Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1N(CCS(O)(=O)=O)CC[O:3]C1.C(S(O)(=O)=O)C.[NH:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21]([OH:23])=[O:22].O=C(CCC(O)=O)C(O)=O.O=C1O[C@H]([C@H](CO)O)C(O)=C1O>>[OH:3][C@H:25]1[CH2:26][NH:19][C@H:20]([C:21]([OH:23])=[O:22])[CH2:24]1
Reactant: O=C(O)[C@@H]1CCCN1
Reactant: O=S(=O)(O)CCN1CCOCC1
Agent: CCS(=O)(=O)O
Agent: O=C(O)CCC(=O)C(=O)O
Agent: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Product: O=C(O)[C@@H]1C[C@@H](O)CN1
Temperature: 100 °C
Reaction time: 0.17 h

Procedure:
The cells, the treated cells or the enzyme preparation are added to 240 mM MES [2- (N-morphorino) ethanesulfonic acid] buffer containing 12 mM L-proline, 24 mM 2-ketoglutaric acid, 4 mM ferrous sulfate and 8 mM L-ascorbic acid to make 250 μl in total. The mixture is kept at 35° C. for 10 minutes. The reaction mixture is heated at 100° C. for 2 minutes to stop the reaction, and the amount of trans-4-hydroxy-L-proline produced in the reaction mixture is determined by HPLC.
Reaction SMILES: [O:1]=[C:2]1[C:10]2([C:14]3=[CH:15][C:16]4[O:20][CH2:19][O:18][C:17]=4[CH:21]=[C:13]3[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][CH2:23][CH:24]=O.[NH2:26][CH2:27][CH:28]1[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C1(OC2C=CC(C=O)=CC=2)C=CC=CC=1>C1COCC1.CCOCC>[CH:28]1([CH2:27][NH:26][CH2:24][CH2:23][CH2:22][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]3([C:14]4=[CH:15][C:16]5[O:20][CH2:19][O:18][C:17]=5[CH:21]=[C:13]4[O:12][CH2:11]3)[C:2]2=[O:1])[CH2:30][CH2:29]1
Reactant: O=CCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21
Reactant: NCC1CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=Cc1ccc(Oc2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=C1N(CCCNCC2CC2)c2ccccc2C12COc1cc3c(cc12)OCO3
Reaction time: 8 h
Yield: 63.7 %

Procedure:
To a solution of 3-(2′-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-1′(2′H)-yl)propanal (0.07 g, 0.20 mmol) in THF (5.00 mL) was added (aminomethyl)cyclopropane (0.30 mmol) and MP-triacetoxyborohydride (0.26 g, 0.60 mmol). After overnight shaking, the polymer-bound 4-phenyloxybenzaldehyde (0.25 g, 0.18 mmol) was added. After another overnight shaking, the mixture was diluted with ether (10.0 mL) and filtered. The filtrate was concentrated in vacuo to dryness. The residue was recrystallized to give the title compound (0.05 g) in 62% yield as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.32-6.92 (m, 4H), 6.49 (s, 1H), 6.12 (s, 1H), 5.83 (m, 2H), 4.86 (m, 1H), 4.64 (m, 1H), 3.97-3.77 (m, 2H), 2.87-2.80 (m, 2H), 2.66-2.56 (m, 2H), 1.02-0.94 (m, 1H), 0.56-0.47 (m, 2H), 0.25-0.18 (m, 2H); MS (ES+) m/z 393.3 (M+1).
Reaction SMILES: [Br-].[C:2]([CH2:5][CH2:6][CH2:7][CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:4])=[O:3].[CH3:28]C(C)([O-])C.[K+].[CH3:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[C:42]([C:47]([NH:49][C:50]3[CH:67]=[CH:66][C:53]([C:54]([N:56]([CH3:65])[C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=4C=O)=[O:55])=[CH:52][CH:51]=3)=[O:48])=[CH:43][CH:44]=[CH:45][CH:46]=2)=[CH:37][CH:36]=1>CN(C)C(=O)C.C(OCC)(=O)C>[CH3:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[C:42]([C:47]([NH:49][C:50]3[CH:51]=[CH:52][C:53]([C:54]([N:56]([CH3:65])[C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=4[CH:28]=[CH:8][CH2:7][CH2:6][CH2:5][C:2]([OH:4])=[O:3])=[O:55])=[CH:66][CH:67]=3)=[O:48])=[CH:43][CH:44]=[CH:45][CH:46]=2)=[CH:37][CH:36]=1
Reactant: Cc1ccc(-c2ccccc2C(=O)Nc2ccc(C(=O)N(C)c3ccccc3C=O)cc2)cc1
Reactant: CC(C)(C)[O-]
Reactant: O=C(O)CCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: Cc1ccc(-c2ccccc2C(=O)Nc2ccc(C(=O)N(C)c3ccccc3C=CCCCC(=O)O)cc2)cc1
Reaction time: 0.5 h
Yield: 67.7 %

