Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([N:18]3[CH:22]=[CH:21][N:20]=[C:19]3[S:23]([CH3:26])(=[O:25])=[O:24])[O:11][C:12]=2[CH2:13][CH2:14][C:15]([OH:17])=O)=[CH:4][CH:3]=1.ON1C2N=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.[CH3:48][N:49]1[CH2:54][CH2:53][CH:52]([CH2:55][N:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)[CH2:51][CH2:50]1>O.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([N:18]3[CH:22]=[CH:21][N:20]=[C:19]3[S:23]([CH3:26])(=[O:25])=[O:24])[O:11][C:12]=2[CH2:13][CH2:14][C:15]([N:59]2[CH2:58][CH2:57][N:56]([CH2:55][CH:52]3[CH2:53][CH2:54][N:49]([CH3:48])[CH2:50][CH2:51]3)[CH2:61][CH2:60]2)=[O:17])=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)c1nccn1-c1nc(-c2ccc(Cl)cc2)c(CCC(=O)O)o1
Reactant: CN1CCC(CN2CCNCC2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: O
Product: CN1CCC(CN2CCN(C(=O)CCc3oc(-n4ccnc4S(C)(=O)=O)nc3-c3ccc(Cl)cc3)CC2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.5 %

Procedure:
A mixture of 3-{4-(4-chlorophenyl)-2-[2-(methylsulfonyl)-1H-imidazol-1-yl]-5-oxazolyl}propionic acid (50 mg), 1-hydroxy-7-aza-1H-1,2,3-benzotriazole (41 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (46 mg), 4-[(1-methyl-4-piperidinyl)methyl]piperazine (60 mg) and N,N-dimethylformamide (0.5 ml) was stirred overnight at room temperature. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was concentrated, introduced into preparative HPLC and purified. Ethyl acetate was added to the obtained oil and the mixture was washed with saturated aqueous sodium hydrogen carbonate. A 4N hydrochloric acid ethyl acetate solution was added to the ethyl acetate layer and the mixture was concentrated to give 1-(3-{4-(4-chlorophenyl)-2-[2-(methylsulfonyl)-1H-imidazol-1-yl]-5-oxazolyl}propanoyl)-4-[(1-methyl-4-piperidinyl)methyl]piperazine 3 hydrochloric acid (65.0 mg, yield 66%).
Reaction SMILES: [C:1]1([NH2:8])[C:2]([NH2:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.C([O:11][C:12](=O)[C:13](=O)[CH3:14])C>C(O)C>[CH3:14][C:13]1[C:12](=[O:11])[NH:7][C:2]2[C:1]([N:8]=1)=[CH:6][CH:5]=[CH:4][CH:3]=2
Reactant: CCOC(=O)C(C)=O
Reactant: Nc1ccccc1N
Solvent: CCO
Product: Cc1nc2ccccc2[nH]c1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of benzene-1,2-diamine (10.8 g, 100 mmol) in ethanol (500 mL) was treated with a solution of ethyl-2-oxopropanoate (11.22 g, 110 mmol) slowly at 0° C., and the resulting suspension was stirred at room temperature for 1 h, then filtered. An off-white solid was collected (15.85 g). MS (ESI): m/z 161 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[C:9](=[S:11])=[S:10].[CH2:12]([N:14]([CH2:17][CH3:18])[CH2:15][CH3:16])[CH3:13]>>[CH2:12]([N:14]([CH2:17][CH3:18])[CH2:15][CH3:16])[CH3:13].[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:9](=[S:10])[SH:11])=[N:3][CH:4]=1
Reactant: Cc1ccc(N)nc1
Reactant: S=C=S
Solvent: CCN(CC)CC
Product: Cc1ccc(NC(=S)S)nc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 66 %

Procedure:
2-Amino-5-methylpyridine (21.6 g., 0.2 mol.) was suspended in triethylamine (60 ml.) and carbon disulphide (30 ml.) was added. The mixture was shaken at room temperature for 3 hours. The pale yellow solid precipitate was filtered off and washed with ether to give 5-methyl-2-pyridyldithiocarbamic acid triethylamine salt (37.7 g., 66%). This material was suspended in ethanol (100 ml.) and stirred at room temperature. Benzyl chloride (16.5 g., 15 ml.) was added dropwise. After 2 hours, a clear solution was obtained. Water was added and the precipitated benzyl ester collected. After washing with water and petrol ether (40°-60° C.), the product weighed 33.8 g. (m.pt. 141° C.).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:26]=[CH:25][C:17]3[C:18]([CH3:24])([CH3:23])[O:19][C:20](=[O:22])[NH:21][C:16]=3[CH:15]=2)=[CH:4][CH:3]=1.[OH:27]O>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:26]=[CH:25][C:17]3[C:18]([CH3:23])([CH3:24])[O:19][C:20](=[O:22])[NH:21][C:16]=3[CH:15]=2)=[O:27])=[CH:6][CH:7]=1
Reactant: Cc1ccc(SCCCCOc2ccc3c(c2)NC(=O)OC3(C)C)cc1
Reactant: OO
Product: Cc1ccc(S(=O)CCCCOc2ccc3c(c2)NC(=O)OC3(C)C)cc1

