Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:47]1([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.FC(F)(F)S(O[C:66]1[CH:75]=[CH:74][CH:73]=[C:72]2[C:67]=1[CH:68]=[CH:69][C:70]([CH3:76])=[N:71]2)(=O)=O>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:76][C:70]1[CH:69]=[CH:68][C:67]2[C:72](=[CH:73][CH:74]=[CH:75][C:66]=2[N:50]2[CH2:51][CH2:52][N:47]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:48][CH2:49]2)[N:71]=1
Reactant: Cc1ccc2c(OS(=O)(=O)C(F)(F)F)cccc2n1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: Cc1ccc2c(N3CCN(C(=O)OC(C)(C)C)CC3)cccc2n1
Temperature: 25 °C

Procedure:
A stirred mixture of Pd(OAc)2 (243 mg), CsCO3 (6.63 g), and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.01 g) in dry toluene (60 mL) was heated under reflux for 15 min, under argon. After cooling, a solution of tert-butyl piperazine-1-carboxylate (3.03 g, 16.3 mmol) and the 2-methylquinolin-5-yl trifluoromethane-sulfonate prepared in example 5 (3.95 g, 13.6 mmol) in toluene (100 mL) was added, and the resulting mixture was heated under reflux for 8 h. The reaction mixture was cooled to room temperature, concentrated to half of its value, and then quenched with saturated solution of NH4Cl (50 mL). The organic layer was separated, the aqueous layer was extracted with EtOAc, and the combined organic solutions were concentrated in vacuo. The residue was purified by column chromatography using CH2Cl2 as eluent. Yield: 4.29 g (96.6%), brown oil. Rf=0.64 (CH2Cl2-MeOH (19:1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[CH:13]=[CH:12][S:11][CH:10]=3)=[N:6][C:5]2=[C:14]([C:16]([OH:18])=O)[CH:15]=1.Cl.Cl.[NH2:21][C@H:22]1[CH:27]2[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]2)[CH2:23]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:24]12[CH2:29][CH2:28][CH:27]([CH2:26][CH2:25]1)[C@H:22]([NH:21][C:16]([C:14]1[CH:15]=[C:2]([Cl:1])[CH:3]=[C:4]3[O:8][C:7]([C:9]4[CH:13]=[CH:12][S:11][CH:10]=4)=[N:6][C:5]=13)=[O:18])[CH2:23]2
Reactant: N[C@@H]1CN2CCC1CC2
Reactant: O=C(O)c1cc(Cl)cc2oc(-c3ccsc3)nc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(N[C@@H]1CN2CCC1CC2)c1cc(Cl)cc2oc(-c3ccsc3)nc12
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 17.5 %

Procedure:
A mixture of 6-chloro-2-(thiophen-3-yl)benzo[d]oxazole-4-carboxylic acid (70 mg, 0.25 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (50 mg, 0.25 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (96 mg, 0.50 mmol) and 1-hydroxybenzotriazole (68 mg, 0.50 mmol) in DMF (2 mL) was stirred at room temperature for 5 min, then triethylamine (0.13 mL, 1.0 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The mixture was diluted with dichloromethane (20 mL), then washed with a saturated solution of sodium bicarbonate (10 mL). The aqueous layer was further extracted with dichloromethane (3×20 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) followed by recrystallization from acetonitrile to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-thiophen-3-ylbenzoxazole-4-carboxamide (17 mg, 18%) as a colorless crystal: 1H NMR (500 MHz, CDCl3) δ 9.41 (d, J=7.5 Hz, 1H), 8.23 (dd, J=3.0, 1.5 Hz, 1H), 8.16 (d, J=2.0 Hz, 1H), 7.73 (dd, J=5.0, 1.0 Hz, 1H), 7.68 (d, J=2.0 Hz, 1H), 7.52 (dd, J=5.0, 3.0 Hz, 1H), 4.29-4.25 (m, 1H), 3.49 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.10-2.83 (m, 4H), 2.77 (dd, J=14.0, 4.5 Hz, 1H), 2.15-2.11 (m, 1H), 2.04-1.98 (m, 1H), 1.78-1.70 (m, 2H), 1.60-1.51 (m, 1H); MS (ESI+) m/z 388 (M+H); HPLC>99% (AUC), tR=12.45 min.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[N:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[CH:18]1([CH:24]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH2:26][OH:27])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.O>CN(C=O)C.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:18]1(/[CH:24]=[C:25](\[C:2]2[CH:7]=[N:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][CH:3]=2)/[CH2:26][OH:27])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: CC1(C)OB(C(=CC2CCCCC2)CO)OC1(C)C
Reactant: CS(=O)(=O)c1ccc(Br)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: O
Product: CS(=O)(=O)c1ccc(/C(=C\C2CCCCC2)CO)cn1
Temperature: 80 °C
Reaction time: 18 h
Yield: 59.2 %