Procedure:
To an ice bath cooled solution of (4-carboxybutyl)triphenylphosphonium bromide (371 mg) in N,N-dimethylacetamide (15 ml) was added potassium t-butoxide (188 mg) and the mixture was stirred at the same temperature for 30 minutes. To the resulting mixture was added 4-(4′-methylbiphenyl-2-carboxamido)-N-methyl-N-(2-formylphenyl)benzamide (250 mg) and the mixture was stirred in an ice bath for 3 hours. The mixture was diluted with ethyl acetate (40 ml) and the solution was washed successively with 1N hydrochloric acid (30 ml), water (20 ml) and brine (20 ml). The organic phase was dried over magnesium sulfate and the solvent was evaporated in vacuo to give an oil. The crude oil was purified by silica gel column (1% methanol in chloroform) to give 4-(4′-methylbiphenyl-2-carboxamido)-N-methyl-N-[2-(5-carboxypenten-1-yl)phenyl]benzamide (201 mg) as a colorless amorphous.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])(=[O:11])=[O:10])=[CH:5][CH:4]=1)#[N:2].Cl.[NH2:21][OH:22].C(=O)([O-])O.[Na+]>C(O)C>[OH:22][NH:21][C:1](=[NH:2])[C:3]1[CH:8]=[CH:7][C:6]([S:9](=[O:10])(=[O:11])[NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])=[CH:5][CH:4]=1
Reactant: NO
Reactant: Cc1ccccc1NS(=O)(=O)c1ccc(C#N)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Cc1ccccc1NS(=O)(=O)c1ccc(C(=N)NO)cc1
Temperature: 60 °C
Reaction time: 18 h
Yield: 89 %

