Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:14]([O:16][CH:17]([O:20][CH2:21][CH3:22])[CH2:18]Br)[CH3:15].Cl>CS(C)=O.CCOCC>[CH2:14]([O:16][CH:17]([O:20][CH2:21][CH3:22])[CH2:18][O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:6][CH:7]=1)[CH3:15]
Reactant: O=C(O)Cc1ccc(O)cc1
Reactant: CCOC(CBr)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CS(C)=O
Product: CCOC(COc1ccc(CC(=O)O)cc1)OCC
Yield: 93.9 %

Procedure:
To a solution of 4-hydroxyphenylacetic acid (50.0 gm, 0.33 mol) in DMSO (300 mL) was added 50% aqueous NaOH (57.0 gm, 0.71 mol) with stirring. After stirring for 10 min at room temperature bromoacetaldehyde diethyl acetal (66.0 gm, 0.33 mol) was added. The solution was heated at 100°-110° C. for 2 hr when an additional 2 gm of 50% NaOH was added. After heating for another hour the reaction mixture was cooled and poured into a mixture of aqueous HCl (30 mL of conc. HCl in 400 mL ice-H2O) and Et2O. The layers were separated and hexane was added to the Et2O layer. The organic layer was washed successively with H2O (twice) and saturated NaCl before being dried over Na2SO4, filtered and evaporated to dryness to give 83.7 gm (0.31 mol) of 4-[(2,2-diethoxy)ethoxy]phenylacetic acid which was suitable for use in the next step.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:10][CH:11]=[CH2:12])=[O:9])=[CH:4][C:3]=1[N+:13]([O-])=O.CO>[Fe].O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:10][CH:11]=[CH2:12])=[O:9])=[CH:4][C:3]=1[NH2:13]
Reactant: C=CCS(=O)c1ccc(N)c([N+](=O)[O-])c1
Agent: [Fe]
Solvent: O
Solvent: CO
Product: C=CCS(=O)c1ccc(N)c(N)c1

Procedure:
2 G. of 1-amino-2-nitro-4-(prop-2-en-1-ylsulfinyl)-benzene is treated for four hours in a refluxing mixture of 160 ml. methanol and 40 ml. water with 4 g. iron powder (added in two portions) and 1 g. ferrous sulfate. The mixture is filtered, and the filtrate concentrated. The residue is dissolved in chloroform and washed with water, then the solvent evaporated affording 1,2-diamino-4-(prop-2-en-1-ylsulfinyl)benzene.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[N:12]1([C:18]2[C:23]([Br:24])=[CH:22][N:21]=[C:20]([CH3:25])[CH:19]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>ClCCl>[N:12]1([C:18]2[CH:19]=[C:20]([CH3:25])[N+:21]([O-:9])=[CH:22][C:23]=2[Br:24])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1cc(N2CCCCC2)c(Br)cn1
Solvent: ClCCl
Product: Cc1cc(N2CCCCC2)c(Br)c[n+]1[O-]
Reaction time: 16 h

Procedure:
m-Chloroperbenzoic acid (7.3 g) in dichloromethane (100 ml) was added dropwise to a stirred solution of 4 -piperidino-5 -bromo-2 -picoline. After 16 hours, the solution was washed with 10 % aqueous sodium carbonate, dried (K2CO3) and stripped. The residue was chromatographed (silica gel, chloroform:methanol) to give 4 -piperidino-5 -bromo-2 -picoline-N-oxide, 6.79 g, m.p. 115°-6 ° from ether.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:25]=[CH:24][C:8]([CH2:9][C@@H:10]([C:21]([OH:23])=O)[NH:11][C:12](=[O:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:7][C:6]=1[Cl:26])[CH:2]=[CH2:3].Cl.[CH3:28][O:29][C:30](=[O:40])[C@H:31]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH2:32].C(N(CC)CC)C.C1CCC(N=C=NC2CCCCC2)CC1>O1CCCC1.C(Cl)(Cl)Cl>[CH3:28][O:29][C:30](=[O:40])[C@H:31]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH:32][C:21](=[O:23])[C@H:10]([CH2:9][C:8]1[CH:24]=[CH:25][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[C:6]([Cl:26])[CH:7]=1)[NH:11][C:12](=[O:20])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: COC(=O)[C@@H](N)Cc1ccccc1
Reactant: C=CCOc1ccc(C[C@H](NC(=O)Cc2ccccc2)C(=O)O)cc1Cl
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: C=CCOc1ccc(C[C@H](NC(=O)Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)OC)cc1Cl
Reaction time: 8 h

