Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C@@H:8]([C@@H:16]1[CH2:18][O:17]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[NH:20]1[CH:24]=[CH:23][N:22]=[CH:21]1>>[C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C@@H:16]([OH:17])[CH2:18][N:20]1[CH:24]=[CH:23][N:22]=[CH:21]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: c1c[nH]cn1
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)[C@@H]1CO1
Product: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)[C@@H](O)Cn1ccnc1

Procedure:
Using general procedure 2 and purification method D with [(1R)-1-{(2R)-oxiran-2-yl}-2-phenyl-ethyl]carbamic acid tert-butylester (0.166 g, 0.63 mmol) and imidazole (0.052 g, 0.76 mmol) gives the title compound.
Reaction SMILES: [C:1]1([C:7]2[N:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[CH:9]=[CH:10][C:11](=[O:17])[NH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[CH3:18][N:12]1[C:13]2[C:8](=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:16]=[CH:15][CH:14]=2)[CH:9]=[CH:10][C:11]1=[O:17]
Reactant: O=c1ccc2c(-c3ccccc3)nccc2[nH]1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1c(=O)ccc2c(-c3ccccc3)nccc21
Reaction time: 1 h
Yield: 72.8 %

Procedure:
A mixture containing 22.2 g of 5-phenyl-1,6-naphthyridin-2(1H)-one, 13.18 g of anhydrous potassium carbonate and 300 ml of dimethylformamide was heated with stirring on a steam bath for 1 hour and to this mixture was added 6.9 g of methyl iodide. The resultig mixture was heated with stirring for an additional 6 hours, allowed to cool and the solvent removed by distillation under reduced pressure. To the residue was added 100 ml of 20% acetic acid and the resulting pale yellow solid was collected, washed with water, dried, recrystallized from methanol and dried at 90° C. to yield 16.4 g of 1-methyl-5-phenyl-1,6-naphthyridin-2(1H)-one, m.p. 190°-192° C.
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[Cl:20])[CH:11]2[CH3:21])=[N:4][C:5]([Cl:9])=[N:6][C:7]=1[CH3:8].[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1>CN(C)C=O>[ClH:9].[CH3:1][C:2]1[C:3]([N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[Cl:20])[CH:11]2[CH3:21])=[N:4][C:5]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([F:22])=[CH:24][CH:25]=2)=[N:6][C:7]=1[CH3:8]
Reactant: Nc1ccc(F)cc1
Reactant: Cc1nc(Cl)nc(N2CCc3c(Cl)cccc3C2C)c1C
Solvent: CN(C)C=O
Product: Cc1nc(Nc2ccc(F)cc2)nc(N2CCc3c(Cl)cccc3C2C)c1C
Product: Cl
Yield: 49.9 %

Procedure:
The same procedures as in Step 2 of Example 3 above were repeated using 5,6-dimethyl-2-chloro-4-(1-methyl-5-chloro- 1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine (0.1 g, 0.31 mmol) prepared in Step 1 above, dimethylformamide (5 ml), and 4-fluoroaniline (0.07 ml, 0.74 mmol) to afford 67 mg (50%) of the titled compound.
Reaction SMILES: C([O:5][C:6](=[O:39])[C@H:7]([NH:9][C:10]([C:12]1[CH:16]=[C:15]([O:17][CH2:18][C:19]([N:21]2[CH2:25][CH2:24][CH2:23][C@H:22]2[C:26](=[O:32])[NH:27][CH:28]2[CH2:31][CH2:30][CH2:29]2)=[O:20])[N:14]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:13]=1)=[O:11])[CH3:8])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[CH:28]1([NH:27][C:26]([C@@H:22]2[CH2:23][CH2:24][CH2:25][N:21]2[C:19](=[O:20])[CH2:18][O:17][C:15]2[N:14]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:13]=[C:12]([C:10]([NH:9][C@H:7]([CH3:8])[C:6]([OH:39])=[O:5])=[O:11])[CH:16]=2)=[O:32])[CH2:29][CH2:30][CH2:31]1
Reactant: C[C@@H](NC(=O)c1cc(OCC(=O)N2CCC[C@H]2C(=O)NC2CCC2)n(-c2ccccc2)n1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C[C@@H](NC(=O)c1cc(OCC(=O)N2CCC[C@H]2C(=O)NC2CCC2)n(-c2ccccc2)n1)C(=O)O
Reaction time: 6 h

