Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=S(Cl)[Cl:3].[CH2:5]([O:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[N:11]=[N:10][C:9]=1[CH2:17]O)[CH3:6]>C(Cl)Cl>[Cl:3][CH2:17][C:9]1[N:10]=[N:11][C:12]([O:14][CH2:15][CH3:16])=[CH:13][C:8]=1[O:7][CH2:5][CH3:6]
Reactant: CCOc1cc(OCC)c(CO)nn1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CCOc1cc(OCC)c(CCl)nn1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Excess SOCl2 is added to a stirred solution of (4,6-diethoxy-pyridazin-3-yl)-methanol (174 mg, 0.88 mmol) in CH2Cl2 (4 mL). The reaction mixture is stirred at room temperature for 4 hours. The solvent is then removed in vacuo; toluene (4 mL) is added and evaporated to dryness. Flash column chromatography purification (silica gel, eluted with 3:1 Hexane, EtOAc) of the residue provides the title compound as a clear oil. H1 NMR δ (CDCl3) 6.28(s, 1H), 4.78 (s, 2H), 4.54 (q, 2H, J=7.2 Hz), 4.11 (q, 2H, J=7.2 Hz), 1.48 (t, 3H, J=7.2 Hz), 1.41 (t, 3H, J=7.2 Hz).
Reaction SMILES: FC(F)(F)[C:3]([NH:5][C:6]1[C:7](=[O:32])[N:8]([CH2:18][C:19]([NH:21][CH:22]([CH:29]([CH3:31])[CH3:30])[C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])=[O:20])[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)=O.C(=O)([O-])[O-].[Na+].[Na+].CI.C(OCC)(=O)C>CN(C)C=O.[Cl-].[Na+].O>[CH3:3][NH:5][C:6]1[C:7](=[O:32])[N:8]([CH2:18][C:19]([NH:21][CH:22]([CH:29]([CH3:30])[CH3:31])[C:23](=[O:28])[C:24]([F:25])([F:26])[F:27])=[O:20])[C:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:10][CH:11]=1
Reactant: CC(C)C(NC(=O)Cn1c(-c2ccccc2)ccc(NC(=O)C(F)(F)F)c1=O)C(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CI
Solvent: CN(C)C=O
Product: CNc1ccc(-c2ccccc2)n(CC(=O)NC(C(=O)C(F)(F)F)C(C)C)c1=O
Reaction time: 8 h
Yield: 48 %

Procedure:
To a solution of 2-(3-trifluoroacetylamino-2-oxo-6-phenyl -1,2-dihydro-1-pyridyl]-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (Example 167 above) (200 mg)in dimethylformamide (2 mL) was added sodium carbonate (128 mg) and methyl iodide (130 μL). The mixture was stirred in a stoppered vessel overnight. Ethyl acetate and brine were added. The organic phase was separated, washed (brine), dried (MgSO4), and evaporated. Chromatography, eluting with dichloromethane:methanol (98:2), gave the title product (80 mg) as a white solid; TLC: Rf =0.15, dichloromethane:methanol (98:2); MS: m/z=506(M+1).
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]([CH2:10][OH:11])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4].[Bi].[OH-].[Na+].OO>[Pt].O>[CH2:1]([C:5]1[NH:6][C:7]([CH:10]=[O:11])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ncc(CO)[nH]1
Agent: [Pt]
Agent: OO
Agent: [Bi]
Solvent: O
Product: CCCCc1ncc(C=O)[nH]1
Yield: 100 %