Procedure:
Prepared analogously to Example 2 from 7-[4-(4-methylphenylmercapto)-butoxy]-4,4-dimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:32])[C:7]([CH2:18][NH:19][C:20](=O)OC3C=CC([N+]([O-])=O)=CC=3)=[CH:8][N:9]2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[F:33][C:34]1[CH:43]=[C:42]2[C:37](C(N)=[N:39][CH:40]=[N:41]2)=[CH:36][CH:35]=1>>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:32])[C:7]([CH2:18][NH:19][C:20]3[C:37]4[C:42](=[CH:43][C:34]([F:33])=[CH:35][CH:36]=4)[N:41]=[CH:40][N:39]=3)=[CH:8][N:9]2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:4][CH:3]=1
Reactant: Nc1ncnc2cc(F)ccc12
Reactant: O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)Oc1ccc([N+](=O)[O-])cc1
Product: O=c1c(CNc2ncnc3cc(F)ccc23)cn(-c2ccccc2)c2cc(Cl)ccc12

Procedure:
7-Chloro-3-[(7-fluoro-quinazolin-4-ylamino)-methyl]-1-phenyl-1H-quinolin-4-one was prepared according to the procedure described above for example 12-1, starting with intermediate M and 7-fluoro-quinazolin-4-amine. MS calcd. for C24H16ClFN4O [(M+H)+] 430.9, obsd. 431.3
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:36])[CH:10]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:11][N:12]1[CH:29]=[N:28][C:14]([CH2:15][C@@H:16]([C:25]([OH:27])=[O:26])[NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:13]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Cl:47]N1C(=O)CCC1=O>O1CCCC1.C(OCC)(=O)C>[Cl:47][C:10]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)([C:9]([C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])=[O:36])[CH2:11][N:12]1[CH:29]=[N:28][C:14]([CH2:15][C@@H:16]([C:25]([OH:27])=[O:26])[NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:13]1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1cn(CC(C(=O)c2ccc(Cl)cc2Cl)c2ccccc2)cn1)C(=O)O
Reactant: O=C1CCC(=O)N1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N[C@@H](Cc1cn(CC(Cl)(C(=O)c2ccc(Cl)cc2Cl)c2ccccc2)cn1)C(=O)O
Temperature: 25 °C
Yield: 48.7 %

Procedure:
A portion of the 1-[3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidine (5.5 g) in dry tetrahydrofuran (50 ml) was added dropwise to a stirred solution of lithium hexamethyldisilazide in tetrahydrofuran (33 ml, 1M solution in tetrahydrofuran) at -78° C. under an atmosphere of nitrogen. After 30 minutes the resulting solution was rapidly transferred, under an atmosphere of nitrogen, into a stirred solution of N-chlorosuccinimide (1.6 g) in dry tetrahydrofuran (50 ml). The resulting mixture was cooled in an ice bath under an atmosphere of nitrogen. The mixture was allowed to warm to room temperature over a period of 20 minutes and was quenched upon an addition of an excess of saturated aqueous potassium dihydrogen orthophosphate. The organic phase was separated and the aqueous phase was extracted twice with ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield a residue. The residue was dissolved in ethyl acetate, washed with water and then brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield a foam which was chromatographed on silica gel using a mixture of methanol:dichloromethane (2:23) as an eluent to yield 1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[ (1,1-dimethylethoxy)carbonyl]-L-histidine (2.85 g) as a mixture of diastereoisomers, (δ (CDCl3) 1.45 (9H, s), 1.48 (9H, s), 3.01 (2H, bd, J=15Hz), 3.23 (2H, bd, J=15Hz), 4.35 (2H, bs), 4.62 (2H, bt, J=17Hz), 4.86 (2H, bt, J=17Hz), 5.48 (2H, m, 4 lines), 6.38 (1H, bs), 6.57 (3H, m), 6.98 (2H, dd, J=9Hz and 2Hz), 7.42 (2H, m), 7.46 (5H, s), 7.49 (5H, s), 7.56 (1H, bs) and 7.60 (1H, bs)), having the formula: ##STR33##
Reaction SMILES: Br.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[O:19][C:18]([NH2:20])=[N:17][N:16]=3)=[CH:11][CH:10]=2)[CH:3]=1.[F:21][C:22]([F:34])([F:33])[O:23][C:24]1[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27]>N1C=CC=CC=1.CO>[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[O:19][C:18]([NH:20][C:26](=[O:27])[C:25]4[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=4[O:23][C:22]([F:21])([F:33])[F:34])=[N:17][N:16]=3)=[CH:13][CH:14]=2)[CH:3]=1
Reactant: Nc1nnc(-c2ccc(Oc3cccnc3)cc2)o1
Reactant: O=C(Cl)c1ccccc1OC(F)(F)F
Agent: Br
Solvent: c1ccncc1
Solvent: CO
Product: O=C(Nc1nnc(-c2ccc(Oc3cccnc3)cc2)o1)c1ccccc1OC(F)(F)F
Reaction time: 18 h
Yield: 9.1 %