Procedure:
To a solution of 745 mg (R)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-propionic acid tert-butyl ester in 5 ml dichloromethane were added 1.6 ml TFA. After stirring for 6 h it was concentrated and codistilled twice with toluene to give the crude product. Yield: 770 mg
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([Cl:15])=[C:10]2[O:14][CH:13]=[CH:12][C:11]=12)=[O:5])C.[OH-].[Na+]>CO.O>[Cl:15][C:9]1[CH:8]=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[C:11]2[C:10]=1[O:14][CH:13]=[CH:12]2
Reactant: CCOC(=O)c1ccc(Cl)c2occc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)c1ccc(Cl)c2occc12
Temperature: 55 °C

Procedure:
A mixture of 7-chloro-benzofuran-4-carboxylic acid ethyl ester (3.90 mmol) and sodium hydroxide (5.85 mmol) in MeOH (4.4 mL) and water (4.4 mL) is heated to 55° C. for 90 min. The mixture is concentrated in vacuo and made acidic by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off and dried in vacuo to give the desired product. 1H-NMR (DMSO-d6): δ=13.3 (bs, 1H); 8.27 (s, 1H); 7.89 (d, J=8.3 Hz, 1H); 7.56 (d, J=8.3 Hz, 1H); 7.42 (s, 1H).
Reaction SMILES: S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]([OH:15])=[O:14])=[N:11][CH:12]=1.[OH2:16].[CH2:17](O)[CH3:18]>>[Cl:6][C:7]1[CH:12]=[N+:11]([O-:16])[C:10]([C:13]([O:15][CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=1
Reactant: O
Reactant: O=C(O)c1ccc(Cl)cn1
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc(Cl)c[n+]1[O-]
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Concentrated sulfuric acid (4 mL) was added to a solution of 5-chloropyridine-2-carboxylic acid (25.3 g) in ethanol (500 mL) under ice-cooling, and the mixture was stirred under reflux for four hours. The reaction solution was cooled to room temperature and water was added, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform only→hexane:ethyl acetate=1:1) and the solvent was evaporated under reduced pressure from the fraction containing ethyl 5-chloropyridine-2-carboxylate. Urea peroxide (30.2 g) was added to a solution of the residue in chloroform (300 mL) under ice-cooling. A mixture of trifluoroacetic anhydride (44.7 mL) and chloroform (300 mL) was added dropwise over 30 minutes, and the mixture was stirred while gradually returning to room temperature for two hours. A saturated sodium thiosulfate solution was added dropwise to the reaction solution, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give ethyl 5-chloropyridine-2-carboxylate 1-oxide as a yellow oil (36.8 g, quant.).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].COCCOCCN(CCOCCOC)CCOCCOC.[OH-].[K+].[F:34][C:35]1[CH:40]=[C:39](F)[C:38]([F:42])=[CH:37][C:36]=1[N+:43]([O-:45])=[O:44]>C(OCC)(=O)C.O>[F:42][C:38]1[CH:37]=[C:36]([N+:43]([O-:45])=[O:44])[C:35]([F:34])=[CH:40][C:39]=1[O:6][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([F:1])[CH:3]=1
Reactant: OCc1cccc(F)c1
Reactant: O=[N+]([O-])c1cc(F)c(F)cc1F
Agent: COCCOCCN(CCOCCOC)CCOCCOC
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1cc(F)c(OCc2cccc(F)c2)cc1F
Temperature: 100 °C
Reaction time: 0.17 h
Yield: 55 %

