Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:38])[C@@H:7]([NH:24][S:25]([C:28]1[CH:33]=[CH:32][C:31]([NH:34][C:35](=[O:37])[CH3:36])=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH2:8][NH:9][C:10](=[O:23])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([O:21]C)=O)=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:39][C:40]1[NH:41][CH2:42][CH2:43][CH2:44][N:45]=1>CN(C)C=O>[C:1]([O:5][C:6](=[O:38])[C@@H:7]([NH:24][S:25]([C:28]1[CH:29]=[CH:30][C:31]([NH:34][C:35](=[O:37])[CH3:36])=[CH:32][CH:33]=1)(=[O:26])=[O:27])[CH2:8][NH:9][C:10](=[O:23])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19](=[O:21])[NH:39][C:40]2[NH:45][CH2:44][CH2:43][CH2:42][N:41]=2)=[CH:13][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: NC1=NCCCN1
Reactant: COC(=O)CCc1ccc(C(=O)NC[C@H](NS(=O)(=O)c2ccc(NC(C)=O)cc2)C(=O)OC(C)(C)C)cc1
Solvent: CN(C)C=O
Product: CC(=O)Nc1ccc(S(=O)(=O)N[C@@H](CNC(=O)c2ccc(CCC(=O)NC3=NCCCN3)cc2)C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
87 mg (0.16 mmol) of (2S)-2-(4-acetylamino-benzenesulfonylamino)-3-(4-(2-methoxycarbonyl-ethyl)-benzoylamino)-propionic acid tert-butyl ester was dissolved in 1 ml of dimethylformamide and 79 mg (0.8 mmol) of 2-amino-1,4,5,6-tetrahydropyrimidine was added. The reaction was stirred at room temperature for 20 hours. The solvent was removed in vacuo and the residue was chromatographed on silica gel eluting with dichloromethane/methanol (1/1), followed by dichloromethane/methanol/acetic acid/water (85/15/1.5/1.5). Yield 57 mg. MS (ES+): m/e=615.3 (M+H+).
Reaction SMILES: S(Cl)(Cl)=O.[CH:5]([NH:7][C:8]1[S:9][CH:10]=[C:11]([C:13](=[O:17])[C:14]([OH:16])=O)[N:12]=1)=[O:6].[CH3:18][CH:19]1[CH:24]=[C:23]([C:25]([OH:27])=[O:26])[N:22]2[C:28](=[O:31])[CH:29]([NH2:30])[C@H:21]2[S:20]1.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.CN(C)C=O>[CH3:18][CH:19]1[CH:24]=[C:23]([C:25]([OH:27])=[O:26])[N:22]2[C:28](=[O:31])[CH:29]([NH:30][C:14](=[O:16])[C:13]([C:11]3[N:12]=[C:8]([NH:7][CH:5]=[O:6])[S:9][CH:10]=3)=[O:17])[C@H:21]2[S:20]1
Reactant: CC1C=C(C(=O)O)N2C(=O)C(N)[C@H]2S1
Reactant: O=CNc1nc(C(=O)C(=O)O)cs1
Agent: C[Si](C)(C)CC(N)=O
Agent: O=C([O-])O
Agent: O=CN=c1[nH]c(C(=O)C(=O)O)cs1
Solvent: O
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CC1C=C(C(=O)O)N2C(=O)C(NC(=O)C(=O)c3csc(NC=O)n3)[C@H]2S1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of thionyl chloride (3.01 g.) in methylene chloride (45 ml.) were added dimethylformamide (0.928 g.) and 2-(2-formylaminothiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid, (3.71 g.) in turn, and the mixture was stirred for 4 hours at room temperature. Thus obtained mixture was added over 5 minutes to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (3.3 g.) and trimethylsilylacetamide (16.2 g.) in methylene chloride (60 ml.) at room temperature for 40 minutes, with stirring under cooling to -25° to -20° C. The mixture was stirred for 30 minutes at -25° to -20° C., for 30 minutes at -10° to 0° C., and then for 30 minutes at room temperature. To the reaction mixture was added water (30 ml.), and the mixture was stirred for 10 minutes. After a saturated aqueous sodium bicarbonate solution was added to the mixture in order to dissolve the precipitates, the aqueous layer was separated. To the aqueous layer was added ethyl acetate, and the mixture was adjusted to pH 2 with 2 N hydrochloric acid, and then the ethyl acetate layer was separated. The remaining aqueous layer was further extracted with ethyl acetate. The ethyl acetate layers were combined together, washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated. Thus obtained crystalline residue was pulverized in diethyl ether, collected by filtration and then dried to give yellow crystalline powder of 2-methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 2-methyl-7-[2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (3.81 g.).
Reaction SMILES: F[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1.C(=O)([O-])[O-].[K+].[K+].[CH:27]([NH2:30])([CH3:29])[CH3:28].CN(C=O)C>O>[CH:27]([NH:30][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1)([CH3:29])[CH3:28]
Reactant: Fc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Reactant: CC(C)N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)Nc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Temperature: 80 °C
Yield: 65.9 %