Procedure:
To a solution of 4-cyano-N-o-tolyl-benzenesulfonamide (214 mg, 0.629 mmol) in ethanol (3 mL), hydroxylamine hydrochloride (437 mg, 6.29 mmol) and sodium hydrogen carbonate (528 mg, 6.29 mmol) were added and the resulting suspension was stirred at 60° C. for 18 hrs. Subsequently the reaction mixture was filtered. The precipitate was washed with ethanol and the combined eluents were evaporated under reduced pressure. The residue was dried under high vacuum (45° C., 3 hrs) to give N-hydroxy-4-o-tolylsulfamoyl-benzamidine (345 mg, 0.56 mmol, 89% crude yield, purity 49.6%) as beige solid.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].[N:12]([O-])=O.[Na+].[CH3:16][C:17](=[O:22])[CH2:18][C:19](=[O:21])[CH3:20].C([O-])(=O)C.[Na+]>Cl.O.C(O)C>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:4]=[C:5]([NH:6][N:12]=[C:18]([C:17](=[O:22])[CH3:16])[C:19](=[O:21])[CH3:20])[CH:7]=[CH:8][CH:9]=1
Reactant: O=N[O-]
Reactant: CC(=O)CC(C)=O
Reactant: Nc1cccc(C(F)(F)F)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC(=O)C(=NNc1cccc(C(F)(F)F)c1)C(C)=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
3-(Trifluoromethyl)aniline (34.6 g, 215 mmol) was dissolved in a mixture of concentrated hydrochloric acid (64 mL) and water (64 mL). To the resulting mixture was added dropwise at 0° C. a solution of sodium nitrite (16.6 g, 240 mmol) in water (100 mL). The mixture was stirred for 1 h at 0° C. To the resulting diazonium salt solution was added dropwise a solution of pentane-2,4-dione (22.0 g, 220 mmol) and sodium acetate (52.5 g, 640 mmol) in ethanol (225 mL) and water (80 mL) at room temperature. The mixture was stirred for 18 h at room temperature with a mechanical stirrer. The orange precipitate was filtered off and washed with water (150 mL×3), 50 percent aqueous ethanol (100 mL×2), and n-hexane (100 mL), and then dried in vacuo at 50° C. for 5 h affording 52.7 g (90%) of 3-{[3-(trifluoromethyl)phenyl]hydrazono}pentane-2,4-dione as an orange solid.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11]Cl)=[CH:7][N:6]=1)[CH3:3].[NH2:13][CH2:14][CH2:15][CH2:16][NH2:17].[OH-].[Na+]>O>[CH2:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:13][CH2:14][CH2:15][CH2:16][NH2:17])=[CH:7][N:6]=1)[CH3:3]
Reactant: CCOc1ccc(CCl)cn1
Reactant: NCCCN
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCOc1ccc(CNCCCN)cn1
Yield: 65.2 %

Procedure:
2-Ethoxy-5-pyridylmethyl chloride hydrochloride (9.6 g) in an aqueous solution was added dropwise to the mixed solution of trimethylenediamine (11.1 g) and 20% aqueous solution (22 g) of sodium hydroxide at 0°-5° C. After the reaction mixture was stirred at room temperature for some time, water and excess trimethylenediamine were distilled off under reduced pressure from the contents and after the inorganic salts were filtered off, the produced viscous and oily substance was evaporated in vacuum to give N-(2-ethoxy-5-pyridylmethyl)trimethylenediamine (6.3 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:12][CH3:13])[C:9]=1[O:10][CH3:11])[CH:5]=[O:6].S(=O)(=O)([OH:16])N.[O-]Cl=O.[Na+]>CC#N.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:12][CH3:13])[C:9]=1[O:10][CH3:11])[C:5]([OH:16])=[O:6]
Reactant: COc1cc(C=O)cc(Br)c1OC
Reactant: NS(=O)(=O)O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: CC#N
Solvent: O
Product: COc1cc(C(=O)O)cc(Br)c1OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93.4 %

Procedure:
To a stirred solution of 3-bromo-4,5-dimethoxybenzaldehyde (5.0 g, 20.5 mmol, 1 eq.) in CH3CN (192 mL) at room temperature was added a solution of sulfamic acid (2.55 g, 26.3 mmol) in H2O (32 mL) followed by a dropwise addition of a solution of NaClO2 (3.03 g, 26.8 mmol, 1.3 eq.) in H2O (32 mL) over 20 min period. After stirring for 30 min at room temperature, the solvent was removed in vacuo. The residue was dissolved in 1.0 M aqueous HCl (300 mL) and extracted with EtOAc (3×100 mL). The combined organic layer was washed with brine (300 mL), dried over Na2SO4 and concentrated in vacuo to give 3-bromo-4,5-dimethoxybenzoic acid (5.0 g). The product was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]([F:12])([F:11])[C:4]([F:10])([F:9])[C:5](OC)=[O:6].[NH3:13]>CCOCC>[CH3:1][O:2][C:3]([F:12])([F:11])[C:4]([F:10])([F:9])[C:5]([NH2:13])=[O:6]
Reactant: COC(=O)C(F)(F)C(F)(F)OC
Reactant: N
Solvent: CCOCC
Product: COC(F)(F)C(F)(F)C(N)=O
Reaction time: 8 h
Yield: 95.4 %