Procedure:
4-Allyloxy-3-chloro-phenylacetyl-(L)-phenylalanine (1.87 g) was dissolved in dry tetrahydrofuran (10 ml). To the solution was added (L)-phenylalanine methyl ester hydrochloride in dry chloroform (10 ml) containing dry triethylamine (0.7 ml). DCC (1.02 g) was added and the reaction mixture was stirred overnight.
Reaction SMILES: [F:1][CH:2]([F:18])[C:3](=[N:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10].Br[C:20]([F:27])([F:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22].C([Zn]CC)C>C1COCC1>[C:14]([S@:12]([NH:11][C@@:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10])([CH:2]([F:18])[F:1])[C:20]([F:27])([F:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:13])([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)[S@@](=O)N=C(c1ccccc1F)C(F)F
Reactant: CCOC(=O)C(F)(F)Br
Agent: CC[Zn]CC
Solvent: C1CCOC1
Product: CCOC(=O)C(F)(F)[C@](N[S@](=O)C(C)(C)C)(c1ccccc1F)C(F)F
Temperature: 0 °C
Reaction time: 2 h
Yield: 63.9 %

Procedure:
To a solution of (R)—N-(2,2-difluoro-1-(2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (4.60 g, 16.6 mmol), ethyl 2-bromo-2,2-difluoro-acetate (6.73 g, 33.18 mmol) and Rh(PPh3)3C1 (469 mg, 498 μmol) in THF (90 mL) was added a solution of diethyl zinc (1 M in THF, 33 mL) dropwise at −78° C. over a period of 20 minutes under Ar, during which the temperature was maintained below −65° C. The reaction mixture was warmed to 0° C. over a period of 10 minutes and stirred at 0° C. for 2 hours. TLC (petroleum ether/ethyl acetate=3:1) showed the starting material was consumed completely. The dark red solution was quenched by water (40 mL) and then filtered. The filtrate was extracted with ethyl acetate (100 mL, twice). The combined organic phases were washed with saturated brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=4:1) to give ethyl (S)-3-(((R)-tert-butylsulfinyl)amino)-2,2,4,4-tetrafluoro-3-(2-fluorophenyl)butanoate (4.26 g, 62.1% yield). 1H NMR (DMSO-d6, 400 MHz): δ 7.65-7.31 (m, 1H), 7.49-7.44 (m, 1H), 7.23-7.12 (m, 2H), 6.93-6.66 (m, 1H), 5.00 (s, 1H), 4.39-4.29 (m, 2H), 1.39 (s, 9H), 1.32 (t, J=8.0 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]([NH:4][C@H:5]1[C@H:10]([C@H:11]([OH:16])[C@H:12]([OH:15])[CH2:13][OH:14])[O:9][C@:8]([O:20]P(OC[C@H]2O[C@@H](N3C(=O)N=C(N)C=C3)[C@H](O)[C@@H]2O)(O)=O)([C:17]([OH:19])=[O:18])[CH2:7][C@@H:6]1[OH:41])=[O:3].OC(C1(O[C@@H]([C@@H]([C@@H](CO)O)O)[C@H](NC(C)=O)[C@@H](O)C1)O)=O.CC(NC1C(C(O)C(O)CO)OC(OP(OC[C@H]2O[C@@H](N3C(=O)N=C(N)C=C3)[C@H](O)[C@@H]2O)([O-])=O)(C(O)=O)CC1O)=O.[Na+].[O:105]([C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O)[C@@H:106]1[O:114][C@H:113]([CH2:115][OH:116])[C@H:111]([OH:112])[C@H:109](O)[C@H:107]1[OH:108].O=C[C@@H]([C@H]([C@H]([C@@H](CO)O)O)O)O>>[OH:19][C:17]([C@@:8]1([O:9][C@@H:10]([C@@H:11]([C@@H:12]([CH2:13][OH:14])[OH:15])[OH:16])[C@H:5]([NH:4][C:2]([CH3:1])=[O:3])[C@@H:6]([OH:41])[CH2:7]1)[O:20][C@H:109]1[C@@H:111]([OH:112])[C@@H:113]([CH2:115][OH:116])[O:114][C@@H:106]([OH:105])[C@@H:107]1[OH:108])=[O:18]
Reactant: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@](OP(=O)(O)OC[C@H]2O[C@@H](n3ccc(N)nc3=O)[C@H](O)[C@@H]2O)(C(=O)O)C[C@@H]1O
Reactant: CC(=O)N[C@@H]1[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](CO)O[C@H]1O
Agent: CC(=O)NC1C(O)CC(OP(=O)([O-])OC[C@H]2O[C@@H](n3ccc(N)nc3=O)[C@H](O)[C@@H]2O)(C(=O)O)OC1C(O)C(O)CO
Agent: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(O)(C(=O)O)C[C@@H]1O
Agent: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Product: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@@](O[C@@H]2[C@@H](O)[C@H](O)O[C@H](CO)[C@@H]2O)(C(=O)O)C[C@@H]1O