Procedure:
Add 5-bromo-2-methanesulfonyl-pyridine (0.47 g, 2.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (163 mg, 0.2 mmol), and Na2CO3 (2.5 mL, 2.0 M, 5.0 mmol) to a solution of 3-cyclohexyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-prop-2-en-1-ol (0.53 g, 2.2 mmol) in DMF (10 mL). Stir at 80° C. for 18 h, monitor completion of the reaction by LCMS. Treat the reaction mixture with water and extract 3 times with MTBE. Dry organic layers over sodium sulfate and remove solvents under vacuum to obtain 0.72 g crude product. Purification by silica gel chromatography, eluting with gradient from 10:0 to 8:2 dichloromethane:MTBE affords 350 mg (E)-3-cyclohexyl-2-(6-methanesulfonyl-pyridin-3-yl)-prop-2-en-1-ol. MS (m/e): 296 (M+H).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH:10]=[CH:9][O:8][C:7]=1[C:11]([C:13]1[N:14]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:15]2[C:20]([C:21]=1[NH2:22])=[CH:19][CH:18]=[C:17]([Cl:23])[CH:16]=2)=[O:12])(=[O:3])[CH3:2].[C:29](Cl)(=[O:33])[CH:30]([CH3:32])[CH3:31]>>[C:1]([O:4][CH2:5][C:6]1[CH:10]=[CH:9][O:8][C:7]=1[C:11]([C:13]1[N:14]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:15]2[C:20]([C:21]=1[NH:22][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])=[CH:19][CH:18]=[C:17]([Cl:23])[CH:16]=2)=[O:12])(=[O:3])[CH3:2]
Reactant: CCOC(=O)n1c(C(=O)c2occc2COC(C)=O)c(N)c2ccc(Cl)cc21
Reactant: CC(C)C(=O)Cl
Product: CCOC(=O)n1c(C(=O)c2occc2COC(C)=O)c(NC(=O)C(C)C)c2ccc(Cl)cc21

Procedure:
The title compound was prepared according to the procedure described in step 1 of Example 2 employing 2-(3-acetoxymethyl-2-furoyl)-3-amino-6-chloro-1-(ethoxycarbonyl)indole (step 1) and isobutyryl chloride.
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.C(N(CC)[C:16](Cl)=[S:17])C.Cl>C1(C)C=CC=CC=1>[N:1]([C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=1)=[C:16]=[S:17]
Reactant: CCN(CC)C(=S)Cl
Reactant: CCOC(=O)c1ccc(N)cc1
Agent: Cl
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(N=C=S)cc1
Yield: 74.5 %

