Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3](=[O:14])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([Br:11])=[CH:6][C:5]=1[CH2:12]Br.[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][NH2:21])=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[Br:11][C:7]1[CH:6]=[C:5]2[C:4](=[C:9]([CH3:10])[CH:8]=1)[C:3](=[O:14])[N:21]([CH2:20][C:19]1[CH:22]=[CH:23][C:16]([Cl:15])=[CH:17][CH:18]=1)[CH2:12]2
Reactant: COC(=O)c1c(C)cc(Br)cc1CBr
Reactant: NCc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1cc(Br)cc2c1C(=O)N(Cc1ccc(Cl)cc1)C2
Temperature: 100 °C
Reaction time: 2 h
Yield: 68.9 %

Procedure:
A mixture of 4-bromo-2-bromomethyl-6-methyl-benzoic acid methyl ester (0.966 g, 3.0 mmol), 4-chloro-benzylamine (0.462 mL, 3.8 mmol), and K2CO3 (0.829 g, 6.0 mmol) in toluene (10 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 5-bromo-7-methyl-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one (0.725 g, 69%). GC-MS: m/z 350 (M)+, 314 (M−36)+.
Reaction SMILES: O[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9](O)[CH:10]=[CH:11][C:12]=3[N+]([O-])=O)[C:7](=[O:21])[C:6]=2[C:5]([N+]([O-])=O)=[CH:4][CH:3]=1.C1(O)C=CC=CC=1>S(=O)(=O)(O)O>[CH:9]1[C:8]2[C:7](=[O:21])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: O=C1c2c(O)ccc([N+](=O)[O-])c2C(=O)c2c(O)ccc([N+](=O)[O-])c21
Agent: O=S(=O)(O)O
Solvent: Oc1ccccc1
Product: O=C1c2ccccc2C(=O)c2ccccc21
Temperature: 70 °C

Procedure:
Referring to FIG. 1d for the preparation of the blue dichroic dye, R9 are defined as mentioned above. 1,5-dihydroxy-4,8-dinitroanthraquinone and H3BO3 are dissolved in concentrated sulfuric acid and allowed to react with phenol at a temperature between −5° C. and −10° C. The product is collected and dissolved in a solvent (such as acetone), then, potassium carbonate and 1-halo-alkane (may have a fluoride substitute, for example, 1-bromo-4-fluorobutane) are added and heated at 70° C. for reaction, forming an anthraquinone compound as shown in FIG. 1d, a blue dichroic dye.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[CH2:8][NH:7][C@H:6]([C:13]([OH:15])=[O:14])[CH2:5]2.Cl.[CH3:17]O>>[CH3:17][O:14][C:13]([C@@H:6]1[CH2:5][C:4]2[C:9](=[CH:10][C:11]([OH:12])=[C:2]([OH:1])[CH:3]=2)[CH2:8][NH:7]1)=[O:15]
Reactant: O=C(O)[C@@H]1Cc2cc(O)c(O)cc2CN1
Reactant: CO
Agent: Cl
Product: COC(=O)[C@@H]1Cc2cc(O)c(O)cc2CN1
Reaction time: 18 h

Procedure:
(S)-6,7-Dihydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (62 g), 200 mL anhydrous MeOH, and 26 mL concentrated hydrochloric acid were stirred together overnight at 70° C. The mixture was then evaporated and the residue resuspended in 500 mL acetonitrile with vigorous stirring to wash all the solid material. Stirring continued for 18 h at r.t., after which the solid product was collected by filtration, washed with 100 mL acetonitrile, and dried under vacuum overnight. Yield 77 g (quantitative). 1H NMR (400 MHz, MeOH-d4): 6.64 (s, 1H), 6.61 (s, 1H), 4.42-4.36 (m, 1H), 4.29-4.24 (m, 2H), 3.89 (s, 3H), 3.29-3.22 (m, 1H), 3.11-3.02 (m, 1H).
Reaction SMILES: C(C1C2(C)OC(=O)C(SCC[N:23]3[CH:27]=[N:26][C:25]([C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[N:24]3)C2C(C)C(=O)C(C)CC(OC)(C)C(O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)C(C)C(=O)C(F)(C)C(=O)O1)C.O=O.OCCN1C=NC(C2C=NC=CC=2)=N1>>[N:30]1[CH:31]=[CH:32][CH:33]=[C:28]([C:25]2[N:26]=[CH:27][NH:23][N:24]=2)[CH:29]=1
Reactant: CCC1OC(=O)C(C)(F)C(=O)C(C)C(O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)C(C)(OC)CC(C)C(=O)C(C)C2C(SCCn3cnc(-c4cccnc4)n3)C(=O)OC12C
Agent: O=O
Agent: OCCn1cnc(-c2cccnc2)n1
Product: c1cncc(-c2nc[nH]n2)c1

