Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)[NH:10][C:11]1[CH:16]=[N:15][C:14]([CH2:17][CH:18]2[O:22][CH2:21][CH2:20][O:19]2)=[CH:13][N:12]=1)C1C=CC=CC=1.C(OCC)(=O)C>CO.[Pd]>[O:22]1[CH2:21][CH2:20][O:19][CH:18]1[CH2:17][C:14]1[N:15]=[CH:16][C:11]([NH2:10])=[N:12][CH:13]=1
Reactant: O=C(Nc1cnc(CC2OCCO2)cn1)OCc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: Nc1cnc(CC2OCCO2)cn1
Reaction time: 1 h
Yield: 157.7 %

Procedure:
A solution of 5-[1,3]dioxolan-2-ylmethyl-pyrazin-2-yl-carbamic acid benzyl ester (240 mg, 0.49 mmol) in methanol (5 mL) was treated with 10% palladium on activated carbon (40 mg). The reaction mixture was then hydrogenated under a hydrogen atmosphere at 25° C. and atmospheric pressure for 60 min, at which time, thin layer chromatography (ethyl acetate) suggested complete conversion to a polar product. The reaction was filtered through celite, and the filtrate was concentrated in vacuo to afford 5-[1,3]dioxolan-2-ylmethyl-pyrazin-2-ylamine (140 mg, 100%) as an oil which crystallized.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([C:16]([NH:18][OH:19])=[NH:17])[N:3]=1.[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[C:25](Cl)=O>C1(C)C=CC=CC=1.N1C=CC=CC=1>[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[C:25]1[O:19][N:18]=[C:16]([C:4]2[N:5]=[C:6]([N:8]([CH3:15])[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:7]=[C:2]([NH2:1])[N:3]=2)[N:17]=1
Reactant: CN(c1ccccc1)c1nc(N)nc(C(=N)NO)n1
Reactant: O=C(Cl)c1ccco1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CN(c1ccccc1)c1nc(N)nc(-c2noc(-c3ccco3)n2)n1

Procedure:
To a suspension of 4-amino-N-hydroxy-6-(methyl-phenyl-amino)-[1,3,5]triazine-2-carboxamidine (Intermediate 1, 95 mg, 0.37 mmol) in anhydrous toluene (3 mL) and anhydrous pyridine (1 mL) was added 2-furoyl chloride (53 mg, 0.41 mmol) in a solution of anhydrous toluene (3 mL) at 0 C in a sealed tube under an atmosphere of nitrogen.
Reaction SMILES: C([O:5][C:6](=[O:29])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH:17]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[S:19](=[O:27])(=[O:26])[NH:18]2)=[C:9]1[CH3:28])(C)(C)C.Br[CH2:31][CH2:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1>>[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([O:33][CH2:32][CH2:31][N:18]2[CH:17]([C:10]3[C:11]4[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=4)[N:8]([CH2:7][C:6]([OH:5])=[O:29])[C:9]=3[CH3:28])[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[S:19]2(=[O:27])=[O:26])=[CH:35][CH:36]=1
Reactant: Clc1ccc(OCCBr)cc1
Reactant: Cc1c(C2NS(=O)(=O)c3ccccc32)c2ccccc2n1CC(=O)OC(C)(C)C
Product: Cc1c(C2c3ccccc3S(=O)(=O)N2CCOc2ccc(Cl)cc2)c2ccccc2n1CC(=O)O

Procedure:
The title compound was prepared by the method described for example 14 using the product from example 3, step c) and 1-(2-bromo-ethoxy)-4-chloro-benzene. MS: ESI (negative): 509 (M−H).
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:11](=[C:12](OS(C(F)(F)F)(=O)=O)[N:13]([CH2:18][CH3:19])[N:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH:28]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)([CH3:30])[CH3:29]>>[CH2:18]([N:13]1[C:12]([C:34]2[CH:35]=[CH:36][C:31]([CH:28]([CH3:30])[CH3:29])=[CH:32][CH:33]=2)=[C:11]2[C:15]([CH2:16][CH2:17][NH:8][CH2:9][CH2:10]2)=[N:14]1)[CH3:19]
Reactant: CC(C)c1ccc(B(O)O)cc1
Reactant: CCn1nc2c(c1OS(=O)(=O)C(F)(F)F)CCN(C(=O)OC(C)(C)C)CC2
Product: CCn1nc2c(c1-c1ccc(C(C)C)cc1)CCNCC2
Yield: 93.2 %

