Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([N:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][CH:10]=[CH2:11])=[CH:6][CH:7]=1.[C:15]([NH:20][NH2:21])([O:17][CH2:18][CH3:19])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>O>[C:15]([NH:20][NH:21][C:2]1[N:3]=[N:4][C:5]([N:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][CH:10]=[CH2:11])=[CH:6][CH:7]=1)([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)NN
Reactant: C=CCN(CC=C)c1ccc(Cl)nn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: C=CCN(CC=C)c1ccc(NNC(=O)OCC)nn1
Temperature: 140 °C
Reaction time: 1 h

Procedure:
A mixture of 4.18 g (0.02 moles) 3-chloro-6-diallylaminopyridazine and 4.16 g (0.04 moles) monocarbethoxyhydrazine is warmed up to 140° C and kept at this temperature for 1 hour. The mixture is taken up with cool water and sodium carbonate is added until neutral pH. It is then extracted with methylene chloride, the organic extracts collected together, dried over sodium sulphate and concentrated. The residual oil is purified by chromatography on silica gel column, eluting with a mixture of chloroform-methanol 9.5:0.5. The unitary fractions on thin layer chromatography with the same Rf are collected together; the solvent is eliminated by evaporation and a yellow oil formed by a 3-(2-carbethoxyhydrazino)-6-diallylaminopyridazine is obtained.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1.Cl[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1
Reactant: COC(=O)c1cc(F)ccc1B1OC(C)(C)C(C)(C)O1
Reactant: Clc1ncccn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: COC(=O)c1cc(F)ccc1-c1ncccn1
Temperature: 74 °C
Reaction time: 8 h
Yield: 35 %

Procedure:
To a 250 mL round-bottomed flask, was added 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (5.9 g, 21.06 mmol) in 2-methyl-THF (50 mL). To the resulting solution was added 2-chloropyrimidine (2.9 g, 25.28 mmol), sodium carbonate (6.7 g, 63.19 mmol), and water (17 mL). The mixture was degassed for 30 minutes. PdCl2(dppf)-dcm adduct (CAS#72287-26-4) (0.688 g, 0.843 mmol) was added and the reaction mixture was degassed once more for 30 minutes. The reaction mixture was warmed to 74° C. and stirred overnight. To the resulting solution was added diethyl ether (100 mL) and water (100 mL). The layers were thoroughly mixed then separated. The aqueous layer was extracted with additional diethyl ether (100 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to a brown crude material (5.85 g, 49% desired, 2.87 actual product). The crude product was further purified through recrystallization in 10% EtOAc/hexanes. The mixture was warmed to 70° C. and cooled slowly to room temperature. After filtration, the desired product was obtained as a brown solid (1.72 g actual product, 35% yield overall after recrystallization.) 1H NMR (400 MHz, CDCl3): 8.78 (d, J=4.9 Hz, 2H), 8.09 (dd, J=8.7, 5.5 Hz, 1H), 7.39 (dd, J=8.6, 2.7 Hz, 1H), 7.30-7.20 (m, 2H), 3.77 (s, 3H).
Reaction SMILES: [C:1]1([CH3:10])[C:2]([N:7]=[C:8]=[O:9])=[CH:3][CH:4]=[CH:5][CH:6]=1.[CH3:11][N:12]([CH3:14])[NH2:13]>C1(C)C=CC=CC=1>[CH3:11][N:12]([CH3:14])[NH:13][C:8]([NH:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH3:10])=[O:9]
Reactant: CN(C)N
Reactant: Cc1ccccc1N=C=O
Solvent: Cc1ccccc1
Product: Cc1ccccc1NC(=O)NN(C)C
Temperature: 5 °C
Reaction time: 0.17 h

