Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[N:9]([C:23]1[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[C:24]=1[O:30][CH3:31])[CH:10]1[CH2:22][CH2:21][C:13]2([O:18][CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][O:14]2)[CH2:12][CH2:11]1)C1C=CC=CC=1>CO.[Ni]>[CH3:19][C:16]1([CH3:20])[CH2:17][O:18][C:13]2([CH2:12][CH2:11][CH:10]([NH:9][C:23]3[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[C:24]=3[O:30][CH3:31])[CH2:22][CH2:21]2)[O:14][CH2:15]1
Reactant: COc1c(N(OCc2ccccc2)C2CCC3(CC2)OCC(C)(C)CO3)ccnc1C
Agent: [Ni]
Solvent: CO
Product: COc1c(NC2CCC3(CC2)OCC(C)(C)CO3)ccnc1C

Procedure:
6.5 g of 4-[O-benzyl-N-(3,3-dimethyl-1,5-dioxaspiro[5.5]undec-9-yl)hydroxylamino]-3-methoxy-2-methylpyridine in 70 ml of methanol are hydrogenated using 2 g of Raney nickel at normal pressure until absorption of hydrogen is complete. After filtering, the filtrate is concentrated and the product is dissolved in diisopropyl ether. Crystallization takes place on addition of hexane. 4.3 g=90%; m.p.: 45° C.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([NH:20][C@H:21]([C@H:91]([OH:107])/[CH:92]=[CH:93]/[CH2:94][CH2:95][CH2:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH2:104][CH2:105][CH3:106])[CH2:22][O:23][C@@H:24]1[O:29][C@H:28]([CH2:30][OH:31])[C@@H:27]([O:32][C@@H:33]2[O:38][C@H:37]([CH2:39][OH:40])[C@H:36]([O:41][C@@H:42]3[O:47][C@H:46]([CH2:48][OH:49])[C@H:45]([OH:50])[C@H:44]([O:51][C@@H:52]4[O:57][C@H:56]([CH2:58][OH:59])[C@H:55]([OH:60])[C@H:54]([OH:61])[C@H:53]4[OH:62])[C@H:43]3[NH:63][C:64]([CH3:66])=[O:65])[C@H:35]([O:67][C@@]3(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)[C@H:34]2[OH:88])[C@H:26]([OH:89])[C@H:25]1[OH:90])=[O:19].C([O-])(=O)C>O>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([NH:20][CH:21]([CH:91]([OH:107])/[CH:92]=[CH:93]/[CH2:94][CH2:95][CH2:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH2:104][CH2:105][CH3:106])[CH2:22][O:23][CH:24]1[O:29][C@H:28]([CH2:30][OH:31])[C@@H:27]([O:32][C@@H:33]2[O:38][C@H:37]([CH2:39][OH:40])[C@H:36]([O:41][C@@H:42]3[O:47][C@H:46]([CH2:48][OH:49])[C@H:45]([OH:50])[C@H:44]([O:51][C@@H:52]4[O:57][C@H:56]([CH2:58][OH:59])[C@H:55]([OH:60])[C@H:54]([OH:61])[C@H:53]4[OH:62])[C@H:43]3[NH:63][C:64]([CH3:66])=[O:65])[C@H:35]([OH:67])[C@H:34]2[OH:88])[C@H:26]([OH:89])[C@H:25]1[OH:90])=[O:19]
Reactant: CCCCCCCCCCCCC/C=C/[C@@H](O)[C@H](CO[C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@H]3NC(C)=O)[C@H](O[C@]3(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O3)[C@H]2O)[C@H](O)[C@H]1O)NC(=O)CCCCCCCCCCCCCCCCC
Agent: CC(=O)[O-]
Solvent: O
Product: CCCCCCCCCCCCC/C=C/C(O)C(COC1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@H]3NC(C)=O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)NC(=O)CCCCCCCCCCCCCCCCC

Procedure:
A 10 ml quantity of 0.05% ganglioside GM1 solution, 10 ml of 40 mM acetate buffer (pH 5.0) and 10 ml of sterilized water were mixed together, and to the mixture was added 10 ml of aqueous Isozyme L (3 U/ml), followed by reaction at 37° C. for 8 hours. The reaction mixture was subjected to purification in the same manner as in Example 1, giving about 2.6 mg of asialo GM1 as a white powder. The production of asialo GM1 was confirmed in the same manner as in Example 1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][C:10](/[CH:13]=[CH:14]/[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=2[CH3:29])=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=2[CH3:29])=[CH:6][CH:7]=1
Reactant: CCOC(=O)/C=C/c1ccn(-c2ccc(Br)cc2)c1-c1ccc(C(N)=O)cc1C
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)CCc1ccn(-c2ccc(Br)cc2)c1-c1ccc(C(N)=O)cc1C
Temperature: 0 °C
Yield: 25 %

