Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1C2C=CC=CC=2C2N=C(O)C=[C:5]3[CH:17]=[CH:18][CH:19]=[C:3]1[C:4]=23.C1(C[C:27]([N:29]2[C:33](=[O:34])[C:32]3=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]3[C:30]2=O)=[O:28])C=CC=CC=1>>[OH:28][C:27]1[N:29]=[C:33]([O:34][C:2](=[O:1])[C:3]2[CH:4]=[CH:5][CH:17]=[CH:18][CH:19]=2)[C:32]2[C:31]([CH:30]=1)=[CH:38][CH:37]=[CH:36][CH:35]=2
Reactant: O=C1c2ccccc2-c2nc(O)cc3cccc1c23
Reactant: O=C(Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Product: O=C(Oc1nc(O)cc2ccccc12)c1ccccc1

Procedure:
7-OXO-7H-dibenzo-[d e,h]-quinolin-2-ol which is useful as an intermediate in the preparation of dyestuffs is prepared by cycloisomerizing the novel compound, N-phenylacetyl phthalimide in an inert solvent and in the presence of a Friedel-Crafts catalyst to form the novel compound O-(3-hydroxy-1-isoquinolinyl)-benzoic acid which is then cyclized by dehydrating condensation to form the 7-oxo-7H-dibenzo-[d e,h]-quinolin-2-ol.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CO.O.Cl[Pd]Cl>[C:12]1([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: OB(O)c1ccccc1
Reactant: COC(=O)c1ccnc(Cl)c1
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: COC(=O)c1ccnc(-c2ccccc2)c1
Temperature: 100 °C
Yield: 58.9 %

Procedure:
Methyl 2-chloroisonicotinate (2.5 g, 14.57 mmol), phenylboronic acid (2.66 g, 21.86 mmol), potassium carbonate (3.02 g, 21.86 mmol) and PdCl2 (dppf) (0.316 g, 0.44 mmol) were mixed in methanol (15 mL) in a 20 mL microwave vial. Two drops of water were added and the vial was capped and heated at 100° C. for 10 min in a single node microwave reactor. The solids were removed by filtration and the filtrate partly evaporated to yield a dark red slurry. DCM and water were added and the phases separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a dark red oil. The compound was purified via Biotage, SNAP 340 g KP-SIL, eluent isocratic heptane/ethyl acetate 9:1 for 2 CV, then linear gradient heptane/ethyl acetate 9:1 to 6:4 over 5 CV to give methyl 2-phenylisonicotinate (1.83 g, 58%) as a colourless oil. 1H NMR (400 MHz, cdcl3) δ 3.98 (s, 3H), 7.39-7.54 (m, 3H), 7.76 (dd, 1H), 8.01-8.09 (m, 2H), 8.29 (s, 1H), 8.82 (d, 1H). MS m/z 214 (M+H)+
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:13][CH:12]([OH:14])[CH2:11]2)=[N:8][CH:9]=1)([O-])=O>[Pd].CCO>[NH2:1][C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:11][CH:12]([OH:14])[CH2:13]2)=[N:8][CH:9]=1
Reactant: O=[N+]([O-])c1cnc(N2CC(O)C2)nc1
Agent: [Pd]
Solvent: CCO
Product: Nc1cnc(N2CC(O)C2)nc1
Reaction time: 18 h
Yield: 94.8 %

Procedure:
Compound (i) (130 mg, 0.66 mmol), 10% Pd on activated carbon (10 mg) and EtOH (5 mL) were combined and stirred under molecular hydrogen for 18 hrs at it. The reaction mixture was filtered to remove Pd/C residues and concentrated in vacuo to give crude (ii) as a yellow oil (104 mg). 1H NMR (400 MHz, Acetone) δ 7.83 (s, 2H), 4.68 (s, 1H), 4.24 (dd, J=9.8, 6.2 Hz, 2H), 3.83 (dd, J=10.1, 4.3 Hz, 2H).
Reaction SMILES: [CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][C@@:9]1([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:10](=O)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([BH3-])#N.[Na+]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:30]([NH:37][C@@H:10]1[CH2:11][CH2:12][C@@H:13]2[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C@@:9]1([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[CH2:15][C@H:14]2[C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: CC(C)(C)OC(=O)[C@@H]1C[C@@]2(c3ccccc3)C(=O)CC[C@@H]1N2Cc1ccccc1
Reactant: NCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)[C@@H]1C[C@@]2(c3ccccc3)[C@H](NCc3ccccc3)CC[C@@H]1N2Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.5 %