Procedure:
A mixture of 0.28 g of 2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole, 0.69 g of potassium carbonate, 0.30 g of isopropylamine and 3 ml of DMF was stirred while heating at 50° C. for 1.5 hours and at 80° C. for 4 hours. To the mixture, 0.30 g of isopropylamine was added and stirred while heating for further three hours. To the reaction mixture, water was added, followed by extraction with ethyl acetate twice. The combined organic layers were washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.21 g of isopropyl-[4-(5-trifluoromethylbenzoxazole-2-yl)pyridin-3-yl]amine (hereinafter, referred to as “active compound 85”).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-:14])=[O:13])=[C:5]2Cl.[CH3:16][C:17]1[C:21]([NH2:22])=[C:20]([CH3:23])[O:19][N:18]=1>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-:14])=[O:13])=[C:5]2[NH:22][C:21]1[C:17]([CH3:16])=[N:18][O:19][C:20]=1[CH3:23]
Reactant: O=[N+]([O-])c1cnc2ccc(Br)cc2c1Cl
Reactant: Cc1noc(C)c1N
Solvent: CC(=O)O
Product: Cc1noc(C)c1Nc1c([N+](=O)[O-])cnc2ccc(Br)cc12
Reaction time: 4 h

Procedure:
A mixture of 6-bromo-4-chloro-3-nitro-quinoline (Stage A.4, 1.1 g, 3.83 mmol) and 3,5-dimethyl-4-aminoisoxazol (Aldrich, Buchs, Switzerland, 472 mg, 4.21 mmol) in acetic acid (10 ml) was stirred at it for 4 h. Then the RM was quenched with H2O (40 ml). The suspension was filtered, the solid cake was washed with H2O (2×) and dried under vacuum, before being dissolved in EtOAc. The solution was washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered and evaporated to dryness to give the title compound as an orange solid (HPLC tR 2.96 min (Method A); M+H=363, 365; M−H=361, 363 MS-ES).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28]C(=O)OC(C)(C)C)[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[N:3]1[CH2:36][C:37]1[N:38]=[CH:39][S:40][CH:41]=1>C(O)(C(F)(F)F)=O>[NH2:28][C:24]1([C:21]2[CH:22]=[CH:23][C:18]([C:9]3[C:10]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[CH:11][C:4]4[N:3]([CH2:36][C:37]5[N:38]=[CH:39][S:40][CH:41]=5)[C:2](=[O:1])[CH2:7][O:6][C:5]=4[N:8]=3)=[CH:19][CH:20]=2)[CH2:25][CH2:26][CH2:27]1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)N(Cc3cscn3)C(=O)CO4)cc2)CCC1
Solvent: O=C(O)C(F)(F)F
Product: NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)N(Cc3cscn3)C(=O)CO4)cc2)CCC1
Reaction time: 0.01 h
Yield: 67.4 %