Procedure:
The resulting CMP-sialic acid analogue (which in FIG. 3 is illustrated as the CMP derivative of Neu5Ac, i.e., CMP-Neu5Ac) is then combined with the derivatized βGal(1→3)βGlcNAc-OR compound in the presence of the βGal(1→3/4)βGlcNAc α(2→3)sialyltransferase under conditions wherein sialic acid is transferred to the 3 position of the galactose to form a αNeu5Ac(2→3)βGal linkage. Suitable conditions, known in the art, include the addition of the sialyltransferase to a mixture of the derivatized βGal(1→4)βGlcNAc-OR compound and of the CMP-sialic acid in a appropriate buffer such as 0.1 M sodium cacodylate in appropriate conditions of pH and temperature such as at a pH of 6.5 to 7.5 and a temperature between 25 and 45° C., preferably 35-40° C., while incubating for 12 hours to 4 days. The resulting sialylated product can be isolated and purified using conventional methodology comprising HPLC, ion exchange-,gel-, reverse-phase- or adsorption chromatography.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][C:24]([O:26]CC2C=CC=CC=2)=[O:25])[C:18]1=[O:34])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]([C@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][C:24]([OH:26])=[O:25])[C:18]1=[O:34])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N(CCc1ccccc1)[C@H]1CCCN(CC(=O)OCc2ccccc2)C1=O
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N(CCc1ccccc1)[C@H]1CCCN(CC(=O)O)C1=O
Reaction time: 2 h
Yield: 97.8 %

Procedure:
To a solution of 43 (1.06 g, 2.27 mmol) in 35 mL of methanol was added 10% Pd/C catalyst (127 mg) and the mixture was hydrogenated on a Parr shaker apparatus at 45 PSI for 2 hrs. The solution was filtered, evaporated, and the residue was dried by pumping at <1mm Hg vacuum for 10 hrs to afford 0.836 g (98% yield) of product 44 as a colorless foam. TLC (silica; CH2Cl2, methanol, acetic acid: 27, 3, 1) Rf=0.40.
Reaction SMILES: [C:1]([NH:8][CH:9]1[CH2:12][CH:11]([CH2:13][OH:14])[CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O[N:16]1[C:20](=[O:21])[C:19]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:18]2[C:17]1=[O:26].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[C:1]([NH:8][CH:9]1[CH2:12][CH:11]([CH2:13][O:14][N:16]2[C:20](=[O:21])[C:19]3[C:18](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:17]2=[O:26])[CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)NC1CC(CO)C1
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC(C)(C)OC(=O)NC1CC(CON2C(=O)c3ccccc3C2=O)C1

Procedure:
Analogously to Example 6a, starting from 1.59 g (0.0079 mol) of 3-(N-BOC-amino)-cyclobutanemethanol (EP 0 366 059 A2), 1.29 g (0.0079 mol) of N-hydroxyphthalimide, 2.07 g (0.0079 mol) of triphenylphosphine and 1.39 ml (0.0083 mol) of diethyl azodicarboxylate (93%), the title compound is obtained, m.p. 108°-109° C.
Reaction SMILES: [CH2:1]([S:4][C:5]1[N:9]=[CH:8][NH:7][N:6]=1)[CH:2]=[CH2:3].SC1N=CNN=1.[CH2:16]([N:19]([CH2:23][CH:24]=[CH2:25])[C:20](Cl)=[O:21])[CH:17]=[CH2:18].C(N(CC)CC)C>O1CCCC1>[CH2:16]([N:19]([CH2:23][CH:24]=[CH2:25])[C:20]([N:7]1[CH:8]=[N:9][C:5]([S:4][CH2:1][CH:2]=[CH2:3])=[N:6]1)=[O:21])[CH:17]=[CH2:18]
Reactant: C=CCSc1nc[nH]n1
Reactant: C=CCN(CC=C)C(=O)Cl
Agent: Sc1nc[nH]n1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C=CCSc1ncn(C(=O)N(CC=C)CC=C)n1