Procedure:
(1R*,5S*,6R*)-8-Benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]octan-2-one (Description 17; 5.0 g, 12.8 mmol), p-toluenesulfonic acid monohydrate (25 mg) and benzylamine (2.1 g, 20 mmol) in toluene (50mL) was heated at reflux under Dean Stark conditions for 24 hours, then cooled and the solvent removed in vacuo. The residue was dissolved in methanol (100 mL) and sodium cyanoborohydride (900 mg, 14 mmol) added. The solution formed was stirred at room temperature for 2 hours then concentrated to approximately ¼ volume. Water (500 mL) was added and the suspension formed was extracted with ethyl acetate (2×500 mL). The extracts were dried (MgSO4) and concentrated, before the residue was purified by silica chromatography to give the title compound (3.87 g, 8 mmol) as a gum.
Reaction SMILES: [Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[C:9]3[CH:10]=[C:11]([CH:15]=C)[CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1.O.I([O-])(=O)(=O)=[O:27].[Na+]>C1COCC1.CC(O)(C)C.[Os](=O)(=O)(=O)=O>[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[C:9]3[CH:10]=[C:11]([CH:15]=[O:27])[CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=Cc1ccc2c(c1)c(-c1c(F)cccc1F)nc1c(Br)n[nH]c12
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(C)(C)O
Solvent: O
Product: O=Cc1ccc2c(c1)c(-c1c(F)cccc1F)nc1c(Br)n[nH]c12
Temperature: 25 °C
Reaction time: 3 h
Yield: 68.3 %

Procedure:
A 150 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 1 g of 3-bromo-5-(2,6-difluorophenyl)-7-vinyl-1H-pyrazolo[4,3-c]isoquinoline in 13 ml of THF and then 7 ml of water, 13 ml of tert-butanol, 0.79 ml of a solution of osmium tetroxide at 2.5% in 2-methyl-2-propanol, and 17 g of sodium periodate are added. The mixture is stirred at RT for 3 h and then poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. This gives 1.047 g of a crude product, which is purified by chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (95/5 by vol.), to give 686 mg of 3-bromo-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde (cream solid). MS (E/I): m/z=388 (M+); 1H NMR: 7.41 (d, J=7.9 Hz, 2H); 7.77 (m, 1H); 8.34 (broad s, 1H); 8.47 (dd, J=8.5, 1.2 Hz, 1H); 8.69 (d, J=8.5 Hz, 1H); 10.15 (s, 1H); 14.89 (broad m, 1H).
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[NH:13][C:14](=[O:16])[CH3:15].Cl[CH2:18][C:19]([CH3:21])=[CH2:20]>CN(C)C=O.O>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[N:13]([CH2:20][C:19]([CH3:21])=[CH2:18])[C:14](=[O:16])[CH3:15]
Reactant: C=C(C)CCl
Reactant: CC(=O)Nc1cc([N+](=O)[O-])ccc1Br
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C=C(C)CN(C(C)=O)c1cc([N+](=O)[O-])ccc1Br
Temperature: 60 °C