Procedure:
tert-Butyl 1-(4-(2-oxo-7-phenyl-1-(thiazol-4-ylmethyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (54 mg, 0.095 mmol) was dissolved in TFA (2 mL) and stirred for 30 seconds. The solution was immediately concentrated to dryness under reduced pressure. The residue was dissolved in diethyl ether (˜2 mL) and concentrated to dryness under reduced pressure three times. The residue was then slurried in diethyl ether (2 mL) and after settling the supernatant solvent removed by pipette. This was repeated three times. The remaining solvent was removed by freeze drying overnight to give the desired compound as an off-white solid (30 mg, 54% yield). 1H-NMR (500 MHz, MeOD) δ 8.97 (1H, s), 7.63 (1H, s), 7.60 (1H, s), 7.32-7.41 (4H, m), 7.20-7.29 (3H, m), 7.05-7.15 (2H, m), 5.39 (2H, s), 5.03 (2H, s), 2.66-2.88 (2H, m), 2.47-2.38 (2H, m), 2.13-2.28 (1H, m), 1.85-1.98 (1H, m). LCMS (Method A) RT=3.81 min, M+2H+=470.18.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH2:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)[CH3:19].O>C1(C)C=CC=CC=1>[CH2:18]([N:20]1[CH2:25][CH2:24][N:23]([C:2]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:22][CH2:21]1)[CH3:19]
Reactant: Clc1cc(-c2ccccc2)c2ccccc2n1
Reactant: CCN1CCNCC1
Solvent: Cc1ccccc1
Solvent: O
Product: CCN1CCN(c2cc(-c3ccccc3)c3ccccc3n2)CC1
Yield: 86.8 %

Procedure:
A solution of 2-chloro-4-phenylquinoline (2.0 g) and 1-ethylpiperazine (2.7 g) in toluene (15 ml) is heated under reflux for 10 hours. To the reaction mixture is added water and the resulting mixture is extracted with ethyl acetate. The extracts are dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel (25 g) using chloroform as an eluent. Fractions containing the title compound are pooled and concentrated to give the title compound (2.3 g).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:14][C:15](=[O:34])[NH:16][C@@H:17]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:35]1[C:47]2[CH:46]([CH2:48][O:49][C:50]([NH:52][C@@H:53]([CH2:57][CH2:58][CH2:59][CH2:60][NH:61][C:62](=[O:100])[CH2:63][N:64]3[CH2:75][CH2:74][N:73]([CH2:76][C:77](=[O:83])[O:78][C:79]([CH3:82])([CH3:81])[CH3:80])[CH2:72][CH2:71][N:70]([CH2:84][C:85](=[O:91])[O:86][C:87]([CH3:90])([CH3:89])[CH3:88])[CH2:69][CH2:68][N:67]([CH2:92][C:93]([O:95][C:96]([CH3:99])([CH3:98])[CH3:97])=[O:94])[CH2:66][CH2:65]3)[C:54](O)=[O:55])=[O:51])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39]=2[CH:38]=[CH:37][CH:36]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:35]1[C:47]2[CH:46]([CH2:48][O:49][C:50](=[O:51])[NH:52][C@@H:53]([CH2:57][CH2:58][CH2:59][CH2:60][NH:61][C:62](=[O:100])[CH2:63][N:64]3[CH2:65][CH2:66][N:67]([CH2:92][C:93](=[O:94])[O:95][C:96]([CH3:97])([CH3:98])[CH3:99])[CH2:68][CH2:69][N:70]([CH2:84][C:85](=[O:91])[O:86][C:87]([CH3:88])([CH3:89])[CH3:90])[CH2:71][CH2:72][N:73]([CH2:76][C:77]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:83])[CH2:74][CH2:75]3)[C:54](=[O:55])[NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C@@H:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[NH:14][C:15](=[O:34])[NH:16][C@H:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39]=2[CH:38]=[CH:37][CH:36]=1
Reactant: CC(C)(C)OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCN)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reactant: CC(C)(C)OC(=O)CN1CCN(CC(=O)NCCCC[C@H](NC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)O)CCN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)[C@H](CCCCNC(=O)CN1CCN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1)NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Yield: 136 %