Procedure:
Preparation of (3R or S, 3aR, 4R or S, 6R, 8R, 9R, 10R, 12S, 15R, 15aS)-15-Ethyl-12-fluorooctahydro-8-methoxy-4,6,8,10,12,15a-hexamethyl-3-[[2-[3-(3-pyridinyl)-1H-1,2,4-triazole-1-yl]ethyl]thio]-9-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-2H-furo [2,3-c] oxacyclotetradecin-2,5,11,13 (3H,6H,12H)-tetrone (I-12), compound of formula I where R1 is [2-[3-(3-pyridinyl)-1H-1,2,4-triazol-1-yl]ethyl]thio, R2 is fluoro, R3 is methyl and Z is oxygen. A] 3-(3-Pyridinyl)-1,2,4-triazole was prepared according to Lin et al. J. Org. Chem. 1979, 44, 4160. B] 1-(2-Hydroxyethyl)-3-(3-pyridinyl)-1H-1,2,4-triazole
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][C:23]([O:26][C@@H:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:22][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([O:16]CC=C)=[O:15])=[CH:11][CH:12]=2)[C:7]([CH3:20])=[C:6]1[CH3:21].N1CCOCC1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:25]=[CH:24][C:23]([O:26][C@@H:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:22][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([OH:16])=[O:15])=[CH:11][CH:12]=2)[C:7]([CH3:20])=[C:6]1[CH3:21]
Reactant: C=CCOC(=O)c1ccc2c(c1)c(C)c(C)n2Cc1cc(O[C@@H](C)C(=O)OC)ccc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: C1COCCN1
Product: COC(=O)[C@H](C)Oc1ccc(Cl)c(Cn2c(C)c(C)c3cc(C(=O)O)ccc32)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of (S)-allyl 1-(2-chloro-5-((1-methoxy-1-oxopropan-2-yl)oxy)benzyl)-2,3-dimethyl-1H-indole-5-carboxylate (0.327 g, 0.72 mmol) and morpholine (0.63 mL, 7.2 mmol) in anhydrous THF (10 mL) was degassed, then Pd(PPh3)4 (0.083 g, 0.072 mmol) was added under argon protection. The reaction mixture was stirred at rt for 1 h. The solvent was removed and the resulting crude was dissolved in MeOH. The mixture was acidified with 2 N HCl to pH 3. The mixture was filtered and the solid was washed with water. The solid was dried for the next Step with no further purification. ESI-MS (m/z): 416 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][NH:17][C:18]([C:20]3[N:21]=[CH:22][C:23]([C:26]([OH:28])=O)=[N:24][CH:25]=3)=[O:19])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.[NH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][NH:17][C:18]([C:20]3[CH:25]=[N:24][C:23]([C:26]([N:51]4[CH2:56][CH2:55][O:54][CH2:53][CH2:52]4)=[O:28])=[CH:22][N:21]=3)=[O:19])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: N#Cc1ccc(-c2ccn(CCNC(=O)c3cnc(C(=O)O)cn3)n2)cc1Cl
Reactant: C1COCCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: N#Cc1ccc(-c2ccn(CCNC(=O)c3cnc(C(=O)N4CCOCC4)cn3)n2)cc1Cl
Reaction time: 8 h

