Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=CC([S:9][CH:10]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@@H:11]([C:20]([OH:22])=[O:21])[NH:12]C(OC(C)(C)C)=O)=CC=1.C1(OC)C=CC=CC=1>>[C:23]1([CH:10]([SH:9])[C@@H:11]([C:20]([OH:22])=[O:21])[NH2:12])[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: COc1ccc(SC(c2ccccc2)[C@H](NC(=O)OC(C)(C)C)C(=O)O)cc1
Solvent: COc1ccccc1
Product: N[C@H](C(=O)O)C(S)c1ccccc1
Reaction time: 36 h

Procedure:
Diasteromeric 3-phenylcysteine is prepared according to the method described by Nagai et al., in Peptide Chemistry, edited by, M. Ueki, Proceedings of the 26th Symposium on Peptide Chemistry, Tokyo, Oct. 24-26, 1988, Protein Research Foundation, Minoh-shi, Osaka, pages 247-52. Using standard methods, this material is converted to S-(4-methoxyphenyl)-N-(t-butoxycarbonyl)-3-phenylcysteine. The protected peptide-resin intermediate, Mba(SEt)-Arg(Tos)-Gly-Asp(O-Bzl)-Pcs(4-MBzl)-MBHA, is synthesized by the solid-phase method on 4-methylbenzhydrylamine resin. All of the amino acids are protected by t-butyloxycarbonyl on the amino group, and are coupled sequentially using N,N-dicyclohexylcarbodiimide/1-hydroxybenzotriazole (DCC/HOBt) as set forth in Example 1. After coupling of the last amino acid, the peptide is cleaved from the resin with deprotection of the side chain protecting groups using anhydrous HF (20 mL) in the presence of anisole (2.0 mL) at 0° C. for 30 min. After the evaporation of HF in vacuo, the residue is washed with anhydrous ether, the crude peptide is extracted with 0.2M acetic acid, and the extract is diluted to 2 L with deionized water. The pH of the aqueous solution is adjusted to 7-8 with concentrated ammonium hydroxide and Nitrogen is bubbled through the solution. After 24-48 hr. The reaction solution is lyophilized to yield a crude product. Chromatography (medium pressure reversed-phase column, acetonitrile/H2O-0.1% TFA) provides the titled product.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]1[O:15][C@:14]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[CH:19]=2)([O:16][CH3:17])[C@H:13]([OH:37])[C@@H:12]([OH:38])[C@@H:11]1[OH:39])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH2:42](Br)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C>[CH2:42]([O:39][C@H:11]1[C@H:12]([O:38][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([O:37][CH2:14][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@:14]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[CH:19]=2)([O:16][CH3:17])[O:15][C@@H:10]1[CH2:9][O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: BrCc1ccccc1
Reactant: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OC(F)(F)F)cc3)c2)O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O)[C@H](O)[C@H]1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OC(F)(F)F)cc3)c2)O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 0 °C
Reaction time: 16 h
Yield: 199.8 %

Procedure:
(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 6j (1.60 g, 2.69 mmol) was dissolved in 15 mL DMF and cooled to 0° C., followed by addition of 60% NaH (0.54 g, 13.5 mmol). Then the reaction mixture was warmed and stirred for 15 minutes at room temperature before benzyl bromide (1.6 mL, 13.5 mmol) was added. After stirring for 16 hours, the reaction mixture was concentrated under reduced pressure after 5 mL methanol were added. Then the resulting residue was dissolved in ethyl acetate (100 mL) and washed with water (50 mL×2). The organic extract was combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound [[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane 6k (2.32 g, yellow grease), which was used directly in the next step without purification.
Reaction SMILES: [I-].[O:2]([CH2:9][CH:10]1[NH+:14]([CH3:15])[C:13]([CH3:17])([CH3:16])[CH2:12][O:11]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1C=CC=CC=1.C(N(CC)CC)C.[N:31]([C:33]1[C:42]([OH:43])=[CH:41][CH:40]=[C:39]2[C:34]=1[CH:35]=[CH:36][CH:37]=[N:38]2)=O>O>[O:2]([C:9]1[C:10]2([N:14]([CH3:15])[C:13]([CH3:17])([CH3:16])[CH2:12][O:11]2)[O:43][C:42]2[CH:41]=[CH:40][C:39]3[N:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:33]=2[N:31]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C[NH+]1C(COc2ccccc2)OCC1(C)C
Reactant: O=Nc1c(O)ccc2ncccc12
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Solvent: O
Product: CN1C(C)(C)COC12Oc1ccc3ncccc3c1N=C2Oc1ccccc1
Reaction time: 8 h
Yield: 2.8 %