Procedure:
To a suspension of 1.34 g of sodium hydride in 10 mL of dimethylformamide under argon is added dropwise, at 0° C., a solution of 5.8 g of N-(2-bromo-5-nitrophenyl)acetamide obtained in stage c) below in 90 mL of dimethylformamide and the reaction medium is stirred at this temperature for 1 hour. 3.3 mL of 3-chloro-2-methylprop-1-ene are then added and the mixture is then heated at 60° C. for 2 hours. After cooling to room temperature, the mixture is diluted with one litre of water and extracted with four times 80 mL of ethyl acetate. The combined organic phases are washed with three times 50 mL of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with a mixture of heptane and ethyl acetate (80/20 by volume) to give 5.2 g of N-(2-bromo-5-nitrophenyl)-N-(2-methylprop-2-en-1-yl)acetamide in the form of a yellow solid, the characteristics of which are as follows:
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([C:21]#[N:22])=[N:5][C:6]([C:11]2[C:16]([CH2:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:19][CH3:20])=[CH:7][C:8]=1[O:9][CH3:10].C([O-])([O-])=O.[K+].[K+].[CH3:29][NH:30][C@@H:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33][CH2:32]1.CCCCCC>CC#N.O>[CH2:19]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([CH2:17][CH3:18])[C:11]=1[C:6]1[N:5]=[C:4]([C:21]#[N:22])[C:3]([CH2:2][N:30]([CH3:29])[C@@H:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][CH2:33][CH2:32]2)=[C:8]([O:9][CH3:10])[CH:7]=1)[CH3:20]
Reactant: CCc1cccc(CC)c1-c1cc(OC)c(CBr)c(C#N)n1
Reactant: CN[C@H]1CCCc2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Solvent: CCCCCC
Product: CCc1cccc(CC)c1-c1cc(OC)c(CN(C)[C@H]2CCCc3ccccc32)c(C#N)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3-bromomethyl-6-(2,6-diethyl-phenyl)-4-methoxy-pyridine-2-carbonitrile (40 mg), K2CO3 (50 mg) and (S)-methyl(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine (40 mg) in CH3CN (2 mL) is stirred at room temperature overnight. Hexane (5 mL) and water (5 mL) are added to the mixture. The organic layer is separated, washed, once with brine, dried (Na2SO4), and concentrated. The crude is purified by PTLC (4.1 hexane/EtOAc) to give (S)-6-(2,6-diethyl-phenyl)-4-methoxy-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridine-2-carbonitrile. 1H NMR (CDCl3) 7.72 (d, 1H), 7.35 (t, 1H), 7.07-7.17 (m, 5H), 6.92 (s, 1H), 4.05 (m, 1H), 3.97 (d, 2H), 3.89 (s, 3H), 2.75 (m, 2H), 2.32 (m, 4H), 2.2 (s, 3H), 2.09 (m, 2H), 2.70-2.95 (m, 2H), 1.08 (t, 6H).
Reaction SMILES: C([Li])(C)(C)C.F[B-](F)(F)F.[CH:11]([S+:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:13])[CH3:12]>CCCCC.O1CCCC1>[C:21]1([S:14]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[C:11]([CH3:13])[CH3:12])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CC(C)[S+](c1ccccc1)c1ccccc1
Agent: F[B-](F)(F)F
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: C1CCOC1
Product: CC(C)=S(c1ccccc1)c1ccccc1
Temperature: -70 °C
Reaction time: 0.5 h