Procedure:
To an ice cooled solution of (E)-ethyl 3-(1-(4-bromophenyl)-2-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-3-yl)acrylate (400 mg, 0.88 mmol) in 95% ethanol (10 mL) were added BiCl3 (554 mg, 1.76 mmol) and portionwise NaBH4 (134 mg, 3.52 mmol), then the resultant mixture was stirred at room temperature for 12 h. The reaction mixture was filtered, and the filtrate was partitioned between water (50 mL) and ethyl acetate (30 mL), the aqueous layer was extracted with ethyl acetate (30 mL×2). The combined organic layers were washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative TLC (eluting with 50% ethyl acetate in petroleum ether for three times) to give ethyl 3-(1-(4-bromophenyl)-2-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-3-yl)propanoate (5-2) (100 mg, yield: 25%).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]([CH3:20])[S:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)(=[O:14])=[O:13])=[C:7]2[C:3]=1[CH:4]=[C:5]([C:21](=[S:23])[NH2:22])[NH:6]2.[C:24]([O:29][CH2:30][CH3:31])(=[O:28])[C:25]#[C:26][CH3:27].C(P(CCCC)CCCC)CCC.O1CCCC1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]([CH3:20])[S:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)(=[O:14])=[O:13])=[C:7]2[C:3]=1[CH:4]=[C:5]([C:21]1[S:23][CH:26]([CH2:25][C:24]([O:29][CH2:30][CH3:31])=[O:28])[CH2:27][N:22]=1)[NH:6]2
Reactant: CC#CC(=O)OCC
Reactant: Cc1ccc(N(C)S(=O)(=O)c2cccs2)c2[nH]c(C(N)=S)cc12
Agent: CCCCP(CCCC)CCCC
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)CC1CN=C(c2cc3c(C)ccc(N(C)S(=O)(=O)c4cccs4)c3[nH]2)S1
Yield: 64 %

Procedure:
A solution of 4-methyl-7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide (1.62 g), ethyl but-2-ynoate (1.2 mL) and tributylphosphine (1.1 mL) in a mixed solvent of tetrahydrofuran (30 mL)-toluene (20 mL) was stirred at room temperature for 4 hr. The reaction solution was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=10:90-35:65). The obtained crystals were crystallized from ethyl acetate-hexane to give the title compound (1.35 g, yield: 64%) as pale-yellow crystals.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:10][C:11]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:12]=1[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:14]>C(Cl)Cl>[C:13]([C:12]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:11]=1[NH:10][C:8]([NH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:9])(=[O:14])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1
Reactant: O=C=Nc1ccccc1
Solvent: ClCCl
Product: O=C(Nc1ccccc1)Nc1ccc(Cl)cc1C(=O)c1ccccc1
Yield: 90.4 %

Procedure:
A solution of 13.1 g (0.11 mole) of phenyl isocyanate and 23.17 g (0.1 mole) of 2-amino-5-chlorobenzophenone in 70 ml of methylene chloride was refluxed for 20 hr, and then evaporated to dryness under reduced pressure. The residue was recrystallized from ethanol to give 31.71 g (90%) of 1-(2-benzoyl-4-chlorophenyl)-3-phenylurea as colorless crystals: mp 145°-147°; 1H nmr (DMSO-d6) δ6.7-8.3 ppm (m, 13H), 9.43 ppm (d, J=7 Hz, 1H, exD2O) and 10.25 ppm (s, 1H, exD2O); 13C nmr (DMSO-d6) δ152.2 ppm (NHCO) and 195.5 ppm (C=O).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][CH:15]=1)[O:6][CH2:7][C:8]([O:10]CC)=[O:9])=O.[OH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=[O:25])[CH3:24])=[CH:19][C:18]=1[CH3:26].[OH-].[K+].Cl>CO.O>[OH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=[O:25])/[CH:24]=[CH:1]/[C:3]2[CH:4]=[C:5]([CH:13]=[CH:14][CH:15]=2)[O:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:19][C:18]=1[CH3:26]
Reactant: CCOC(=O)COc1cccc(C=O)c1
Reactant: CC(=O)c1ccc(O)c(C)c1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1cc(C(=O)/C=C/c2cccc(OCC(=O)O)c2)ccc1O
Temperature: 0 °C
Reaction time: 8 h
Yield: 64 %