Procedure:
The title compound (131 mg) was prepared according to Example 193 using 205 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 245 mg of 4-isopropylphenylboronic acid. MS (ESI): exact mass calculated for C18H25N3, 283.20; found, m/z 284.5 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.48-7.46 (m, 2H), 7.34-7.33 (m, 2H), 4.12 (q, J=7.3 Hz, 2H), 3.50-3.45 (m, 2H), 3.36-3.33 (m, 2H), 3.27-3.25 (m, 2H), 3.01 (m, 1H), 2.87-2.85 (m, 2H), 1.34 (t, J=7.3 Hz, 3H), 1.31 (d, J=6.9 Hz, 6H).
Reaction SMILES: OC1C=CC(C(OC)=O)=CC=1.C(Br)CCCCCCCCCCC.[CH2:25]([O:43][C:44]1[CH:53]=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][CH:45]=1)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]CCCCCC>>[CH2:25]([O:43][C:44]1[CH:45]=[CH:46][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:52][CH:53]=1)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: CCCCCCCCCCCCCCCCCCOc1ccc(C(=O)OC)cc1
Agent: COC(=O)c1ccc(O)cc1
Solvent: CCCCCCCCCCCCBr
Product: CCCCCCCCCCCCOc1ccc(C(=O)OC)cc1

Procedure:
This compound was prepared from methyl 4-hydroxybenzoate and dodecylbromide in an analogous manner to that described above for methyl 4-octadecyloxybenzoate.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12](/[CH:13]=[CH:14]/[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=2)[CH2:11][O:10][C:9]1([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH2:21])=[CH:19][CH:20]=2)[CH2:11][O:10][C:9]1([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1[C@@H](/C=C/c2ccc([N+](=O)[O-])cc2)COC1(C)C
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1[C@@H](CCc2ccc(N)cc2)COC1(C)C
Temperature: 60 °C
Yield: 82.6 %

Procedure:
To a stirred suspension of (S)-2,2-dimethyl-4-[(E)-2-(4-nitro-phenyl)-vinyl]-oxazolidine-3-carboxylic acid tert-butyl ester (2.08 g) in methanol (140 ml) were added ammonium formate (5.66 g) and palladium on charcoal (0.51 g, 10 wt %) and the mixture was heated at 60° C. for 2 hours. The mixture was then cooled to room temperature, filtered through celite and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (S)-4-[2-(4-amino-phenyl)-ethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.58 g, 82%) as a yellow oil. MS (ISP): 321.4 ([M+H]+).
Reaction SMILES: [CH2:1]([C:3]1[C:4]([O:25][C@H:26]2[C@@H:31]3[O:32]C(=O)[O:34][C@@H:30]3[C@@H:29]([O:36][CH3:37])[C:28]([CH3:39])([CH3:38])[O:27]2)=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][C:10](=[O:13])[C:9]([NH:14][C:15](=[O:24])OCC1C=CC=CC=1)=[CH:8]2)[CH3:2].CCN=C=NCCCN(C)C.[CH3:51][O:52][C:53]1[CH:54]=[C:55]([C:59]2[C:64]([O:65][CH3:66])=[CH:63][CH:62]=[C:61](C(O)=O)[CH:60]=2)[CH:56]=[CH:57][CH:58]=1.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(N(CC)CC)C>[OH:32][C@@H:31]1[C@H:30]([OH:34])[C@@H:29]([O:36][CH3:37])[C:28]([CH3:38])([CH3:39])[O:27][C@H:26]1[O:25][C:4]1[C:3]([CH2:1][CH3:2])=[C:12]2[C:7]([CH:8]=[C:9]([NH:14][C:15]([C:61]3[CH:60]=[C:59]([C:55]4[CH:56]=[CH:57][CH:58]=[C:53]([O:52][CH3:51])[CH:54]=4)[C:64]([O:65][CH3:66])=[CH:63][CH:62]=3)=[O:24])[C:10](=[O:13])[O:11]2)=[CH:6][CH:5]=1
Reactant: CCc1c(O[C@@H]2OC(C)(C)[C@H](OC)[C@H]3OC(=O)O[C@@H]23)ccc2cc(NC(=O)OCc3ccccc3)c(=O)oc12
Reactant: COc1cccc(-c2cc(C(=O)O)ccc2OC)c1
Agent: [Pd]
Agent: CCN=C=NCCCN(C)C
Agent: O=C([O-])[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCc1c(O[C@@H]2OC(C)(C)[C@H](OC)[C@@H](O)[C@H]2O)ccc2cc(NC(=O)c3ccc(OC)c(-c4cccc(OC)c4)c3)c(=O)oc12
Reaction time: 12 h
Yield: 3.5 %