Procedure:
2 ml of a solution of 1.6M of tert.-butyllithium in pentane was added dropwise at -70° C. under an inert atmosphere to a stirred mixture of 950 mg of the tetrafluoroborate of isopropyldiphenylsulfonium in 15 ml of tetrahydrofuran and the mixture was stirred at -70° C. for 30 minutes to obtain a solution of diphenylisopropylidene sulfurane. The said solution at -70° C. was added slowly with stirring under an inert atmosphere to a mixture of 350 mg of 5(RS) methoxy-2,5-dihydrofuran-2-one [prepared by method of Schroeter et al, Liebigs Ann. Chem., Vol. 697 (1966), p. 42] and 15 ml of tetrahydrofuran cooled to -90° C. and the mixture was allowed to stand at -78° C. for one hour and then at -50° C. for another hour. The mixture was poured into an aqueous monosodium phosphate solution and the mixture was extracted with methylene chloride. The organic phase was evaporated to dryness under reduced pressure and the residue was chromatographed over silica gel. Elution with a 1-1 ether-petrolum ether mixture yielded 480 mg of diphenyl sulfide, 260 mg of (1RS, 5SR) 6,6-dimethyl-4(RS)-methoxy-3-oxabicyclo [3,1,0]-hexan-2-one and 100 mg of unreacted lactone.
Reaction SMILES: [H-].[Na+].CS(C)=O.[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][C:9]=1[O:15][CH3:16].Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH3:31])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1>O>[CH3:29][O:28][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][C:24]=1[O:30][CH3:31])[N:21]=[CH:20][N:19]=[C:18]2[O:14][C:11]1[CH:12]=[CH:13][C:8]([NH2:7])=[C:9]([O:15][CH3:16])[CH:10]=1
Reactant: COc1cc(O)ccc1N
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc(Oc2ncnc3cc(OC)c(OC)cc23)ccc1N
Temperature: 50 °C
Reaction time: 0.33 h
Yield: 71.6 %

Procedure:
Sodium hydride (60 wt %, 3.2 g) was added to dimethyl sulfoxide (50 ml), and the mixture was stirred at 50° C. for 20 min. 4-Amino-3-methoxyphenol (5.6 g) was added thereto, and the mixture was stirred at room temperature for 10 min. Next, 4-chloro-6,7-dimethoxyquinazoline (7.0 g) was added thereto, and the mixture was stirred at 100° C. overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was then washed with a saturated aqueous sodium hydrogencarbonate solution and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. Methanol was added to the residue, and the precipitated crystal was collected by suction filtration to give the title compound (7.3 g, yield 72%).
Reaction SMILES: [C:1]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[C:7](=[C:8]([NH:17][CH:18]4[CH2:23][CH2:22][CH:21]([NH:24][C:25](=O)OC(C)(C)C)[CH2:20][CH2:19]4)[N:9]=[CH:10][N:11]=3)[C:6]1=2)(=[O:3])[NH2:2].Cl.[BH3-][C:34]#N.[Na+]>ClCCl>[CH3:34][N:24]([CH3:25])[CH:21]1[CH2:20][CH2:19][CH:18]([NH:17][C:8]2[N:9]=[CH:10][N:11]=[C:12]3[C:7]=2[C:6]2[C@@H:5]([CH2:4][C:1]([NH2:2])=[O:3])[CH2:16][CH2:15][C:14]=2[S:13]3)[CH2:23][CH2:22]1
Reactant: CC(C)(C)OC(=O)NC1CCC(Nc2ncnc3sc4c(c23)[C@@H](CC(N)=O)CC4)CC1
Reactant: [BH3-]C#N
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Product: CN(C)C1CCC(Nc2ncnc3sc4c(c23)[C@@H](CC(N)=O)CC4)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 31.9 %