Procedure:
A mixture of 2.35 g (18.6 mmol) of 3-fluorobenzylalcohol and 0.55 g (1.7 mmol) of tris[2-(2-methoxyethoxy)ethyl]amine is treated portionwise under stirring with 1.06 g (18.6 mmol) of potassium hydroxide. Stirring is continued for 10 min if necessary under slight heating to reach a homogenous reaction mixture. Thereafter, 3.0 g (16.9 mmol) of 2,4,5-trifluoronitrobenzene are added dropwise. The reaction mixture becomes solid and is heated to 100° C. for 2 hours. For the working-up, the mixture is cooled to RT, then 25 ml water and 25 ml ethyl acetate are added and stirring continued for 30 min. The organic layer is separated and the aqueous layer is extracted twice with ethyl acetate. The combined organic layers are washed with water, then twice with 2N hydrochloric acid and finally with water. After drying over magnesium sulfate, the solution is evaporated under reduced pressure. During evaporation, the byproduct, 1-fluoro-2,4-bis-(3-fluorobenzyloxy)-5-nitro-benzene precipitates. For purification, the material obtained is chromatographed on silica gel using a 4:1-mixture of n-hexane and ethyl acetate as the eluent. There are obtained 2.63 g (55% of theory) of the 1,4-difluoro-2-(3-fluorobenzyloxy)-5-nitro-benzene as an off-white solid. MS: m/e=283 (M)+.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH2:7]CBr)=[N:4][S:5][CH:6]=1.[NH2:10][CH2:11][CH2:12][SH:13]>>[BrH:1].[Br:1][C:2]1[C:3]([CH2:7][S:13][CH2:12][CH2:11][NH2:10])=[N:4][S:5][CH:6]=1
Reactant: BrCCc1nscc1Br
Reactant: NCCS
Product: Br
Product: NCCSCc1nscc1Br

Procedure:
The reaction of 4-bromo-3-(bromoethyl)isothiazole (8.5 g) with cysteamine (from cysteamine hydrochloride (3.76 g)) was performed under conditions similar to those described in Example 72. From the reaction there was obtained 4-bromo-3-[(2-aminoethyl)thiomethyl]isothiazole hydrobromide, which, following recrystallisation from ethanol-ether and acetonitrile, gave needles (4.05 g), m.p. 111°-112°. The amine base (2.73 g) was isolated by basification with sodium hydroxide and extraction with chloroform.
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[C:21]([Cl:23])[C:5]2[O:6][C:7]3[C:16]([CH3:17])=[CH:15][C:14]([C:18]([OH:20])=[O:19])=[CH:13][C:8]=3[S:9](=[O:12])(=[O:11])[CH2:10][C:4]=2[CH:3]=1.[CH:24](=O)[CH:25]([CH3:27])[CH3:26].FC(F)(F)C(O)=O.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>O.CO>[Cl:23][C:21]1[C:5]2[O:6][C:7]3[C:16]([CH3:17])=[CH:15][C:14]([C:18]([OH:20])=[O:19])=[CH:13][C:8]=3[S:9](=[O:11])(=[O:12])[CH2:10][C:4]=2[CH:3]=[C:2]([NH:1][CH2:24][CH:25]([CH3:27])[CH3:26])[CH:22]=1
Reactant: CC(C)C=O
Reactant: Cc1cc(C(=O)O)cc2c1Oc1c(Cl)cc(N)cc1CS2(=O)=O
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: Cc1cc(C(=O)O)cc2c1Oc1c(Cl)cc(NCC(C)C)cc1CS2(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.74 %

Procedure:
To a mixture of the methyl ester of Example 35j (0.1 g, 0.27 mmol), isobutyraldehyde (0.098 g, 1.35 mmol)), trifluoro acetic acid (0.27 mmol) and sodium cyanoborohydride (0.67 mmol) was added MeOH (15 mL) at 0-5° C. The reaction mixture was stirred overnight at room temperature, treated with chilled water, neutralized with 10% aqueous NaHCO3, extracted with EtOAc, concentrated and subjected to hydrolysis as described in Example 11 to obtain the title compound (Tet. Lett. 38, 5831-5834, (1997)). Yield: 64.74%; 1H NMR (DMSO-d6): δ 0.90 (d, 6H, 2CH3), 1.80 (m, 1H, CH), 2.60 (s, 3H, CH3), 2.90 (d, 2H, N—CH2), 5.10 (s, 2H, CH2), 6.70 (s, 2H, Ar), 8.10 (d, 2H, Ar); MS: m/e (EI+) 409 (M+).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:10][O:11][P:12](=[O:39])([OH:38])[O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20]C(=O)OCC1C2C=CC=CC=2C2C1=CC=CC=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].O>N1CCCCC1>[NH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][O:13][P:12]([O:11][CH2:10][CH:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:40]([O:42][C:43]([CH3:45])([CH3:46])[CH3:44])=[O:41])([OH:39])=[O:38]
Reactant: CC(C)(C)OC(=O)NC(COP(=O)(O)OCCCCCCNC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OC(C)(C)C
Solvent: C1CCNCC1
Solvent: O
Product: CC(C)(C)OC(=O)NC(COP(=O)(O)OCCCCCCN)C(=O)OC(C)(C)C