Procedure:
A solution of 140 g (0.74 mol) of methyl 3-methoxytetrafluoropropionate in 100 ml of ether was treated at 0° with 15.3 g (0.90 mol) of NH3. The resulting viscous mixture was stirred at 25° overnight and evaporated to dryness at 25° (10 mm). The crude residue was then recrystallized from ether/hexane to give 123.6 g (95%) of 3-methoxytetrafluoropropionamide, mp 78°-80°. An analytical sample was recrystallized from ether/hexane, mp 83°-85°. IR (KBr): 2.95, 3.02 and 3.10 (NH2), 3.37 and 3.49 (sat'd CH), 5.92 (C=O), 6.19 (NH2), 7.5-10μ (CF, C--O). NMR ((CD3)2CO): 1H 6.67 (broad, 2H, NH2) and 3.66 ppm (s, 3H, OCH3l ); 19F -120.6 (t, JFF 4.7 Hz, 2F, CF2) and -121.8 ppm (t, JFF 4.7 Hz, of d, JHF 2.1 Hz, 2F, CF2).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:17][F:18]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:17][F:18])[CH:5]=[C:6]([Br:8])[CH:7]=1
Reactant: Oc1cc(Br)cc(Br)c1
Reactant: FCCl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: FCOc1cc(Br)cc(Br)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 71 %

Procedure:
To a tared, sealed 350 mL round-bottomed pressure flask containing a suspension of 3,5-dibromophenol (10.0 g, 39.7 mmol; see step (ii) above) and Cs2CO3 (20.7 g, 63.5 mmol) in DMF (150 mL) at −78° C. was added chlorofluoromethane via bubbling for 5 min through the septum. The septum was replaced with a Teflon stopper and the flask was then sealed and allowed to warm to room temperature where the flask was weighed and determined to contain 9.0 g (131 mmol) of chlorofluoromethane. The solution was heated in an oil bath set at 70° C. overnight. The flask was cooled to room temperature, the pressure cautiously released and the contents diluted with water (100 mL). The aqueous layer was extracted with Et2O (3×200 mL) then, the combined organics were dried (Na2SO4), filtered and concentrated in vacuo. Flash chromatography on silica gel eluting with hexanes afforded the sub-title compound (7.9 g, 71%) as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[NH:4][C:3]1=[O:14].I[CH2:22]C>>[CH2:1]([C:2]1([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[NH:4][C:3]1=[O:14])[CH3:22]
Reactant: CCI
Reactant: CCOC(=O)CC1(C)C(=O)Nc2cccc([N+](=O)[O-])c21
Product: CCOC(=O)CC1(CC)C(=O)Nc2cccc([N+](=O)[O-])c21

Procedure:
Essentially following the procedures described for Intermediate 17, but using iodoethane in place of iodomethane, the title compound was prepared. MS: m/z=293 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[N:10][C:9]2[C:4](=[CH:5][C:6]([O:14][CH3:15])=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1.[O:16]1CCOCC1>>[CH3:13][O:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][C:6]=1[O:14][CH3:15])[N:3]=[C:2]([CH:1]=[O:16])[CH:11]=[N:10]2
Reactant: C1COCCO1
Reactant: COc1cc2ncc(C)nc2cc1OC
Product: COc1cc2ncc(C=O)nc2cc1OC
Yield: 73 %