Procedure:
To a solution of tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]amino]cyclohexyl)carbamate (187 mg, 0.42 mmol, 1.00 equiv) in dichloromethane (5 mL) was added hydrogen chloride (12 M, 1 mL). The resulting solution was stirred for 2 h at room temperature. After evaporation, the residue was dissolved in CH3OH (10 mL) and HCHO (1.5 mL) was added. The resulting solution was stirred for 1 h at room temperature. To the above solution was added NaBH3CN (79 mg, 1.26 mmol, 3.00 equiv). The resulting solution was allowed to react, with stirring, overnight at room temperature. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×50 mL of dichloromethane and the organic layers combined. The crude product (100 mg) was purified by preparative HPLC under the following conditions: Column: Xbridge Prep C18, 5 μm, 19*150 mm; mobile phase, water (with 50 mL NH4CO3) and CH3CN (10.0% CH3CN up to 32.0% in 10 min, up to 95.0% in 1 min, down to 10.0% in 2 min); UV detection at 254 nm. This procedure afforded 50 mg (32%) of 2-[(3R)-12-[[4-(dimethylamino)cyclohexyl]amino]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]acetamide as a white solid. MS (ES): m/z 374 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 1.35-1.60 (m, 4H), 1.95-2.04 (m, 2H), 2.09-2.10 (m, 2H), 2.28-2.38 (m, 7H), 2.40-2.45 (m, 3H), 2.68-2.80 (m, 1H), 2.89-2.30 (m, 1H), 3.05-3.15 (m, 1H), 4.05-4.15 (m, 1H), 3.87 (dd, J=14.1, 6.3 Hz, 1H), 8.23 (s, 1H).
Reaction SMILES: O.[Pd:2].[Pd+2].[C:4]([O-:7])(=O)[CH3:5].[Pd+2].[C:9]([O-:12])(=O)[CH3:10].[CH2:13]([C:17]([CH3:19])=[O:18])C(C)C>>[Pd:2].[CH3:19]/[C:17](/[O-:18])=[CH:13]/[C:4]([CH3:5])=[O:7].[CH3:19]/[C:17](/[O-:18])=[CH:13]/[C:9]([CH3:10])=[O:12].[Pd+2:2]
Reactant: CC(=O)[O-]
Reactant: CC(=O)CC(C)C
Agent: [Pd+2]
Agent: [Pd]
Solvent: O
Product: CC(=O)/C=C(/C)[O-]

Procedure:
In the prior art, preparation of metal colloids has typically been carried out in aqueous solution in the presence of additives such as surfactants, oil microemulsions, nonpolar water-soluble polymers or amphiphilic block or graft copolymers. In addition, preparation of palladium (0) sols with particle diameter ranges between 7 nm and 260 nm has been carried out by thermal decomposition of organopalladium compounds in various organic solvents using refluxing conditions without any additives. This was accomplished by dissolving organopalladium compounds, such as bis(2,4-pentanedionate) palladium (II) [Pd(acac)2] or palladium acetate, in various organic solvents and refluxing the solutions at their boiling point for a period of minutes to several hours. See for example Esumi et al. in Langmuir, 5, 1, 268 (1989) and Tano et al. in J. Colloid Interface Sci., 133, 2, 530 (1989). Stable and relatively monodisperse palladium (0) sols, with particle diameter ranges between 8 nm and 10 nm were only obtained from [Pd(acac)2] in the organic solvent methyl isobutyl ketone which exhibits a high dipole moment of D˜2.7 and a relatively low boiling point of 115.9° C. Bimetallic Pd—Cu colloids, Pd—Cu2O, such as from mixed palladium acetate and copper (II) acetate have similarly been prepared by thermal decomposition in various organic solvents without any additives. See, for example, Esumi et al in Chem. Mater., 2, 5, 564, (1990). The average diameters of the Pd—Cu2O sols ranged between 50 and 130 nm with a decrease of the molar ratio of palladium acetate in the mixed acetates. The prior art of Esumi et al. and Tano et al. describe a critical thermal decomposition temperature for formation of stable metal colloids that ranges between 110° C. and 116° C. in organic solvents of low viscosity, i.e., significantly less than 10 centipoises.
Reaction SMILES: [NH2:1][C@@H:2]1[C:9](=[O:10])[N:8]2[C@@H:3]1[S:4][CH2:5][C:6](/[CH:14]=[C:15]1/[C:16](=[O:24])[N:17]([CH2:20][CH:21]3[CH2:23][CH2:22]3)[CH2:18][CH2:19]/1)=[C:7]2[C:11]([OH:13])=[O:12].C(=O)(O)[O-].[Na+].[S:30]1[CH:34]=[CH:33][CH:32]=[C:31]1[CH2:35][C:36](Cl)=[O:37]>CN(C)C=O>[CH:21]1([CH2:20][N:17]2[CH2:18][CH2:19]/[C:15](=[CH:14]\[C:6]3[CH2:5][S:4][C@H:3]4[N:8]([C:9](=[O:10])[C@H:2]4[NH:1][C:36](=[O:37])[CH2:35][C:31]4[S:30][CH:34]=[CH:33][CH:32]=4)[C:7]=3[C:11]([OH:13])=[O:12])/[C:16]2=[O:24])[CH2:23][CH2:22]1
Reactant: O=C(Cl)Cc1cccs1
Reactant: N[C@@H]1C(=O)N2C(C(=O)O)=C(/C=C3\CCN(CC4CC4)C3=O)CS[C@H]12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(Cc1cccs1)N[C@@H]1C(=O)N2C(C(=O)O)=C(/C=C3\CCN(CC4CC4)C3=O)CS[C@H]12
Temperature: 0 °C