Procedure:
In 500 ml of toluene was dissolved 82.5 g of ethyl p-aminobenzoate and after adding thereto 83.4 g of N,N-diethylthiocarbamoyl chloride, the mixture was refluxed for 8 hours. After ice cooling the reaction mixture, 100 ml of concentrated hydrochloric acid was added to the mixture and the toluene layer thus formed was collected and washed with water. After distilling off toluene under reduced pressure, the oily material thus formed was crystallized from methanol to provide 77.1 g of ethyl p-isothiocyanatobenzoate. The yield was 74.5% and the melting point was 52° C.
Reaction SMILES: [N:1]1([S:11]([C:14]2[N:15]=[N:16][CH:17]=[CH:18][CH:19]=2)(=[O:13])=[O:12])[C:10]2[CH:5]([CH2:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.FS(C1N=N[C:27]([O:30]C)=CC=1)(=O)=O.N1C2C(=CC=CC=2)CCC1>>[CH3:27][O:30][C:17]1[N:16]=[N:15][C:14]([S:11]([N:1]2[C:10]3[CH:5]([CH2:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3][CH2:2]2)(=[O:13])=[O:12])=[CH:19][CH:18]=1
Reactant: O=S(=O)(c1cccnn1)N1CCCC2CC=CC=C21
Reactant: COc1ccc(S(=O)(=O)F)nn1
Agent: c1ccc2c(c1)CCCN2
Product: COc1ccc(S(=O)(=O)N2CCCC3CC=CC=C32)nn1
Temperature: 140 °C
Yield: 73 %

Procedure:
3-Methoxy-6-(tetrahydroquinoline-1-sulfonyl-pyridazine. A mixture of 3-fluorosulfonyl-6-methoxypyridazine (2 mmol, 384 mg) and tetrahydroquinoline (4 mmol, 532 mg) was heated at 140° C. for two hours. The reaction mixture was cooled, extracted with EtOAc (20 mL), and the EtOAc extract was dried, filtered and evaporated to obtain 3-methoxy-6-(tetrahydroquinoline-1-sulfonyl)-pyridazine (73%, 451 mg).
Reaction SMILES: [CH3:1][N:2]1[C:10]([CH:11]=O)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:19]1[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]1[CH3:28])=[N:6][C:7]=2[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[CH3:29][C:30]1([CH2:34][NH2:35])[CH2:33][O:32][CH2:31]1>>[CH3:1][N:2]1[C:10]([CH2:11][NH:35][CH2:34][C:30]2([CH3:29])[CH2:33][O:32][CH2:31]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:19]1[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]1[CH3:28])=[N:6][C:7]=2[N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1
Reactant: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C=O)n(C)c2n1
Reactant: CC1(CN)COC1
Product: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CNCC3(C)COC3)n(C)c2n1

Procedure:
Following General Procedure L for reductive amination, 9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purine-8-carbaldehyde and (3-methyloxetan-3-yl)methanamine were reacted to give 259. [M+H]+ 463.6.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([OH:14])=O)=[CH:6]2.[CH2:15]([NH:18][CH2:19][CH2:20][CH3:21])[CH2:16][CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(OCC)C>[CH2:15]([N:18]([CH2:19][CH2:20][CH3:21])[C:12]([C:7]1[NH:8][C:9]2[C:5]([CH:6]=1)=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)=[O:14])[CH2:16][CH3:17]
Reactant: COc1ccc2[nH]c(C(=O)O)cc2c1
Reactant: CCCNCCC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCCN(CCC)C(=O)c1cc2cc(OC)ccc2[nH]1
Temperature: 25 °C
Reaction time: 12 h
Yield: 73.7 %

Procedure:
To a solution of 5-methoxyindole-2-carboxylic acid (500 mg, 2.62 mmol) in 13 mL of N,N-dimethylformamide was added di-n-propylamine (1.07 mL, 7.8 mmol) and HATU (1.09 g, 2.88 mmol) at 0° C. After the reaction mixture was stirred at room temperature for 12 h, the reaction mixture was diluted with diethyl ether, and washed with water and brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography to obtain the title compound (0.53 g, 74%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[N:10]=[C:11]([C:15]([OH:17])=O)[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=[N:33][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32]C1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1(N)CCCC1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[N:10]=[C:11]([C:15](=[O:17])[NH:33][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)[N:12]([CH3:14])[CH:13]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: Cn1cc(NC(=O)OC(C)(C)C)nc1C(=O)O
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: NC1CCCC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cn1cc(NC(=O)OC(C)(C)C)nc1C(=O)NC1CCCC1
Reaction time: 24 h
Yield: 37.3 %