Procedure:
5-[4-(Pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-amine hydrobromide salt (167.5 mg, 0.5 mmol) was suspended in 2 mL of anhydrous pyridine. Neat 2-trifluoromethoxybenzoyl chloride (100 uL) was added directly into the solution. It was left to stir for 18 hours. The reaction mixture formed an orange solution with a yellow precipitate. Then it was diluted with ca. 1 mL of MeOH, filtered through 0.22 u syringe filter and purified by reverse phase preparative HPLC using acetonitrile/water mixture containing 0.01% of TFA. Fractions, containing the product, were combined and partitioned between ca. 40 mL of EtOAc and ca. 40 mL of saturated aqueous NaHCO3. The EtOAc layer was washed with brine, dried over anhydrous sodium sulfate and filtered. Solvent was removed in vacuo to give the title product as a bright-yellow solid (20.2 mg). Yield 9.1%.
Reaction SMILES: [S:1]([O-:5])([O-:4])(=[O:3])=[S:2].[Na+:6].[Na+].[I-].[Na+].Cl[CH2:11][CH2:12][N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH3:23])[CH:21]=2)[CH:16]([CH3:24])[CH2:15][C:14]1([CH3:26])[CH3:25].O>C(O)C>[S:1]([O-:5])([S:2][CH2:11][CH2:12][N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH3:23])[CH:21]=2)[CH:16]([CH3:24])[CH2:15][C:14]1([CH3:25])[CH3:26])(=[O:4])=[O:3].[Na+:6]
Reactant: O=S([O-])([O-])=S
Reactant: Cc1ccc2c(c1)N(CCCl)C(C)(C)CC2C
Agent: [I-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1ccc2c(c1)N(CCSS(=O)(=O)[O-])C(C)(C)CC2C

Procedure:
A mixture of sodium thiosulfate (49.6 g, 0.2 m), sodium iodide (1 g), N-(2-chloroethyl)-2,2,4,7-tetramethyl-1,2,3,4-tetrahydroquinoline (25.2 g, 0.1 m), water (100 ml), and ethanol (100 ml) was refluxed for 3 hrs. The mixture was cooled and extracted with two 75 ml portions of toluene. The aqueous layer then containing essentially pure product and aliquots were used to prepare dyes without further purification.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([CH2:19][CH2:20]OS(C)(=O)=O)[CH2:13]OS(C)(=O)=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:27][OH:28].C([O-])(O)=O.[Na+]>CCN(CC)CC.CS(C)=O.Cl>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:19][CH2:20][N:27]([OH:28])[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)OCC[C@H](COS(C)(=O)=O)NC(=O)OCc1ccccc1
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: O=C(N[C@@H]1CCN(O)C1)OCc1ccccc1
Temperature: 60 °C
Yield: 85 %