Procedure:
3 g of tert-butyl 15-[(tert-butoxycarbonyl)amino]-1-(9H-fluoren-9-yl)-12-hydroxy-3-oxo-2,11,13-trioxa-4-aza-12-phosphahexadecan-16-oate 12-oxide are stirred in 0.62 ml of piperidine and 3 ml of water for 12 hours at ambient temperature. The reaction medium is filtered and the crystals obtained are washed twice with 50 ml of acetonitrile and then recrystallized from 100 ml of acetonitrile.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([O:14]C)=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][CH2:17]OC)=[C:4]([CH:20](O)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:3]=1.Cl>CO.O1CCOCC1>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[C:9]([O:16][CH3:17])=[CH:10][CH:11]=[CH:12][C:13]=3[O:14][CH:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:4]=2[CH:3]=1
Reactant: COCOc1cccc(OC)c1-c1ccc(N)cc1C(O)c1ccccc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: COc1cccc2c1-c1ccc(N)cc1C(c1ccccc1)O2
Temperature: 85 °C
Reaction time: 16 h
Yield: 86.9 %

Procedure:
The compound of Example 5E (3.449 g., 9.45 mmole) was dissolved in methanol (80 mL) containing 4N HCl in dioxane (80 mL)was stirred for 16 hours. The mixture was concentrated under reduced pressure, dissolved in chloroform washed with aqueous KHCO3, dried (Na2SO4), filtered and reduced under pressure. The residue was dissolved in toluene (450 mL), toluenesulfonic acid H2O (7.18 g.) was added and the solution was heated at 85° C. for 30 minutes. The mixture was cooled, washed with aqueous KHCO3, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on silica eluting with CH2Cl2 to provide the titled compound (2.49 g, 87%).
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:10][C@H:11]2[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]2)=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[CH3:26][CH:27]([CH3:33])[CH2:28][S:29](Cl)(=[O:31])=[O:30]>ClCCl>[Br:1][C:2]1[C:3]([NH:10][C@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([S:29]([CH2:28][CH:27]([CH3:33])[CH3:26])(=[O:31])=[O:30])[CH2:12]2)=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1
Reactant: CC(C)CS(=O)(=O)Cl
Reactant: CSc1ncc(Br)c(N[C@H]2CCCNC2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CSc1ncc(Br)c(N[C@H]2CCCN(S(=O)(=O)CC(C)C)C2)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.6 %

Procedure:
A solution of (5-bromo-2-methylsulfanyl-pyrimidin-4-yl)-(S)-piperidin-3-yl-amine (1.0 g, 3.3 mmol) from Scheme 1, step 1, Example 76 and diisopropylethylamine (1.6 ml, 6.6 mmol) in dichloromethane (15 ml) was cooled to 5° C. and treated with a solution of 2-methylpropane-1-sulfonyl chloride (0.52 g, 3.3 mmol) in dichloromethane (2 ml) similar to step 2. This was stirred at room temperature for 16 hours, washed with water, dried (MgSO4) and evaporated to give an oil. This was purified by silica gel chromatography (50-80% ethyl acetate/hexane) to give 1.0 g (65%) (5-bromo-2-methylsulfanyl-pyrimidin-4-yl)-[(S)-1-(2-methyl-propane-1-sulfonyl)-piperidin-3-yl]-amine. MS (ES+): 424
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([F:10])=[C:7]([OH:9])[CH:8]=1)[CH3:2].N1C=CN=C1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>CN(C=O)C.CCOC(C)=O>[C:19]([Si:16]([O:9][C:7]1[CH:8]=[C:3]([CH2:1][CH3:2])[CH:4]=[CH:5][C:6]=1[F:10])([CH3:18])[CH3:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CCc1ccc(F)c(O)c1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCc1ccc(F)c(O[Si](C)(C)C(C)(C)C)c1
Reaction time: 18 h
Yield: 67.2 %