Procedure:
5-(2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)ethylcarbamoyl)pyrazine-2-carboxylic acid (0.11 g; 0.29 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.083 g: 0.43 mmol), anhydrous HOBt (0.058 g; 0.43 mmol), dipea (0.075 ml; 0.43 mmol) and morpholine (0.025 g; 0.29 mmol) were dissolved in 5 ml of dry DCM and stirred overnight. The solution was diluted with 10 ml of DCM and washed with 3×5 ml water. The combined water phases were extracted with 2×5 ml DCM and the combined organic phases dried over Na2SO4, filtered and evaporated to dryness. The product was purified using flash chromatography DCM/MeOH as gradient eluent. Yield 0.06 g. 1H-NMR (400 MHz; d6-DMSO): δ 3.45 (t, 2H), 3.56 (t, 2H), 3.69 (s, 4H), 3.76-3.80 (m, 2H), 4.42 (t, 2H), 6.97 (d, 1H), 7.87 (d, 1H), 7.94-8.01 (m, 2H), 8.01 (s, 1H), 8.93 (d, 1H), 9.13 (s, HA), 9.22-9.25 (t, 1H).
Reaction SMILES: Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[Br:12][C:13]1[S:17][C:16]([C:18](O)=[O:19])=[CH:15][CH:14]=1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:18]([C:16]1[S:17][C:13]([Br:12])=[CH:14][CH:15]=1)=[O:19])[CH2:4]2
Reactant: N[C@H]1CN2CCC1CC2
Reactant: O=C(O)c1ccc(Br)s1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN(C)C=O
Product: O=C(N[C@H]1CN2CCC1CC2)c1ccc(Br)s1
Yield: 92.7 %

Procedure:
A mixture of (R)-1-azabicyclo[2.2.2]oct-3-ylamine dihydrochloride (4 g), 5-bromothiophene-2-carboxylic acid (4.25 g), 1-hydroxybenzotriazole hydrate (2.77 g), O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (6.6 g), and N,N-diisopropylethylamine (14 mL), in N,N-dimethylformamide (100 mL) was stirred at room temperature overnight. The solution was evaporated, and the residue was partitioned between aqueous sodium hydroxide and chloroform. The chloroform layer was dried over magnesium sulfate, filtered, and evaporated. The residue was purified by flash chromatography on silica gel and eluted with 5%-20% 3.5N methanolic ammonia chloroform mixtures. Evaporation of solvent gave yellow solid (5.87 g); MS (ES+) 315, 317 (MH+).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]([OH:28])[CH2:15][S:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)=[CH:4][CH:3]=1.[CH2:29]([O:31][C:32](=[O:49])[CH2:33][C:34]1[CH:39]=[CH:38][C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][CH:35]=1)[CH3:30]>>[CH2:29]([O:31][C:32](=[O:49])[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[O:12][N:11]=[C:10]([CH3:13])[C:9]=3[CH:14]([OH:28])[CH2:15][S:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:26])[F:27])[CH:19]=3)=[CH:6][CH:7]=2)=[CH:36][CH:35]=1)[CH3:30]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(O)CSCc1cccc(C(F)(F)F)c1
Reactant: CCOC(=O)Cc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Product: CCOC(=O)Cc1ccc(-c2ccc(-c3onc(C)c3C(O)CSCc3cccc(C(F)(F)F)c3)cc2)cc1

Procedure:
Prepared according to the procedure described in Example 1, Step 7, using 1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-2-(3-trifluoromethyl-benzylsulfanyl)-ethanol and [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester.
Reaction SMILES: F[CH:2]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[NH:34][N:33]=[N:32][N:31]=2)[CH:25]=1)[C:3]1[CH:23]=[CH:22][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[C:11]([OH:18])[C:10]=2[CH2:19][CH2:20][CH3:21])=[CH:5][CH:4]=1.C(C1C=CC(OCC2C=CC(CC3C=C(C=CC=3)C#N)=CC=2)=C(CCC)C=1O)(=O)C>>[OH:18][C:11]1[C:10]([CH2:19][CH2:20][CH3:21])=[C:9]([O:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([CH2:2][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]4[NH:34][N:33]=[N:32][N:31]=4)[CH:25]=3)=[CH:23][CH:22]=2)[CH:14]=[CH:13][C:12]=1[C:15](=[O:17])[CH3:16]
Reactant: CCCc1c(OCc2ccc(C(F)c3cccc(-c4nnn[nH]4)c3)cc2)ccc(C(C)=O)c1O
Agent: CCCc1c(OCc2ccc(Cc3cccc(C#N)c3)cc2)ccc(C(C)=O)c1O
Product: CCCc1c(OCc2ccc(Cc3cccc(-c4nnn[nH]4)c3)cc2)ccc(C(C)=O)c1O
Yield: 58 %