Procedure:
To a stirred suspension of 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-imidazole-2-carboxylic acid (724 mg, 3.0 mmol) in DMF (6 mL) is added TBTU (1.16 g, 3.6 mmol). After 15 min cyclopentylamine (0.44 mL, 4.5 mmol) is added. After 20 h an additional portion of cyclopentylamine (0.44 mL, 4.5 mmol) is added, and stifling continued for a further 24 h. The mixture is diluted with EtOAc and washed in turn with 1M aqueous NaHSO4, Na2CO3 and brine. The organic layer is dried (MgSO4) and evaporated. The crude material is purified by column chromatography using a gradient of 10-100% EtOAc/heptane to afford the title compound (345 mg, 37%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]([CH3:15])[CH3:14])=[C:6]([CH:8]=[N:9][CH:10]2[CH2:12][CH2:11]2)[CH:7]=1>[Pt].CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]([CH3:15])[CH3:14])=[C:6]([CH:7]=1)[CH2:8][NH:9][CH:10]1[CH2:12][CH2:11]1
Reactant: CC(C)c1ccc(Cl)cc1C=NC1CC1
Agent: [Pt]
Solvent: CO
Product: CC(C)c1ccc(Cl)cc1CNC1CC1
Reaction time: 8 h
Yield: 94.6 %

Procedure:
Platinum on activated carbon (5 g, 5% Pt, dry) was added to a solution of N-[(5-chloro-2-isopropylphenyl)methylene]cyclopropanamine (III) (160.8 g, 0.725 mol) in methanol (1350 ml). The reaction vessel was subsequently flushed with nitrogen and pressurized with 6 bar of hydrogen at a maximum of 25° C. for 8 hours. The contents of the autoclave were filtered through Celite, washed with methanol and the solvent was distilled off under reduced pressure. N-(5-Chloro-2-isopropylbenzyl)cyclopropanamine of the formula (I) (153.5 g, 97.1 GC-% by area, 91.9% of theory) was obtained as a light-yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][NH:5][CH2:6][C:7]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[CH:9][C:8]=1[O:15][CH3:16].Br[C:22]#[N:23].Cl.[C:25]([OH:28])(=[O:27])[CH3:26]>C(O)C.O1CCOCC1.CCCCC>[C:25]([OH:28])(=[O:27])[CH3:26].[CH3:16][O:15][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([O:13][CH3:14])[C:7]=1[CH2:6][N:5]1[CH2:4][C:3]2[C:2](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:1]=[C:22]1[NH2:23]
Reactant: COc1cccc(OC)c1CNCc1ccccc1N
Reactant: N#CBr
Agent: Cl
Solvent: CCO
Solvent: C1COCCO1
Solvent: CCCCC
Product: COc1cccc(OC)c1CN1Cc2ccccc2N=C1N

Procedure:
A mixture of 2.78 g (10.21 mmol) (2-aminobenzyl)(2,6-dimethoxybenzyl)amine and 1.5 g BrCN in 60 mL ethanol was heated at reflux for 10 hours. After evaporation, the resulting residue was dissolved in a small amount of dioxane, mixed with one equivalent 4N HCl in dioxane, the resulting solids were filtered out and dried. The resulting crude product was purified by MPLC (silica gel: Bischoff Prontoprep 60-2540-C18E, 32 μm; mobile phase: CH3CN/H2O+0.1% acetic acid), the resulting product was then dissolved in acetone and converted to the corresponding acetate by adding one equivalent of glacial acetic acid. Stirring the resulting solids [in] n-pentane and drying yielded 580 mg white solids.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH3:9][N:10]1[CH:14]=[CH:13][CH:12]=[C:11]1[C:15]#[N:16]>CN(C)C=O>[Br:1][C:13]1[CH:12]=[C:11]([C:15]#[N:16])[N:10]([CH3:9])[CH:14]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cn1cccc1C#N
Solvent: CN(C)C=O
Product: Cn1cc(Br)cc1C#N
Temperature: 25 °C
Reaction time: 15 h