Procedure:
Palladium on carbon (10%, 12 mg) was added to 25h (121 mg, 0.22 mmol) in anhydrous THF (5.00 mL) and the solution was placed under an atmosphere of H2. After 12 hours, the solution was filtered through SiO2 (1:1 CH2Cl2:Acetone) and the eluent was concentrated to afford a yellow solid, which was used without further purification (90.0 mg, 99%). EDCI (46.2 mg, 0.24 mmol) and 3′,6-dimethoxybiphenyl-3-carboxylic acid (43.9 mg, 0.19 mmol) were added to the amine (39.0 mg, 0.096 mmol) in 30% pyridine/CH2Cl2 (2.65 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford a colorless solid, which was used without further purification (39.1 mg, 66%). Triethylamine (150 μL) was added to the carbonate (13.0 mg, 0.020 mmol) in MeOH (1.5 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26h as a colorless amorphous solid (4.10 mg, 33%, 22% over 3 steps): 1H NMR (CD2Cl2, 500 MHz) δ 8.70 (s, 1H), 8.61 (s, 1H), 7.83 (dd, J=8.5, 2.5 Hz, 1H), 7.78 (d, J=2.5 Hz, 1H), 7.31 (d, J=9.0 Hz, 1H), 7.27 (t, J=7.8 Hz, 1H), 7.17 (d, J=8.5 Hz, 1H), 7.03-6.99 (m, 3H), 6.85-6.82 (m, 1H), 5.49 (d, J=1.5 Hz, 1H), 4.15 (t, J=8.5 Hz, 1H), 4.14 (d, J=8.5 Hz, 1H), 3.90 (s, 2H), 3.87 (s, 3H), 3.81 (s, 3H), 3.28 (s, 3H), 3.27 (d, J=8.5 Hz, 1H), 2.76 (q, J=4.5 Hz, 2H), 1.29 (s, 3H), 1.09 (t, J=7.4 Hz, 3H), 1.08 (s, 3H); 13C NMR (CD2Cl2, 125 MHz) δ 164.5, 159.0, 158.6, 158.5, 155.1, 147.9, 138.1, 130.1, 129.1, 128.3, 127.4, 125.4, 125.2, 123.1, 121.4, 121.2, 119.4, 114.5, 113.5, 112.1, 110.8, 110.2, 97.6, 83.4, 77.7, 70.6, 67.8, 61.0, 55.1, 54.5, 28.2, 21.6, 15.6, 12.9; IR (film) νmax 3404, 2968, 2934, 2359, 2341, 1715, 1605, 1524, 1504, 1367, 1244, 1101, 1024, 995, 960, 800 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C34H37NO10, 620.2496. found, 620.2507.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:48]=[CH:49][C:50]=1[O:51][CH3:52])[CH2:6][CH2:7][NH:8][C:9](=[O:47])[CH:10]([NH:26][C:27](=[O:46])[C@@H:28]([S:36]CC1C=CC(OC)=CC=1)[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:11]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=1)=[O:12].C1(OC)C=CC=CC=1.C1(OC)C(=CC=CC=1)OC.ClCCl.C(OCC)(=O)C.CCCCCC>ClCCl.C([O-])(=O)C.[Hg+2].C([O-])(=O)C.ClCCl.C(OCC)(=O)C>[CH3:25][O:24][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[O:22][CH3:23])[CH2:15][CH2:14][NH:13][C:11](=[O:12])[CH:10]([NH:26][C:27](=[O:46])[C@@H:28]([SH:36])[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:9]([NH:8][CH2:7][CH2:6][C:5]1[CH:48]=[CH:49][C:50]([O:51][CH3:52])=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:47]
Reactant: COc1ccc(CS[C@@H](Cc2ccccc2)C(=O)NC(C(=O)NCCc2ccc(OC)c(OC)c2)C(=O)NCCc2ccc(OC)c(OC)c2)cc1
Agent: CC(=O)[O-]
Agent: [Hg+2]
Solvent: CCCCCC
Solvent: ClCCl
Solvent: COc1ccccc1OC
Product: COc1ccc(CCNC(=O)C(NC(=O)[C@@H](S)Cc2ccccc2)C(=O)NCCc2ccc(OC)c(OC)c2)cc1OC
Reaction time: 3 h