Procedure:
Into a dry 250 ml three-necked flask kept under dry nitrogen and fitted with a distillation column and internal thermometer was added 2-phenoxymethyl-3,4,4-trimethyl-1,3-oxazolidinium iodide (6.00 grams, 18.1 mmole) and 80 ml dry benzene. To the heterogeneous stirred solution was added in one portion triethylamine (3.64 grams, 36 mmole) followed by 5-nitroso-6-quinolinol (2.61 grams, 15 mmole). The solution was heated to reflux and maintained at reflux for 3 hours during which time water that formed during the course of the reaction was azeotropically removed. The solution was cooled with stirring overnight, decanted away from the tarry residue, and concentrated in vacuo. The product was isolated by flash chromatography to yield 0.16 grams of 2'-phenoxy-3,4,4-trimethylspiro[oxazolidine-2,3'-[3H]pyrido[3,2-f] [1,4]benzoxazine], which was characterized by appropriate spectral techniques. A toluene solution of the product changed to red when irradiated with ultraviolet light. The solution returned to its original hue after the UV light was removed.
Reaction SMILES: F[C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].[C:12](=[S:17])(OCC)[S-:13].[K+].Cl>CN(C=O)C.O>[N+:9]([C:6]1[CH:7]=[CH:8][C:2]2[S:13][C:12]([SH:17])=[N:4][C:3]=2[CH:5]=1)([O-:11])=[O:10]
Reactant: CCOC(=S)[S-]
Reactant: Nc1cc([N+](=O)[O-])ccc1F
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc2sc(S)nc2c1
Temperature: 110 °C
Yield: 93.5 %

Procedure:
A mixture of 2-fluoro-5-nitro aniline (11, 1.00 g, 6.40 mmol) and potassium O-ethyl dithiocarbonate (1.53 g, 9.60 mmol) in DMF (15 mL) was heated overnight at 110-110° C. under N2. After cooling, the reaction mixture was diluted with water and acidified with 1N HCl. The precipitate was collected by filtration, washed with water, and dried under vacuum to yield compound 12 (1.27 g, 94%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:18]=[CH:17]N=C1.C(Cl)(=O)C.Cl.[NH2:24][CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[CH3:17][C:18]1[N:24]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:4](=[O:6])[C:3]2[C:2](=[CH:10][CH:9]=[C:8]([N+:11]([O-:13])=[O:12])[CH:7]=2)[N:1]=1
Reactant: c1c[nH]cn1
Reactant: Nc1ccc([N+](=O)[O-])cc1C(=O)O
Reactant: NC1CCC(=O)NC1=O
Agent: Cl
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Solvent: CC#N
Solvent: O
Solvent: CC(=O)Cl
Product: Cc1nc2ccc([N+](=O)[O-])cc2c(=O)n1C1CCC(=O)NC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 59.8 %