Procedure:
o-Tolyl isocyanate (10.0 g) was dissolved in 75 mL toluene under N2. The solution was cooled to 5° C. and to this was slowly added a solution in toluene of 1,1-dimethylhydrazine (5.7 mL). After addition, the ice-bath was removed and the resulting slurry allowed to stir an additional 10 minutes. The solid was filtered off rinsing successively with hexane, a small amount of 20% diethylether/hexane, then hexanes again. This afforded 11.1 g (77%) of the title compound of Step A. 1 H NMR (CDCl3) δ8.1 (bs,1H), 7.94 (d,1H), 7.21-7.15 (m,3H), 6.99 (t,1H), 5.23 (bs,1H), 2.63 (s,6H) 2.27 (s,3H).
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[C:5]([O-:8])(=[O:7])[CH3:6].[C:9]([O-:12])(=[O:11])[CH3:10].C([O-])(=O)C.[Pb+4:17].[Br:18][C:19]1[CH:24]=[C:23]([CH2:25][CH3:26])[C:22](B(O)O)=[C:21]([CH2:30][CH3:31])[CH:20]=1>>[C:1]([O-:4])(=[O:3])[CH3:2].[C:5]([O-:8])(=[O:7])[CH3:6].[C:9]([O-:12])(=[O:11])[CH3:10].[Br:18][C:19]1[CH:24]=[C:23]([CH2:25][CH3:26])[C:22]([Pb+3:17])=[C:21]([CH2:30][CH3:31])[CH:20]=1
Reactant: [Pb+4]
Reactant: CCc1cc(Br)cc(CC)c1B(O)O
Agent: CC(=O)[O-]
Product: CCc1cc(Br)cc(CC)c1[Pb+3]
Temperature: 60 °C
Yield: 44.1 %

Procedure:
To a mixture of lead tetraacetate (9.5 g, 0.02 mol) and mercuric diacetate (0.25 g, 0.78 mmol), thoroughly flushed with nitrogen, is added anhydrous chloroform (25 ml) and toluene (25 ml). This mixture is warmed to 60° C. and 4-bromo-2,6-diethylphenylboronic acid (5 g, 0.019 mol) is added in one portion and the mixture is stirred and heated at this temperature for 4 hours. After cooling in an ice bath, the mixture is filtered through a plug of diatomaceous earth and the filtrate is concentrated to approximately a quarter of its volume. Hexane is added to induce crystallization and the solvents evaporated under reduced pressure. Trituration with hexane gives 4-bromo-2,6-diethylphenyllead triacetate (5 g).
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:21])[NH:6][C:7](=[O:20])[NH:8][C:9]=1[C:10](=[O:19])[C:11]1[CH2:12][C:13](=[CH2:18])[CH2:14][C:15](=[CH2:17])[CH:16]=1)([CH3:3])[CH3:2].C1(C)C(S(O[CH2:32][CH2:33][CH:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)(=O)=O)=CC=CC=1>>[CH2:35]1[CH2:36][CH2:37][CH2:38][CH:34]1[CH:33]([N:8]1[C:9]([C:10](=[O:19])[C:11]2[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=2)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:21])[NH:6][C:7]1=[O:20])[CH3:32]
Reactant: Cc1ccccc1S(=O)(=O)OCCC1CCCC1
Reactant: C=C1C=C(C(=O)c2[nH]c(=O)[nH]c(=O)c2C(C)C)CC(=C)C1
Product: Cc1cc(C)cc(C(=O)c2c(C(C)C)c(=O)[nH]c(=O)n2C(C)C2CCCC2)c1
Yield: 24.9 %

Procedure:
5-Isopropyl-6-(3,5-dimethlylbenzoyl)-2,4-pyrimidinedione and (2-cyclopentyl)ethyl toluenesulfonate were reacted by the same method with example 44 to obtain the titled compound (95 mg).
Reaction SMILES: S(=O)(=O)(O)O.[CH2:6]([NH:13][C:14](=[O:21])[C:15](OC)(OC)[CH3:16])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C([O-])(O)=O.[Na+]>>[CH3:16][C:15]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[N:13][C:14]=1[OH:21]
Reactant: COC(C)(OC)C(=O)NCc1ccccc1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: Cc1c(O)ncc2ccccc12
Temperature: 55 °C
Reaction time: 8 h