Procedure:
Ethyl 2-(3-formylphenoxy)acetate (20.8 g, 0.1 mol) and 4′-hydroxy-3′-methylacetophenone (15.0 g, 0.1 mol) were dissolved in 150 mL of methanol and 50 mL of water. The solution was cooled with an ice-water bath, to which was added potassium hydroxide (21.0 g, 0.375 mol). The reaction mixture was stirred overnight. The resulted mixture was poured on to 600 mL of ice-water, acidified to pH=4-5 with 1 N HCl, and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with water and brine (200 mL each), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained yellow oil was dried under high-vacuum, 20 g (64%) of yellowish solid was obtained. 1H NMR (400 MHz, CDCl3): δ 9.95 (s, 1H), 8.40 (br, 1H), 7.80 (s, 1H), 7.65 (m, 2H), 7.22-7.55 (m, 5H), 6.85 (d, 1H), 4.75 (s, 2H), 2.22 (s, 3H). MS (EI): 313 (MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]=[CH:16][CH2:17][OH:18])=[CH:11][C:10]=1[O:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].Cl.Cl[CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[CH2:17][O:18][CH2:25][CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:11][C:10]=1[O:19][CH3:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1cc(C=CCO)ccc1OCc1ccccc1
Reactant: ClCCCN1CCCCC1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Product: COc1cc(/C=C/COCCCN2CCCCC2)ccc1OCc1ccccc1
Yield: 84.3 %

Procedure:
Following the procedure described in example 2, but starting from 3-(4-benzyloxy-3-methoxyphenyl)prop-2-en-1-ol (600 mg), potassium hydroxide (308 mg 85% wt) and 1-(3-chloropropyl)piperidine, hydrochloride (440 mg) in dimethylsufoxide (5 mL) affords 740 mg of trans-1-{3-[3-(4-benzyloxy-3-methoxyphenyl)-allyloxy]-propyl}piperidine containing 28% wt/wt DMSO used without any further purification. 3-(4-benzyloxy-3-methoxyphenyl)prop-2-en-1-ol can be prepared according to S. V. Reddy et al Chem. Lett. 32(11) 1038-9 (2003) or W. Gu et al Tetrahedron Lett. 41(32) 6079-82 (2000).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:16][S:17](Cl)(=[O:19])=[O:18]>CN(C=O)C.C(OCC)(=O)C>[CH3:16][S:17]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)(=[O:19])=[O:18]
Reactant: O=Cc1ccc(O)cc1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CS(=O)(=O)Oc1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 24.4 %

Procedure:
A mixture of 4-hydroxybenzaldehyde (5.0 gm, 1.0 eq, 40.98 mmol), anhydrous K2CO3 (17 g, 3 eq, 123 mmol), and methanesulfonylchloride (4.76 mL, 1.5 eq, 61.37 mmol) in dry DMF (200 mL) was stirred at RT for 16 h. The reaction mixture was diluted with ethyl acetate (200 mL) and washed with water and brine. Organic layer was dried (Na2SO4), condensed, and the residue obtained was chromatographed using ethyl acetate and hexanes to obtain the title compound as white solid (2.0 g, 25%).
Reaction SMILES: [F:1][C:2]([F:16])([CH2:12][CH2:13][CH2:14][CH3:15])[C:3](=[O:11])[CH2:4]P(=O)(OC)OC.[OH-].[K+].[C:19]([O:22][C@@H:23]1[C@H:27]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])[C@@H:26]([CH:38]=O)[C@H:25]([O:40][CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)[CH2:24]1)(=[O:21])[CH3:20].O>COC(C)(C)C>[C:19]([O:22][C@@H:23]1[C@H:27]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])[C@@H:26](/[CH:38]=[CH:4]/[C:3](=[O:11])[C:2]([F:1])([F:16])[CH2:12][CH2:13][CH2:14][CH3:15])[C@H:25]([O:40][CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)[CH2:24]1)(=[O:21])[CH3:20]
Reactant: COC(=O)CCCCCC[C@@H]1[C@@H](C=O)[C@H](OC2CCCCO2)C[C@@H]1OC(C)=O
Reactant: CCCCC(F)(F)C(=O)CP(=O)(OC)OC
Agent: [K+]
Agent: [OH-]
Solvent: COC(C)(C)C
Solvent: O
Product: CCCCC(F)(F)C(=O)/C=C/[C@@H]1[C@@H](CCCCCCC(=O)OC)[C@@H](OC(C)=O)C[C@H]1OC1CCCCO1
Temperature: 25 °C
Reaction time: 1.2 h
Yield: 80.6 %