Procedure:
To a suspension of 300.0 mg (0.86 mmol) (E)-(6R,7R)-7-amino-3-(1-cyclopropylmethyl-2-oxo-pyrrolidin-3-ylidenemethyl)-8-oxo-5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid in 8 ml N,N-dimethylformamide was added 80.0 mg (0.95 mmol) sodium bicarbonate. After cooling to 0° C. 101.0 μl (0.95 mmol) 2-thiopheneacetyl chloride were added. After 1.5 h the solvent was stripped off at a rotary evaporator and the residue was poured on diethyl ether. The solid was collected by filtration and was triturated with 25 ml ethyl acetate and 15 ml water for 1.5 h.
Reaction SMILES: [F:1][C:2]1[CH:18]=[C:17]([CH2:19][CH2:20][C:21](=[O:37])[C:22]2[S:23][C:24]([C:27]3[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=3)=[CH:25][CH:26]=2)[CH:16]=[CH:15][C:3]=1[O:4][CH:5]([CH2:13][CH3:14])[C:6]([O:8]C(C)(C)C)=[O:7].FC(F)(F)C(O)=O>>[F:1][C:2]1[CH:18]=[C:17]([CH2:19][CH2:20][C:21](=[O:37])[C:22]2[S:23][C:24]([C:27]3[CH:28]=[CH:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[CH:16]=[CH:15][C:3]=1[O:4][CH:5]([CH2:13][CH3:14])[C:6]([OH:8])=[O:7]
Reactant: CCC(Oc1ccc(CCC(=O)c2ccc(-c3ccc(C(F)(F)F)cc3)s2)cc1F)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CCC(Oc1ccc(CCC(=O)c2ccc(-c3ccc(C(F)(F)F)cc3)s2)cc1F)C(=O)O

Procedure:
2-(2-Fluoro-4-(3-oxo-3-(5-(4-(trifluoromethyl)phenyl)thien-2-yl)propyl)-phenoxy)butanoic acid is prepared from tert-butyl 2-(2-fluoro-4-(3-oxo-3-(5-(4-(trifluoromethyl)phenyl)thien-2-yl)propyl)phenoxy)butanoate according to general procedure E using 17 equivalents of trifluoroacetic acid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:6](Cl)=[N:7][C:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)=[N:9][C:10]=1[Cl:11].[CH:24]([N:27](CC)[CH:28](C)C)(C)C.Cl.CNC>CN(C=O)C>[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:10]([Cl:11])=[N:9][C:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)=[N:7][C:6]=1[N:27]([CH3:28])[CH3:24]
Reactant: CCN(C(C)C)C(C)C
Reactant: COC(=O)Cc1c(Cl)nc(Cc2ccc([N+](=O)[O-])cc2)nc1Cl
Agent: CNC
Agent: Cl
Solvent: CN(C)C=O
Product: COC(=O)Cc1c(Cl)nc(Cc2ccc([N+](=O)[O-])cc2)nc1N(C)C
Temperature: 85 °C
Reaction time: 16 h
Yield: 98.9 %

