[C@@H]1CC[C@H]2CN(Cc3ccccc3)C[C@H]21
Reactant: CC[C@H](C(=O)O)c1ccccc1
Product: CC(C)Cc1ccc([C@H](C)C(=O)N[C@H]2CC[C@@H]3CN(Cc4ccccc4)C[C@@H]32)cc1

Procedure:
The title compound was prepared by substituting (3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine from Step A of Example 33 for (3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine and substituting (S)-2-(4-isobutylphenyl)propanoic acid for (S)-2-phenylbutanoic acid in Step F of the procedure used to prepare Example 16: 1H NMR (400 MHz, CDCl3) δ ppm 7.28 (d, J=4.4, 3H), 7.25-7.18 (m, 1H), 7.15 (dd, J=2.3, 8.2, 2H), 7.09 (dd, J=1.8, 8.2, 2H), 5.17 (d, J=7.2, 1H), 4.03-3.89 (m, 1H), 3.58 (d, J=13.0, 1H), 3.51-3.41 (m, 2H), 2.55-2.48 (m, 3H), 2.45 (d, J=7.2, 2H), 2.39 (dd, J=7.3, 9.0, 1H), 2.27-2.20 (m, 1H), 2.19-2.06 (m, 1H), 2.05-1.91 (m, 1H), 1.85 (dt, J=6.8, 13.5, 1H), 1.72-1.61 (m, 2H), 1.48 (d, J=7.2, 3H), 1.44-1.28 (m, 2H), 0.89 (d, J=6.6, 6H); MS (ESI+) m/z 405 (M+H)+.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH3:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1>C(OCC)(=O)C>[CH3:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:2]2[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=2[N+:8]([O-:10])=[O:9])=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1ccc(O)cc1F
Reactant: Cc1ccc(N)cc1
Solvent: CCOC(C)=O
Product: Cc1ccc(Nc2cc(O)ccc2[N+](=O)[O-])cc1
Temperature: 140 °C
Reaction time: 14 h

Procedure:
1.3 g of 3-fluoro-4-nitrophenol and 2.7 g of 4-methylaniline were mixed and stirred for 14 hours at 140° C. After cooling, it was dissolved in ethyl acetate and extracted three times with 4N aqueous hydrochloric acid. The organic phase was washed with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation in a vacuum, and the residue was crystallized from diisopropyl ether. 1.70 g was obtained.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[O:6][C@@H:5]2[O:7][C@H:8]([CH:10]([OH:12])[CH3:11])[CH2:9][C@@H:4]2[O:3]1.[C:14](Cl)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:14]([O:12][CH:10]([C@H:8]1[O:7][C@H:5]2[O:6][C:2]([CH3:1])([CH3:13])[O:3][C@H:4]2[CH2:9]1)[CH3:11])(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CC(O)[C@@H]1C[C@@H]2OC(C)(C)O[C@@H]2O1
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(OC(=O)c1ccccc1)[C@@H]1C[C@@H]2OC(C)(C)O[C@@H]2O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.9 %

Procedure:
To a cooled solution of 1-[(3aS,5S,6aS)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethanol (compound 25g, 200 mg, 1.06 mmol) in DCM (8 mL) was added benzoyl chloride (178 mg, 1.28 mmol) and DMAP (259 mg, 2 mmol). After the addition, the mixture was warmed naturally to room temperature and stirred at room temperature overnight. The resulting mixture was diluted with EtOAc and washed with a saturated aqueous solution of NH4Cl. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 1:3 EtOAc in petroleum ether) to afford 170 mg of 1-[(3aS,5S,6aS)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethyl benzoate (compound 25h).
Reaction SMILES: [C:1]([NH:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][CH:12]=1)[NH2:9])(=[O:4])[CH2:2][CH3:3].[C:13]1([CH3:30])[CH:18]=[CH:17][C:16](S(OCCCCCCC)(=O)=O)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCO>[C:1]([NH:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][CH:12]=1)[NH:9][CH2:30][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])(=[O:4])[CH2:2][CH3:3]
Reactant: CCC(=O)Nc1cccc(N)c1
Reactant: CCCCCCCOS(=O)(=O)c1ccc(C)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCO
Product: CCCCCCCNc1cccc(NC(=O)CC)c1

Procedure:
3-Propionylaminoaniline (16.4 parts) was reacted with n-heptyl p-toluenesulfonate (27 parts) at 100° C. for 4 hours in methyl cellosolve (200 parts) in the presence of anhydrous sodium carbonate (5.3 parts) to obtain 3-propionylamino-N-heptylaniline. Thereafter, reaction was further continued at 100° to 110° C. for 4 hours with addition of n-amyl p-toluenesulfonate (24.2 parts) and anhydrous sodium carbonate (5.3 parts) to obtain 3-propionylamino-N-n-heptyl-N-n-pentylaniline (coupling component). In the same manner as in Example 1, 2-cyano-4-nitro-6-chloroaniline was diazotized and coupled with the above coupling component to obtain 45.9 parts of a dye (7).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:23])[C:9]2[CH:14]=[CH:13][C:12]([O:15]C(=O)C)=[C:11]([O:19]C(=O)C)[CH:10]=2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Cl>CO>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:23])[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([OH:19])[CH:10]=2)[CH2:4][CH2:3]1
Reactant: CC(=O)Oc1ccc(C(=O)N2CCN(C)CC2)cc1OC(C)=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CN1CCN(C(=O)c2ccc(O)c(O)c2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 32.6 %