Procedure:
2.0 g of 2-n-butyl-5-hydroxymethylimidazole, 0.3 g of 5 percent platinum and 5 percent bismuth on activated carbon (comprising 61.3 percent water), 13 ml of 1 N NaOH solution and 7 g of H2O were heated to about 60° C. with stirring. At 60° to 64° C., 3.4 g of 15 percent strength aqueous H2O2 solution was added dropwise over the course of 45 min. The reaction mixture was then allowed to react for 15 min and then filtered. The pH of the filtrate was adjusted from 13.4 to 9.0 using 20 percent H2SO4, as a result of which a pale yellow suspension formed. This was cooled, and the crude product was able to be filtered off and/or extracted with methylene chloride. The reaction was monitored by GC analysis. The reaction yield was 100 percent (0 percent of starting material).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][C@H:11]([CH2:13][OH:14])[O:10][C:9]2=[O:15])[CH:5]=[CH:6][CH:7]=1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.CO.C(Cl)(Cl)Cl.CCCCCC.C(OCC)(=O)C>N1C=CC=CC=1>[CH3:26][C:16]1[CH:21]=[CH:20][C:19]([S:22]([O:14][CH2:13][C@@H:11]2[O:10][C:9](=[O:15])[N:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH2:12]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: O=C1O[C@@H](CO)CN1c1cccc(F)c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@H]2CN(c3cccc(F)c3)C(=O)O2)cc1
Reaction time: 8 h

Procedure:
A mixture of (R)-3-(3-fluorophenyl)-5-(hydroxymethyl)-2-oxooxazolidine (PREPARATION 14, 1.800 g, 8.52 mmol) in dry pyridine (10 ml) is cooled to 5° and then treated with p-toluenesulfonyl chloride (1.706 g, 8.95 mmol). The mixture is left at this temperature overnight. TLC with methanol/chloroform (5/95) or hexane/ethyl acetate (1/1) indicates the starting material is consumed. The reaction mixture is dumped into ice water (30 ml) and the resultant precipitate collected by vacuum filtration through a medium-porosity sintered glass funnel. The collected solids are thoroughly washed with cold water, dried under reduced pressure and recrystallized from ethyl acetate/hexane to give the title compound, mp 114°-115°; [α]25D -62.6° (c 1.0, CH3CN); IR (mineral oil mull): 1751, 1617, 1591, 1499, 1415, 1362, 1227, 1202, 1191, 1172, 1093, 967 cm-1 ; NMR (CDCl3, 300 MHz) δ 7.78, 7.38, 7.36, 7.33, 7.16, 6.86, 4.84, 4.29, 4.24, 4.10, 3.88, 2.46; MS (m/z) 365, 149, 122, 91; HRMS (m/z) 365.0738 (calc'd for C17H16FNO5S: 365.0733).
Reaction SMILES: [C:1]12[CH2:9][CH:5]([C:6]1([CH3:8])[CH3:7])[CH2:4][CH2:3][C:2]=2[CH3:10].C12CC(CC1)C=C2.FC1C(B(C2C(F)=C(F)C(F)=C(F)C=2F)C2C(F)=C(F)C(F)=C(F)C=2F)=C(F)C(F)=C(F)C=1F.C([Al](CC)CC)C>C1CCCCC1.C(OC(=O)CCCCC)C.[Ni].[Ni].CO.ClC1C=CC=CC=1>[CH3:7][C:6]1([CH3:8])[CH:1]2[CH2:9][CH:5]1[CH2:4][CH2:3][C:2]2=[CH2:10]
Reactant: CC1=C2CC(CC1)C2(C)C
Agent: [Ni]
Agent: C1=CC2CCC1C2
Agent: CC[Al](CC)CC
Solvent: Clc1ccccc1
Solvent: C1CCCCC1
Solvent: CO
Product: C=C1CCC2CC1C2(C)C
Reaction time: 1 h

