Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][OH:3].C[O-].[Na+].[C:7]([C:9]1[CH:10]=[CH:11][C:12]([NH2:19])=[C:13]([S:15]([NH2:18])(=O)=[O:16])[CH:14]=1)#[N:8].[OH2:20]>CO>[OH:3][NH:2][C:7]([C:9]1[CH:10]=[CH:11][C:12]([NH2:19])=[C:13]([S:15]([NH2:18])(=[O:16])=[O:20])[CH:14]=1)=[NH:8]
Reactant: O
Reactant: NO
Reactant: N#Cc1ccc(N)c(S(N)(=O)=O)c1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: N=C(NO)c1ccc(N)c(S(N)(=O)=O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 17 %

Procedure:
A mixture of hydroxylamine hydrochloride (764 mg; 11 mmol) and NaOMe (616 mg; 11.4 mmol) in MeOH (10 ml) was stirred at rt. for 1 h and then added 5-cyano-2-aminobenzenesulfonamide (1 g; 5 mmol). The reaction mixture was left with stirring for 48 h and poured into water and extracted with EtOAc (2×50 ml). The combined organic fractions were dried (Na2SO4), evaporated to dryness and purified by column chromatography to give 200 mg (17%) of product.
Reaction SMILES: Br/[C:2](/[CH:27]=[CH:28]/[C:29]1[C:30]([CH3:47])([CH3:46])[C:31]2[C:32]([N:45]=1)=[N+:33]([CH2:38][CH2:39][CH2:40][S:41]([O-:44])(=[O:43])=[O:42])[CH:34]=[C:35](Cl)[CH:36]=2)=[CH:3]\[CH:4]=[C:5]1\[N:6]([CH2:20][CH2:21][CH2:22][S:23]([O-:26])(=[O:25])=[O:24])[C:7]2[C:12]([C:13]\1([CH3:15])[CH3:14])=[CH:11][C:10]([S:16]([O-:19])(=[O:18])=[O:17])=[CH:9][CH:8]=2.[Na+:48].[Na+].[Cl-:50].[C:51]([CH2:54][CH2:55]/C(=C\NC1C=CC=CC=1)/C=[NH+]/C1C=CC=CC=1)([OH:53])=[O:52]>>[C:51]([CH2:54][CH2:55]/[C:2](/[CH:27]=[CH:28]/[C:29]1[C:30]([CH3:47])([CH3:46])[C:31]2[C:32]([N:45]=1)=[N+:33]([CH2:38][CH2:39][CH2:40][S:41]([O-:44])(=[O:43])=[O:42])[CH:34]=[C:35]([Cl:50])[CH:36]=2)=[CH:3]\[CH:4]=[C:5]1\[N:6]([CH2:20][CH2:21][CH2:22][S:23]([O-:26])(=[O:25])=[O:24])[C:7]2[C:12]([C:13]\1([CH3:15])[CH3:14])=[CH:11][C:10]([S:16]([O-:19])(=[O:18])=[O:17])=[CH:9][CH:8]=2)([OH:53])=[O:52].[Na+:48].[Na+:48]
Reactant: O=C(O)CCC(/C=[NH+]/c1ccccc1)=C\Nc1ccccc1
Reactant: [Cl-]
Reactant: CC1(C)C(/C=C/C(Br)=C/C=C2/N(CCCS(=O)(=O)[O-])c3ccc(S(=O)(=O)[O-])cc3C2(C)C)=Nc2c1cc(Cl)c[n+]2CCCS(=O)(=O)[O-]
Agent: [Na+]
Product: CC1(C)C(/C=C/C(=C/C=C2/N(CCCS(=O)(=O)[O-])c3ccc(S(=O)(=O)[O-])cc3C2(C)C)CCC(=O)O)=Nc2c1cc(Cl)c[n+]2CCCS(=O)(=O)[O-]