Procedure:
Concentrated sulfuric acid (18 M; 6.0 mL) was added to N-benzyl-2,2-dimethoxypropionamide (1.38 g, 6.18 mmol) at ambient temperature, and the solution was stirred at ambient temperature for 30 min and at 55° C. overnight. The reaction mixture was added to ≈100 mL of ice, and the pH of the yellow solution was adjusted to 7-8 with NaHCO3 solution. Small amounts of a brown solid that precipitated very soon during the addition (pH was still <2) were filtered off, and neutralization was continued. The yellow precipitate was filtered off, washed with water, and dried in vacuo, giving the title compound as yellow solid. It was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ=10.6 (very brs, 1H), 8.74 (s, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.83 (dd, J=0.8, 8.6 Hz, 1H), 7.61 (ddd, J=1.6, 6.4, 8.4 Hz, 1H), 7.31 (ddd, J=0.8, 6.4, 8.0 Hz, 1H), 2.37 (d, J=0.4 Hz, 3H). MS(ES+): m/z=160.10 (100) [MH+]. HPLC: tR=2.3 min (polar—5 min, ZQ3).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[C:5]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=1)(=[O:7])[CH3:6]>CC(C)=O.O>[C:5]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([S:15]([N:1]=[N+:2]=[N-:3])(=[O:17])=[O:16])=[CH:13][CH:14]=1)(=[O:7])[CH3:6]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)Nc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.4 %

Procedure:
Sodium azide (7.8 g, 120 mmol) was charged in a 1 L round bottom flask with water. 4-Acetamidobenzene-1-sulfonyl chloride (23.4 g, 100 mmol) was dissolved in acetone, and this solution was slowly added to the solution of sodium azide. The reaction was then stirred for 16 hours at room temperature and diluted with water. The acetone was then removed. The solid was filtered to give 4-acetamidobenzenesulfonyl azide (21 g, 87%) as a white solid.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([S:19][CH3:20])=[CH:16][CH:17]=3)[CH:12]=[C:11]2[CH:21]([C:23]2[O:27][C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:25][CH:24]=2)O)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)C.C(O)(=O)C.[C].[Pd]>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([S:19][CH3:20])=[CH:16][CH:17]=3)[CH:12]=[C:11]2[CH2:21][C:23]2[O:27][C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:25][CH:24]=2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1ccc(C(O)c2cc3cc(SC)ccc3n2S(=O)(=O)c2ccccc2)o1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)c1ccc(Cc2cc3cc(SC)ccc3n2S(=O)(=O)c2ccccc2)o1
Temperature: 50 °C
Reaction time: 15 h
Yield: 52.8 %

Procedure:
To a solution of the compound obtained in Example 30 (2) (0.3586 g) in ethanol (8 ml), acetic acid (1 ml) and 10% palladium carbon (0.3586 g) were added and the mixture was stirred at 50° C. for 15 hours under hydrogen atmosphere. The reaction solution was filtered. The filtrate was concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain 0.183 g of the desired product.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]([CH3:13])[CH2:11][OH:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.S(=O)(=O)=O.P([O-])(O)(O)=O.[K+]>CS(C)=O>[Si:1]([O:8][CH2:9][C@H:10]([CH3:13])[CH:11]=[O:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: C[C@H](CO)CO[Si](C)(C)C(C)(C)C
Agent: O=P([O-])(O)O
Agent: O=S(=O)=O
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: C[C@H](C=O)CO[Si](C)(C)C(C)(C)C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 82.7 %