Procedure:
A mixture of 7.1 g. 3-allylthio-1,2,4-triazole, (m.p. 27° - 30° C., prepared from 3-mercapto-1,2,4-triazole in an analogous manner to that described in Example 1), 8.0 g. diallylcarbamoyl chloride, 7.5 ml. dry triethylamine and 100 ml. dry tetrahydrofuran was refluxed under anhydrous conditions for 48 hours. The reaction mixture was worked up as described in Example 1 to give 1-diallylcarbamoyl-3-allylthio-1,2,4-triazole, b.p. 120° - 122° C./0.1 mm. (95.2% 1-isomer by GLC assay).
Reaction SMILES: [F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:16]=[C:15]([CH:17]=O)[CH:14]=[CH:13][C:6]=1[NH:7][S:8]([CH2:11]C)(=[O:10])=[O:9].C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[C:31]2[CH2:36][CH2:35][O:34][C:32]2=[O:33])C=CC=CC=1>CS(C)=O.C(OCC)(=O)C>[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:16]=[C:15]([CH:14]=[CH:13][C:6]=1[NH:7][S:8]([CH3:11])(=[O:10])=[O:9])[CH:17]=[C:31]1[CH2:36][CH2:35][O:34][C:32]1=[O:33]
Reactant: CCS(=O)(=O)Nc1ccc(C=O)cc1Oc1ccc(F)cc1F
Reactant: O=C1OCCC1=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CS(=O)(=O)Nc1ccc(C=C2CCOC2=O)cc1Oc1ccc(F)cc1F
Temperature: 80 °C
Reaction time: 6 h
Yield: 73.4 %

Procedure:
A mixture of 2'-(2,4-difluorophenoxy)-4'-formylethanesulfonanilide (2 g) and α-triphenylphosphoranylidene-γ-butyrolactone (2.2 g) in dimethyl sulfoxide (10 ml) was stirred at 80° C. for 6 hours. The mixture was dissolved in ethyl acetate, and the resulting mixture was washed with water, dried, and concentrated to dryness. The residue was purified by column chromatography on acetate (1:1) to give a powder of α-[3-(2,4-difluorophenoxy)-4-(methanesulfonamido)benzylidene]-γ-butyrolactone (1.7 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:17]([C:18]3[N:19]([CH3:23])[CH:20]=[CH:21][N:22]=3)[C:16](=O)[C:15]3[C:14]([C:25]([O:27]CC)=O)=[CH:13][CH:12]=[CH:11][C:10]=3[NH:9]2)=[CH:4][CH:3]=1.O.[NH2:31][NH2:32]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[NH:9][C:10]3[C:15]4[C:16](=[N:31][NH:32][C:25](=[O:27])[C:14]=4[CH:13]=[CH:12][CH:11]=3)[CH:17]2[C:18]2[N:19]([CH3:23])[CH:20]=[CH:21][N:22]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cccc2c1C(=O)C(c1nccn1C)C(c1ccc(F)cc1)N2
Reactant: NN
Solvent: O
Solvent: CO
Product: Cn1ccnc1C1c2n[nH]c(=O)c3cccc(c23)NC1c1ccc(F)cc1
Temperature: 45 °C
Reaction time: 8 h
Yield: 19 %