Procedure:
To a reaction flask under argon is added 1,4-dioxane (20 mL), 2-methyl-6,7-dimethoxyquinoxaline (1.09 g, 5.3 mmol) and SeO2 (1.8 g, 16 mmol). The mixture is heated to 100IC for 2 hours 45 minutes, cooled, and filtered through Celite. The pad is washed with portions of EtOAc and CH2Cl2. The resulting solution is concentrated, taken up in MeOH/CH2Cl2, loaded onto a silica gel column, and chromatographed (30% EtOAc/CH2Cl2) to provide an off-white solid (73% yield).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:20][C:21]1[CH:22]=[N:23][C:24]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)=[N:25][CH:26]=1>CN(C=O)C.O>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([NH:27][C:24]2[N:23]=[CH:22][C:21]([CH2:20][O:1][C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]4)=[CH:26][N:25]=2)=[CH:33][CH:32]=1
Reactant: O=c1ccc2cc(O)ccc2[nH]1
Reactant: ClCc1cnc(Nc2ccc(Cl)cc2)nc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1ccc2cc(OCc3cnc(Nc4ccc(Cl)cc4)nc3)ccc2[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 29.8 %

Procedure:
A mixture of 6-hydroxyquinolin-2(1H)-one (0.057 g, 0.354 mmol), Cs2CO3 (0.192 g, 0.590 mmol) and 5-(chloromethyl)-N-(4-chlorophenyl)pyrimidin-2-amine (0.1 g, 0.394 mmol) in DMF (2.5 mL) was stirred at room temperature for 18 h. The reaction was diluted with water and the resulting suspension filtered. The bright yellow filter cake was taken up in methanol and the mixture was stirred for 1 h. The suspension was filtered and the yellow solid was washed with methanol and dried. The solid was further stirred in DCM/MeOH for 2 days. The mixture was filtered, and the filter cake washed with methanol and dried to give 6-((2-(4-chlorophenylamino)pyrimidin-5-yl)methoxy)quinolin-2(1H)-one as a brown solid (0.04 g, 26%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.68 (1H, s), 9.95 (1H, s), 8.64 (2H, s), 7.72-7.92 (3H, m), 7.12-7.47 (5H, m), 6.52 (1H, d, J=9.54 Hz), 5.04 (2H, s). LCMS: R.T.=3.77 min; [M+H]+=378.93.
Reaction SMILES: NCC[C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.C1C([OH:19])=CC2C(CCN)=CNC=2C=1.CNCCC1C2C=C(O)C=CC=2NC=1.COC1C=C2C(NC=C2CCNC)=CC=1>>[OH:19][N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:4]=[CH:5]1
Reactant: NCCc1c[nH]c2ccccc12
Reactant: NCCc1c[nH]c2ccc(O)cc12
Agent: CNCCc1c[nH]c2ccc(O)cc12
Agent: CNCCc1c[nH]c2ccc(OC)cc12
Product: On1ccc2ccccc21

Procedure:
1-hydroxyindole can be prepared in 2 stages from indole by reducing it to triethylsilane in trifluoroacetic acid then by treating the indoline obtained with an aqueous solution of H2O2 (30%) in the presence of a catalytic quantity (20%) of sodium tungstate dihydrate (Na2WO4.H2O) in methanol at 0° C. according to a procedure described in M. Somei, F. Yamada, T. Kurauchi, Y. Nagahama, M. Hasegawa, K. Yamada, S. Teranishi, H. Sato, C. Kaneko Chem. Pharm. Bull. 2001, 49, 87-96. This procedure was used in the preparation, from tryptamine derivatives, of several compounds oxygenated in position 5 of the indole ring such as for example serotonin, the N-methylserotonin and 5-methoxy-N-methyltryptamine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:11]=2[NH:12][CH2:13][CH2:14][NH:15]3)=[O:9])[CH:5]=[CH:6][CH:7]=1.N1C=CC=CC=1.[C:26](Cl)([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[C:8]([C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[NH:12][CH2:13][CH2:14][N:15]2[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:9]
Reactant: O=C(c1cccc(Cl)c1)c1cccc2c1NCCN2
Reactant: O=C(Cl)OCc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(c1cccc(Cl)c1)c1cccc2c1NCCN2C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 80 %