Procedure:
To a mixture of 5-ethyl-2-fluorophenol (10 g, 71.4 mmol) and imidazole (5.4 g, 78.5 mmol) in DMF (100 mL) was added t-butyldimethylsilylchloride (10.8 g, 71.4 mmol) and stirred 18 h. Diluted with EtOAc and washed with H2O (3×50 mL) and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient) to afford 12.2 g of intermediate 368.1. 1H NMR (400 MHz, CDCl3) δ ppm 0.15 (s, 6H) 0.97 (s, 9H) 1.16 (t, J=7.47 Hz, 3H) 2.52 (q, J=7.76 Hz, 2H) 6.63-6.72 (m, 2H) 6.90 (dd, J=10.77, 8.13 Hz, 1H).
Reaction SMILES: CCCCCCCCCCCCCCCCCC(N[C@H:21]([C@H:91](O)/[CH:92]=[CH:93]/[CH2:94][CH2:95][CH2:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH2:104][CH2:105][CH3:106])[CH2:22][O:23][C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@H]3NC(C)=O)[C@H](O[C@@]3(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)[C@H]2O)[C@H](O)[C@H]1O)=O.[OH2:108]>>[C:22]([OH:23])(=[O:108])[CH2:21][CH2:91][CH2:92][C:93]#[C:94][C:95]#[C:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH2:104][CH2:105][CH2:106][CH2:22][CH2:21][CH2:91][CH3:92]
Reactant: O
Reactant: CCCCCCCCCCCCC/C=C/[C@@H](O)[C@H](CO[C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@H]3NC(C)=O)[C@H](O[C@]3(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O3)[C@H]2O)[C@H](O)[C@H]1O)NC(=O)CCCCCCCCCCCCCCCCC
Product: CCCCCCCCCCCCCCC#CC#CCCCC(=O)O

Procedure:
Ganglioside GM1, cholera toxin from Vibrio Cholerae, human serum albumin, and wheat germ agglutinin were purchased from Sigma. 5,7-docosadiynoic acid was synthesized. Deionized water was obtained by passing distilled water through a Millipore μF ultrapurification train. Solvents used were reagent grade. The ganglioside GM1 was mixed at 5 mol % with the diacetylene “matrix lipid” monomers. Liposomes were prepared using the probe sonication method and polymerized by UV irradiation (254 nm). The conjugated ene-yne backbone of polydiacetylene liposomes results in the appearance of a deep blue/purple solution. The visible absorption spectrum of the freshly prepared purple liposomes is shown in FIG. 25.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][N:6]=[CH:7][CH:8]=2)[N:3]=1.[CH:12]1(B(O)O)[CH2:14][CH2:13]1.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[BH4-].[Na+]>>[CH2:18]([N:6]1[CH2:5][C:4]2[N:3]=[C:2]([CH:12]3[CH2:14][CH2:13]3)[CH:11]=[CH:10][C:9]=2[CH2:8][CH2:7]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Clc1ccc2ccncc2n1
Reactant: OB(O)C1CC1
Reactant: BrCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Product: c1ccc(CN2CCc3ccc(C4CC4)nc3C2)cc1

Procedure:
2-Chloro-1,7-naphthyridine was subjected to a Suzuki reaction with cyclopropylboronic acid; the product was reacted with benzyl bromide, and then reduced with sodium borohydride to afford 7-benzyl-2-cyclopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine. Protecting group removal with 1-chloroethyl carbonochloridate provided 2-cyclopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:13][C:14]1[CH:21]=[CH:20][C:17]([NH:18][CH3:19])=[CH:16][CH:15]=1>>[Cl:1][C:2]1[N:11]=[C:10]([N:18]([C:17]2[CH:20]=[CH:21][C:14]([CH3:13])=[CH:15][CH:16]=2)[CH3:19])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: CNc1ccc(C)cc1
Reactant: Clc1nc(Cl)c2ccccc2n1
Product: Cc1ccc(N(C)c2nc(Cl)nc3ccccc23)cc1