Procedure:
To a solution of methyl[4,6-dichloro-2-(4-nitrobenzyl)pyrimidin-5-yl]acetate (0.5 g, 1.40 mmol) in anhydrous DMF (5 mL) at room temperature under Ar atmosphere was added N,N-diisopropylethylamine (0.0.54 mL, 3.09 mmol) and dimethylamine hydrochloride (0.126 g, 1.54 mmol). The resulting solution was stirred at 85° C. for 16 hours at which time the reaction mixture was concentrated to dryness and the residue chromatographed over silica gel eluting with 50% EtOAc in n-hexane to give methyl[4-chloro-6-(dimethylamino)-2-(4-nitrobenzyl)pyrimidin-5-yl]acetate (0.505 g, 99% yield) as a brown oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=1)/[C:6]([CH3:21])=[C:5]2[CH2:22][CH2:23][O:24][NH2:25].[O:26]=[C:27]([CH3:31])[C:28](O)=[O:29]>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=1)/[C:6]([CH3:21])=[C:5]2[CH2:22][CH2:23][O:24][N:25]=[C:28]([OH:29])[C:27](=[O:26])[CH3:31]
Reactant: CC(=O)C(=O)O
Reactant: CC1=C(CCON)c2cc(F)ccc2/C1=C\c1ccc(S(C)=O)cc1
Product: CC(=O)C(O)=NOCCC1=C(C)/C(=C/c2ccc(S(C)=O)cc2)c2ccc(F)cc21

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylsulfinylphenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with 2-oxopropionic acid by the method of Example 1.
Reaction SMILES: [OH:1][C:2]1[C:9]([OH:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[OH-].[Na+].[CH2:13](Br)Br>O>[CH2:13]1[O:10][C:9]2[C:2](=[C:3]([CH:6]=[CH:7][CH:8]=2)[CH:4]=[O:5])[O:1]1
Reactant: BrCBr
Reactant: O=Cc1cccc(O)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=Cc1cccc2c1OCO2
Yield: 42.6 %

Procedure:
(a) A mixture of 2,3-dihydroxybenzaldehyde (6.4 g, 50 mmol) and sodium hydroxide (5 g in 25 ml of water) was added over 110 mins to a refluxing mixture of methylene bromide (17.3 g, 100 mmol), N,N,N-[tri-(C8 to C10 alkyl)]-N-methylammonium chloride (0.5 g; supplied by Aldrich Chemicals under the Trade Name "Adogen" 464) and water (10 ml). The mixture was heated at reflux for a further 5 hr under nitrogen and then steam distilled. The distillate was extracted with dichloromethane. Evaporation of the dried (MgSO4) organic extract gave 2,3-methylenedioxybenzaldehyde (3.2 g, 46%) as a yellow oil. Pmr spectrum (CDCl3 ; δ in ppm): 6.03 (2H,s); 6.66-6.99 (2H,m); 7.02-7.25 (1H,m); 9.97 (1H,s).
Reaction SMILES: [CH:1]12[CH2:6][CH:5]1[CH2:4][C@H:3]([C:7]([O:9]CC)=[O:8])[N:2]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].O[Li].O>O1CCOCC1.O>[C:15]([O:14][C:12]([N:2]1[CH:3]([C:7]([OH:9])=[O:8])[CH2:4][CH:5]2[CH:1]1[CH2:6]2)=[O:13])([CH3:18])([CH3:16])[CH3:17]
Reactant: CCOC(=O)[C@H]1CC2CC2N1C(=O)OC(C)(C)C
Agent: [Li]O
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1C(C(=O)O)CC2CC21
Reaction time: 18 h
Yield: 91 %

Procedure:
To a mixture of (3R)-2-tert-butyl 3-ethyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate (D26) (diastereoisomer mixture) (3.4 g, 13.3 mmol) in dioxane (15 ml) and water (15 ml), LiOH H2O (2.2 g, 53 mmol). The mixture was stirret at RT for 18 h. Dioxane was evaporated off and water was washed with Et2O (2×40 ml) then the pH was adjusted to ˜4 by addition of citric acid and the resulting aqueous phase was extacted with DCM (200 ml), washed with water (20 ml), dried over Na2SO4 and evaporated in vacuo to afford the title compound (D27) (2.75 g) as diastereoisomer mixture with syn-anti ratio 10/2.