Procedure:
To a solution of 1-methyl-4-(3,4-diacetoxybenzoyl)piperazine (295 mg) n methanol (3 ml) was added a saturated potassium carbonate solution is methanol (6 ml) and the mixture was stirred at room temperature for 30 minutes. The mixture was poured into ice water and adjusted to pH 9 with 1N hydrochloric acid. The mixture was extracted several times with a mixture of chloroform and methanol (20:1 V/V) and the organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was crystallized by addition of ethyl acetate to give 1-methyl-4-(3,4-dihydroxybenzoyl)piperazine (71 mg) as white crystal.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][CH:15]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16]2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:27]I>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][CH:15]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16]2)=[CH:11][CH:10]=1)[CH3:27])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOC(=O)CC1CCc2ccc(NC(=O)OC(C)(C)C)cc2C1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC1CCc2ccc(N(C)C(=O)OC(C)(C)C)cc2C1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 96 %

Procedure:
In 10 ml of N,N-dimethylformamide, 0.67 g of ethyl 7-[N-(t-butoxycarbonyl)amino]-1,2,3,4-tetrahydro-naphthalene-2-acetate was dissolved and 0.096 g of 60% sodium hydride was added under cooling and stirred for 5 minutes at room temperature. To the mixture, 0.57 g of methyl iodide was dropwise added and allowed to stand overnight at room temperature. The reaction mixture was concentrated under reduced pressure and the concentrated residue was extracted with ethyl acetate. The ethyl acetate solution was dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, then the obtained crude product was purified by silica gel column chromatography using a mixture, ethyl acetate:n-hexane=1:10, as a developer to give 0.67 g of ethyl 7-[N-(t-butoxycarbonyl)-N-methylamino]-1,2,3,4-tetrahydronaphthalene-2-acetate.
Reaction SMILES: [H-].[Na+].[CH3:3]C1C=CNN=1.[N:9]1[C:14]2[NH:15][C:16]3[CH:41]=[CH:40][CH:39]=[CH:38][C:17]=3[N:18]([C:20]([C:22]3[CH:27]=[CH:26][C:25]([N:28]4[CH:32]=[CH:31][C:30]([CH3:33])=[N:29]4)=[CH:24][C:23]=3[C:34]([F:37])([F:36])[F:35])=[O:21])[CH2:19][C:13]=2[CH:12]=[CH:11][CH:10]=1.CI>CCCCCC>[CH3:3][N:15]1[C:16]2[CH:41]=[CH:40][CH:39]=[CH:38][C:17]=2[N:18]([C:20]([C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH:32]=[CH:31][C:30]([CH3:33])=[N:29]3)=[CH:24][C:23]=2[C:34]([F:37])([F:36])[F:35])=[O:21])[CH2:19][C:13]2[CH:12]=[CH:11][CH:10]=[N:9][C:14]1=2
Reactant: Cc1ccn(-c2ccc(C(=O)N3Cc4cccnc4Nc4ccccc43)c(C(F)(F)F)c2)n1
Reactant: Cc1cc[nH]n1
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CCCCCC
Product: Cc1ccn(-c2ccc(C(=O)N3Cc4cccnc4N(C)c4ccccc43)c(C(F)(F)F)c2)n1
Reaction time: 0.5 h
Yield: 45.1 %

Procedure:
Sodium hydride (60% suspension in oil, 0.12 g, 3.0 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (20 mL). Neat 3-methylpyrazole (0.13 mL, 1.61 mmol) was added dropwise at ambient temperature. Stirring was continued until the gas evolution subsided, and then the (5,11-dihydro-pyrido [2,3-b][1,5]benzodiazepin-6-yl)-(4-fluoro-2-trifluoromethyl-phenyl)methanone of Example 4, Step B (0.52 g, 1.34 mmol) was added in one portion to the clear solution. The mixture was placed in an oil bath (preheated at 130° C.) for 30 minutes. After cooling, sodium hydride (60% suspension in oil, 0.080 g, 2.0 mmol, washed with hexane) and methyl iodide (0.25 mL, 4.0 mmol) were added. The reaction mixture was stirred for an additional 15 minutes, and then partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with 20% ethyl acetate in hexane provided the title product (0.28 g, 45.1%) as a foam which crystallized by sonication from ethanol-hexane as a white solid, m.p. 188-190° C.