Procedure:
A mixture of ethyl 2-(4-fluorophenyl)-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (210 mg) in 85% hydrazine monohydrate (10 mL) and methanol (10 mL) was stirred at 45° C. for overnight. Methanol was removed under reduced pressure. The mixture was filtered and washed with water to give 8-(4-fluorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one 36 mg, yield 19%). 1H-NMR (400 MHz, DMSO-d) δ (ppm): 3.42 (s, 3H), 4.66 (d, J=8.0 Hz, 1H), 4.95 (d, J=8.0 Hz, 1H), 6.72 (s, 1H), 6.89 (s, 1H), 7.11-7.17 (m, 3H), 7.30 (s, 1H), 7.40 (d, 1H), 7.43-7.44 (m, 2H), 7.58 (d, 1H), 12.17 (s, 1H); 19F-NMR (400 MHz, DMSO-d6) δ (ppm): −114.58; LC-MS (ESI) m/z: 362 (M+1)+.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([Li])(C)(C)C.I[C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21](=[O:26])[CH:20]=[CH:19]2.[Cl-].[NH4+].[Na+].[Na+].C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O>O1CCCC1.CCCCC.O.[Cl-].[Zn+2].[Cl-].CO.C(Cl)(Cl)Cl>[CH3:9][O:8][C:5]1[CH:4]=[CH:3][C:2]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[NH:22][C:21](=[O:26])[CH:20]=[CH:19]3)=[CH:7][N:6]=1
Reactant: O=c1ccc2cc(I)ccc2[nH]1
Reactant: COc1ccc(Br)cn1
Agent: O=C([O-])CN(CCN(CC(=O)O)CC(=O)O)CC(=O)[O-]
Agent: [Cl-]
Agent: [Li]C(C)(C)C
Solvent: CO
Solvent: C1CCOC1
Solvent: CCCCC
Product: COc1ccc(-c2ccc3[nH]c(=O)ccc3c2)cn1
Temperature: 25 °C

Procedure:
A solution of 5-bromo-2-methoxypyridine (1.50 g) in tetrahydrofuran (THF) (10 cm3) was stirred at -70° under nitrogen during the addition of t-butyllithium (8.0 cm3 of a 2.0M solution in pentane). After 10 minutes a solution of anhydrous zinc chloride (1.09 g) in tetrahydrofuran (THF) (10 cm3) was added and the mixture was allowed to warm to room temperature over 1 hour. A suspension of 6-iodo-2-(1H)-quinolone (0.813 g) and tetrakis (triphenylphosphine) palladium(O) (0.03 g) in THF (10 cm3) was then added and the mixture was heated under reflux for 3 hours. Saturated ammonium chloride solution (1 cm3) was added to the cooled mixture followed by a solution of ethylenediaminetetraacetic acid disodium salt (6.0 g) in water (100 cm3). Chloroform (100 cm3) and methanol (30 cm3) were added and the mixture was warmed until all the solid material dissolved. The phases were separated, the aqueous layer was further extracted with chloroform:methanol 9:1 (3×50 cm3), and the combined and dried (MgSO4) extracts were concentrated in vacuo to afford a solid which was recrystallised from isopropanol to give 6-(2-methoxypyrid-5-yl)-2-(1H)-quinolone, m.p. 248°-252°, (0.56 g).
Reaction SMILES: [CH:1]12[N:12](Cl)[C:10](=[O:11])[N:9](Cl)[CH:2]1[N:3](Cl)[C:4]([N:6]2Cl)=[O:5]>O>[CH:1]12[NH:12][C:10](=[O:11])[NH:9][CH:2]1[NH:3][C:4]([NH:6]2)=[O:5]
Reactant: O=C1N(Cl)C2C(N1Cl)N(Cl)C(=O)N2Cl
Solvent: O
Product: O=C1NC2NC(=O)NC2N1

Procedure:
The purpose of the present example was to determine the pH conditions required to dissolve approximately 1% 1,3,4,6-tetrachloroglycoluril in water in the presence of detergent.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]([C:23]2[S:24][CH:25]=[CH:26][N:27]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH:19]([CH3:21])[CH2:18][O:17][C:16]=3[CH:22]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.F[C:31]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:32]=1[C:33]#[N:34].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C)C=O>[C:33]([C:32]1[CH:35]=[C:36]([C:39]([F:40])([F:41])[F:42])[CH:37]=[CH:38][C:31]=1[N:20]1[CH:19]([CH3:21])[CH2:18][O:17][C:16]2[CH:22]=[C:12]([S:9]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:29][CH:28]=3)[C:23]3[S:24][CH:25]=[CH:26][N:27]=3)(=[O:11])=[O:10])[CH:13]=[CH:14][C:15]1=2)#[N:34]
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCC(C)N3)cc1
Reactant: N#Cc1cc(C(F)(F)F)ccc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCC(C)N3c2ccc(C(F)(F)F)cc2C#N)cc1
Temperature: 90 °C
Yield: 56 %