Procedure:
To a stirred mixture of 2-amino-5-nitrobenzoic acid (5.0 g, 28 mmol) and imidazole (2.2 g, 33 mmol) in acetonitrile (50 mL), was added acetyl chloride (2.3 mL, 33 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (4.5 g, 28 mmol), imidazole (4.1 g, 60 mmol) and triphenyl phosphite (8.7 mL, 33 mmol) and heated to reflux for 22 hours. To the mixture, was added water (60 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL) to give 3-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (5.3 g, 61% yield): 1H NMR (DMSO-d6) δ 2.19-2.26 (m, 1H, CHH), 2.60-2.69 (m, 2H, 2CHH), 2.72 (s, 3H, CH1), 2.79-2.87 (m, 1H, CHH), 5.37 (dd, J=5, 11 Hz, 1H, NCH), 7.83 (d, J=9 Hz, 1H, Ar), 8.56 (dd, J=3, 9 Hz, 1H, Ar), 8.74 (dt, J=3 Hz 1H, Ar), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.69, 23.82, 30.57, 56.98, 119.46, 120.20, 122.21, 128.45, 128.74, 144.90, 150.85, 159.13, 159.78, 169.12, 172.53.
Reaction SMILES: [OH:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([OH:18])=[CH:4][CH:3]=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>C(O)(=O)C>[C:2]1(=[O:1])[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](=[O:18])[CH:4]=[CH:3]1
Reactant: O=C1c2ccccc2C(=O)c2c(O)ccc(O)c21
Agent: CC(=O)[O-]
Agent: [Pb+4]
Solvent: CC(=O)O
Product: O=c1ccc(=O)c2c(=O)c3ccccc3c(=O)c1=2
Reaction time: 0.17 h
Yield: 82.7 %

Procedure:
A mixture of 1,4-dihydroxyanthraquinone (10.0 g), lead tetraacetate (20 g) and acetic acid (25 ml) was ground together in mortar and pestle for 10 minutes at 25°. The reaction mixture was filtered and the solid washed with acetic acid, water, and ether. The red solid was taken up in a large volume of aceton (700 ml), the solution filtered through Celite, dried over sodium sulfate and evaporated under reduced pressure to give 1,4,9,10 anthradiquinone (8.2 g, 81% yield) as a brown solid. m.p. 213°-215° C. (benzene/pet. ether) lit m.p. 211°-213° NMR (CDCl3) δ8.2-7.8 (m, 4H aryl), 6.88 (s, 2H); IR 5.95, 610 (sh), 6.15 (sh), 6.3μ.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH2:33][O:34][C:35]1[CH:44]=[CH:43][CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38]>CN(C)C=O>[NH2:24][C:15]1[N:14]=[C:13]([O:12][CH2:8][CH2:9][CH2:10][CH3:11])[N:21]=[C:20]2[C:16]=1[N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH2:33][O:34][C:35]1[CH:44]=[CH:43][CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38]
Reactant: CCCCOc1nc(N)c2nc(OC)[nH]c2n1
Reactant: COC(=O)c1ccccc1OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: CCCCOc1nc(N)c2nc(OC)n(CCOc3ccccc3C(=O)OC)c2n1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
The compound obtained in Example 2-1 step (v) was dissolved in dimethylformamide (50 ml), and potassium carbonate (3.52 g) and methyl 2-(2-bromoethoxy)benzoate (2.2 g) were added thereto. The mixture was stirred at room temperature for 96 hours and partitioned between ethyl acetate and 2M hydrochloric acid. The organic layer was dried and concentrated under reduced pressure. The residue was dissolved in methanol and purified by RPHPLC to give the titled compound. Yield: 0.768 g (22%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1>CS(C)=O>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][S:8][C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:4][CH:3]=1
Reactant: Oc1ccc(S)cc1
Solvent: CS(C)=O
Product: Oc1ccc(SSc2ccc(O)cc2)cc1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
p-Hydroxybenzenethiol (25 g) was dissolved in DMSO (155 ml) and the solution was stirred for 4 hours and poured into ice water (1 L). The precipitated crystals were dried under reduced pressure to give bis(p-hydroxyphenyl)disulfide quantitatively.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18](/[C:21](/[CH3:25])=[CH:22]/[CH2:23][OH:24])=[CH:17][CH:16]=1>[O-2].[O-2].[Mn+4]>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18](/[C:21](/[CH3:25])=[CH:22]/[CH:23]=[O:24])=[CH:19][CH:20]=1
Reactant: C/C(=C\CO)c1ccc(OCc2nc(-c3ccccc3)oc2C)cc1
Agent: [Mn+4]
Agent: [O-2]
Product: C/C(=C\C=O)c1ccc(OCc2nc(-c3ccccc3)oc2C)cc1