Procedure:
Combine of N,N′-di-(3,4-dimethoxyphenethyl)-2-((S)-2-(p-methoxybenzylmercapto)-3-phenylpropionylamino)malonamide (0.139 g, 0.19 mmol), mercury (II) acetate (0.076 g), and anisole (0.3 mL), and veratrole (0.24 mL) in dichloromethane (10 mL). Cool in an ice bath and degas by repeatedly applying vacuum and filling the vessel with nitrogen. Add trifluoroacetic acid (4 mL). After 3 hours, purge with hydrogen sulfide (gas) for about 10 minutes. Filter and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 3/1 dichloromethane/ethyl acetate/hexane and then 3/2 dichloromethane/ethyl acetate to give the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH:23]([CH2:26]OS(C)(=O)=O)[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][C@@H:23]([CH2:26][N:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[CH:7]=[CH:8][C:9]2=[O:13])[CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)C1
Reactant: COc1ccc2ccc(=O)[nH]c2c1
Product: COc1ccc2ccc(=O)n(C[C@@H]3CCN(C(=O)OC(C)(C)C)C3)c2c1
Yield: 23 %

Procedure:
Using the procedure of Example 2, step 2.i, but starting from 7-methoxy-2(1H)-quinolinone (prepared according to WO 2006/134378; 500 mg) and 3-[[(methylsulfonyl)oxy]methyl]-1-pyrrolidinecarboxylic acid tert-butyl ester (797 mg; prepared according to J. Med. Chem. (1999), 42, 677-690), the second eluting compound was isolated as a colourless oil (240 mg; 23% yield).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=[CH:21][C:16]=2[C:17]([O:19]C)=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=[CH:21][C:16]=2[C:17]([OH:19])=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1
Temperature: 50 °C
Reaction time: 16 h
Yield: 91.2 %

Procedure:
In a 50 ml RBF was suspended methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-tert-butylbenzoate (2.4 g, 6.1 mmol) in 25 ml of 3:1 THF:water to give a light emulsion, then was added solid LiOH monohydrate (567 mg, 13.5 mmol), the flask was fitted with a reflux condenser, and the mixture was heated at 50° C. with stirring for 16 h. The mixture was diluted with 75 ml water and washed twice with diethyl ether. The aqueous layer was acidified to about pH 2 with 1 N NaHSO4, and the resulting slurry extracted twice with 100 ml portions of EtOAc. The combined EtOAc layers were washed with brine, dried, then concentrated in vacuo to afford 2.1 g (91%) of the title acid as a brittle white foam.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][S:14]([CH2:17][C:18](NC1N=NN(CCCCCCCCCCCC)N=1)=[O:19])(=[O:16])=[O:15])([CH3:3])[CH3:2].[CH2:38]([NH:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45]>>[CH:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5]=1[NH:13][S:14]([CH2:17][C:18]([N:46]([CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])=[O:19])(=[O:16])=[O:15])([CH3:11])[CH3:12]
Reactant: CCCCCCCCNCCCCCCCC
Reactant: CCCCCCCCCCCCn1nnc(NC(=O)CS(=O)(=O)Nc2c(C(C)C)cccc2C(C)C)n1
Product: CCCCCCCCN(CCCCCCCC)C(=O)CS(=O)(=O)Nc1c(C(C)C)cccc1C(C)C

Procedure:
This compound was prepared in the same manner as for the title compound of Example 2, except that 2-DAT was replaced with N,N-dioctylamine, mp 107°-109° C.
Reaction SMILES: [CH2:1]([C:3]1[S:4][C:5]([C:9]([OH:11])=O)=[C:6]([CH3:8])[N:7]=1)[CH3:2].C(Cl)([Cl:14])=O>C1(C)C=CC=CC=1>[CH2:1]([C:3]1[S:4][C:5]([C:9]([Cl:14])=[O:11])=[C:6]([CH3:8])[N:7]=1)[CH3:2]
Reactant: O=C(Cl)Cl
Reactant: CCc1nc(C)c(C(=O)O)s1
Solvent: Cc1ccccc1
Product: CCc1nc(C)c(C(=O)Cl)s1