Procedure:
To a solution of N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (900 mg, 2.08 mmol) and 2-fluoro-5-(trifluoromethyl)benzonitrile (546 mg, 2.49 mmol, Alfa Aesar) in dimethylformamide (20 mL) was added Cs2CO3 (1.35 g, 4.16 mmol, GLR) and the mixture was heated at 90° C. for 3 h. The reaction mixture was cooled to room temperature and water (200 mL) was added. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was further purified by column chromatography (silica gel 100-200 mesh and 0-3% methanol in dichloromethane) to obtain 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (700 mg, 56%) as off white solid. 1H NMR (400 MHz, DMSO) δ 8.50 (s, 1H), 8.17 (d, J=8.7 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.44 (d, J=3.6 Hz, 1H), 7.35 (d, J=3.6 Hz, 1H), 7.30-7.12 (m, 4H), 6.85 (d, J=8.7 Hz, 2H), 6.55 (d, J=8.6 Hz, 1H), 5.02 (s, 2H), 4.23 (m, 2H), 4.19-4.06 (m, 1H), 3.70 (s, 3H), 1.21-1.09 (m, 3H); MS (ESI, positive ion) m/z 601.1 (M+H).
Reaction SMILES: C1(C[O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([NH:18][C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[CH:13]=[CH:12]3)C=CC=CC=1>[Pd].C(O)C>[N:22]1[CH:23]=[CH:24][C:19]([NH:18][N:14]2[C:15]3[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=3)[CH:12]=[CH:13]2)=[CH:20][CH:21]=1
Reactant: c1ccc(COc2ccc3c(ccn3Nc3ccncc3)c2)cc1
Agent: [Pd]
Solvent: CCO
Product: Oc1ccc2c(ccn2Nc2ccncc2)c1
Reaction time: 4 h
Yield: 147 %

Procedure:
To 0.8 g of 10% palladium on carbon in 10 ml of absolute ethanol was added a solution of 5-(phenylmethoxy)-1-(4-pyridinylamino)-1H-indole (4.0 g) in 240 ml of absolute ethanol and this was hydrogenated on a Parr apparatus for four hours at 50° C. at 50 psig H2. The mixture was cooled and filtered, and the filtrate was concentrated to yield an oil (4.2 g), which was eluted with ethyl acetate on a silica gel column via HPLC. The desired fractions were concentrated to yield an oil (3.72 g). This material was eluted with 10% methanol/dichloromethane on a silica gel column via HPLC. The desired fractions were concentrated to yield a foam (1.8 g), which was recrystallized from ethyl acetate to yield a solid (1.5 g), m.p. 232°-234° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:17]=[C:16]([NH:18][NH2:19])[N:15]=[C:14]3[C:10]=2[N:11]=[CH:12][N:13]3[CH3:20])=[CH:4][CH:3]=1.[CH3:21][CH2:22][C:23](=O)[CH2:24][C:25](=O)[CH2:26][CH3:27]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:17]=[C:16]([N:18]3[C:25]([CH2:26][CH3:27])=[CH:24][C:23]([CH2:22][CH3:21])=[N:19]3)[N:15]=[C:14]3[C:10]=2[N:11]=[CH:12][N:13]3[CH3:20])=[CH:4][CH:3]=1
Reactant: Cn1cnc2c(Nc3ccc(Cl)cc3)nc(NN)nc21
Reactant: CCC(=O)CC(=O)CC
Product: CCc1cc(CC)n(-c2nc(Nc3ccc(Cl)cc3)c3ncn(C)c3n2)n1

Procedure:
Was prepared according to Example 9 from (4-chloro-phenyl)-(2-hydrazino-9-methyl-9H-purin-6-yl)-amine and 3,5-heptanedione.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:22]=[CH:23][CH:24]=1)[CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:18])[C:13]([NH2:19])=[C:12]2[C:20]#[N:21])([O-])=O.C([O-])([O-])=O.[K+].[K+]>CO.O=[Pt]=O>[NH2:1][C:4]1[CH:5]=[C:6]([CH:22]=[CH:23][CH:24]=1)[CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:18])[C:13]([NH2:19])=[C:12]2[C:20]#[N:21]
Reactant: Cn1c(N)c(C#N)c2cc(OCc3cccc([N+](=O)[O-])c3)ccc21
Agent: O=[Pt]=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: Cn1c(N)c(C#N)c2cc(OCc3cccc(N)c3)ccc21
Yield: 0.1 %