Procedure:
A solution of (S)-di-tert-butyl 2-(3-((S)-6-amino-1-(tert-butoxy)-1-oxohexan-2-yl)ureido)pentanedioate (0.048 g, 0.10 mmol), (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-(2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)hexanoic acid (56 mg, 0.0607 mmol), EDCI (19 mg, 0.10 mmol), HOBt (13.5 mg, 0.10 mmol) and DIPEA (0.10 mL) in DCM (5.0 mL) was stirred at room temperature for 2 hrs. The solvent was evaporated to give a residue, which was purified by Biotage eluting with DCM to 10% MeOH in DCM to give (5S,12S,16S)-tri-tert-butyl 1-(9H-fluoren-9-yl)-3,6,14-trioxo-5-(4-(2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)butyl)-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate (115 mg) containing some impurity. MS (ESI), 697.0 (M+H)+.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7](/[C:10](=[N:18]/[OH:19])/[CH2:11][CH2:12][C:13]([O:15]CC)=[O:14])=[CH:6][CH:5]=1.Cl[CH2:21][C:22]1[CH:41]=[CH:40][C:25]([O:26][CH2:27][C:28]2[N:29]=[C:30]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:31][C:32]=2[CH3:33])=[CH:24][CH:23]=1.Cl.C(=O)(O)[O-].[Na+]>CN(C)C=O>[F:3][C:4]1[CH:5]=[CH:6][C:7](/[C:10](=[N:18]/[O:19][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:26][CH2:27][C:28]3[N:29]=[C:30]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[O:31][C:32]=3[CH3:33])=[CH:40][CH:41]=2)/[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:9]=1
Reactant: CCOC(=O)CC/C(=N\O)c1ccc(F)cc1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [H-]
Solvent: CN(C)C=O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CO/N=C(\CCC(=O)O)c2ccc(F)cc2)cc1
Reaction time: 1 h
Yield: 46.7 %

Procedure:
Sodium hydride (60% in oil, 153 mg) was added under a nitrogen atmosphere to a solution of ethyl E-4-(4-fluorophenyl)-4-hydroxyiminobutyrate (763 mg) and 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (1.00 g) in N,N-dimethylformamide (10 ml) at room temperature and the mixture was stirred for 1 hour. After adding 1N HCl (7 ml), aqueous sodium bicarbonate was added, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residue was subjected to column chromatography on silica gel to obtain an oil from a fraction eluted with ethyl acetate-hexane (1:4, v/v). This oil was dissolved in tetrahydrofuran (20 ml)-methanol (10 ml), and 1N aqueous solution of sodium hydroxide (10 ml) was added and the mixture was stirred at room temperature for 1 hour. 1N HCl (7.5 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residual crystal was recrystallized from ethyl acetate-hexane to obtain E-4-(4-fluorophenyl)-4-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]butyric acid (727 mg, yield 47%) as colorless crystals. m.p. 139-140° C.
Reaction SMILES: C(O[C:4]1[CH:9]=[CH:8][N:7]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[S:12][CH2:11]2)[C:6](=[O:17])[N:5]=1)C.[NH3:18].CO>>[OH:16][CH2:15][C@@H:13]1[S:12][CH2:11][C@H:10]([N:7]2[CH:8]=[CH:9][C:4]([NH2:18])=[N:5][C:6]2=[O:17])[O:14]1
Reactant: N
Reactant: CCOc1ccn([C@H]2CS[C@@H](CO)O2)c(=O)n1
Solvent: CO
Product: Nc1ccn([C@H]2CS[C@@H](CO)O2)c(=O)n1
Temperature: 70 °C
Yield: 89 %

Procedure:
A solution of (2S*,5R*)-4-ethoxy-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one (0.21g) in ammonia/methanol (8 mL of methanol saturated with ammonia gas at 0° C. for 45 minutes) was placed in a steel bomb with a teflon liner, sealed and heated at 70° C. for 18 hours. Solvent was evaporated in vacuo and the residue subjected to flash chromatography to give the desired product (0.16g, 89%) as a white solid: mp 184-185° C.; 1H NMR (DMSO-d6): δ3.00 (dd, J=11.8, 5.0 Hz, 1H), 3.38 (dd, J=11.8, 5.5 Hz, 1H), 3.63-3.80 (m, 2H), 5.15 (t, J=4.5 Hz, 1H), 5.30 (t, J=6.0 Hz, 1H), 5.70 (d, J=7.3 Hz, 1H); 6.18 (t, J=5.0 Hz, 1H), 7.20 (brd, 2H, NH2), 7.79 (d, J=7.3 Hz, 1H); MS m/z 229.8 (M+1, 4%), 112(100%). Anal. Calcd. for C8H11N3O3S: C, 41.91; H, 4.84; N, 18.33; S, 13.99. Found: C, 41.97; H, 4.83; N, 18.24; S, 13.93
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[N:6]=[C:7]([NH:20][C:21](=[O:30])[C:22]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=2[F:29])[S:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=1)=O.[C:31](=[S:34])([NH2:33])[CH3:32]>CCO>[F:29][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([F:28])[C:22]=1[C:21]([NH:20][C:7]1[S:8][C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)=[C:5]([C:3]2[N:33]=[C:31]([CH3:32])[S:34][CH:2]=2)[N:6]=1)=[O:30]
Reactant: CC(N)=S
Reactant: O=C(CBr)c1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Solvent: CCO
Product: Cc1nc(-c2nc(NC(=O)c3c(F)cccc3F)sc2-c2cccc(C(F)(F)F)c2)cs1
Temperature: 25 °C
Reaction time: 4 h
Yield: 85.2 %