Procedure:
To a 50 ml glass vial equipped with a Teflon® coated stirbar was added -pinene (2.5 ml), norbornene (5 g, 53.1 mmol) and chlorobenzene (35 ml). To this stirred solution at ambient temperature was added nickel ethylhexanoate (0.01 ml of an 8% w nickel solution in mineral spirits, 13 μmol) tris(pentafluorophenyl)boron (117 μmol in petroleum naphtha) and triethylaluminum (0.077 ml of a 1.7 molar solution in cyclohexane, 130 μmol). Immediately upon addition of the trialkylaluminum the reaction mixture became yellow and hot. The reaction was allowed to run for 60 minutes after which time methanol (3 ml) was injected to kill the reaction and the resulting solution was poured into excess methanol. The polymer was filtered off and washed with excess methanol and dried overnight in a heated vacuum oven to afford the copolymer (4.0 g). GPC analysis showed the polymer to have a molecular weight (Mw) of 39,800 and a polydispersity of 2.1.
Reaction SMILES: F[C:2]1[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:4]([CH3:21])[C:5]([C:19]#[N:20])=[C:6]2[C:10]=1[O:9][C:8](/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[N:7]2.C(N(CC)CC)C.[CH3:35][N:36]([CH3:42])[C@H:37]1[CH2:41][CH2:40][NH:39][CH2:38]1.C(OCC)(=O)C>CS(C)=O.O>[CH3:35][N:36]([CH3:42])[C@H:37]1[CH2:41][CH2:40][N:39]([C:2]2[C:3]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:4]([CH3:21])[C:5]([C:19]#[N:20])=[C:6]3[C:10]=2[O:9][C:8](/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:7]3)[CH2:38]1
Reactant: Cc1c(-c2ccccc2)c(F)c2oc(/C=C/c3ccccc3)nc2c1C#N
Reactant: CN(C)[C@H]1CCNC1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1c(-c2ccccc2)c(N2CC[C@H](N(C)C)C2)c2oc(/C=C/c3ccccc3)nc2c1C#N
Temperature: 90 °C
Reaction time: 15 h
Yield: 64.9 %

Procedure:
7-Fluoro-5-methyl-6-phenyl-2-[(E)-2-phenylethenyl]-1,3-benzoxazole-4-carbonitrile (I-92) (200 mg, 0.56 mmol) was dissolved in dimethylsulfoxide (2 ml), triethylamine (190 μl, 1.35 mmol) and (3S)-3-(dimethylamino)pyrrolidine (86 μl, 0.68 mmol) were added, followed by stirring at 90° C. for 15 hours under nitrogen atmosphere. After cooling to room temperature, ethyl acetate was added, followed by fractionation with water. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was evaporated away and the resulting residue was subjected to silica gel column chromatography, eluted with a mixed solvent of chloroform/methanol (50:1, v/v), recrystallized and purified with n-hexane/ethyl acetate to obtain the entitled compound (163 mg, 65%) as a yellow solid.
Reaction SMILES: O1CCCC1.[N:6]1([C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:20])[C:18]#[N:19])=[CH:13][CH:12]=2)[CH:10]=[CH:9][N:8]=[CH:7]1.CC(C)([O-])C.[K+].[CH3:27][N:28]=[C:29]=[S:30]>O>[CH3:27][NH:28][C:29](=[S:30])[C:17]([C:14]1[CH:13]=[CH:12][C:11]([N:6]2[CH:10]=[CH:9][N:8]=[CH:7]2)=[CH:16][CH:15]=1)([C:18]#[N:19])[CH3:20]
Reactant: CN=C=S
Reactant: CC(C#N)c1ccc(-n2ccnc2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CNC(=S)C(C)(C#N)c1ccc(-n2ccnc2)cc1
Reaction time: 0.5 h
Yield: 54.4 %

Procedure:
To a 10 ml tetrahydrofuran solution containing 1.00 g (5.1 mmole) of 2-[4-(1-imidazolyl)-phenyl]propionitrile was added a 10 ml tetrahydrofuran solution containing 0.69 g (6.2 mmole) of potassium tert-butoxide at 0 C. After stirring for 0.5 hour, a 5 ml tetrahydrofuran solution containing 0.45 g (6.2 mmole) of methyl isothiocyanate was added to the mixture and the mixture was stirred at room temperature for 2 hours. Water was added to the mixture and the mixture was extracted with 20 ml of ethyl acetate, dried and condensed under reduced pressure, and then purified by silica gel chromatography and condensed. The resulting condensate was suspended in 30 ml of toluene and the suspension was refluxed under heating for 0.5 hour and a solid was collected by filtration to obtain 0.75 g (yield: 54 %) of N-methyl-2-[4-(1-imidazolyl)-phenyl]-2cyanothiopropionamide as a crystalline solid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([S:30][CH3:31])=[C:8]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[C:15]([N+:27]([O-])=O)[CH:14]=2)(=[O:12])=[O:11])[CH:9]=1)=[O:4].[CH3:32]CO.CC(O)=O>[Fe].C(O)=O>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([S:30][CH3:31])=[C:8]([S:10]([C:13]2[CH:18]=[CH:17][C:16]3[N:19]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH:32]=[N:27][C:15]=3[CH:14]=2)(=[O:12])=[O:11])[CH:9]=1)=[O:4]
Reactant: COC(=O)c1cc(S(=O)(=O)c2ccc(NCc3ccccn3)c([N+](=O)[O-])c2)c(SC)s1
Reactant: CCO
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O=CO
Product: COC(=O)c1cc(S(=O)(=O)c2ccc3c(c2)ncn3Cc2ccccn2)c(SC)s1