Procedure:
N-Bromosuccinimide (6.2 g, 34.9 mmol) is added to a solution of 1-methyl-1H-pyrrole-2-carbonitrile (3.7 g, 34.9 mmol) in N,N-dimethylformamide (150 mL). The solution is stirred for 15 hours at ambient temperature. Another amount of N-bromosuccinimide (2.0 g, 11 mmol) is added and the mixture is stirred for 3 hours. Silica (7 g) is then added and the suspension is then evaporated to dryness. The material pre-absorbed onto the silica is placed on a silica gel column and the product is purified by chromatography over silica gel using ethyl acetate and heptane as eluants to obtain the expected product in the form of a solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH2:9])[CH:5]=[CH:6][CH:7]=1.Cl[C:11]1[CH:21]=[C:15]2[N:16]([CH3:20])[CH2:17][CH2:18][CH2:19][N:14]2[C:13](=[O:22])[N:12]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][NH:9][C:11]1[CH:21]=[C:15]2[N:16]([CH3:20])[CH2:17][CH2:18][CH2:19][N:14]2[C:13](=[O:22])[N:12]=1
Reactant: NCc1cccc(F)c1
Reactant: CN1CCCn2c1cc(Cl)nc2=O
Product: CN1CCCn2c1cc(NCc1cccc(F)c1)nc2=O

Procedure:
The title compound or its salt was prepared by a procedure similar to that described for E59 starting from (3-fluorophenyl)methanamine and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH2:10][CH2:11][CH3:12])[C:4](=[O:13])[C:3]=1[N:14]=O.[NH4+]=S.[CH:18]([C:20]1[CH:30]=[CH:29][C:23]([CH:24]=[CH:25][C:26]([OH:28])=[O:27])=[CH:22][CH:21]=1)=O>>[CH3:8][N:7]1[C:2]2[NH:1][C:18]([C:20]3[CH:30]=[CH:29][C:23](/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27])=[CH:22][CH:21]=3)=[N:14][C:3]=2[C:4](=[O:13])[N:5]([CH2:10][CH2:11][CH3:12])[C:6]1=[O:9]
Reactant: CCCn1c(=O)c(N=O)c(N)n(C)c1=O
Reactant: O=Cc1ccc(C=CC(=O)O)cc1
Product: CCCn1c(=O)c2nc(-c3ccc(/C=C/C(=O)O)cc3)[nH]c2n(C)c1=O

Procedure:
6-Amino-1-methyl-3-propyl-2,4(1H,3H)pyrimidinedione (V. Papesch and E. F. Schroeder, J.Org.Chem. 1951, 16, 1879) (5.53 g, 27.5 mmol) was dissolved in hot 95% ethanol (20 ml)-water (120 ml). Sodium nitrite (2.32 g) and glacial acetic acid (2.4 ml) were added. The resulting mixture was allowed to cool to room temperature. Orange-pink crystals were filtered off and dried at 50° C. under vacuum to give purple crystals of 6-amino-1-methyl-5-nitroso-3-propyl-2,4 (1H,3H)-pyrimidinedione (2.92 g, 80%); mp 250° dec. Analysis for (C8H12N4O3): C,45.28; H,5.70; N,26.40. Found: C,45.12; H,5.74; N,26.34. 5,6-Diamino-1-methyl-3-propyl-2,4(1H,3H)pyrimidinedione was prepared freshly from 6-amino-1-methyl-5-nitroso-3-propyl-2,4(1H,3H)pyrimidinedione by ammonium sulfide reduction using the method of V. Papesch, M. Grove, and E. F. Schroeder (U.S. Pat. No. 2 602 795). This diamine (2.00 g, 10.0 mmol) was condensed with 4-formylcinnamic acid (1.76 g, 10.0 mmol) by the procedure of Example 2 to give the title compound as an ivory powder, after crystallization from N,N-dimethylformamide-water; mp>300° C. Analysis for (C18H18N4O4.1/5 DMF): C,60.54; H,5.30; N,15.94. Found: C,60.52; H,5.22; N,16.03.
Reaction SMILES: [O:1]([C@@H:13]1[C@@H:19]([CH2:20][OH:21])[O:18][CH:16]([OH:17])[C@H:15]([NH2:22])[C@H:14]1[O:23][C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]1O)[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].CC1OC(OP(OP(OCC2OC(N3C4NC(N)=NC(=O)C=4N=C3)C(O)C2O)(O)=O)(O)=O)C(O)C(O)C1O>>[O:1]([C@@H:13]1[C@@H:19]([CH2:20][OH:21])[O:18][CH:16]([OH:17])[C@H:15]([NH2:22])[C@H:14]1[OH:23])[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: C[C@@H]1O[C@@H](O[C@H]2[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)[C@@H](CO)OC(O)[C@@H]2N)[C@@H](O)[C@H](O)[C@@H]1O
Agent: CC1OC(OP(=O)(O)OP(=O)(O)OCC2OC(n3cnc4c(=O)nc(N)[nH]c43)C(O)C2O)C(O)C(O)C1O
Product: N[C@H]1C(O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@@H]1O