Procedure:
Compound 19 is prepared analogously to compound 9 (Example 9), except that compound 18 is used as a starting material. λMeOH=680 nm.
Reaction SMILES: [CH:1]1([CH:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][OH:18])[CH:12]=2)[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28].O>C1COCC1>[CH:1]1([CH:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][O:18][S:27]([CH3:26])(=[O:29])=[O:28])[CH:12]=2)[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:2][CH2:3]1
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)CC(c1cccc(CO)c1)C1CC1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CC(c1cccc(COS(C)(=O)=O)c1)C1CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of ethyl 3-cyclopropyl-3-(3-(hydroxymethyl)phenyl)propanoate (690 mg) in THF (14 mL) were added triethylamine (775 μL) and methanesulfonyl chloride (258 μL) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was cooled to 0° C., water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (934 mg) as a colorless oil.
Reaction SMILES: Cl.Cl.[CH2:3]([NH:10][CH2:11][CH2:12][CH2:13][S:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)Cl>[CH2:3]([N:10]([CH2:11][CH2:12][CH2:13][S:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: c1ccc(CNCCCSc2ccncc2)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccccc1)N(CCCSc1ccncc1)Cc1ccccc1
Yield: 50.2 %

Procedure:
To a solution of 400 mg (1.21 mmol) of 4-[3-(N-benzylamino)propylthio]pyridine dihydrochloride and 0.55 ml (4.00 mmol) of triethylamine in 5 ml of methylene chloride, 0.17 mi (1.45 mmol) of benzoyl chloride was added under ice-cooling with stirring. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate and water and dried, and then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain 0.22 g of the desired compound (yield: 50.4%, yellow oil).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]3[CH2:15][CH2:16][S:17][C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=4[C:10]3=[N:9]2)=[CH:4][CH:3]=1.[OH:25]O.O>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]3[CH2:15][CH2:16][S:17](=[O:25])[C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=4[C:10]3=[N:9]2)=[CH:4][CH:3]=1
Reactant: OO
Reactant: O=c1cc2c(nn1-c1ccc(Cl)cc1)-c1cc(F)ccc1SCC2
Solvent: O
Solvent: CC(=O)O
Product: O=c1cc2c(nn1-c1ccc(Cl)cc1)-c1cc(F)ccc1S(=O)CC2
Temperature: 25 °C

Procedure:
To a solution of 1.8 g of 2-(4-chlorophenyl)-10-fluoro-5,6-dihydro-[1]benzothiepino[5,4-c]pyridazin-3(2H)one, prepared in Example 22, in 20 ml of acetic acid is added 1.3 ml of 35% hydrogen peroxide with stirring at room temperature and furthermore stirred for 5 hours at the same temperature. To the resultant mixture is added water, and the precipitated crystals are collected by filtration and recrystallized from dimethylformamide-water to give 1.3 g of 2-(4-chlorophenyl)-10-fluoro-5,6-dihydro[1]benzothiepino[5,4-c]pyridazin-3(2H)-one 7-oxide, melting at 233°-235° C. with decomposition.
Reaction SMILES: [CH3:1][O-:2].[Na+].[N:4]1([C:9]2[CH:28]=[CH:27][C:12]([CH2:13][C:14]3[C:15](Cl)=[N:16][C:17]4[C:22]([C:23]=3[Cl:24])=[CH:21][C:20]([I:25])=[CH:19][CH:18]=4)=[CH:11][CH:10]=2)[CH:8]=[N:7][CH:6]=[N:5]1.ClCCl>C1(C)C=CC=CC=1>[N:4]1([C:9]2[CH:28]=[CH:27][C:12]([CH2:13][C:14]3[C:15]([O:2][CH3:1])=[N:16][C:17]4[C:22]([C:23]=3[Cl:24])=[CH:21][C:20]([I:25])=[CH:19][CH:18]=4)=[CH:11][CH:10]=2)[CH:8]=[N:7][CH:6]=[N:5]1
Reactant: C[O-]
Reactant: Clc1nc2ccc(I)cc2c(Cl)c1Cc1ccc(-n2cncn2)cc1
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1nc2ccc(I)cc2c(Cl)c1Cc1ccc(-n2cncn2)cc1
Temperature: 105 °C
Reaction time: 2 h