Procedure:
The procedure in Example 318: part e was followed using 5-methylsulfanyl-4-{3-nitro-4-[(pyridin-2-ylmethyl)-amino]-benzenesulfonyl}-thiophene-2-carboxylic acid methyl ester ((Example 264: step c) 41 mg, 0.08 mmol), iron (110 mg, 2 mmol), and EtOH/aq. AcOH, followed by treatment with formic acid to yield the title compound. 1H-NMR (CD3OD): δ 8.50 (m, 1H), 8.42 (s, 1H), 8.08 (m, 1H), 7.97 (d, 1H, J=2.5 Hz), 7.85 (m, 1H), 7.72 (m, 1H), 7.71 (dt, 1H, J=1.9, 7.7 Hz), 7.57 (m, 1H), 7.29 (m, 1H), 7.22 (d, 1H J=7.8 Hz), 6.95 (d, 1H, J=9.0 Hz), 5.57 (s, 2H), 3.82 (s, 3H), 2.56 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:22])=[CH:4][C:5]([Cl:21])=[C:6]([CH:20]=1)[O:7][C:8]1[CH:19]=[CH:18][CH:17]=[CH:16][C:9]=1[O:10][CH2:11][C:12]([O:14][CH3:15])=[O:13].Cl[C:24]([O:26][CH3:27])=[O:25].O1CCCC1.Cl>N1C=CC=CC=1>[Cl:21][C:5]1[CH:4]=[C:3]([F:22])[C:2]([NH:1][C:24]([O:26][CH3:27])=[O:25])=[CH:20][C:6]=1[O:7][C:8]1[CH:19]=[CH:18][CH:17]=[CH:16][C:9]=1[O:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]
Reactant: COC(=O)COc1ccccc1Oc1cc(N)c(F)cc1Cl
Reactant: COC(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: COC(=O)COc1ccccc1Oc1cc(NC(=O)OC)c(F)cc1Cl
Temperature: 25 °C

Procedure:
Into a mixture of methyl [2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediate compound A3-22], methyl chloroformate and tetrahydrofuran is added dropwise pyridine, and the mixture is stirred at room temperature. Dilute hydrochloric acid is added to the reaction solution, and this is extracted with ethyl acetate. The organic layer is washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated to obtain methyl [2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenoxy]acetate [Intermediate compound A9-22].
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:8]2[C:9]([C:20]([OH:22])=[O:21])=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.OS(O)(=O)=O.[CH3:28]O>>[CH3:7][C:4]1[N:3]([C:8]2[C:9]([C:20]([O:22][CH3:28])=[O:21])=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:13]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1
Reactant: COc1nc(C(=O)O)c(-n2c(C)ccc2C)cc1C(F)(F)F
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1nc(OC)c(C(F)(F)F)cc1-n1c(C)ccc1C