Procedure:
To a solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (1.113 g, 4.31 mmol) in t-butyl methyl ether (17 ml), potassium hydroxide (0.225 g, 4.00 mmol) was added and the mixture was stirred for approximately 1.2 hours at room temperature. A solution of methyl 7-[(1R,2R,3R,5s)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (2) (0.965 g, 2.42 mmol) in t-butyl methyl ether (3 ml) solution, and water (0.32 ml) were added thereto. The mixed solution was heat refluxed for approximately 48 hours. After cooling to room temperature, water (5.6 ml) was added to the solution and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with ethyl acetate (4 ml). The organic layers were combined, sequentially washed with 3% aqueous sodium chloride (6 ml) and saturated aqueous sodium chloride (6 ml), and dried with anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 33 g; ethyl acetate:hexane=1:4) to give methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (3) (1.035 g; 1.950 mmol; yield: 80.6%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9]([NH:11][C:12]([O:14]CC)=O)[CH3:10])=[CH:4][CH:3]=1.O.[NH2:19][NH2:20]>C(O)CCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]([CH3:10])[NH:11][C:12](=[O:14])[NH:19][N:20]=2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)NC(C)C(=O)c1ccc(Br)cc1
Reactant: NN
Solvent: CCCCO
Solvent: O
Product: CC1NC(=O)NN=C1c1ccc(Br)cc1
Yield: 43.8 %

Procedure:
A mixture of 4'-bromo-2-ethoxycarbonylaminopropiophenone (4.29 g), hydrazine hydrate (8 g) and n-butanol (50 ml) was refluxed under heating for 68 hours. The solution was evaporated to dryness, and the resultant residue was dissolved in a mixture of chloroform and methanol. The solution was washed with water and the washings were extracted with chloroform. The combined organic layer was dried over magnesium sulfate and evaporated to dryness. The resultant residue was washed with diisopropyl ether and recrystallized from ethanol to give colorless crystals of 6-(4-bromophenyl)-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (1.68 g), m.p. 213.5°~215° C.
Reaction SMILES: [CH:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N+:15]([O-])=O)[CH:11]=2)[N:6]=1)([CH3:3])[CH3:2]>ClCCl.CO>[CH:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH2:15])[CH:11]=2)[N:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Nc1ccc2cc([N+](=O)[O-])ccc2n1
Solvent: CO
Solvent: ClCCl
Product: CC(C)Nc1ccc2cc(N)ccc2n1

Procedure:
Prepared analogously to Example 3.1.b. from isopropyl-(6-nitroquinolin-2-yl)amine. Yield: 0.51 g (78.1% of theory); C12H15N3 (M=201.27); calc.: molecular ion peak (M+H)+: 202; found: molecular ion peak (M+H)+: 202; Rf value: 0.25 (silica gel, dichloromethane/methanol (19:1)).
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:8][CH3:9])=[N:4][CH:5]=[CH:6][CH:7]=1.O.O.[C:12](O)(=[O:16])[C:13](O)=[O:14]>>[CH3:9][N:8]1[C:13](=[O:14])[C:12](=[O:16])[NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[N:4][C:3]1=2
Reactant: O=C(O)C(=O)O
Reactant: CNc1ncccc1N
Solvent: O
Product: Cn1c(=O)c(=O)[nH]c2cccnc21

Procedure:
3-amino-2-(N-methylamino)-pyridine (0.1 mol)and oxalic acid dihydrate (0,12mol) was dissloved in 4N HCI (400 ml). The solution was refluxed for 8 hours and then cooled to room temperature whereby the title compound precipitated as crystals. The crystals were separated by filtration and then washed with water. m.p. 271°-272° C.
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[C:5]([N:10]=1)=[N:6][CH:7]=[CH:8][CH:9]=2.[C:11]([NH:30][C:31]1[S:32][CH:33]=[C:34](/[C:36](=[N:63]/[O:64][CH3:65])/[C:37]([NH:39][CH:40]2[C:61](=[O:62])[N:42]3[C:43]([C:49]([O:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=4)=[O:50])=[C:44]([CH2:47]Cl)[CH2:45][S:46][C@H:41]23)=[O:38])[N:35]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[C:11]([NH:30][C:31]1[S:32][CH:33]=[C:34](/[C:36](=[N:63]/[O:64][CH3:65])/[C:37]([NH:39][CH:40]2[C:61](=[O:62])[N:42]3[C:43]([C:49]([O:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=4)=[O:50])=[C:44]([CH2:47][S:1][C:2]4[S:3][C:4]5[C:5]([N:10]=4)=[N:6][CH:7]=[CH:8][CH:9]=5)[CH2:45][S:46][C@H:41]23)=[O:38])[N:35]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CO/N=C(\C(=O)NC1C(=O)N2C(C(=O)OCc3ccc(OC)cc3)=C(CCl)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: Sc1nc2ncccc2s1
Product: CO/N=C(\C(=O)NC1C(=O)N2C(C(=O)OCc3ccc(OC)cc3)=C(CSc3nc4ncccc4s3)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Yield: 62 %