Procedure:
In a similar apparatus to Example 1, 8.6 g (0.05 mole) of 2-ethyl-4methylthiazole-5carboxylic acid were suspended in 200 ml of toluene. Under heating and reflux, phosgene was blown at a rate of 350 ml/hr for 11 hours (0.17 mole). After completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated to obtain 9.3 g of 2-ethyl-4-methylthiazole-5-carboxylic acid chloride. Its purity and yield were 94.5% and 97.5%, respectively. NMR (δCDCl 3/TMS, ppm):1.36(3H,t,J=8Hz), 2.62(3H,s), 2.93(2H,q,J=8Hz).
Reaction SMILES: [N:1]#[C:2][NH2:3].CC(C)([O-])C.[K+].N#CN.[K].Cl[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([S:21][CH3:22])[N:16]=1>CN(C=O)C>[C:2]([NH:3][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([S:21][CH3:22])[N:16]=1)#[N:1]
Reactant: CSc1nccc(Cl)n1
Reactant: N#CN
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [K]
Solvent: CN(C)C=O
Product: CSc1nccc(NC#N)n1

Procedure:
Cyanamide (1.05 g.) was added to potassium t-butoxide (2.8 g.) in DMF (10 ml.) with stirring to produce a fine suspension of potassium cyanamide. To this was added 4-chloro-2-methylthiopyrimidine (4 g.) and the mixture stirred at ambient temperature for 17 hours. The DMF was evaporated in vacuo and the residue suspended in water (20 ml.), the pH adjusted to 11 with dilute aqueous sodium hydroxide and the mixture extracted with EtOAc (2×10 ml.). The aqueous layer was separated, acidified to pH 3 with dilute hydrochloric acid and the precipitate collected, washed with water and dried to give 4-cyanoamino-2-methylthiopyrimidine, m.p. 189-191 (decomp.).
Reaction SMILES: [C:1]([CH:3]1[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[N:2].[C:11]([OH:16])(=[O:15])[C:12]([OH:14])=[O:13].C[N:18]1[N:22]=N[C:20]([CH:23]2C3CCN(CC3)C2)=[N:19]1.[N+](=CC)=[N-]>>[C:11]([OH:16])(=[O:15])[C:12]([OH:14])=[O:13].[CH2:20]([N:19]1[N:18]=[N:22][C:1]([CH:3]2[CH:8]3[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]3)[CH2:4]2)=[N:2]1)[CH3:23]
Reactant: Cn1nnc(C2CN3CCC2CC3)n1
Reactant: N#CC1CN2CCC1CC2
Agent: CC=[N+]=[N-]
Agent: O=C(O)C(=O)O
Product: CCn1nnc(C2CN3CCC2CC3)n1