Procedure:
The title compound was prepared from 2,4-dichloroquinazoline (250 mg, 1.25 mmol) and 4-methyl-N-methylaniline (196 mg, 1.43 mmol) by a procedure similar to Example 1b and was isolated as white powder (210 mg, 84%). 1H NMR (CDCl3): 8.69 (d, J=8.4 Hz, 1H), 7.75 (dd, J=8.1 and 7.5 Hz, 1H), 7.39 (d, J=7.8 Hz, 2H), 7.25 (d, J=7.8 Hz, 2H), 7.13 (d, J=8.2 Hz, 1H), 6.74 (d, J=8.7 Hz, 1H), 3.81 (s, 3H), 2.49 (s, 3H).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:33])[C:10]1[CH:15]=[C:14](Br)[C:13]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][C:11]=1[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:34](N)[CH2:35][CH2:36]C>CC(O)C.O.O>[CH2:1]([O:8][C:9](=[O:33])[C:10]1[CH:15]=[C:14]([C:35]([CH3:36])=[CH2:34])[C:13]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][C:11]=1[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)c1cc(Br)c(OCc2ccccc2)cc1OCc1ccccc1
Reactant: CCCCN
Solvent: CC(C)O
Solvent: O
Product: C=C(C)c1cc(C(=O)OCc2ccccc2)c(OCc2ccccc2)cc1OCc1ccccc1
Yield: 119.5 %

Procedure:
A mixture of 2,4-bis-benzyloxy-5-bromo-benzoic acid benzyl ester (10.0 g, 20 mmol), potassium isopropenyl trifluoroborate (4.0 g, 27.2 mmol) and n-butylamine (6.0 mL, 60 mmol) in 2-propanol/water (2:1, 200 mL) was purged with N2 for 5 minutes. To this mixture was added [1,1′-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II) (816 mg, 1.09 mmol) and the mixture was heated at reflux for 20 h. The mixture was allowed to cool to ambient then diluted with water (400 mL) and extracted with EtOAc (2×300 mL). The combined organic extracts were washed with 1M aqueous HCl, brine, dried (MgSO4), filtered through a plug of Celite and the filtrate reduced in vacuo to give the title compound (11.1 g) as a brown gum.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[S:11][CH:12]=2)[CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)C(C)C)C.[CH3:33][O:34][CH2:35]Cl.O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:13]([CH2:33][O:34][CH3:35])[S:14]([C:17]3[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=3)(=[O:16])=[O:15])[S:11][CH:12]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: COCCl
Reactant: Cc1ccc(S(=O)(=O)Nc2nc(-c3cccc(Br)c3)cs2)cc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCN(c1nc(-c2cccc(Br)c2)cs1)S(=O)(=O)c1ccc(C)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of 0.72 g of N-[4-(3-bromo-phenyl)-thiazol-2-yl]-4-methyl-benzenesulfonamide and 0.6 ml of ethyldiisopropylamine in 10 ml of methylene chloride was cooled to 0° C. and, after the addition of 0.13 ml of chloromethyl methyl ether, stirred at 0° C. for 2 h. Thereafter, the mixture was treated with 40 ml of water and extracted with methylene chloride. The organic phase was dried with magnesium sulphate and concentrated. After chromatography on 60 g of Kieselgel 60 with ethyl acetate/hexane (1:3) as the eluent the product-containing fractions were concentrated. 0.64 g of colorless N-[4-(3-bromo-phenyl)-thiazol-2-yl]-N-methoxymethyl-4-methyl-benzenesulfonamide, obtained in amorphous form, was processed without further purification.
Reaction SMILES: [CH2:1]([N:5]1[CH2:9][C@H:8]2[CH2:10][C:11](=O)[CH2:12][C@H:7]2[CH2:6]1)[CH2:2][CH2:3][CH3:4].Cl.[NH2:15][OH:16].C([O-])(=O)C.[Na+]>C(O)C.O>[CH2:1]([N:5]1[CH2:9][C@H:8]2[CH2:10][C:11](=[N:15][OH:16])[CH2:12][C@H:7]2[CH2:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN1C[C@H]2CC(=O)C[C@H]2C1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCCCN1C[C@H]2CC(=NO)C[C@H]2C1

Procedure:
A suspension of (3aS,6aR)-2-butylhexahydrocyclopenta[c]pyrrol-5-one (0.467 g, 2.58 mmol), hydroxylamine hydrochloride (0.430 g, 6.19 mmol) and sodium acetate (0.842 g, 6.19 mmol) in ethanol (21 ml) and water (7 ml) is heated to reflux for 1 hour. The ethanol is evaporated and the residue partitioned between saturated aqueous NaHCO3 and EtOAc. The organic phase is washed with brine, dried (MgSO4) and evaporated to afford (3aS,6aR)-2-butylhexahydrocyclopenta[c]pyrrol-5-one oxime, MH+197.