Procedure:
The title compound is prepared in a similar manner to 1-[4-(4-{fluoro-[3-(1H-tetrazol-5-yl)-phenyl]-methyl}-benzyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone employing 3-[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-benzyl]-benzonitrile. The crude product is purified via reversed phase C18 preparative chromatography over 8 runs to provide the title compound as a tan solid (6.3 g, 58%). 1H NMR (DMSO-d6) δ 12.86 (s, 1H), 7.96 (s, 1H), 7.86-7.89 (m, 1H), 7.81 (d, 1H), 7.48-7.58 (m, 2H), 7.33-7.42 (m, 4H), 6.73 (d, 1H), 5.23 (s, 2H), 4.08 (s, 2H), 2.56-2.61 (m, 5H), 1.45-1.53 (m, 2H), 0.88 (t, 3H). LCMS M−1 441.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[NH2:7][C:8]1[CH:9]=[C:10]2[C:19](=[CH:20][CH:21]=1)[O:18][CH2:17][C:16]1[N:11]2[CH:12]([CH3:23])[C:13](=[O:22])[NH:14][N:15]=1.CS(O[C:29]1([CH3:46])[CH2:32][N:31]([CH:33]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:30]1)(=O)=O>CC(O)C>[CH:33]([N:31]1[CH2:32][C:29]([NH:7][C:8]2[CH:9]=[C:10]3[C:19](=[CH:20][CH:21]=2)[O:18][CH2:17][C:16]2[N:11]3[CH:12]([CH3:23])[C:13](=[O:22])[NH:14][N:15]=2)([CH3:46])[CH2:30]1)([C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: CC1(OS(C)(=O)=O)CN(C(c2ccccc2)c2ccccc2)C1
Reactant: CC1C(=O)NN=C2COc3ccc(N)cc3N21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Product: CC1C(=O)NN=C2COc3ccc(NC4(C)CN(C(c5ccccc5)c5ccccc5)C4)cc3N21
Temperature: 80 °C
Reaction time: 8 h
Yield: 58.1 %

Procedure:
A mixture of K2CO3 (0.238 g, 1.722 mmol), 6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #2, Step E, 0.20 g, 0.861 mmol), and 1-benzhydryl-3-methylazetidin-3-yl methanesulfonate (Preparation #3, Step B, 0.428 g, 1.292 mmol) in propan-2-ol (10 ml) was stirred at 80° C. overnight. The solution was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 0 to 50% EtOAc in petroleum ether) to give 6-(1-benzhydryl-3-methyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.234 g, 58%). LC/MS (Table 1, Method 2) Rt=0.948 min; MS m/z: 468 [M+H]+.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17]([O:23][C:24]3[C:25]([F:34])=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][C:28]([CH3:33])=[CH:27]4)=[CH:18][N:19]=[N:20]2)=[CH:15][C:14]=1[O:35][CH3:36]>CN(C=O)C>[F:34][C:25]1[C:24]([O:23][C:17]2[C:16]3[C:21](=[CH:22][C:13]([O:12][CH2:11][CH2:10][CH2:9][N:5]4[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]4)=[C:14]([O:35][CH3:36])[CH:15]=3)[N:20]=[N:19][CH:18]=2)=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[C:28]([CH3:33])[NH:29]2
Reactant: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)cnnc2cc1OCCCBr
Reactant: OC1CCNCC1
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)cnnc2cc1OCCCN1CCC(O)CC1
Yield: 8 %