Procedure:
Synthesis of Galβ1-4(Fucα1-3)GlcNH2 βSEt. Galβ1-4GlcNH2 βSEt is prepared as described above and used directly or after isolation as acceptor for a α1-3-fucosyltransferase (e.g. EC 2.4.1.152 or 65) reaction with a suitable glycosyl donor such as GDP-Fuc.
Reaction SMILES: [C:1]1(/[CH:7]=[CH:8]/[CH2:9][C:10](=[S:12])[NH2:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:14][C:15](=O)/[CH:16]=[CH:17]/[C:18]([OH:20])=[O:19]>C(O)C>[CH2:9]([C:10]1[S:12][CH:14]=[C:15](/[CH:16]=[CH:17]/[C:18]([OH:20])=[O:19])[N:11]=1)[CH:8]=[CH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC(=S)C/C=C/c1ccccc1
Reactant: O=C(O)/C=C/C(=O)CBr
Solvent: CCO
Product: O=C(O)/C=C/c1csc(CC=Cc2ccccc2)n1
Reaction time: 1 h
Yield: 48.8 %

Procedure:
(E)-4-phenylbut-3-enethioamide (120 mg, 0.68 mmol) was dissolved in ethanol (20 mL). (E)-5-bromo-4-oxopent-2-enoic acid (290 mg, 1.50 mmol) was then added at room temperature and the reaction mixture was stirred for 1 h. The solution was concentrated and the crude residue was purified by column chromatography to give (E)-3-(2-cinnamylthiazol-4-yl)acrylic acid (90 mg). ES+ (M+H)+ 272.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[CH3:12][NH:13][CH2:14][CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:23]=2)[NH:18][CH:17]=1.C(N(C(C)C)CC)(C)C.O>C1COCC1>[C:6]1([CH2:5][O:4][C:2](=[O:3])[N:13]([CH2:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:23]=3)[NH:18][CH:17]=2)[CH3:12])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CNCCc1c[nH]c2ccc(CNS(C)(=O)=O)cc12
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: O
Product: CN(CCc1c[nH]c2ccc(CNS(C)(=O)=O)cc12)C(=O)OCc1ccccc1
Reaction time: 0.5 h

Procedure:
Benzyl chloroformate (1.1 ml) was added to a stirred, ice-cooled solution of N-[[3-[2-(methylamino)ethyl]-1H-indol-5-yl]methyl]methanesulphonamide (1.3 g) and diisopropylethylamine (1.5 ml) in dry THF (40 ml). After 1/2 h, water (3 ml) was added and the stirring was continued for 1 h.
Reaction SMILES: CC(C)(C)C(OC[N:7]1[CH:11]=[N:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][NH:25][CH:26]4[CH2:34][C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[CH2:27]4)[CH:19]=3)=[CH:14][CH:13]=2)=[N:8]1)=O.C[O-].[Na+].CO.[ClH:42].C([O-])([O-])=O.[Na+].[Na+]>CCO.O>[ClH:42].[NH:7]1[CH:11]=[N:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][NH:25][CH:26]4[CH2:27][C:28]5[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH2:34]4)[CH:19]=3)=[CH:14][CH:13]=2)=[N:8]1
Reactant: CC(C)(C)C(=O)OCn1cnc(-c2ccc(-c3cccc(CNC4Cc5ccccc5C4)c3)cc2)n1
Agent: C[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCO
Solvent: CO
Product: c1cc(CNC2Cc3ccccc3C2)cc(-c2ccc(-c3nc[nH]n3)cc2)c1
Temperature: 25 °C
Reaction time: 0.83 h
Yield: 89 %