Procedure:
To the solution of Compound 85 (51 mg, 0.1 mmol) in 5 mL of EtOH was added ethanethioamide (0.2 mmol) at room temperature. The resulting solution was stirred at room temperature for 4 hours. The solvent was removed under reduced pressure and the residue was redissolved in ethyl acetate. The solution was treated with saturated solution of NaHCO3 and extracted with ethyl acetate. The combined extracts were dried (Na2SO4) and concentrated. Column chromatography on silica gel (eluted with ethyl acetate) gave Compound 86 (41 mg, 86%) as a yellow solid.
Reaction SMILES: [C:1]12[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH:6][C:5](=[O:12])[O:4][C:2]2=[O:3].Cl.Cl[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.[H-].[Na+].O>CN(C=O)C>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:1]=2[C:2](=[O:3])[O:4][C:5]1=[O:12]
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Reactant: ClCc1ccccn1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=c1oc(=O)n(Cc2ccccn2)c2ccccc12
Temperature: 25 °C
Reaction time: 42 h
Yield: 33.8 %

Procedure:
To a solution of isatoic anhydride (25.4 g, 0.156 mol) in DMF (300 mL) were added 2-(chloromethyl)pyridine hydrochloride (28.1 g, 0.171 mol) and sodium hydride (66% in oil, 12.5 g, 0.34 mol) under ice-cooling. The obtained mixture was stirred at room temperature for 42 hr. Water (750 mL) was added to the reaction mixture and the mixture was ice-cooled. The precipitated solid was collected by filtration, and recrystallized from acetone-diisopropyl ether to give the title compound (13.4 g, 34%).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:14]([O:16]C)=O)=[N:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][N:7]=1.[NH2:18][NH2:19].CO>O>[NH2:1][C:2]1[C:3]([C:14]([NH:18][NH2:19])=[O:16])=[N:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][N:7]=1
Reactant: COC(=O)c1nc(-c2cccnc2)cnc1N
Reactant: NN
Solvent: O
Solvent: CO
Product: NNC(=O)c1nc(-c2cccnc2)cnc1N
Yield: 58.5 %

Procedure:
A mixture of methyl 3-amino-6-(3-pyridyl)pyrazine-2-carboxylate (2 g, 8.687 mmol) was heated in Hydrazine (1.392 g, 1.363 mL, 43.43 mmol) with a minimal amount of MeOH (5 mL) added at 80° C. for 2 hours. Water was added and the product collected by filtration, washed with methanol and dried to furnish the product as a brown solid (1.17 g, 58% Yield). 1H NMR (400.0 MHz, DMSO) d 4.52 (br s, 2H), 7.43 (m, 1H), 7.71 (s, 2H), 8.54 (2H, m), 8.90 (1H, s), 9.39 (1H, s), 10.16 (1H, s) ppm; MS (ES+) 231
Reaction SMILES: [C:1]1([N:7]2[C:11]([CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=O)=[N:10][N:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>S(Cl)(Cl)=O>[CH2:1]([N:7]([CH2:11][CH3:12])[C:16](=[O:18])[CH2:15][CH2:14][CH2:13][CH2:12][C:11]1[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]=[N:9][N:10]=1)[CH3:2]
Reactant: O=C(O)CCCCc1nnnn1-c1ccccc1
Solvent: O=S(Cl)Cl
Product: CCN(CC)C(=O)CCCCc1nnnn1-c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 190.7 %