Procedure:
Sodium methoxide (741 mg, 13.7 mmol) was added to a solution of 3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-2,4-dichloro-6-iodoquinoline (1.1 g, 2.3 mmol, Intermediate 20: step b) in toluene (11 mL) with stirring. The mixture was heated to 105° C. After 2 hours, additional sodium methoxide (250 mg, 4.6 mmol) was added. After 3 hours, the flask was allowed to cool to 23° C. Dichloromethane (50 mL) was added and then the mixture was filtered through Celite®. The filter cake was washed with dichloromethane. The filtrate was concentrated to provide the title compound as a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1Br)([O-:3])=[O:2].I[C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1>C(Cl)Cl>[CH3:18][C:15]1[CH:16]=[CH:17][C:12]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])=[CH:13][CH:14]=1
Reactant: Cc1ccc(I)cc1
Reactant: O=[N+]([O-])c1ccccc1Br
Solvent: ClCCl
Product: Cc1ccc(-c2ccccc2[N+](=O)[O-])cc1
Temperature: 195 °C

Procedure:
11.2 g of 2-nitrobromobenzene are mixed with 15 g of 4-iodotoluene and the mixture is heated to 195° C. and stirred at this temperature for 3 and a half hours. After returning to room temperature, it is taken up in DCM and heated to the reflux point, the hot solution is filtered on Celite® and the DCM is then evaporated off.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[CH:12]#[N:13].[CH:14](=O)[CH:15]([CH3:17])[CH3:16]>O>[CH3:16][CH:15]([CH3:17])[CH:14]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:10])[F:11])=[CH:4][CH:3]=1)[C:12]#[N:13]
Reactant: Nc1ccc(C(F)(F)F)cc1
Reactant: C#N
Reactant: CC(C)C=O
Solvent: O
Product: CC(C)C(C#N)Nc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Yield: 83 %

Procedure:
To 17.7 g (110 mmol) of 4-amino-benzotrifluoride at 10° was added 3.5 g (130 mmol) of hydrogen cyanide. This solution was placed in a -15° dry ice-isopropyl alcohol bath. Pure isobutyraldehyde (7.9 g, 110 mmol) was added dropwise to the solution, maintaining a solution temperature of 15°-16°. The initial reaction mixture contained no water, and the water produced in the reaction did not exceed 6.8 wt. % of the reaction mixture. The ice bath was removed and the mixture was heated briefly to 48° and then allowed to cool to room temperature. The mixture was poured into ether, washed with 2.5N sodium hydroxide and then with water, dried over sodium sulfate, filtered and stripped to give the crude product, which upon recrystallization in ether/hexane yielded 3-methyl-2-(4-trifluoromethylphenylamino)butyronitrile, m.p. 64.5°-67°, 83% yield.
Reaction SMILES: [C:1]([O:5][C:6](=[O:30])[N:7]([CH:9]([C:11](=[O:29])[NH:12][C:13]1[CH:18]=[CH:17][C:16]([NH2:19])=[C:15]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[N:14]=1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C1C[O:34][CH2:33]C1>>[C:1]([O:5][C:6](=[O:30])[N:7]([CH:9]([C:11](=[O:29])[NH:12][C:13]1[N:14]=[C:15]2[N:20]([CH2:21][C:22]3[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=3)[C:33](=[O:34])[NH:19][C:16]2=[CH:17][CH:18]=1)[CH3:10])[CH3:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: C1CCOC1
Reactant: CC(C(=O)Nc1ccc(N)c(NCc2ccc(Cl)cc2)n1)N(C)C(=O)OC(C)(C)C
Product: CC(C(=O)Nc1ccc2[nH]c(=O)n(Cc3ccc(Cl)cc3)c2n1)N(C)C(=O)OC(C)(C)C
Temperature: 70 °C
Reaction time: 8 h