Procedure:
According to the method described for Reference Example 34, (E)-3-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]-2-buten-1-ol was subjected to oxidation with activated manganese dioxide to give (E)-3-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]-2-buten-1-al. Recrystallization from ethyl acetate--hexane gave colorless prisms, m.p.94°-95° C.
Reaction SMILES: [NH2:1][C:2]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:19]=[CH:18]N=C1.C(Cl)(=O)C.Cl.[NH2:25][CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]1=[O:33].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[CH3:18][C:19]1[N:25]([CH:26]2[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]2=[O:33])[C:4](=[O:6])[C:3]2[C:2](=[C:10]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:8][CH:7]=2)[N:1]=1
Reactant: Nc1c(C(=O)O)cccc1C(F)(F)F
Reactant: c1c[nH]cn1
Reactant: NC1CCC(=O)NC1=O
Agent: Cl
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Solvent: CC#N
Solvent: CC(=O)Cl
Solvent: O
Product: Cc1nc2c(C(F)(F)F)cccc2c(=O)n1C1CCC(=O)NC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 10 %

Procedure:
To a stirred mixture of 2-amino-3-(trifluoromethyl)benzoic acid (2.0 g, 9.8 mmol) and imidazole (0.8 g, 12 mmol) in acetonitrile (20 mL), was added acetyl chloride (0.83 mL, 12 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (1.6 g, 9.8 mmol), imidazole (1.5 g, 22 mmol) and triphenyl phosphite (3.1 mL, 12 mmol) and heated to reflux for 22 hours. To the mixture, was added water (60 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), sodium hydrogen carbonate (sat, 50 mL) and water (50 mL) to give 3-(2-methyl-4-oxo-8-trifluoromethyl-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white so id (0.32 g, 10% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 35/65 CH3CN/0.1% H3PO4, 7.57 min (99.8%); mp: 351-353° C.; 1H NMR (DMSO-d6) δ 2.19-2.26 (m, 1H, CHH), 2.59-2.70 (m, 5H, CH3, 2CHH), 2.81-2.93 (m, 1H, CHH), 5.34 (dd, J=5, 11 Hz, 1H, NCH), 7.64 (t, J=8 Hz, 1H, Ar), 8.20 (d, J=8 Hz 1H, Ar), 8.31 (d, J=8 Hz, 1H, Ar), 11.09 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.67, 24.05, 30.57, 56.84, 121.48, 123.52 (q, JC-F=274 Hz), 124.77 (q, JC-F=30 Hz), 125.98, 130.74, 132.29 (q, JC-F=5 Hz), 144.20, 156.71, 159.68, 169.28, 172.58; LCMS: MH=340; Anal Calcd for C15H12N3O3F3+0.3H2O+0.1 CH3CN: C, 52.34; H. 3.72; N, 12.45; F, 16.34. Found: C, 52.71; H, 3.52; N, 12.31; F, 15.99.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:8]([O-:10])=[O:9].[Na+]>>[N:8]([C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=1)=[O:10].[N:8]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:9]
Reactant: O=N[O-]
Reactant: Nc1ccccc1
Agent: [Na+]
Product: Nc1ccc(N=O)cc1
Product: O=NNc1ccccc1

Procedure:
Conventionally, 4-nitrosoaniline is prepared by contacting aniline with sodium nitrite (NaNO2) to produce N-nitrosoaniline and then subjecting the N-nitrosoaniline to Fischer-Hepp rearrangement in acidic condition (Tetrahedron, 1975, 31, 1343-9), or by contacting p-nitrosophenol with ammonia or ammonium chloride (NH4Cl) (U.S. Pat. No. 3,338,966; and J. Chem. Soc., 1955, 2049).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:29])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[N:31]1[C:35](=[O:36])[CH2:34][CH2:33][C:32]1=[O:37]>CN1C(=O)CCC1>[O:37]=[C:32]1[CH2:33][CH2:34][C:35](=[O:36])[N:31]1[O:27][C:26](=[O:28])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:29]
Reactant: O=C1CCC(=O)N1O
Reactant: O=C(O)CCCCCCCCCCCCCCCCC(=O)OCc1ccccc1
Solvent: CN1CCCC1=O
Product: O=C(CCCCCCCCCCCCCCCCC(=O)ON1C(=O)CCC1=O)OCc1ccccc1
Temperature: 60 °C