Procedure:
Thionyl chloride (10 ml) is added to 5-(1-phenyl-1,2,3,4-tetrazol-5-yl)valeric acid (1.8 g) and the mixture is refluxed for 1 hour. After excess thionyl chloride is distilled off under reduced pressure, dry benzene is added to the residue and the remaining small amount of thionyl chloride is removed as the benzene azeotrope. The resulting residue is dissolved in dry pyridine (50 ml) and thereto is added dropwise with stirring N,N-Diethylamine (1.5 g) under ice-cooling. The mixture is stirred at room temperature for 1 hour and benzene is added to the reaction mixture. The mixture is washed with diluted hydrochloric acid, aqueous saturated sodium bicarbonate solution and aqueous saturated sodium chloride solution and dried over sodium sulfate. After benzene is distilled off, the residue is subjected to column chromatography (Kieselgel 60 produced by Merck) by eluting the column with chloroform to give N,N-diethyl-5-(1-phenyl-1,2,3,4-tetrazol-5-yl)valeramide (2.1 g), colorless liquid, nD25 =1.5303.
Reaction SMILES: [CH:1]1[CH2:5][CH2:4][CH2:3][CH:2]=1.[Cl:6][SiH:7]([Cl:9])[Cl:8].C(O)(C)C>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH:1]1([Si:7]([Cl:9])([Cl:8])[Cl:6])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cl[SiH](Cl)Cl
Reactant: C1=CCCC1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: Cl[Si](Cl)(Cl)C1CCCC1
Temperature: 150 °C
Reaction time: 0.5 h

Procedure:
In a 100 ml autoclave were charged 13.0 g (0.191 mole) of cyclopentene, 23.5 g (0.173 mole) of trichlorosilane and 25 μl of a 0.077 m mole/ml chloroplatinic acid solution in isopropyl alcohol (platinum content 1.92×10 mole), which were then stirred at 150° C. for 30 minutes. Cyclopentyl trichlorosilane was obtained quantitatively.
Reaction SMILES: [Br:1][C:2]1[C:3]([C@@H:19]([NH:29][S@:30]([C:32]([CH3:35])([CH3:34])[CH3:33])=[O:31])[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)=[N:4][CH:5]=[C:6](N2C(=O)C3C(=CC=CC=3)C2=O)[CH:7]=1.[Br:36]C1C(/C=N\[S@](C(C)(C)C)=O)=NC(Br)=CC=1>>[Br:1][C:2]1[C:3]([C@@H:19]([NH:29][S@:30]([C:32]([CH3:35])([CH3:34])[CH3:33])=[O:31])[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)=[N:4][C:5]([Br:36])=[CH:6][CH:7]=1
Reactant: CC(C)(C)[S@](=O)N[C@@H](Cc1cc(F)cc(F)c1)c1ncc(N2C(=O)c3ccccc3C2=O)cc1Br
Reactant: CC(C)(C)[S@](=O)/N=C\c1nc(Br)ccc1Br
Product: CC(C)(C)[S@](=O)N[C@@H](Cc1cc(F)cc(F)c1)c1nc(Br)ccc1Br

Procedure:
The title compound (42D) was prepared according to the method presented for the synthesis of compound 30D of Example 30 utilizing 42C. MS (m/z) 496.99 [M+H]+
Reaction SMILES: [CH3:1][C:2]1[C:16](=[O:17])[N:15]=[C:14]2[N:4]([C@@H:5]3[O:9][C@H:8]([CH2:10][OH:11])[C@@H:7]([OH:12])[C@@H:6]3[O:13]2)[CH:3]=1.[CH3:18][SH:19].CN(C)C(N(C)C)=N>CN(C)C=O>[CH3:18][S:19][C@@H:6]1[C@H:7]([OH:12])[C@@H:8]([CH2:10][OH:11])[O:9][C@H:5]1[N:4]1[CH:3]=[C:2]([CH3:1])[C:16](=[O:17])[NH:15][C:14]1=[O:13]
Reactant: CS
Reactant: Cc1cn2c(nc1=O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
Agent: CN(C)C(=N)N(C)C
Solvent: CN(C)C=O
Product: CS[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cc(C)c(=O)[nH]c1=O
Reaction time: 12 h
Yield: 74.1 %

Procedure:
2.2'-Anhydro-5-methyluridine (17.02 g, 70.6 mmol), methanethiol (16.3 g, 339 mmol), 1,1,3,3-tetramethylguanidine (40.6 g, 353 mmol), and dimethylformamide (150 ml) were heated together at 60° C. After 12 hr, the products were cooled and concentrated under reduced pressure. The residual oil was purified by short silica gel (300 g) column chromatography. Concentration of appropriate fractions, which were eluted with CH2Cl2 -MeOH (93:7, v/v), furnished the title compound as a white foam (15.08 g, 74.1%). Crystallization from EtOH-CH2Cl2 furnished white needles.