Procedure:
This compound was prepared from (±) 3-cyano-1-azabicyclo[2.2.2]octane (EP-A-0 261 763, Description 1) in a similar manner to the compound of Example 2 using an ethereal solution of diazoethane prepared from N-nitroso-N-ethyl urea1,2. The resulting oil was purified by column chromatography using neutral alumina and eluting with 2% MeOH/EtOAc. 1H NMR indicated that the mixture contained a 12:1 ratio of the 2-ethyl isomer to 1-ethyl isomer and this mixture (100 mg, 17%) was crystallised and the title compound E9 recrystallised from methanol/diethyl ether as the oxalate salt (containing 8% of the 1-ethyl isomer).
Reaction SMILES: [S:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[S:3].[OH-].[Na+].Cl[CH2:11][C:12]([C:14]1[CH:23]=[CH:22][C:17]2[O:18][CH2:19][CH2:20][O:21][C:16]=2[CH:15]=1)=[O:13]>CCO.O>[O:18]1[C:17]2[CH:22]=[CH:23][C:14]([C:12](=[O:13])[CH2:11][S:3][C:2]3[S:1][CH2:7][C:5](=[O:6])[N:4]=3)=[CH:15][C:16]=2[O:21][CH2:20][CH2:19]1
Reactant: O=C(CCl)c1ccc2c(c1)OCCO2
Reactant: O=C1CSC(=S)N1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C1CSC(SCC(=O)c2ccc3c(c2)OCCO3)=N1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Rhodanine (0.052 g, 0.388 mmol, 1.0 eq.) was dissolved in EtOH (2 ml) and 2 M NaOH (0.275 ml, 0.550 mmol, 1.42 eq.) with vigorous stirring. Once the Rhodanine was completely dissolved, 6-Chloroacetyl-1,4-benzodioxane (0.080 g, 0.380 mmol, 0.98 eq.) was added with constant stirring. (It should be noted that α-chloro ketones were used when the corresponding α-bromo ketones were not available.) The reaction was mixed overnight at 40° C. After 18 hrs the reaction was removed from the heat and left stirring at room temp for 48 hrs. The resulting reaction mixture was then diluted with water (5 ml) and extracted with dichloromethane (3×5 ml). The organic layer was dried over Na2SO4 and then evaporated to yield an oil. The oil was purified by chromatotron using a 50/50 mixture of ethyl acetate in hexanes as the mobile phase. The purified product, Compound 34, was then recrystallized in hexanes to complete its purification (20 mg, 0.0646 mmol, 17%). The product was characterized by 1H-NMR: (CDCl3) 7.55 (q, 2H), 6.93 (d, 1H), 4.93 (s, 2H), 4.31 (m, 4H), 4.02 (s, 2H) ppm. In addition LCMS [ES+] analysis yielded a single peak, 310 [M]+ m/e.
Reaction SMILES: [CH3:1][C:2]1[C:7](N)=[C:6]([CH3:9])[CH:5]=[CH:4][C:3]=1[B:10]([OH:12])[OH:11].B(O)O.CC1C=C(C)C=CC=1Br.[N+:25]([O-:28])(O)=[O:26].C(O)(C(F)(F)F)=O.CC1C=C(C)C=CC=1B(O)O>>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:9])[C:5]([N+:25]([O-:28])=[O:26])=[CH:4][C:3]=1[B:10]([OH:11])[OH:12]
Reactant: Cc1ccc(B(O)O)c(C)c1N
Reactant: O=[N+]([O-])O
Agent: Cc1ccc(B(O)O)c(C)c1
Agent: Cc1ccc(Br)c(C)c1
Agent: OBO
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(C)c([N+](=O)[O-])cc1B(O)O
Temperature: -40 °C
Reaction time: 1 h
Yield: 47 %

Procedure:
Example 40(c) was prepared in a similar manner to that of Example 40(a) except that in step (i) 2,4-dimethyl-3-amino-phenyl boronic acid (prepared as described below) was used in place of m-amino-phenyl boronic acid: 1H NMR (DMSO-d6) δ 8.62 (d, 1H, J=3.78 Hz), 8.32 (d, 1H, J=8.48 Hz), 7.99 (d, 1H, J=16.35 Hz), 7.83 (td, 1H, J=7.68 Hz, J=1.8 Hz), 7.80 (s, 1H), 7.69 (d, 1H, J=7.80 Hz), 7.64 (dd, 1H, J=8.47 Hz, J=1.27 Hz), 7.62 (d, 1H, J=16.36 Hz), 7.29 (m, 1H), 6.94 (s, 1H), 6.64 (s, 1H), 4.87 (bs, 2H), 2.12 (s, 3H), 2.10 (s, 3H). LCMS (ESI+) [M+H]/z Calc'd 369, found 369. Anal. Calc'd: C, 74.98; H, 5.47; N, 15.21. Found: C, 73.85; H, 5.56; N, 14.49. The starting material was prepared as follows: 2,4-Diemthylphenyl boronic acid was made in a similar manner as that of Example 24(a), step (vii), except 2,4-dimethyl bromobenzene was used as starting material. 1H NMR (CD3OD) δ 7.13 (d, 1H, J=7.43 Hz), 7.00 (s, 1H), 6.97 (d, 1H. J=7.49 Hz), 2.28 (s, 3H), 2.28 (s, 3H). LCMS (ESI+) [M+H]/z Calc'd 151, found 151. To fuming nitric acid (1 ml) cooled to −40° C. was added TFA (1 ml). The resulting mixture was allowed to warm slightly to −35° C. and 2,4-dimethyl phenyl boronic acid (150 mg, 1 mmol) was added in one portion. After 1 h, ice was added and the heterogenous mixture was filtered. The resulting solid was suspended in Et2O and extracted with 3N NaOH (aq) (1 ml) then water (2 ml). The aqueous phase was acidified with 3N HCl (aq) (1 ml) and back extracted with EtOAc (3×5 ml). The pooled organics were washed with brine, dried with Na2SO4 decanted and concentrated to give 2,4-dimethyl-5-nitro-phenyl boronic acid (93 mg, 47%). LCMS (ESI+) [M+H]/z Calc'd 196, found 196. 3-Amino-4,6-dimethylphenyl boronic acid was prepared in a similar as that described for Example 40(b), step (i). 1H NMR (CD3OD)δ 6.83 (s, 2H), 6.64 (s, 1H), 2.17 (s, 3H), 2.13 (s, 3H).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:9]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:10](=O)[CH2:11][CH2:12][C:13](=[O:25])[C:14]1[CH:19]=[CH:18][C:17]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])=[CH:16][CH:15]=1)[CH3:8].CC1C=C(C(=O)C)C=CC=1NS(C)(=O)=O.[Na].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[K+]>O1CCCC1.C(OCC)(=O)C>[CH2:7]([N:9]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:10][CH2:11][CH2:12][CH:13]([C:14]1[CH:15]=[CH:16][C:17]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])=[CH:18][CH:19]=1)[OH:25])[CH3:8]
Reactant: CCCCCCCN(CC)C(=O)CCC(=O)c1ccc(NS(C)(=O)=O)cc1
Agent: CC(=O)c1ccc(NS(C)(=O)=O)c(C)c1
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [Al+3]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCCCCN(CC)CCCC(O)c1ccc(NS(C)(=O)=O)cc1