Procedure:
1,18-octadecanedioic acid mono benzyl ester (120 g, 0.3 mol), N-hydroxysuccinimide (41 g, 0.36 mol) and N,N-dicyclohexylcarbodiimide (74 g, 0.36 mol) were dissolved in NMP (1200 ml) and heated to 60° C. for 2.5 hr. The reaction mixture was cooled to 25° C. and the precipitate was removed by filtration and washed with water (4.7 L). The crude precipitate was recystallised from 2-propanol (1250 ml), affording benzyl 18-[(2,5-dioxo-1-pyrrolidinyl)oxy]-18-oxooctadecanoate. Yield 138 g (92%).
Reaction SMILES: C(OC([N:6]1[CH:15]=[C:14]([CH:16]=[O:17])[C:13]2[C:8](=[CH:9][C:10]([O:23][CH3:24])=[C:11]([O:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH:12]=2)[CH:7]1[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=1)=O)C.[OH-].[K+]>CO>[CH2:19]([O:18][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[O:23][CH3:24])[CH:7]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=1)[NH:6][CH:15]=[C:14]2[CH:16]=[O:17])[CH2:20][CH2:21][CH3:22]
Reactant: CCCCOc1cc2c(cc1OC)C(Cc1cccc(OC)c1)N(C(=O)OCC)C=C2C=O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CCCCOc1cc2c(cc1OC)C(Cc1cccc(OC)c1)NC=C2C=O
Temperature: 25 °C
Reaction time: 15 h
Yield: 87.4 %

Procedure:
To a stirred solution of 6-butoxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (286 mg, 0.60 mmol) in methanol (12 mL) was added powdered potassium hydroxide (341 mg, 6.08 mmol). The reaction mixture was stirred at room temperature for 15 hrs. The solvent was evaporated and the residue was diluted with ethyl acetate (20 mL) and water (20 mL). The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford 6-butoxy-7-methoxy-1-(3-methoxy-benzyl)-1,2-dihydro-isoquinoline-4-carbaldehyde (200 mg, 87% yield) as a yellow oil. The crude product was used without further purification.
Reaction SMILES: [CH:1]1[C:5]2=[CH:6][C:7]3[CH:14]=[CH:13][C:11](=[O:12])[O:10][C:8]=3[CH:9]=[C:4]2[O:3][CH:2]=1.C1CCCCC=1>C(O)C.[Pd]>[CH2:1]1[C:5]2[CH:6]=[C:7]3[C:8](=[CH:9][C:4]=2[O:3][CH2:2]1)[O:10][C:11](=[O:12])[CH:13]=[CH:14]3
Reactant: O=c1ccc2cc3ccoc3cc2o1
Agent: [Pd]
Solvent: CCO
Solvent: C1=CCCCC1
Product: O=c1ccc2cc3c(cc2o1)OCC3
Yield: 72.3 %