Procedure:
A solution of the product from Step 3, in THF (3 mL), was added to a solution of N,N′-carbonyldiimidazole (110 mg, 0.68 mmol) in THF (3 mL). The mixture was then heated at 70° C. for 3 hours. After allowing to cool, the mixture was concentrated in vacuo, treated with water and then left overnight. The product was extracted with EtOAc. The EtOAc layer was washed successively with aqueous potassium hydrogensulfate solution, brine and then dried (MgSO4). The solution was concentrated to ˜1 mL and then Et2O (3 mL) was added. The resulting precipitate was collected by filtration to give {1-[3-(4-chloro-benzyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-ylcarbamoyl]ethyl}-methyl-carbamic acid tert-butyl ester (90 mg) as a white crystalline solid. MS: [M+H]+=460.
Reaction SMILES: [F:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]([C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.F[B-](F)(F)F.[CH3:20][O+](C)C>C(OCC)(=O)C.O>[F:1][C:2]1[C:10]2[C:6](=[CH:7][N:8]([CH3:20])[N:9]=2)[C:5]([C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc(F)c2[nH]ncc12
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1ccc(F)c2nn(C)cc12
Reaction time: 5 h
Yield: 66.8 %

Procedure:
To a solution of methyl 7-fluoro-1H-indazole-4-carboxylate (2.93 g, 15.1 mmol) in ethyl acetate (60 mL) was added trimethyloxonium tetrafluoroborate (2.90 g, 19.6 mmol) at room temperature, and the mixture was stirred for 5 hr. The reaction solution was diluted with water, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by flash silica gel column chromatography (ethyl acetate/hexane=1/2) to give the title compound (2.10 g, yield 67%).
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[S:15][C:16]([S:19]C#N)=[CH:17][N:18]=2)=[O:12])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].SC[C@@H]([C@@H](CS)O)O.Cl[CH2:37][CH2:38][N:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1>>[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]([CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]2)[C:11]([NH:13][C:14]2[S:15][C:16]([S:19][CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[CH:17][N:18]=2)=[O:12])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCC(N(C(=O)Nc2ncc(SC#N)s2)C2CCCCC2)CC1
Reactant: ClCCN1CCOCC1
Agent: O[C@H](CS)[C@@H](O)CS
Product: CC(=O)N1CCC(N(C(=O)Nc2ncc(SCCN3CCOCC3)s2)C2CCCCC2)CC1

Procedure:
Prepared as described in general procedure (H) and (I) using 1-(1-acetyl-piperidin-4-yl)-1-cyclohexyl-3-(5-thiocyanato-thiazol-2-yl)-urea, dithioerythritol and N-(2-chloroethyl)morpholine
Reaction SMILES: [C:1]([OH:10])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][C:6](O)=O>C1CCCCC1>[C:1]1(=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1.[CH:1]1([OH:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(O)CCCCC(=O)O
Solvent: C1CCCCC1
Product: O=C1CCCCC1
Product: OC1CCCCC1

Procedure:
Adipic acid is generally synthesized from cyclohexane by oxidation of the latter to give a cyclohexanone/cyclohexanol mixture, followed by oxidation of this mixture by nitric acid to give adipic acid.
Reaction SMILES: [C:1]([O:5][C:6]([CH:8]([C:12]1[CH:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1)[CH2:9][NH:10][CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][NH2:26]>C(OCC)(=O)C.CO>[C:1]([O:5][C:6]([CH:8]([C:12]1[CH:17]=[CH:16][C:15]([C@H:18]2[CH2:23][CH2:22][C@H:21]([NH:26][CH3:25])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1)[CH2:9][NH:10][CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN
Reactant: CNCC(C(=O)OC(C)(C)C)c1ccc(C2CCC(=O)CC2)cc1
Solvent: CO
Solvent: CCOC(C)=O
Product: CNCC(C(=O)OC(C)(C)C)c1ccc([C@H]2CC[C@H](NC)CC2)cc1