Procedure:
(R)-2-(Benzyloxycarbonylamino)-1,4-dimethanesulfonyloxybutane (2.0 g; 5.06 mmol) was dissolved in a Et3N/DMSO mixture (1:1, 20 ml). Hydroxylamine hydrochloride (1.4 g; 20.2 mmol) was added and the mixture was heated at 60° C. over night. The mixture was poured in aqueous HCl (the pH was adjusted to pH=6 with NaHCO3) and extracted twice with AcOEt. The organic phase was washed with water and dried over Na2SO4. The solids were filtered off and the solvent was removed. A light yellow oil (1.4 g, purity 73%) was obtained (yield: 85%). The crude title compound was used as is.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([F:23])[C:21]=1F)[CH:17]=[O:18].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:21]2[C:14]([F:13])=[CH:15][C:16]([CH:17]=[O:18])=[CH:19][C:20]=2[F:23])=[CH:4][C:3]=1[C:9]([F:10])([F:11])[F:12]
Reactant: O=Cc1cc(F)c(F)c(F)c1
Reactant: Oc1ccc(Cl)c(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1cc(F)c(Oc2ccc(Cl)c(C(F)(F)F)c2)c(F)c1
Temperature: 60 °C
Yield: 79.2 %

Procedure:
The mixture of 4-chloro-3-(trifluoromethyl)phenol (3.4 g, 17.30 mmol), 3,4,5-trifluorobenzaldehyde (2.7 g, 16.87 mmol) and K2CO3 (2.80 g, 20.24 mmol) in DMF was heated with a microwave reactor at 60° C. for 1 h. Purification via a flash column chromatography then afforded the title compound (4.5 g, 79% yield). LCMS: rt=3.88 min, [M+H+]=337
Reaction SMILES: [CH3:1][CH:2]([C:4]1[CH:5]=[N:6][N:7]2[C:12]([C:13]3[CH:14]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:17][CH:18]=3)=[CH:11][CH:10]=[N:9][C:8]=12)[OH:3].C(O)(=O)C>[O-2].[O-2].[O-2].[Cr+6].O>[F:21][C:19]([F:20])([F:22])[C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:12]2[N:7]3[N:6]=[CH:5][C:4]([C:2]([CH3:1])=[O:3])=[C:8]3[N:9]=[CH:10][CH:11]=2)[CH:14]=1
Reactant: CC(O)c1cnn2c(-c3cccc(C(F)(F)F)c3)ccnc12
Agent: [Cr+6]
Agent: [O-2]
Solvent: O
Solvent: CC(=O)O
Product: CC(=O)c1cnn2c(-c3cccc(C(F)(F)F)c3)ccnc12
Reaction time: 1 h

Procedure:
A mixture of 3.0 g. of α-methyl-7-(α,α,α-trifluoro-m-tolyl)pyrazolo[1,5-a]pyrimidine-3-methanol and one gram of chromium trioxide in 75 ml. glacial acetic acid is allowed to remain at room temperature for 1 hour and then poured into water. The resultant solid is removed by filtration and then recrystallized from methylene chloride-n-hexane to yield the desired methyl ketone, m.p. 127°-130° C.
Reaction SMILES: O=[O+][O-].[CH2:4]([CH:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH3:19])[CH:14]=2)[C:9]21[CH2:23][CH2:22][CH2:21][CH2:20]2)C=CC.[CH3:24][OH:25]>ClCCl>[O:25]=[CH:24][CH2:4][CH:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH3:19])[CH:14]=2)[C:9]21[CH2:20][CH2:21][CH2:22][CH2:23]2
Reactant: CC=CCC1C(=O)c2cc(OC)ccc2C12CCCC2
Reactant: CO
Agent: O=[O+][O-]
Solvent: ClCCl
Product: COc1ccc2c(c1)C(=O)C(CC=O)C21CCCC1
Reaction time: 0.83 h
Yield: 97 %