Procedure:
(R)-(+)-3-(t-Butyldimethylsilyloxy)-2-methyl-1-propanol (3.0 g; 14.7 mmol) was added to a mixture of dimethylsulfoxide (20 ml) and triethylamine (13.4 ml), and a solution of the pyridine complex of sulfur trioxide (6.9 g; 43.3 mmol) in dimethylsulfoxide (20 ml) was added thereto at a temperature below 20° C. under stirring. Stirring was continued for 10 minutes, and an aqueous solution (80 ml) of 2M potassium dihydrogenphosphate and ice (40 g) were added thereto to stop the reaction. Insoluble materials were removed by filtration, and the filtrate was extracted with hexane (100 ml) three times. The organic layer was washed successively with water and aqueous sodium chloride and dried over anhydrous sodium sulfate. Removal of the solvent by distillation under reduced pressure gave (S)-(+)-3-(t-butyldimethylsilyloxy)-2-methylpropanal (2.46 g; yield, 81%) as a colorless oil. The NMR spectrum of this product was identical to that of the product as obtained in Reference Example 2-1.
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][N:5]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:19]=[C:18]([CH:20]=O)[CH:17]=[CH:16][N:15]=2)[CH2:4][CH2:3]1.[F:22][C:23]1[C:24]([CH3:31])=[C:25]([NH2:30])[C:26]([NH2:29])=[CH:27][CH:28]=1>CN(C=O)C>[F:22][C:23]1[CH:28]=[CH:27][C:26]2[NH:29][C:20]([C:18]3[CH:17]=[CH:16][N:15]=[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][N:5]4[CH2:6][CH2:7][CH2:8][N:2]([CH3:1])[CH2:3][CH2:4]4)[CH:19]=3)=[N:30][C:25]=2[C:24]=1[CH3:31]
Reactant: Cc1c(F)ccc(N)c1N
Reactant: CN1CCCN(CCCCOc2cc(C=O)ccn2)CC1
Solvent: CN(C)C=O
Product: Cc1c(F)ccc2[nH]c(-c3ccnc(OCCCCN4CCCN(C)CC4)c3)nc12
Yield: 5.6 %

Procedure:
5-Fluoro-4-methyl-2-{2-[4-(4-methyl-[1,4]diazepan-1-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole. To a stirred solution of 2-[4-(4-methyl-[1,4]diazepan-1-yl)-butoxy]-isonicotinonitrile (1.0 g, 3.47 mmol, 1.0 equiv) in toluene (5.0 mL) at 0° C. was added 1.0 M diisobutylaluminum hydride in toluene (5.2 mL, 5.2 mmol, 1.5 equiv). After 3 h, methanol (9 mL) and 1.0 M H2SO4 (10 mL) were added. The mixture was stirred for 30 min, and then 1.0 M NaOH (10 mL) was added, followed by satd. aq. sodium potassium tartrate (40 mL) and dichloromethane (100 mL). After stirring for 30 min, the mixture was extracted with chloroform (3×50 mL) and the combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was partially purified by Method 2 to afford 268 mg of a mixture of 2-[4-(4-methyl-[1,4]diazepan-1-yl)-butoxy]-pyridine-4-carbaldehyde and several other unidentified products. A portion of the impure 2-[4-(4-methyl-[1,4]diazepan-1-yl)-butoxy]-pyridine-4-carbaldehyde (63 mg), 4-fluoro-3-methyl-benzene-1,2-diamine (30.3 mg), and Na2S2O5 (53.4 mg) were stirred in DMF (3 mL) at 90° C. for 18 h. The reaction mixture was loaded directly on silica gel and purified by Method 2, which afforded 5.0 mg of the title compound. MS (electrospray): mass calculated for C23H30FN5O, 411.24; m/z found, 412.5 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.27 (dd, J=4.8, 0.5 Hz, 1H), 7.63 (dd, J=4.0, 1.4 Hz, 1H), 7.52-7.40 (m, 2H), 7.10-7.01 (m, 1H), 4.27 (t, J=6.3 Hz, 2H), 2.86-2.77 (m, 4H), 2.77-2.68 (m, 4H), 2.65-2.57 (m, 2H), 2.53 (s, 3H), 2.37 (s, 3H), 1.90-1.66 (m, 6H).
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([O:14][C:15]([N:17]1[C:25]2[C:20](=[CH:21][C:22]([NH2:26])=[CH:23][CH:24]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].C(N(CC)CC)C>ClCCl>[C:10]([O:14][C:15]([N:17]1[C:25]2[C:20](=[CH:21][C:22]([NH:26][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:23][CH:24]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]
Reactant: CC(C)(C)OC(=O)N1CCc2cc(N)ccc21
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCc2cc(NC(=O)c3ccccc3)ccc21
Reaction time: 0.25 h
Yield: 100 %