Procedure:
A stirred suspension of lithium aluminum hydride (0.86 g, 0.0227 mol) in dry tetrahydrofuran (30 ml) under nitrogen is cooled to 0° to -5° C. and treated dropwise during 25 minutes with a solution of N-ethyl-N-heptyl-γ-oxo-4-[(methylsulfonyl)amino]benzenebutanamide as prepared in Preparation 3 (3.0 g, 0.00757 mole) in THF (30 ml). After 2.5 hours this mixture is treated dropwise with a saturated solution of sodium, potassium tartrate (10 ml) and then with ethyl acetate. The mixture is filtered and the solid is extracted with ethyl acetate. The organic solutions are dried (MgSO4) and concentrated; the residual product is combined to give 2.10 g of N-[4-[4-(ethylheptylamino)-1-hydroxybutyl]phenyl]methanesulfonamide. By NMR this material is the same as an authentic sample obtained from another reaction and purified by silica gel chromatography with 0.5% NH4OH-6% MeOH--CH2Cl2.
Reaction SMILES: I[C:2]1[O:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([I:7])[N:6]=1.[CH3:13][C:14]1[C:15]([Sn](C)(C)C)=[CH:16][C:17]([NH:20][C:21](=[O:23])[CH3:22])=[N:18][CH:19]=1.[Cl-].[Li+]>O1CCOCC1.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.[Cu]I>[C:21]([NH:20][C:17]1[CH:16]=[C:15]([C:2]2[O:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([I:7])[N:6]=2)[C:14]([CH3:13])=[CH:19][N:18]=1)(=[O:23])[CH3:22]
Reactant: CC(=O)Nc1cc([Sn](C)(C)C)c(C)cn1
Reactant: CCOC(=O)c1oc(I)nc1I
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Solvent: C1COCCO1
Product: CCOC(=O)c1oc(-c2cc(NC(C)=O)ncc2C)nc1I
Temperature: 100 °C
Reaction time: 2 h
Yield: 41.4 %

Procedure:
A mixture of ethyl 2,4-diiodo-1,3-oxazole-5-carboxylate (0.37 g, 0.93 mmol), N-[5-methyl-4-(trimethylstannyl)pyridine-2-yl]acetamide (0.32 g, 1.0 mmol), tetrakis(triphenylphosphine)palladium(0) (0.054 g, 0.047 mmol), copper(I) iodide (0.053 g, 0.28 mmol) and lithium chloride (0.12 g, 2.8 mmol) in 1,4-dioxane (9 mL) was degassed with argon three times. The mixture was allowed to stir at 100° C. for 2 h under an atmosphere of argon and was then filtered while hot. The reaction mixture was concentrated and the residue was purified by column chromatography to give ethyl 2-[2-(acetylamino)-5-methylpyridin-4-yl]-4-iodo-1,3-oxazole-5-carboxylate (0.16 g, 42%).