Procedure:
An ozone stream (2.5 g ozone/hour) was conducted for 50 minutes while stirring through a solution, cooled to -70°, of 6.2 g of (RS)-2'-(2-buten-1-yl)-5'-methoxy-2',3'-dihydro-spiro[cyclopentane-1,1'-[1H]indene]-3'-one in 80 ml of anhydrous dichloromethane and 20 ml of anhydrous methanol. Subsequently, the solution was flushed with oxygen for 5 minutes and with argon for 10 minutes. After the addition of 2.52 ml of dimethyl sulfide, the mixture was stirred at room temperature for 17 hours. The reaction mixture was evaporated in a vacuum. The residue was treated with 100 ml of dichoromethane and, after the addition of 15 ml of water and 15 ml of trifluoroacetic acid, stirred at room temperature for 2.5 hours. The mixture was subsequently poured into 150 ml of water and neutralized by the spatula-wise addition of sodium hydrogen carbonate while stirring. An additional 50 ml of water were added. The phases were separated and the aqueous phase was extracted twice with 100 ml of dichloro-methane each time. The combined organic phases were dried over magnesium sulfate and concentrated in a vacuum. 5.74 g (97%) of (RS)-2'-(2-oxoethyl)-5'-methoxy-2',3'-dihydro-spiro[cyclopentane-1,1'-[1H]indene]-3'-one were obtained as a light yellow oil.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@H:5]([OH:12])[C@H:4]1[OH:13].[OH-].[K+].O.[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:13][C@@H:4]1[C@@H:5]([O:12][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:6]([O:11][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:7]([CH2:9][O:10][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:8][C@@H:3]1[O:2][CH3:1])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: ClCc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: CO[C@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Methyl-α-D-glucopyranoside 9 (75 g) is dissolved in benzyl chloride (400 mL). To this solution is added potassium hydroxide (250 g). The resulting suspension is heated at 100° C. (water bath temp.) with stirring (mechanical) for 4 h, then cooled to r.t. The mixture is washed with saturated NaCl in ether (500 mL) and dried with MgSO4. The ether is evaporated. The residue is distilled under vacuum (~0.1 mm Hg) at a temperature of 120° C. until no more distillate is collected or the temperature at the distilling head begins to fall. The pot residue is used for the next reaction without further purification.
Reaction SMILES: [Cl:1][C:2]1[C:13]([Cl:14])=[CH:12][CH:11]=[CH:10][C:3]=1/[CH:4]=[CH:5]/[C:6](=[N:8][OH:9])[NH2:7].[C:15](OC(=O)CC)(=O)[CH2:16][CH3:17]>>[Cl:1][C:2]1[C:13]([Cl:14])=[CH:12][CH:11]=[CH:10][C:3]=1/[CH:4]=[CH:5]/[C:6]1[N:7]=[C:15]([CH2:16][CH3:17])[O:9][N:8]=1
Reactant: CCC(=O)OC(=O)CC
Reactant: NC(/C=C/c1cccc(Cl)c1Cl)=NO
Product: CCc1nc(/C=C/c2cccc(Cl)c2Cl)no1
Yield: 58.2 %

Procedure:
7.0 g (0.03 tool) of (E)-2,3-dichlorocinnamamide oxime are initially introduced into 7 ml of propionic anhydride and the mixture is then stirred at reflux temperature for 2 hours. Subsequently, the whole batch is concentrated in vacuo, and the residue is stirred with sodium carbonate solution and extracted with methylene chloride. The organic phase is dried over sodium sulphate and the solvent is distilled off. 4.7 g (58.2% of theory) of (E) -3- (2,3 -dichloro-styryl) -5-ethyl-1,2,4-oxadiazole are obtained.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[C:17]([N+:18]([O-:20])=[O:19])=[C:16]([O:21][CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[N:15]=[CH:14][N:13]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[N:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34](Cl)=[O:35].N1C=CC=CC=1C(O)=O.O=S(Cl)Cl>CN(C=O)C.C(N(CC)CC)C>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[N:13]=[CH:14][N:15]=[C:16]([O:21][CH:22]3[CH2:27][CH2:26][N:25]([C:34]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][N:28]=4)=[O:35])[CH2:24][CH2:23]3)[C:17]=2[N+:18]([O-:20])=[O:19])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc(Nc2ncnc(OC3CCNCC3)c2[N+](=O)[O-])cc1
Reactant: O=C(Cl)c1ccccn1
Agent: O=C(O)c1ccccn1
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccc(Nc2ncnc(OC3CCN(C(=O)c4ccccn4)CC3)c2[N+](=O)[O-])cc1