Procedure:
Using 111 mg of 2-mercaptothiazolo[4,5-b]pyridine in place of 2-mercaptothiazolo[4,5-c]pyridine and 477 mg of p-methoxybenzyl 7-{(Z)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetamido}-3-chloromethyl-3-cephem-4-carboxylate, the reaction and purification were carried out in the same manner as in Example 1(a) to obtain 345 mg of the title compound in a yield of 62%.
Reaction SMILES: [CH3:1][O:2][CH:3]1[O:8][CH2:7][CH:6]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH2:17][S:18][C:19]3[NH:23][C:22]4[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=4[N:20]=3)[C:12]=2[CH3:28])[CH2:5][O:4]1.ClC1C=CC=C(C(OO)=[O:37])C=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.CO>[CH3:1][O:2][CH:3]1[O:8][CH2:7][CH:6]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH2:17][S:18]([C:19]3[NH:20][C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[N:23]=3)=[O:37])[C:12]=2[CH3:28])[CH2:5][O:4]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COC1OCC(COc2ccnc(CSc3nc4ccccc4[nH]3)c2C)CO1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Product: COC1OCC(COc2ccnc(CS(=O)c3nc4ccccc4[nH]3)c2C)CO1
Reaction time: 2 h
Yield: 65.9 %

Procedure:
To a toluene/methanol (10:1) (20 ml) solution of the 2-(((4-((2-methoxy-1,3-dioxan-5-yl)methoxy)-3-methylpyridin-2-yl)methyl)thio)-1H-benzimidazole (324 mg, 807 μmol) obtained in the step (6d), a toluene/methanol (10:1) (5 ml) solution of 3-chloroperbenzoic acid (193 mg, 726 μmol as the content was regarded as 65%) was added dropwise at −50° C. to −60° C. for 5 minutes in a nitrogen atmosphere. The mixture was stirred for 2 hours in the same conditions. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate was added and the resultant mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/methanol) to obtain the title compound (222 mg, 65.9% yield), which is a cis and trans (1:1) mixture, as a light yellow foam.
Reaction SMILES: [CH:1]([C:4]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:5]=1[NH2:6])([CH3:3])[CH3:2].C([Li])CCC.[CH3:17][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>O>[CH:1]([C:4]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:5]=1[NH:6][C:22](=[NH:23])[C:21]1[CH:24]=[CH:25][C:18]([CH3:17])=[CH:19][CH:20]=1)([CH3:3])[CH3:2]
Reactant: Cc1cccc(C(C)C)c1N
Reactant: Cc1ccc(C#N)cc1
Agent: [Li]CCCC
Solvent: O
Product: Cc1ccc(C(=N)Nc2c(C)cccc2C(C)C)cc1
Reaction time: 8 h
Yield: 82.4 %