Procedure:
Benzoyl chloride (305 μL, 1.5 eq.) was added to a solution of 5-amino-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (407 mg, 1.74 mmol) and triethylamine (1.2 mL, 5.0 eq.) in dichloromethane (5 mL) at 0° C. and the resulting mixture was stirred for 15 min. The reaction was then quenched by addition of sat. NaHCO3 and the mixture was extracted with 3×EtOAc. The combined extracts were dried over Na2SO4, filtered, concentrated and the product was purified by chromatography (20 to 100% EtOAc-hexanes) to give 5-benzoylamino-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (588 mg, 100%).
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[NH2:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[CH:25][CH:24]=1>CN(C=O)C>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:20][CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([S:29]([NH2:32])(=[O:30])=[O:31])=[CH:27][CH:28]=2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Reactant: NCCc1ccc(S(N)(=O)=O)cc1
Solvent: CN(C)C=O
Product: CC(C)(C)N1C(=O)C(NCCc2ccc(S(N)(=O)=O)cc2)=C(c2ccccc2)S1(=O)=O
Temperature: 130 °C
Yield: 45.4 %

Procedure:
2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.175 g, 0.58 mmol), 4-(2-aminoethyl)benzenesulfonamide (0.139 g, 0.69 mmol) and TEA (0.23 g, 2.31 mmol) was dissolved in dry DMF (3 ml) and heated in a microwave reactor at 130° C. for 30 mins. The reaction mixture was purified by preparative HPLC to yield the title compound (0.122 g, 45%). 1H NMR (500 MHz, d8-THF): δ 7.70-7.65 (m, 2H), 7.58-7.52 (m, 2H), 7.51-7.45 (m, 3H), 6.90-6.84 (m, 2H), 6.53-6.47 (m, 1H), 6.38-6.34 (m, 1H), 3.19-3.12 (m, 2H), 2.64-2.58 (m, 1H), 1.70 (s, 9H); 13C NMR (125 MHz, d8-THF): δ 159.7, 143.3, 142.4, 135.2, 132.0, 129.4, 128.8, 128.6, 126.4, 126.3, 107.2, 60.6, 44.7, 35.6, 27.0; Mass Spectrum: M−H+ 464.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([CH3:19])[O:7][C@@H:6]1[O:20][CH2:21][C@@H:22]([C:24]([OH:26])=[O:25])[NH2:23])(=[O:3])[CH3:2].C1C(=O)N([O:34][C:35]([O:37][CH2:38][CH:39]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[C:45]3[C:40]2=[CH:41][CH:42]=[CH:43][CH:44]=3)=O)C(=O)C1>N1C=CC=CC=1>[CH:50]1[C:51]2[CH:39]([CH2:38][O:37][C:35]([NH:23][C@H:22]([C:24]([OH:26])=[O:25])[CH2:21][O:20][C@H:6]3[O:7][C@@H:8]([CH3:19])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:5]3[O:4][C:1](=[O:3])[CH3:2])=[O:34])[C:40]3[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:46]=2[CH:47]=[CH:48][CH:49]=1
Reactant: O=C(OCC1c2ccccc2-c2ccccc21)ON1C(=O)CCC1=O
Reactant: CC(=O)O[C@H]1[C@H](OC(C)=O)[C@@H](OC[C@H](N)C(=O)O)O[C@@H](C)[C@H]1OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1[C@H](OC(C)=O)[C@@H](OC[C@H](NC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)O)O[C@@H](C)[C@H]1OC(C)=O
Yield: 59.8 %