Procedure:
A solution of 4-hydroxypiperidine (0.5 g, 4.95 mmol) and 7-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline (0.3 g, 0.65 mmol) in DMF (4 ml) was stirred at 60° C. for 30 minutes. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with ethyl acetate/methylene chloride (1/1) followed by ethyl acetate/methanol/methylene chloride (4/1/5) followed by methylene chloride/methanol saturated with ammonia (9/1). The fractions containing the expected product were combined and evaporated to give 4-(4-fluoro-2-methylindol-5-yloxy)-7-(3-(4-hydroxypiperidin-1-yl)propoxy)-6-methoxycinnoline (25 mg, 8%).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C@H:11]([C:13]([OH:15])=[O:14])[CH3:12])[CH:2]=[CH2:3].Cl.[C:17](=O)(O)[O-].[Na+]>CO>[CH3:17][O:14][C:13](=[O:15])[C@H:11]([CH3:12])[NH:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH2:1][CH:2]=[CH2:3]
Reactant: O=C([O-])O
Reactant: C=CCc1ccccc1N[C@@H](C)C(=O)O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: C=CCc1ccccc1N[C@@H](C)C(=O)OC

Procedure:
A solution of 0.06 mol of N-(2-allylphenyl)alanine, prepared as described by A. Padwa, H. L. Gingrich, and R. Lim in J. Org. Chem.,1982, 47, 2447-2456, and 0.066 mol of HCl in 100 mL of CH3OH is stirred at reflux for 8 hours. The solution is then cooled and treated with 0.066 mol of sodium bicarbonate. The solvent is removed by rotary evaporator, and the residue is dissolved in diethyl ether, filtered, dried over MgSO4, and filtered. The solvent is removed by rotary evaporator to give N-(2-allylphenyl)alanine methyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=3[N+:23]([O-])=O)[O:10][N:9]=2)=[CH:4][CH:3]=1.O1CCCC1>[Pd].C(OCC)(=O)C>[NH2:23][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:13]=1[C:11]1[O:10][N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:12]=1)[C:17]([O:19][CH3:20])=[O:18]
Reactant: COC(=O)c1ccc(-c2nc(-c3ccc(Cl)cc3)no2)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COC(=O)c1ccc(-c2nc(-c3ccc(Cl)cc3)no2)c(N)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 77.9 %

Procedure:
A mixture of methyl 4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-3-nitrobenzoate (0.700 g), 5% palladium on carbon (0.700 g), tetrahydrofuran (15 ml) and ethyl acetate (30 ml) was stirred under a hydrogen atmosphere at room temperature and normal pressure for 30 min. Palladium on carbon was filtered off, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1, volume ratio) to give methyl 3-amino-4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]benzoate (0.50 g, yield 79%). Recrystallization from hexane-ethyl acetate gave colorless prism crystals. melting point: 227–228° C.
Reaction SMILES: C([O:3][C:4](=[O:42])[C@H:5]([CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])[NH:6][C:7](=[O:34])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][S:15]([C:18]2[CH:19]=[CH:20][C:21]3[CH2:30][CH2:29][C:28]4[N:27]=[C:26]([CH3:31])[NH:25][C:24](=[O:32])[C:23]=4[C:22]=3[CH:33]=2)(=[O:17])=[O:16])=[CH:10][CH:9]=1)C.Cl>>[CH3:31][C:26]1[NH:25][C:24](=[O:32])[C:23]2[C:22]3[CH:33]=[C:18]([S:15]([NH:14][C:11]4[CH:12]=[CH:13][C:8]([C:7]([NH:6][C@H:5]([C:4]([OH:42])=[O:3])[CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:34])=[CH:9][CH:10]=4)(=[O:16])=[O:17])[CH:19]=[CH:20][C:21]=3[CH2:30][CH2:29][C:28]=2[N:27]=1
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(NS(=O)(=O)c2ccc3c(c2)-c2c(nc(C)[nH]c2=O)CC3)cc1)C(=O)OCC
Agent: Cl
Product: Cc1nc2c(c(=O)[nH]1)-c1cc(S(=O)(=O)Nc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)ccc1CC2
Temperature: 25 °C
Reaction time: 4 h
Yield: 95.9 %