Procedure:
3-(2,5-Dimethyl-pyrrol-1-yl)-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate D2)(500 mg, 1.591 mmol) in methanol (15.91 ml) was treated with H2SO4 (0.0424 ml, 0.795 mmol) and the solution was heated at reflux for overnight. The solvent removed was removed in vacuo and the resulting brown oil was neutralised to pH 7 using saturated sodium bicarbonate. The mixture was extracted with EtOAc (20 ml) and the combined organic extracts were washed with water (20 ml), brine (20 ml), passed though a phase separator and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with iso-hexane: EtOAc (gradient of 0 to 10% EtOAc) afforded the title compound as an off-white powder.
Reaction SMILES: [O:1]1[C@H:3]2[CH2:4][C@H:5]3[C@:20]([CH3:22])([CH2:21][C@@H:2]12)[C@@H:19]1[C@H:8]([C@H:9]2[C@:16]([CH3:24])([CH2:17][C:18]1=[O:23])[C@@H:12]([C:13](=[O:15])[CH3:14])[CH2:11][CH2:10]2)[CH2:7][CH2:6]3.[Br:25]CCO.S(=O)(=O)(O)O.C(=O)(O)[O-].[K+]>CCOCC>[Br:25][C@H:2]1[CH2:21][C@@:20]2([CH3:22])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:19]2[C:18](=[O:23])[CH2:17][C@@:16]2([CH3:24])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:13](=[O:15])[CH3:14])[CH2:4][C@@H:3]1[OH:1]
Reactant: OCCBr
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]5O[C@@H]5C[C@]4(C)[C@H]3C(=O)C[C@]12C
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: CCOCC
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)[C@@H](Br)C[C@]4(C)[C@H]3C(=O)C[C@]12C
Temperature: 25 °C

Procedure:
2α, 3α-Epoxy-5α-pregnane-11,20-dione (660 mg.) was dissolved in ether (70 ml.) and 2-bromoethanol (1 ml.) added to the solution. Concentrated sulphuric acid (0.5 ml.) was then added and the mixture stirred at room temperature for one-half hour. 10% Potassium bicarbonate solution (18 ml.) was added and when effervescence had ceased the aqueous layer was removed and extracted with ether (20 ml.). The combined organic extracts were washed with water (100 ml.), dried over anhydrous sodium sulphate and evaporated in vacuo to a pale yellow oil (794 mg.) which was purified by preparative tlc. The main band (RF ~ 0.3) gave 2β-bromo-3α-hydroxy-5α-pregnane-11,20-dione (230 mg.), m.p. 172°-3°C identical with a previously prepared sample.
Reaction SMILES: [O:1]=[C:2]([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:17][CH2:18][CH2:19][C:20]1[C:25](O)=[C:24]([C:27]([CH3:29])=[O:28])[CH:23]=[CH:22][C:21]=1[OH:30].N1CCCC1>C1(C)C=CC=CC=1>[O:28]=[C:27]1[C:24]2[CH:23]=[CH:22][C:21]([OH:30])=[C:20]([CH2:19][CH2:18][CH3:17])[C:25]=2[O:1][C:2]([CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:29]1
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Reactant: CCOC(=O)CCC(=O)CCC(=O)OCC
Solvent: C1CCNC1
Solvent: Cc1ccccc1
Product: CCCc1c(O)ccc2c1OC(CCC(=O)OCC)(CCC(=O)OCC)CC2=O
Reaction time: 4 h

Procedure:
A stirred solution of 12.3 g (53.5 mmol) of diethyl 4-oxopimelate, 10.4 g (53.5 mmol) of 2,4-dihydroxy-3-propylacetophenone, and 3.8 g (55 mmol) of pyrrolidine in 62 ml of toluene was refluxed under a water separator. After 4 hours, the mixture was allowed to cool. The solvent was removed under reduced pressure and the resultant oil was chromatographed on silica gel using ethyl acetate-hexane as eluent. The titled diester (4.98 g) was found to be homogeneous by thin-layer chromatography (20% by volume ethyl acetate/hexane on silica gel plates) and was used in subsequent reactions without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:7](Cl)=[N:6][S:5][N:4]=1.[S:9]([NH2:19])(=[O:18])([C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1)=[O:10].C(=O)([O-])[O-].[K+].[K+].CS(C)=O>>[CH3:1][O:2][C:3]1[C:7]([NH:19][S:9]([C:11]2[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=2)(=[O:10])=[O:18])=[N:6][S:5][N:4]=1
Reactant: Nc1ccc(S(N)(=O)=O)cc1
Reactant: COc1nsnc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COc1nsnc1NS(=O)(=O)c1ccc(N)cc1
Yield: 86 %