Procedure:
from 4-[4-(1-tert.butoxycarbonyl-methylaminoethyl)-phenyl]-cyclohexanone and methylamine. Oil. Rf value: 0.5 (alumina, ethyl acetate/methanol=10:1, v:v).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[C:39](B3OC(C)(C)C(C)(C)O3)[CH:38]=[CH:37][N:36]=2)[CH2:31][CH2:30]1.C([O-])([O-])=O.[Na+].[Na+]>O.CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:37]2[CH:38]=[CH:39][CH:40]=[C:35]([N:32]3[CH2:31][CH2:30][N:29]([CH3:28])[CH2:34][CH2:33]3)[N:36]=2)[CH:3]=1)=[O:16]
Reactant: Cc1cc(C)c(CNC(=O)c2cc(Br)cc3c2c(C)nn3C(C)C)c(=O)[nH]1
Reactant: CN1CCN(c2cc(B3OC(C)(C)C(C)(C)O3)ccn2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(C)c(CNC(=O)c2cc(-c3cccc(N4CCN(C)CC4)n3)cc3c2c(C)nn3C(C)C)c(=O)[nH]1
Temperature: 120 °C
Yield: 32 %

Procedure:
A stirred solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide, 3 (200 mg, 0.464 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (154 mg, 0.510 mmol) and Na2CO3 (123 mg, 1.160 mmol) in a mixture of water (3 mL) and DMF (15 mL) was degassed with argon gas for 30 min. Then PdCl2(PPh3)2 (16.28 mg, 0.023 mmol) was added and heated to 120° C. for 3 h. Then the reaction mixture was filtered through Celite bed and the Celite bed was washed with ice cold water (2×100 mL). The filtrate was extracted with EtOAc (20 mL), dried over anhydrous sodium sulphate, filtered, and concentrated to afford 150 mg of crude product. The crude product was purified by silica gel chromatography over (eluent: 5% MeOH/DCM) to afford the title compound as an off-white solid (85 mg, 32%). 1H NMR (DMSO-d6, 400 MHz): δ 0.889 (t, J=14.4 Hz, 3H), 1.554-1.483 (m, 8H), 2.134 (s, 3H), 2.55 (s, 3H), 4.411 (d, J=1.6 Hz, 2H), 5.059 (m, 1H), 5.913 (s, 1H), 7.830 (s, 1H), 8.047 (s, 1H), 8.08 (s, 1H), 8.306 (s, 1H), 8.462 (s, 1H), 11.53 (s, 1H), 13 (brs, 1H). LCMS (ES+) m/z=528.2.
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([C:11]([F:14])([F:13])[F:12])([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:19])([F:18])[F:17])[S:3]1.C(N(CC)CC)C.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1(C)C=CC=CC=1>[C:28]([NH:1][C:2]1[S:3][C:4](=[C:15]([F:20])[C:16]([F:17])([F:18])[F:19])[C:5]([C:7]([F:10])([F:9])[F:8])([C:11]([F:12])([F:13])[F:14])[N:6]=1)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: N=C1NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Reactant: O=C(Cl)c1ccccc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C(NC1=NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
In toluene (10 ml) were dissolved 2-imino-4,4-bis(trifluoromethyl)-5-(tetrafluoroethylidene)-1,3-thiazolidine (0.7 g) and triethylamine (1 ml), and benzoyl chloride (0.3 g) was gradually added thereto and the mixture was stirred at room temperature for 3 hours.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[O:18][C:19]3[C:25]([C:26]([O:28]C)=O)=[CH:24][CH:23]=[CH:22][C:20]=3[N:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH4+:30]>CO>[C:26]([C:25]1[C:19]2[O:18][C:17]([CH:14]3[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[CH2:16][CH2:15]3)=[N:21][C:20]=2[CH:22]=[CH:23][CH:24]=1)(=[O:28])[NH2:30]
Reactant: COC(=O)c1cccc2nc(C3CCN(C(=O)OCc4ccccc4)CC3)oc12
Reactant: [NH4+]
Solvent: CO
Product: NC(=O)c1cccc2nc(C3CCN(C(=O)OCc4ccccc4)CC3)oc12
Temperature: 25 °C
Reaction time: 48 h
Yield: 37 %