Procedure:
Compound A26 was prepared in a similar manner as described above using (4-methanesulfonyl-phenyl)-[5-nitro-6-(piperidin-4-yloxy)-pyrimidin-4-yl]-amine (i.e., Compound A2) (16 mg, 0.037 mmol), triethylamine (50 μl), pyridine-2-carbonyl chloride (10 mg, 0.046 mmol)[Pyridine-2-carbonyl chloride was prepared by refluxing picolinic acid with SOCl2 for 3 hours and worked up in general method], DMF (1 mL), 1H NMR (CDCl3, 400 MHz) δ 1.95 (m,2H), 2.13 (m,2H), 3.07 (s, 3H), 3.65 (m, 2H), 3.79 (m, 2H), 4.13 (m, 1H), 5.72 (m,1H), 7.37 (m, 1H), 7.67 (m, 1H), 7.81 (m,1H), 7.87 (d, 2H), 7.97 (d, 2H), 8.41 (s, 1H), 8.60 (m, 2H), 10.19 (s, 1H). Exact mass calculated for C22H22N6O6S 498.13, found 499.3 (MH+).
Reaction SMILES: [N:1]1([C:7]([NH:9][C:10]2([C:16]([OH:18])=O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:19][C:20]([NH:23][C:24](=[O:33])[CH:25]([OH:32])[C@@H:26]([NH2:31])[CH2:27][CH2:28][CH2:29][CH3:30])([CH3:22])[CH3:21].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>C(Cl)Cl.C(OCC)(=O)C>[OH:32][CH:25]([C@@H:26]([NH:31][C:16]([C:10]1([NH:9][C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)=[O:8])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1)=[O:18])[CH2:27][CH2:28][CH2:29][CH3:30])[C:24]([NH:23][C:20]([CH3:19])([CH3:21])[CH3:22])=[O:33]
Reactant: O=C(NC1(C(=O)O)CCCCC1)N1CCOCC1
Reactant: CCCC[C@H](N)C(O)C(=O)NC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCCC[C@H](NC(=O)C1(NC(=O)N2CCOCC2)CCCCC1)C(O)C(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.1 %

Procedure:
0.26 g (1.26 mmol) of 1-[N-(morpholine-4-carbonyl)amino]cyclohexanecarboxylic acid (1.26 mmol), 0.27 g (1.26 mmol) of (2RS,3S)-N-(2-methyl-2-propyl)-3-amino-2-hydroxyheptanamide and 0.24 g (1.5 mmol) of 1-hydroxybenzotriazole were dissolved in 15 ml of anhydrous methylen chloride and then, under air current of nitrogen, 0.29 g (1.5 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide was added thereto at 0° C. Thereafter, the reaction solution was warmed to the room temperature and stirred overnight. The reaction solution was concentrated under reduced condition. The residue thus obtained was dissolved in 100 ml of ethyl acetate and washed successively with water, aqueous solution of 10% potassium hydrogensulfate, aqueous solution of saturated sodium hydrogencarbonte and saturated brine. After drying over anhydrous magnesium sulfate, the reaction mixture was concentrated under reduced pressure. The residue was separated out with the silicagel column chromatography, whereby 0.35 g of N-[(2RS,3S)-2-hydroxy-1-[N-(2-methyl-2-propyl)amino]-1-oxo-3-heptyl]-1-[N-(morpholine-4-carbonyl)amino]cyclohexanecarboxamide was obtained.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH3:12])[NH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:13]#[N:14].Br[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH3:12])[N:7]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:6]=2[CH:5]=[CH:4][C:3]=1[C:13]#[N:14]
Reactant: CCc1nc2c(Cl)c(C#N)ccc2[nH]1
Reactant: CC(C)(C)OC(=O)CBr
Product: CCc1nc2c(Cl)c(C#N)ccc2n1CC(=O)OC(C)(C)C

Procedure:
Synthesized as described in Example 197B from 4-chloro-2-ethyl-1H-benzimidazole-5-carbonitrile and 1,1-dimethylethyl bromoacetate: MS (ESI) m/z 320 (M+1).
Reaction SMILES: [CH3:1][O:2][CH:3]([O:6][CH3:7])[CH2:4][NH2:5].F[C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1.C(=O)([O-])O.[Na+].CS(C)=O>O>[CH3:1][O:2][CH:3]([O:6][CH3:7])[CH2:4][NH:5][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1
Reactant: COC(CN)OC
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COC(CNc1ccc([N+](=O)[O-])cc1)OC
Reaction time: 12 h
Yield: 95.6 %

Procedure:
To 5.05 g (0.048 mole) of aminoacetaldehyde dimethylacetal were added 5.64 g (0.040 mole) of p-fluoronitrobenzene, 4.03 g (0.048 mole) of sodium hydrogencarbonate and 5 ml of dimethyl sulfoxide and reaction was carried out at 80° C. for 12 hours. After the reaction, the reaction mixture was poured into 100 ml of water to precipitate a yellow solid. The solid was dissolved in 150 ml of benzene, and the solution was washed with a liquid mixture comprising 50 ml of water and 1 ml of hydrochloric acid and with 50 ml of water two times. The residual benzene layer was dried with anhydrous sodium carbonate. After the drying, the benzene layer was concentrated and the obtained yellow solid was washed with hexane and dried under reduced pressure to obtain 8.65 g (the yield was 95.6%) of a crystal of 4-nitrophenylaminoacetaldehyde dimethyl acetal.