Procedure:
75.3 g of 3-methoxy-4-chloro-1,2,5-thiadiazole (0.5 mole), 103.32 g of sulfanilamide (0.6 mole) and 712.25 g of potassium carbonate (1.25 mole) were reacted in 78.13 g of dimethyl sulfoxide (1 mole) and were further treated as described in Example 1. 123.1 g of crude 3-methoxy-4-(4'-aminobenzene-sulfonamido)-1,2,5-thiadiazole (85.99% of theory) were obtained.
Reaction SMILES: [F:1][C:2]1[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[CH:23]=[CH:22][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:12]=[C:13](I)[C:6]=12.[CH3:29][N:30]([CH3:34])[CH2:31][C:32]#[CH:33].C(Cl)Cl>C(N(CC)CC)C.C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[CH3:29][N:30]([CH3:34])[CH2:31][C:32]#[C:33][C:13]1[C:6]2[C:7](=[N:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]2[CH:22]=[CH:23][C:24]([N+:26]([O-:28])=[O:27])=[CH:25][C:2]=2[F:1])[N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:12]=1
Reactant: C#CCN(C)C
Reactant: CC(C)(C)OC(=O)n1cc(I)c2c(Oc3ccc([N+](=O)[O-])cc3F)ccnc21
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: [Fe+2]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: C1CCOC1
Product: CN(C)CC#Cc1cn(C(=O)OC(C)(C)C)c2nccc(Oc3ccc([N+](=O)[O-])cc3F)c12
Temperature: 70 °C
Yield: 93.5 %

Procedure:
A stream of Ar was bubbled through a mixture of tert-butyl 4-(2-fluoro-4-nitrophenoxy)-3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (200 mg, 0.4 mmol), N,N-dimethylprop-2-yn-1-amine (66 mg, 0.8 mmol), Pd(dppf)2Cl2:CH2Cl2 (33 mg, 0.04 mmol), and CuI (20 mg) in triethylamine (0.4 mL) and THF (3 mL) for 5 min. The reaction mixture was heated in a sealed tube at 70° C. for 2 h and the solvent was removed in vacuo. The crude compound was purified by flash column chromatography (silica gel, 5% MeOH/EtOAc) to afford the desired product (170 mg, 95%) as a yellow oil. LC/MS(ESI+) mnz 455 (M+H)+.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([C:14]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:15]=1[C:16](O)=[O:17])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Li].[H-].[OH-].[Na+]>CCOCC.O>[CH2:7]([C:14]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:15]=1[CH2:16][OH:17])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C(O)c1ccc(Cl)cc1Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Product: OCc1ccc(Cl)cc1Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 28.4 g (0.75 mole) of lithium aluminum hydride in 800 ml of ether, which was cooled to 0°, was added dropwise 85.1 g (0.345 mmole) of 2-benzyl-4-chlorobenzoic acid in 250 ml of ether. The mixture was allowed to warm to room temperature, and was stirred for 2 hr. The excess lithium alluminum hydride was discharged by the addition of 28.5 ml of water, 28.5 ml of 10% aqueous sodium hydroxide, and 85.5 ml of water. The precipitate was removed by filtration and the filtrate was dried with sodium sulfate. Removal of the ether at reduced pressure gave a colorless oil which crystallized upon standing, mp 46.5°-49°.
Reaction SMILES: Cl.Cl.C([N:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]2[CH2:22][CH2:21][O:20][C:19]2=[O:23])[CH2:12][CH2:11]1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[N:13]1([CH2:16][CH2:17][N:18]2[CH2:22][CH2:21][O:20][C:19]2=[O:23])[CH2:14][CH2:15][NH:10][CH2:11][CH2:12]1
Reactant: [H][H]
Reactant: O=C1OCCN1CCN1CCN(Cc2ccccc2)CC1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: O=C1OCCN1CCN1CCNCC1