Procedure:
Diethyl-N-(4-((1,2,5,6-tetrahydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)sulfonamido)benzoyl)-L-glutamate (4.53 g, 7.6 mmole) was dissolved in N-NaOH (64 ml) and the solution stirred at room temperature for 4 hours. The pH of the solution was adjusted to 3.00 with 1N HCl, the solid collected by filtration, washed with water and dried under high vacuum to yield the product as an off white solid (3.94 g,96%). 1HNMR (DMSO-d6,300 MHz) δ: 1.84-1.96 (m,1H,glu CH); 2.00-2.10 (m, 1H, glu CH); 2.32(s, 3H, CH3, superimposed over t, 2H, glu CH2); 2.71 (m, 2H, Ar CH2); 2.89 (m, 2H, Ar CH2); 4.28-4.36 (m, 1H, glu CH); 7.20 (d, J=9 Hz, 2H, Ar); 7.39 (d, J=8 Hz, 1H, Ar); 7.62 (dd, J=8,2 Hz, 1H, Ar); 7.74 (d, J=9 Hz, 2H, Ar); 8.44 (d, J=8 Hz, 1H, glutH); 9.21 (d, J=2 Hz, 1H, Ar); 10.73 (s, 1H, SO2NH); 12.36 (br s, 2H, CO2H); 12.72 (br s, 1H, NH). Anal Calculated for C25H24N4O8S. 3/2H2O: C,52.91; H,4.792 N,9.87; S,5.65. Found: C,52.98; H,4.78; N,9.87; S,5.58.
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][C:5]1([CH2:15][N+:16]([O-])=O)[CH2:14][CH2:13][C:8]2([O:12][CH2:11][CH2:10][O:9]2)[CH2:7][CH2:6]1>CO.[Ni]>[O:12]1[C:8]2([CH2:13][CH2:14][C:5]3([CH2:4][C:3](=[O:2])[NH:16][CH2:15]3)[CH2:6][CH2:7]2)[O:9][CH2:10][CH2:11]1
Reactant: COC(=O)CC1(C[N+](=O)[O-])CCC2(CC1)OCCO2
Agent: [Ni]
Solvent: CO
Product: O=C1CC2(CCC3(CC2)OCCO3)CN1
Yield: 95.9 %

Procedure:
A solution of (8-nitromethyl-1,4-dioxa-spiro[4.5]dec-8-yl)-acetic acid methyl ester (5.34 g, 19.5 mmol) in 35 mL of methanol was purged with nitrogen. A portion of about 430 mg of Raney 2800 nickel was added. The reaction mixture was purged with hydrogen and a positive pressure of hydrogen was maintained overnight using a balloon. Then, the final mixture was purged with nitrogen and filtered through a pad of celite washing with methanol. The filtrate was concentrated to afford 1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-11-one (3.95 g, 96%) as a white solid.
Reaction SMILES: [CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1.ClCCl.[Cl:11][C:12]([Cl:16])([Cl:15])[C:13]#[N:14]>>[Cl:11][C:12]([Cl:16])([Cl:15])[C:13](=[NH:14])[O:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1
Reactant: OC1C=CCCC1
Reactant: N#CC(Cl)(Cl)Cl
Solvent: ClCCl
Product: N=C(OC1C=CCCC1)C(Cl)(Cl)Cl
Temperature: -20 °C
Reaction time: 3 h