Procedure:
To a solution of (3-{3′-[(2,3-dihydro-1H-inden-2-ylamino)methyl]-4-biphenylyl}-1H-1,2,4-triazol-1-yl)methyl 2,2-dimethylpropanoate (0.084 g, 0.17 mmol, Example X-3) in EtOH (1.5 mL) was added a 4.37 M solution of NaOMe in MeOH (0.08 mL, 0.35 mmol). The mixture was stirred for 50 min at RT. A 1.2M solution of concentrated HCl in EtOH was added (1.2 mL), and the mixture was heated at 80° C. for 1 h. The reaction mixture was cooled, diluted with water, and basified to a pH of 10 with addition of saturated Na2CO3 (aq). The mixture was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried with anhydrous Na2SO4, and concentrated in vacuo. The residue was dissolved in CH2Cl2 and MeOH, and 4N HCl in dioxane was added (0.2 mL). After stirring for 15 min, the precipitate was filtered, washed with CH2Cl2, and dried, affording the title compound as a colorless solid (0.057 g, 89%). (M+H) 367, 1.74 min (LC/MS Method B).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][N:11]([C:13]3[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=3)[C:16]([NH2:18])=[O:17])[C:10](=[O:22])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O)#[N:24].N(C)(C)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[O:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][N:11]([C:13]3[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=3)[C:16]([NH2:18])=[O:17])[C:10](=[O:22])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1)#[N:24]
Reactant: NC(=O)c1cccc(N2CC(c3cccc(O)c3)CC2=O)c1
Reactant: N#Cc1ccccc1B(O)O
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: CN(C)C
Solvent: ClCCl
Product: N#Cc1ccccc1Oc1cccc(C2CC(=O)N(c3cccc(C(N)=O)c3)C2)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 43.1 %

Procedure:
A mixture of 3-[4-(3-hydroxyphenyl)-2-oxo-pyrrolidin-1-yl]benzamide (30 mg), 2-cyanobenzeneboronic acid (12 mg), and copper acetate (2 eq) was created in a dry tube. The mixture was dissolved in 2 mL CH2Cl2 followed by the addition of (CH3)3N (3 eq). The mixture was stirred at r.t. for 24 h, and then diluted with 10 mL CH2Cl2. The resulting mixture was filtered and washed with NH4Cl solution, water and brine. After removal of solvent, the residue was purified by preparative LC-MS to give 14 mg of the desired product. Yield: 35%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C@@H:4]1[CH2:8][C@@H:7](S(C)(=O)=O)[CH2:6][N:5]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[N-:21]=[N+:22]=[N-:23].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:20])[C@@H:4]1[CH2:8][C@H:7]([N:21]=[N+:22]=[N-:23])[CH2:6][N:5]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]
Reactant: COC(=O)[C@@H]1C[C@@H](S(C)(=O)=O)CN1C(=O)OC(C)(C)C
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)[C@@H]1C[C@H](N=[N+]=[N-])CN1C(=O)OC(C)(C)C

Procedure:
N-Boc-(2S,4R)-4-methanesulfonylproline methylester was taken in DMF (10 mL) to which sodium azide (1.30 g, 20.0 mmol) was added and heated at 75–80° C. overnight. DMF was removed and the product was extracted with ethyl acetate (100 mL) and washed with water (50 mL). The azide product 9c (P=Boc, m=1, R9=azide) was obtained (0.98 g, 90%) on removal of solvent.