Procedure:
Methyl 2-(1-(benzyloxycarbonyl)piperidin-4-yl)benzo[d]oxazole-7-carboxylate (560 mg, 1.4 mmol) was added to a solution of ammonium in methanol (10 mL) in a sealing tube and the mixture was stirred at room temperature for 2 days. The resulting mixture was evaporated and the crude product was purified by prep-HPLC to give benzyl 4-(7-carbamoylbenzo[d]oxazol-2-yl)piperidine-1-carboxylate (200 mg, yield 37%). 1H-NMR (400 MHz, CDCl3) δ (ppm): 1.94-1.98 (m, 2H), 2.18-2.22 (m, 2H), 3.06-3.12 (m, 2H), 3.20-3.23 (m, 1H), 4.26 (brs, 2H), 5.16 (s, 2H), 6.30 (s, 1H), 6.92 (s, 1H), 7.32-7.38 (m, 5H), 7.42-7.46 (t, J=8.0 Hz, 1H), 7.84-7.87 (dd, J1=8.0 Hz, J2=1.2 Hz, 1H), 8.06-8.08 (dd, J1=8.0 Hz, J2=1.2 Hz, 1H); LC-MS (ESI) m/z: 380 (M+1)+.
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[CH:6][N:5]=[C:4]1[CH:8]=O)[CH3:2].[CH:10](=[N:17]/[C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[CH2:20][O:21][C:22]2=[O:27])\[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:28][O-:29].[Na+].C(OCC)(=O)CC>>[CH2:1]([N:3]1[CH:7]=[CH:6][N:5]=[C:4]1[CH:8]1[C:28](=[O:29])[C:19]2[C:23]([C:22]([O:21][CH3:20])=[O:27])=[CH:24][CH:25]=[CH:26][C:18]=2[NH:17][CH:10]1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:2]
Reactant: O=C1OCc2c(/N=C/c3ccccc3)cccc21
Reactant: CCn1ccnc1C=O
Reactant: C[O-]
Agent: [Na+]
Solvent: CCOC(=O)CC
Product: CCn1ccnc1C1C(=O)c2c(cccc2C(=O)OC)NC1c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 12.1 %

Procedure:
To 1-ethyl-1H-imidazole-2-carbaldehyde (520 mg, 4.19 mmol), (E)-4-(benzylideneamino) isobenzofuran-1(3H)-one (994 mg, 4.19 mmol), sodium methanolate (385 mg, 16.8 mmol) and ethyl propionate (15 mL) were added and the mixture was stirred at room temperature overnight. Then the resulting mixture was evaporated under reduced pressure and extracted with ethyl acetate (100 mL×4) and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1 to 5:1). 190 mg of methyl 3-(1-ethyl-1H-imidazol-2-yl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate was obtained. LC-MS (ESI) m/z: 390 (M+1)+.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:9]=[CH:8][CH:7]=[CH:6][C:4]=1[NH2:5].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([C:25](Cl)=[O:26])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(N(CC)CC)C.O>ClCCl>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:9]=[CH:8][CH:7]=[CH:6][C:4]=1[NH:5][C:25]([CH:22]1[CH2:23][CH2:24][NH:19][CH2:20][CH2:21]1)=[O:26].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([C:25](=[O:26])[NH:5][C:4]2[CH:6]=[CH:7][CH:8]=[CH:9][C:3]=2[C:2]([F:10])([F:11])[F:1])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)Cl)CC1
Reactant: Nc1ccccc1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(C(=O)Nc2ccccc2C(F)(F)F)CC1
Product: O=C(Nc1ccccc1C(F)(F)F)C1CCNCC1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a stirred solution of 2-(trifluoromethyl)aniline (0.5 mL, 4.20 mmol) in dichloromethane (10.0 mL) was added 4-chlorocarbonylpiperidine-1-carboxylic acid tert-butyl ester (1.000 g, 4.00 mmol). The reaction mixture was stirred at ambient temperature for 10 minutes, then followed by the addition of triethylamine (0.6 mL, 4.20 mmol). The reaction mixture was stirred at ambient temperature for another 10 minutes. Water (5.0 mL) was added to the mixture and the organic phase separated and washed with saturated NaCl (10 mL), dried over MgSO4 and then concentrated in vacuo. The obtained crude product was purified by column chromatography to yield the desired product, 4-(2-trifluoromethylphenylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester, in 30% yield (0.450 g). 1H NMR (300 MHz, CDCl3) δ 7.97 (d, J=8.0 Hz, 1H), 7.61 (s. 1H), 7.53 (d, J=7.9 Hz, 1H), 7.47 (t, J=7.5 Hz, 1H), 7.18 (t, J=7.6 Hz, 1H), 4.13-4.04 (m, 2H), 2.77-2.69 (m, 2H), 2.44-2.34 (m, 1H), 1.87-1.93 (m, 2H), 1.70-1.57 (m, 2H), 1.40 (s. 9H). MS (ES−) m/z 371 (M−1).
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([OH:9])[CH2:5][C:6]([CH3:8])=[CH2:7].[Br:16][C:17]1[CH:22]=[CH:21][C:20]([C@@H:23]([N:25]=[C:26]=[O:27])[CH3:24])=[CH:19][C:18]=1[CH3:28].BrC1C=CC([C@@H](N2CC[C@](CC(C)=C)(C3C=CC=CC=3)OC2=O)C)=CC=1>>[Br:16][C:17]1[CH:22]=[CH:21][C:20]([C@@H:23]([N:25]2[CH2:2][CH2:3][C@:4]([CH2:5][C:6]([CH3:8])=[CH2:7])([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[O:9][C:26]2=[O:27])[CH3:24])=[CH:19][C:18]=1[CH3:28]
Reactant: Cc1cc([C@H](C)N=C=O)ccc1Br
Reactant: C=C(C)CC(O)(CCCl)c1ccccc1
Agent: C=C(C)C[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)O1
Product: C=C(C)C[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(Br)c(C)c2)C(=O)O1