Procedure:
To a solution of (3-chlorophenyl)(1,2,3,4-tetrahydroquinoxalin-5-yl)methanone (50 g, 183 mmol) in DCM (200 mL) at 0° C. was added pyridine (17.79 mL, 220 mmol). Then CBZ—Cl (26.2 mL, 183 mmol) in DCM (1.0 mL) was added dropwise. The reaction mixture was warmed up to room temperature and stirred at room temperature for 3 h. The reaction mixture was washed with H2O, saturated NaHCO3, and brine, dried over Na2SO4, filtered, concentrated to give crude material. This crude material was purified via BIOTAGE®, eluted with 10% EtOAC/hexane to afford benzyl 5-(3-chlorobenzoyl)-3,4-dihydroquinoxaline-1(2H)-carboxylate, Intermediate E-1D (60 g, 147 mmol, 80% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.5 (1H, bs), 7.6 (1H, s), 7.45 (2H, m), 7.4 (7H, m), 7.25 (1H, m), 6.5 (1H, m), 5.2 (2H, m), 3.9 (2H, m), 3.6 (2H, m).
Reaction SMILES: [F:1][C:2]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH:11]=[C:12]([NH:14][C:15]([CH:17]3[CH2:19][CH2:18]3)=[O:16])[N:13]=2)[CH:10]=1.O1CCCC1.OS(C(F)(F)[F:37])(=O)=O.FN1C(Cl)=CC=CC1Cl.Cl>C(#N)C.C(OCC)(=O)C>[F:37][C:11]1[N:9]2[CH:10]=[C:5]([O:4][C:3]3[CH:20]=[CH:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][C:2]=3[F:1])[CH:6]=[CH:7][C:8]2=[N:13][C:12]=1[NH:14][C:15]([CH:17]1[CH2:19][CH2:18]1)=[O:16]
Reactant: O=C(Nc1cn2cc(Oc3ccc([N+](=O)[O-])cc3F)ccc2n1)C1CC1
Reactant: O=S(=O)(O)C(F)(F)F
Agent: Cl
Agent: FN1C(Cl)=CC=CC1Cl
Solvent: CC#N
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C(Nc1nc2ccc(Oc3ccc([N+](=O)[O-])cc3F)cn2c1F)C1CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 11.9 %

Procedure:
To a solution of N-[6-(2-fluoro-4-nitrophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (121.6 mg, 0.341 mmol) in acetonitrile (0.5 mL)/tetrahydrofuran (0.5 mL) was added 1-fluoro-2,6-dichloropyridine triflate (129 mg, 0.409 mmol), and the mixture was stirred at room temperature for 2 hr. Tetrahydrofuran, ethyl acetate and 1N hydrochloric acid were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=1/2→1/1) to give the title compound (15.2 mg, 12%) as a white solid.
Reaction SMILES: [N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:23][O:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1>>[N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:29][C:28]3[CH:30]=[CH:31][C:25]([O:24][CH3:23])=[CH:26][CH:27]=3)=[O:19])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: COc1ccc(N)cc1
Reactant: O=C(O)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1
Product: COc1ccc(NC(=O)c2ccc(S(=O)(=O)N3CCCc4ccccc43)cc2)cc1