Procedure:
A solution was prepared of 1.86 g (0.010 moles) of psoralen (7H-furo[3,2-g][1]benzopyran-7-one) in 200 ml of 95% ethanol, heated to reflux and treated by the addition of 5.0 ml of cyclohexene and a slurry of 5.0 g of 10% palladium on carbon in 30 ml of 95% ethanol. After 30 minutes of reflux with magnetic stirring the medium was filtered, evaporated in vacuo and the residue was recrystallized from 95% ethanol to give 1.36 g (72% yield) of tiny white needles, mp 198°-200° C.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[CH:39][C:38]2=[N:42][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:48][CH2:47][C:16]([CH3:49])([O:17][CH2:18][CH:19]=[CH:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([CH3:45])[C:27]([CH3:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].C(O[C@@H](C1C(C)=CC2=NC3=CN2C=1N1CCC(C)(OCCCC[C@H](C)OC2C=C(F)C=CC=2C2C=C3C=CC=2)CC1)C(OC)=O)(C)(C)C>>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[CH:39][C:38]2=[N:42][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:48][CH2:47][C:16]([CH3:49])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([CH3:45])[C:27]([CH3:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc3cn2c1N1CCC(C)(CC1)OCC=CC[C@H](C)Oc1cc(C)c(C)cc1-c1cccc-3c1
Agent: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc3cn2c1N1CCC(C)(CC1)OCCCC[C@H](C)Oc1cc(F)ccc1-c1cccc-3c1
Product: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc3cn2c1N1CCC(C)(CC1)OCCCC[C@H](C)Oc1cc(C)c(C)cc1-c1cccc-3c1
Yield: 43 %

Procedure:
Prepared in 43% yield from methyl(2S)-2-(tert-butoxy)-2-[(22S)-4,17,18,22,28-pentamethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3-yl]acetate following the procedure for methyl(2S)-2-(tert-butoxy)-2-[(22S)-18-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate. 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J=8.0 Hz, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.35-7.30 (m, 2H), 7.15 (s, 1H), 6.82 (s, 1H), 6.05 (br. s., 1H), 4.55 (br. s., 1H), 3.93 (t, J=10.9 Hz, 1H), 3.77 (t, J=11.0 Hz, 1H), 3.69 (s, 3H), 3.54-3.43 (m, 2H), 3.10 (d, J=11.3 Hz, 1H), 2.69 (d, J=9.8 Hz, 1H), 2.45 (s, 3H), 2.32 (s, 3H), 2.26 (s, 3H), 1.99-1.70 (m, 10H), 1.28 (s, 3H), 1.25 (s, 9H), 1.15 (d, J=6.0 Hz, 3H); LCMS (ESI, M+1): 668.35.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([F:13])[C:3]=1[C:4](Cl)=[O:5].[NH3:14]>COCCOCCOC>[F:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([F:13])[C:3]=1[C:4]([NH2:14])=[O:5]
Reactant: COc1cc(F)c(C(=O)Cl)c(F)c1
Reactant: N
Solvent: COCCOCCOC
Product: COc1cc(F)c(C(N)=O)c(F)c1

Procedure:
The crude acid chloride (25) was dissolved in dry diglyme (60 ml) and added dropwise at room temperature with gentle stirring to 35% ammonia (750 ml). The resulting colourless precipitate was filtered off and dried (CaCl2) in vacuo to give a colourless solid.
Reaction SMILES: C(O[C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)C.ClC1C=CC(C2[C:25]([C:26]3[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][N:42]([CH2:45][CH3:46])[CH2:43][CH3:44])=[CH:35][CH:34]=4)[N:27]=3)=[CH:24][NH:23][N:22]=2)=CC=1>>[CH2:45]([N:42]([CH2:43][CH3:44])[CH2:41][CH2:40][O:39][C:36]1[CH:37]=[CH:38][C:33]([NH:32][C:28]2[N:27]=[C:26]([C:25]3[C:4]([C:5]4[CH:6]=[CH:7][C:8]([O:11][CH3:12])=[CH:9][CH:10]=4)=[N:22][NH:23][CH:24]=3)[CH:31]=[CH:30][N:29]=2)=[CH:34][CH:35]=1)[CH3:46]
Reactant: CCN(CC)CCOc1ccc(Nc2nccc(-c3c[nH]nc3-c3ccc(Cl)cc3)n2)cc1
Reactant: CCOC(=O)c1ccc(OC)cc1
Product: CCN(CC)CCOc1ccc(Nc2nccc(-c3c[nH]nc3-c3ccc(OC)cc3)n2)cc1

Procedure:
The title compound is prepared as described in Example 1 using 4-methoxy-benzoic acid ethyl ester (Aldrich W24,200-4) and 4-(2-diethylamino-ethoxy)-phenylamine (see Example 3).