Procedure:
A solution of 5-(3-nitrobenzyloxy)-2-amino-1-methyl-1H-indole-3-carbonitrile (40 mg; 0.12 mol) in MeOH (6 ml) was treated with K2CO3 (6 mg) and hydrogenated over PtO2 (6 mg) at 45 psi at room temperature for 1 hour. After filtration and evaporation to dryness, the residue was purified by flash chromatography eluting with MeOH/CH2Cl2 (5% MeOH) and the appropriate factions were evaporated to give 5-(3-aminobenzyloxy)-2-amino-1-methyl-1H-indole-3-carbonitrile (32 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[S:9][CH2:10][C:11]1[C:15]([CH2:16][OH:17])=[C:14]([CH:18]([CH3:20])[CH3:19])[O:13][N:12]=1.O[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[C:30]3[C:35](=[CH:36][CH:37]=2)[N:34]=[C:33]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:32]=[CH:31]3)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[S:9][CH2:10][C:11]1[C:15]([CH2:16][O:17][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:29]=[C:30]4[C:35](=[CH:36][CH:37]=3)[N:34]=[C:33]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:32]=[CH:31]4)=[CH:26][CH:27]=2)=[C:14]([CH:18]([CH3:20])[CH3:19])[O:13][N:12]=1
Reactant: CC(C)c1onc(CSc2c(Cl)cccc2Cl)c1CO
Reactant: CCOC(=O)c1ccc2cc(-c3ccc(O)cc3)ccc2n1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOC(=O)c1ccc2cc(-c3ccc(OCc4c(CSc5c(Cl)cccc5Cl)noc4C(C)C)cc3)ccc2n1
Reaction time: 4.5 h
Yield: 64.8 %

Procedure:
To a solution of [3-{[(2,6-dichlorophenyl)thio]methyl}-5-(1-methylethyl)-4-isoxazolyl]methanol (22 mg, 0.066 mmol), ethyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (19 mg, 0.066 mmol) and triphenylphosphine (35 mg, 0.13 mmol) in dichloromethane (1 mL) was added di-tert-butyl azodicarboxylate (30 mg, 0.13 mmol). The solution was stirred at ambient temperature approximately 4.5 hours and then was adsorbed onto silica gel. Purification was done by chromatography (silica gel, 0-75% ethyl acetate in hexanes gradient elution) to afford ethyl 6-[4-({[3-{[(2,6-dichlorophenyl)thio]methyl}-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (26 mg, 65%). 1H-NMR (400 MHz, CDCl3) δ 8.36-8.31 (m, 2H), 8.20 (d, J=9 Hz, 1H), 8.03-8.00 (m, 2H), 7.69 (d, J=9 Hz, 2H), 7.32-7.13 (m, 3H), 7.08 (d, J=9 Hz, 2H), 5.08 (s, 2H), 4.56 (q, J=7 Hz, 2H), 4.16 (s, 2H), 3.20 (septet, J=7 Hz, 1H), 1.49 (t, J=7 Hz, 3H), 1.31 (d, J=7 Hz, 6H). LRMS (APCI) m/z 607 (M+H)+.
Reaction SMILES: [CH3:1][CH:2]1[O:6][C:5]([C:8]2[CH:9]=[C:10]([S:14][C:15]3[CH:20]=[CH:19][C:18]([C:21](=O)[CH3:22])=[CH:17][CH:16]=3)[CH:11]=[CH:12][CH:13]=2)([CH3:7])[CH2:4][O:3]1.Cl.[NH2:25][OH:26]>>[CH3:1][CH:2]1[O:6][C:5]([C:8]2[CH:9]=[C:10]([S:14][C:15]3[CH:20]=[CH:19][C:18]([C:21](=[N:25][OH:26])[CH3:22])=[CH:17][CH:16]=3)[CH:11]=[CH:12][CH:13]=2)([CH3:7])[CH2:4][O:3]1
Reactant: NO
Reactant: CC(=O)c1ccc(Sc2cccc(C3(C)COC(C)O3)c2)cc1
Agent: Cl
Product: CC(=NO)c1ccc(Sc2cccc(C3(C)COC(C)O3)c2)cc1
Yield: 82 %

Procedure:
Using an analogous procedure to that described in Example 68, 4'-[3-(2,4-dimethyl-1,3-dioxolan-4-yl)phenylthio]acetophenone was reacted with hydroxylamine hydrochloride to give 4'-[3-(2,4-dimethyl-1,3-dioxolan-4-yl)phenylthio]acetophenone oxime in 82% yield as a gum.