Procedure:
A solution of 3-O-(2,3,4-tri-O-acetyl-β-L-fucopyranosyl)-L-serine (FIG. 1D) (209.6 mg, 0.82 mmol) and Fmoc N-hydroxysuccinimide ester (9-fluorenylmethyl-N-succinimidyl carbonate) (375.7 mg, 1.63 mmol) in dry pyridine (25 ml) was stirred for 15 h at room temperature. Evaporation and co-evaporation of the reaction mixture with toluene left a syrup which was purified by chromatography on silica gel using dichloromethane-methanol 95:5 as eluent. Pure N-(9-Fluorenylmethyloxycarbonyl)-3-O-(2,3,4-tri-O-acetyl-β-L-fucopyrano syl)-L-serine (294 mg, 88%) was obtained as a white powder, Rf =0.40 (9:1, dichloromethane:methanol). 1H-NMR (CD3OD): ε 7.82-7.25 (m, 8 H, aromatic), 5.18 (m, 1 H, sec. order, H-4), 5.08-4.98 (m, 2 H, sec. order, H-2, 3), 4.50 (d, 1 H, J1,2 =7.5 Hz, H-1), 4.44-3.95 (complex, 6 H, Fmoc-H and serine H's), 3.83 (q, J5,6 =6.25 Hz, H-6), 2.11, 1.99 and 1.92 (each s, 3 H, Ac), 1.10 (d, 3 H, H-6). 13C: ε 102.6 (C-1), 72.5, 71.8 and 70.3 (C-2, 3 and 4), 71.5 and 67.9 (FMOC and serine CH2), 56.5 (serine CHN), 20.8, 20.5 and 20.4 (COCH3), 16.3 (C-6).
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]2[CH:8]=[CH:9][C:10]([CH2:16]P(OCC)(OCC)=O)=[N:11][C:12]=2[CH:13]=[CH:14][CH:15]=1)=[O:5])C.[H-].[Na+].[O:27]1[CH2:32][CH2:31][N:30]([C:33]2[C:34]3[N:35]([C:39]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[C:40]([CH:42]=O)[N:41]=3)[N:36]=[CH:37][CH:38]=2)[CH2:29][CH2:28]1>C1COCC1>[O:27]1[CH2:28][CH2:29][N:30]([C:33]2[C:34]3[N:35]([C:39]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)=[C:40](/[CH:42]=[CH:16]/[C:10]4[CH:9]=[CH:8][C:7]5[C:6]([C:4]([OH:3])=[O:5])=[CH:15][CH:14]=[CH:13][C:12]=5[N:11]=4)[N:41]=3)[N:36]=[CH:37][CH:38]=2)[CH2:31][CH2:32]1
Reactant: CCOC(=O)c1cccc2nc(CP(=O)(OCC)OCC)ccc12
Reactant: O=Cc1nc2c(N3CCOCC3)ccnn2c1-c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(O)c1cccc2nc(/C=C/c3nc4c(N5CCOCC5)ccnn4c3-c3ccccc3)ccc12
Temperature: 25 °C

Procedure:
A solution of compound 73d (119 mg, 0.339 mmol) in THF (6 mL) was treated with NaH (36.9 mg, 0.924 mmol) at 0° C. and the resulting mixture was allowed to warm to room temperature over 10 min. Compound 74a (95.0 mg, 0.308 mmol) was then added in one portion and the resultant mixture was heated to 55° C. for 1 h. The reaction was allowed to cool to rt, quenched with saturated sodium bicarbonate (2 mL) and extracted with DCM (10 mL). The DCM layer was separated, dried over Na2SO4, filtered, and concentrated, and the resultant residue was purified by flash column chromatography over silica gel (0-100% EtOAc/DCM) to afford compound 74b. Mass spectrum (LCMS, ESI pos.) Calcd. For C28H23N5O3 478.2 (M+H). found 478.1.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:18]([N:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH3:7]
Reactant: CCCCCCCCCCCCBr
Reactant: C1CCNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCCCCCCCCN1CCCC1
Temperature: 55 °C
Yield: 64.1 %