Procedure:
4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)benzoic acid (1) (100 mg, 0.32 mmol) was treated with 4-methoxyaniline (30 mg, 0.24 mmol) using method B. The residue was purified using flash chromatography eluting with 0-40% EtOAc in hexanes. The resulting solid was triturated with dichloromethane/hexanes to give 4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)-N-(4-methoxyphenyl)benzamide as a white solid. Yield: 47 mg (46%). 1H-NMR: 10.33 (s, 1H), 8.04 (d, J=8.5 Hz, 2H), 7.73 (d, J=8.5 Hz, 2H), 7.66-7.61 (m, 3H), 7.24-7.18 (m, 1H), 7.11-7.08 (m, 2H), 6.93 (d, J=9.0, 2 Hz, 2H), 3.84-3.80 (m, 2H), 2.45 (t, J=6.5 Hz, 2H), 1.66-1.58 (m, 2H).
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@H:9]([CH3:20])[O:8][C@@H:6]1[SH:7])(=[O:3])[CH3:2].[CH2:21](I)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]/[CH:29]=[CH:30]\[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38].C(N(CC)CC)C>ClCCl>[C:1]([O:4][C@H:5]1[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@H:9]([CH3:20])[O:8][C@@H:6]1[S:7][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]/[CH:29]=[CH:30]\[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@H](C)O[C@H](S)[C@H]1OC(C)=O
Reactant: CCCCCCCC/C=C\CCCCCCCCI
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCCS[C@H]1O[C@@H](C)[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reaction time: 48 h

Procedure:
A solution of 2,3,4-tri-O-acetyl-1-thio-β-L-fucopyranose (2.0 g, 6.5 mmol) and oleyl iodide (2.5 g, 6.6 mmol) in dichloromethane (40 ml) containing triethylamine (1 ml) is kept under nitrogen for 2 days at room temperature. The solution is worked up in the normal manner and the resulting syrup is column chromatographed on silica gel with 2-10% ethyl acetate in chloroform as eluents. Oleyl 2,3,4-tri-O-acetyl-1-thio-β-L-fucopyranoside is isolated as a syrup (1.2 g, 32%), [α]D +26° (c, 2.19, chloroform).
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]([CH2:12][CH3:13])[C:8]([NH:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.[Cl:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH2:20]Br.C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[Cl:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH2:20][O:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH:7]([CH2:12][CH3:13])[C:8]([NH:10][CH3:11])=[O:9])=[CH:14][CH:15]=1
Reactant: Clc1cccc(CBr)c1
Reactant: CCC(Oc1ccc(O)cc1)C(=O)NC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCC(Oc1ccc(OCc2cccc(Cl)c2)cc1)C(=O)NC

Procedure:
In analogy to the procedure described in Example 3b), the alkylation of (RS)-2-(4-hydroxy-phenoxy)-N-methyl-butyramide with 3-chloro-benzylbromide in 2-butanone using potassium carbonate as the base yielded the (RS)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-butyramide as a white solid; MS: m/e=334 (M+H)+.
Reaction SMILES: C(N(CC)CC)C.[C:8]([N:12]([C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[NH2:13])([CH3:11])([CH3:10])[CH3:9].[N:22]1[CH:27]=[CH:26][N:25]=[CH:24][C:23]=1[C:28](O)=[O:29].CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:8]([N:12]([C:14](=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[NH:13][C:28]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][N:22]=1)=[O:29])([CH3:11])([CH3:9])[CH3:10]
Reactant: CC(C)(C)N(N)C(=O)c1ccccc1
Reactant: O=C(O)c1cnccn1
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)N(NC(=O)c1cnccn1)C(=O)c1ccccc1
Temperature: 23 °C
Reaction time: 3 h

Procedure:
Triethylamine (1.0 g, 0.01 mol) was added to a solution of N'-t-butyl-N'-benzoylhydrazine (0.86 g, 0.0031 mol) and pyrazine carboxylic acid (0.56 g, 0.0045 mol) in 10 ml of methylene chloride at 23° C. This mixture was added to a solution of methanesulfonyl chloride (0.6 g, 0.0052 mol) in 10 ml of methylene chloride at 0° C. The mixture was stirred at 23° C. for 3 hours and then allowed to stand at 23° C. overnight. Aqueous sodium bicarbonate was added and the layers were separated. The organic extracts were evaporated to give crude product which was triturated with ether to afford N'-t-butyl-N-(pyrazinecarbonyl)-N'-benzoylhydrazine as a white solid: m.p. 181°-183° C.