Procedure:
The title compound was prepared from 1-chloro-5-methyl-3-phenyl-hex-5-en-3-ol and (S)-1-bromo-4-(1-isocyanato-ethyl)-2-methyl-benzene following a procedure analogous to that described in Step 1 of Example 96. Mass spectrum (ESI+): m/z=428/430 (Br) [M+H]+; 1H NMR (400 MHz, DMSO-d6) 1.40 (d, J=6.9 Hz, 3H), 1.55 (s, 3H), 2.13 (s, 3H) superimposed on 2.07-2.18 (m, 2H), 2.42-2.47 (m, 1H), 2.53 (broad s, 2H), 2.92-3.03 (m, 1H), 4.60 (hardly resolved m, 1H), 4.77 (hardly resolved m, 1H), 5.33 (q, J=6.9 Hz, 1H), 6.62 (dd, J=8.2 Hz, 2.0 Hz, 1H), 6.76 (hardly resolved d, 1H), 7.26-7.33 (m, 4H), 7.34-7.40 (m, 2H). The assignment of the stereogenic centers of the title compound is based on the comparison of the 1H NMR data with the data of the known analog 3-[(S)-1-(4-bromo-phenyl)-ethyl]-(R)-6-(2-methyl-allyl)-6-phenyl-[1,3]oxazinan-2-one.
Reaction SMILES: O=C[C@@H]([C@H]([C@H](CO)O)O)O.[O:11]=[CH:12][C@@H:13]([C@H:15]([C@H:17]([C@@H:19]([CH3:21])[OH:20])[OH:18])[OH:16])[OH:14]>>[OH:11][CH2:12][C:13]([C@H:15]([C@H:17]([C@@H:19]([CH3:21])[OH:20])[OH:18])[OH:16])=[O:14]
Reactant: C[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C=O
Agent: O=C[C@H](O)[C@@H](O)[C@@H](O)CO
Product: C[C@@H](O)[C@H](O)[C@H](O)C(=O)CO

Procedure:
The colour response obtained with 0.5 M D-fucose was 46% of the corresponding response seen with L-arabinose. The molar ratio between the D-fucose and L-arabinose activity could not be calculated, since no standard curve was obtained for D-fuculose