Procedure:
47 g pyrrolidine, 149.5 g 1-bromododecane and 83 g potassium carbonate were added to 560 mL acetone. The reaction mixture was heated at 55° C. for 24 hr, then filtered. Solvent was removed from the filtrate, yielding 92 g N-dodecylpyrrolidine. 80 g N-dodecylpyrrolidine and 52.6 g 1-bromo-3-chloropropane were dissolved in 133 mL methanol and the reaction mixture was heated at 65° C. for 18 hr. After cooling to room temperature, methanol was removed under reduced pressure. The residue was poured into 2 L diethylether with stirring and the mixture was allowed to stand for another 6 hr. The white precipitate thus formed was filtered and was dried at 40° C. under a vacuum for 24 hr yielding 85 g (3-chloropropyl)dodecylpyrrolidinium bromide as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:3]=1[C:4](O)=[O:5].CN(C=O)C.C(Cl)(=O)C([Cl:20])=O>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:3]=1[C:4]([Cl:20])=[O:5]
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cc1cccc(Cl)c1C(=O)O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1cccc(Cl)c1C(=O)Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 2-chloro-6-methylbenzoicacid (339) (300 g, 1.76 mol, 1.0 eq) and DMF (0.5 mL) in DCM (500 mL) at RT, oxalyl chloride (249 g, 1.92 mol, 1.1 eq) was added slowly (over 5 min). The resulting mixture was stirred at RT for 2 h and then concentrated in vacuo to afford 2-chloro-6-methylbenzoyl chloride (340) which was used directly in the next step.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Si]([O:14][CH2:15][C@H:16]([CH3:36])[O:17][C:18]1[CH:19]=[C:20]([CH:32]=[C:33]([OH:35])[CH:34]=1)[C:21]([NH:23][C:24]1[CH:28]=[CH:27][N:26]([CH:29]([CH3:31])[CH3:30])[N:25]=1)=[O:22])(C(C)(C)C)(C)C.[Cl:37][C:38]1[CH:39]=[C:40]([CH:47]=[CH:48][C:49]=1F)[C:41]([N:43]1[CH2:46][CH2:45][CH2:44]1)=[O:42]>C(#N)C>[N:43]1([C:41]([C:40]2[CH:47]=[CH:48][C:49]([O:35][C:33]3[CH:32]=[C:20]([CH:19]=[C:18]([O:17][C@@H:16]([CH3:36])[CH2:15][OH:14])[CH:34]=3)[C:21]([NH:23][C:24]3[CH:28]=[CH:27][N:26]([CH:29]([CH3:30])[CH3:31])[N:25]=3)=[O:22])=[C:38]([Cl:37])[CH:39]=2)=[O:42])[CH2:46][CH2:45][CH2:44]1
Reactant: CC(C)n1ccc(NC(=O)c2cc(O)cc(O[C@@H](C)CO[Si](C)(C)C(C)(C)C)c2)n1
Reactant: O=C(c1ccc(F)c(Cl)c1)N1CCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)n1ccc(NC(=O)c2cc(Oc3ccc(C(=O)N4CCC4)cc3Cl)cc(O[C@@H](C)CO)c2)n1
Temperature: 160 °C
Yield: 79.7 %

Procedure:
Potassium carbonate (182 mg, 1.32 mmol) was added to a mixture of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-hydroxy-N-(1-isopropyl-1H-pyrazol-3-yl)benzamide (350 mg, 0.81 mmol) and 1-(3-Chloro-4-fluorobenzoyl)azetidine (181 mg, 0.85 mmol) in acetonitrile (5 mL) and the stirred mixture heated at 160° C. in a ‘Smith Creator Microwave’ for 15 hours. The mixture was allowed to reach ambient temperature and pressure and reduced in vacuo. The residual oil was partitioned between ethyl acetate (50 mL) and water (50 mL). The ethyl acetate layer was separated, washed with brine, dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (331 mg)
Reaction SMILES: [C:1]1([NH:7][CH2:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:12]([N:14]=[C:15]=[O:16])[CH3:13]>C1(C)C=CC=CC=1>[C:1]1([N:7]2[CH2:8][C:9](=[O:11])[N:14]([CH2:12][CH3:13])[C:15]2=[O:16])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCN=C=O
Reactant: O=C(O)CNc1ccccc1
Solvent: Cc1ccccc1
Product: CCN1C(=O)CN(c2ccccc2)C1=O
Reaction time: 8 h
Yield: 41.6 %

Procedure:
A mixture of N-phenyl glycine (30.2 grams, 0.2 moles), ethylisocyanate (17.8 grams, 0.25 moles) and 30 ml of toluene was refluxed for 9 hours and allowed to stand overnight at room temperature (21° C.). The suspended product was collected by filtration and washed with toluene. After drying (21° C.) it was crystallized from ethanol to produce 17 grams (42% yield) of the above-identified product having a melting point of about 142° C.