Procedure:
Procedure as described for Amidine I using the following amounts: 7.80 mL of 2-isopropyl-6-methylaniline (50.0 mmol); 25.0 mL of 2.0 M butyllithium (50.0 mmol), 5.86 g of 4-methylbenzonitrile (50.0 mmol). After refluxing overnight, the solution was dark brown. Addition of water yielded an orange-brown solution with suspended solid. Solution was filtered and taken to dryness. The residue was treated with 100 mL of pentane stirred overnight and filtered yielding 10.98 g (83%) of beige material. 1H NMR (400 MHz, CDCl3): 7.82 (d, 2H), 7.26 (d, 2H), 7.15 (d, 1H), 7.05 (d, 1H), 6.98 (t, 1 H), 4.56 (s, 2H), 3.09 (septet, 1H), 2.42 (s, 3H), 2.15 (s, 3H), 1.21 (d, 3H), 1.16 (d, 3H).
Reaction SMILES: O[CH2:2][C:3]([NH:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:9]=1)([CH3:5])[CH3:4].S(Cl)(Cl)=O>C(OCC)C>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[O:22][CH2:2][C:3]([CH3:4])([CH3:5])[N:6]=2)=[CH:9][C:10]=1[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCOc1cc(C(=O)NC(C)(C)CO)ccc1OC
Solvent: CCOCC
Solvent: O=S(Cl)Cl
Product: CCCCCOc1cc(C2=NC(C)(C)CO2)ccc1OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
N-(2-Hydroxy-1,1-dimethylethyl)-4-methoxy-3-pentyloxybenzamide (5.498 g, 0.0178 mol, 1 eq) was dissolved in thionyl chloride (4.29 ml, 0.0214 mol, 3.3 eq), and the solution was stirred at room temperature for 1 hour. The reaction mixture was poured into diethyl ether (40 ml). The obtained hydrochloride compound was collected by filtration, and excess thionyl chloride was removed. A 1N aqueous sodium hydroxide solution (about 20 ml) was added to this hydrochloride compound under ice-cooling, whereby the mixture was alkalized (pH=10). The solution was extracted twice with diethyl ether (30 ml). The organic layers were combined, washed with saturated brine (60 ml) and dried over anhydrous sodium sulfate. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure to give 2-(4-methoxy-3-pentyloxyphenyl)-4,4-dimethyl-4,5-dihydrooxazole (4.46 g, 86%) as colorless crystals.
Reaction SMILES: [N:1]1[C:2]2[C:14](=O)[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:3]=2[NH:4][C:5](=[O:7])[CH:6]=1.Cl.[NH2:17][OH:18]>N1C=CC=CC=1>[OH:18][N:17]=[C:14]1[C:2]2[N:1]=[CH:6][C:5](=[O:7])[NH:4][C:3]=2[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]1=2
Reactant: NO
Reactant: O=C1c2ccccc2-c2[nH]c(=O)cnc21
Agent: Cl
Solvent: c1ccncc1
Product: O=c1cnc2c([nH]1)-c1ccccc1C2=NO
Temperature: 80 °C
Reaction time: 18 h
Yield: 48.8 %

Procedure:
A mixture of 9H-indeno[1,2-b]pyrazine-3,9(4H)-dione (1.0 g, 5.0 mmol), pyridine (40 ml) and hydroxylamine hydrochloride (0.42 g, 6.0 mmol) was stirred at 80° C. for 18 hours. The reaction mixture was cooled to room temperature, and the precipitate was filtered off and washed with water, acetic acid and water and dried. The crude material (0.81 g) was recrystallized from DMF to afford 0.52 g (49%) of the title compound. M.p.>300° C. 1H-NMR (DMSO-d6, δ): 7.49-7.62 (m, 2H), 7.88 (d, 1H), 7.95 (s, 1H), 8.36 (d, 1H), 12.5-13.2 (broad, 1H), 12.83 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13]([OH:15])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.Cl.[NH:48]1[CH2:53][CH2:52][CH2:51][CH:50]([C:54]([OH:59])([CH2:57][CH3:58])[CH2:55][CH3:56])[CH2:49]1>CN(C=O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13]([N:48]2[CH2:53][CH2:52][CH2:51][CH:50]([C:54]([OH:59])([CH2:57][CH3:58])[CH2:55][CH3:56])[CH2:49]2)=[O:15])=[CH:6][CH:7]=1
Reactant: Cc1ccc(-c2oncc2C(=O)O)cc1
Reactant: CCC(O)(CC)C1CCCNC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCC(O)(CC)C1CCCN(C(=O)c2cnoc2-c2ccc(C)cc2)C1
Reaction time: 2 h
Yield: 44.9 %

Procedure:
A solution of 5-(4-methylphenyl)isoxazole-4-carboxylic acid (10 mg, 0.05 mmol), TBTU (19 mg, 0.06 mmol, 1,2 equ.) and N-ethyl-N-isopropylpropan-2-amine (17 μL, 0.010 mmol, 2 equ) in DMF (0.3 mL) was added to 3-piperidin-3-ylpentan-3-ol hydrochloride (10 mg, 0.05 mmol) and the reaction mixture was left at rt for 2 h. The solvent was evaporated and the crude product was purified by RP-HPLC. After evaporation of the solvents the product was dried in vacuum to yield the title compound (8 mg). MS (ESI, pos. ion) m/z calcd for C21H28N2O3: 356.2100, found 356.2099.