Procedure:
To a solution of 2-cylohexen-1-ol (16) (18 g, 0.183 mol) in dry dichloromethane (275 ml) DBU (41.88 g, 0.275 mol) was added and the mixture was cooled to −20° C. To this solution, trichloroacetonitrile (47.66 g, 0.330 mol) was added dropwise. The reaction was stirred for 3 h at −20° C. and quenched with aqueous ammonium chloride solution. The organic phase was separated and dried over potassium carbonate. The solvent was removed under vacuum to yield the intermediate cyclohex-2-en-1-yl 2,2,2-trichloroethanimidoate. This was dissolved in toluene (100 ml) and treated with potassium carbonate (30 g). The mixture was refluxed for 12 h. After cooling the mixture was filtered through Celite and the filtrate was evaporated to afford 9 g (20%) of (22) as a solid. LC/MS: Mass found (m/z, MS, 242.9) Method: A—0.1% HCOOH, B—ACN (70%), Flow—0.8 ml/min Column: GENESIS C18 50×4.6 mm 3U, Rt (min): 1.645: 1H NMR (CDCl3, 400 MHz) δ 1.64-1.74 (3H, m), 1.96-2.12 (3H, m), 4.46-4.47 (1H, m), 5.64-5.67 (1H, m), 5.97-5.6.01 (1H, m), 6.59 (1H, bs).
Reaction SMILES: [C:1]1([CH:7]2[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].Cl[C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:31][CH3:32])=[C:26]([O:29][CH3:30])[CH:27]=2)[N:22]=[CH:21][N:20]=1.O>O1CCCC1.C(OCC)(=O)C>[CH3:30][O:29][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[O:31][CH3:32])[N:22]=[CH:21][N:20]=[C:19]2[C:7]1([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:9][CH2:8]1
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Reactant: c1ccc(C2CC2)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: COc1cc2ncnc(C3(c4ccccc4)CC3)c2cc1OC
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 13.4 %

Procedure:
A solution of 2.4 grams of phenylcyclopropane in 20 ml of tetrahydrofuran was added with 20 ml of 1M lithium diisopropylamide in tetrahydrofuran at 0° C. The mixture was stirred at 0° C. for 30 minutes and room temperature for 20 minutes. This was then added with 3.0 grams of 4-chloro-6,7-dimethoxyquinazoline in 20 ml of tetrahydrofuran. The mixture was then stirred at room temperature overnight, poured into a mixture of cold water and ethyl acetate. The ethyl acetate layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude was then purified on a silica gel column with dichloromethane and methanol as the solvent to provided 550 mg of 6,7-dimethoxy-4-(1phenylcyclopropyl)-quinazoline.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[N:13]=[C:14]([C:16]1[CH:17]=[CH:18][C:19]2[C:20]3[CH:21]=[CH:22][CH:23]=[C:24]4[C:38]=3[C:28]([C:29]3[C:34]=2[C:33]=1[C:32]([C:35]([OH:37])=[O:36])=[CH:31][CH:30]=3)=[CH:27][CH:26]=[C:25]4[C:39]#[C:40][CH2:41][CH2:42][CH2:43][CH2:44]OS(C1C=CC(C)=CC=1)(=O)=O)[OH:15])([CH3:3])[CH3:2].[N-:56]=[N+:57]=[N-:58].[Na+]>CN(C=O)C>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[N:13]=[C:14]([C:16]1[CH:17]=[CH:18][C:19]2[C:20]3[CH:21]=[CH:22][CH:23]=[C:24]4[C:38]=3[C:28]([C:29]3[C:34]=2[C:33]=1[C:32]([C:35]([OH:37])=[O:36])=[CH:31][CH:30]=3)=[CH:27][CH:26]=[C:25]4[C:39]#[C:40][CH2:41][CH2:42][CH2:43][CH2:44][N:56]=[N+:57]=[N-:58])[OH:15])([CH3:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1ccc(S(=O)(=O)OCCCCC#Cc2ccc3c4ccc(C(=O)O)c5c(C(O)=Nc6c(C(C)C)cccc6C(C)C)ccc(c6cccc2c36)c54)cc1
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)c1cccc(C(C)C)c1N=C(O)c1ccc2c3cccc4c(C#CCCCCN=[N+]=[N-])ccc(c5ccc(C(=O)O)c1c52)c43

Procedure:
A solution of 1.00 g (1.36 mmol) N-(2,6-diisopropylphenyl)-9-(6-tosyloxy-1-hexinyl)-perylene-3,4-dicarboxylic acid imide and 0.60 g (9.1 mmol) sodium azide in 144 ml DMF were stirred for 20 hours at room temperature under nitrogen atmosphere.