Procedure:
291 g of 3-[2-(4-benzyl-1-piperazinyl)-ethyl]-2-oxazolidinone dihydrochloride in 7 litres of methanol are hydrogenated in the presence of 70 g of palladium/carbon (5%) at 50° C and 10 atmospheres of hydrogen. The mixture is filtered and concentrated under reduced pressure. The residue is treated with sodium hydroxide, extracted with chloroform, filtered through diatomaceous earth and concentrated. There is obtained 3-[2-(1-piperazinyl)-ethyl]-2-oxazolidinone as a yellow oil. The dihydrochloride of melting point 203° C (decomposition) is obtained by treatment with an excess of hydrochloric acid in methanol/ether.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([NH:7][S:8]([C:11]2[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=2)(=[O:10])=[O:9])[O:4][N:3]=1.[CH3:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>O>[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][S:8]([C:11]2[CH:16]=[CH:15][C:14]([C:22]3[CH:23]=[CH:24][C:19]([CH3:18])=[CH:20][CH:21]=3)=[CH:13][CH:12]=2)(=[O:10])=[O:9])[O:4][N:3]=1
Reactant: Cc1ccc(B(O)O)cc1
Reactant: Cc1cc(NS(=O)(=O)c2ccc(Br)cc2)on1
Solvent: O
Product: Cc1ccc(-c2ccc(S(=O)(=O)Nc3cc(C)no3)cc2)cc1
Reaction time: 24 h
Yield: 101.5 %

Procedure:
Nitrogen was bubbled through a biphasic mixture of ethanol (15 ml), toluene (15 ml) and 2M sodium carbonate solution (15 ml). N-(3-methyl-5-isoxazolyl)-4-bromobenzene sulfonamide (0.951 g, 3 mmol), 4-methylbenzeneboronic acid (0.56 g, 4 mmol) and tetrakistriphenylphosphine palladium (O) (300 mg) were added. The reaction mixture was kept at 80° C., under a N2 atmosphere for 24 h, with stirring, and was then diluted with water (50 ml) and extracted with ether (50 ml) to remove neutral impurities and excess 4-methylbenzeneboronic acid. The aqueous phase was neutralized to pH 2 using concentrated hydrochloric acid and the resultant solid was filtered. This was dried under vacuum and recrystallized using hexanelethyl acetate giving N-(3-methyl-5-isoxazolyl)-4-(4-methylphenyl)benzenesulfonamide (1.0 g, 100% yield, 30 m.p. 194-198° C.).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](O)=[O:7])#[N:2].S(Cl)([Cl:14])=O.CN(C)C=O>C1(C)C=CC=CC=1>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([Cl:14])=[O:7])#[N:2]
Reactant: O=S(Cl)Cl
Reactant: N#Cc1cccc(C(=O)O)c1
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: N#Cc1cccc(C(=O)Cl)c1
Temperature: 80 °C

Procedure:
In 1 liter of toluene, 200 g of 3-cyanobenzoic acid were suspended, followed by the addition of 128 ml of thionyl chloride and 1 ml of N,N-dimethylformamide. The resulting mixture was stirred under heating at 80° C. for 5 hours. After cooling of the reaction mixture, the solvent was distilled off under reduced pressure. To the residue, n-hexane was added. By distilling off the solvent under reduced pressure, 3-cyanobenzoyl chloride was obtained. The resulting 3-cyanobenzoyl chloride was dissolved in 3 liters of dried 1,2-dichloroethane, followed by the addition of 200 g of 2-amino-4-methoxycarbonyl-1,3-thiazole. The resulting mixture was heated under reflux for 5 hours. The reaction mixture was cooled. Crystals so precipitated were collected by filtration and then washed with water, whereby 289 g of 2-[N-(3-cyanobenzoyl)amino]-4-methoxycarbonyl-1,3-thiazole.hydrochloride were obtained. Yield: 80%.