Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N1C=CC=CC=1.[Si:7]([N:14]1[C@H:17]([CH2:18][CH:19]([OH:34])[CH2:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])[C@@H:16]([C@H:35]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH3:36])[C:15]1=[O:45])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]>C(Cl)Cl.[O-2].[O-2].[O-2].[Cr+6]>[Si:7]([N:14]1[C@H:17]([CH2:18][C:19](=[O:34])[CH2:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])[C@@H:16]([C@H:35]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:39])[CH3:40])[CH3:36])[C:15]1=[O:45])([C:10]([CH3:12])([CH3:11])[CH3:13])([CH3:9])[CH3:8]
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N([Si](C)(C)C(C)(C)C)[C@@H]1CC(O)CC(=O)OCc1ccc([N+](=O)[O-])cc1
Agent: [Cr+6]
Agent: [O-2]
Solvent: c1ccncc1
Solvent: ClCCl
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N([Si](C)(C)C(C)(C)C)[C@@H]1CC(=O)CC(=O)OCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Anhydrous chromium trioxide (10.0 mmol) is added to a soution of anhydrous pyridine (20.0 mmol) in 30 ml of anhydrous methylene chloride. After stirring at room temperature for 15 min., the reaction mixture is treated all at once with a solution of (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[3-(4-nitrobenzyl)oxycarbonyl-2-hydroxypropyl]azetidin-2-one (1.00 mmol) in anhydrous methylene chloride (8 ml). The resulting mixture is stirred at room temperature for 5 min. The CH2Cl2 layer is decanted from the dark, tarry residue which is triturated with more CH2Cl2. The combined CH2Cl2 phase is concentrated in vacuo. The residue is triturated with ether (100 ml) and the ether extracts are filtered. The filtrate is washed with 5% aqueous sodium bicarbonate solution, 2.5N HCl, 5% NaHCO3 and brine, dried over magnesium sulfate and concentrated in vacuo to yield (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1 -(t-butyldimethylsilyloxy)ethyl]-4-[3-(4-nitrobenzyl)oxycarbonyl-2-oxopropyl]azetidin-2-one. n.m.r. (CDCl3) δ7.85(2d-aromatic, 4), δ5.27(s,2), δ4.05(m,2), δ3.6(s,2), δ2.4-3.2(dd overlapping ABq,3), δ1.2(d,3,J=6.6), δ0.9(2s,18), δ0.22(s,6), δ0.05(s,6).
Reaction SMILES: [N+](=C)=[N-].CN(N=O)C(N[N+]([O-])=O)=N.[OH-].[Na+].N[C:17](N)=N.[C:20]([O:28][CH:29]([P:33]([O:38][CH2:39][CH3:40])([O:35][CH2:36][CH3:37])=[O:34])[C:30]([OH:32])=[O:31])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>ClCCl.C(OCC)C>[C:20]([O:28][CH:29]([P:33]([O:35][CH2:36][CH3:37])([O:38][CH2:39][CH3:40])=[O:34])[C:30]([O:32][CH3:17])=[O:31])(=[O:27])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CCOP(=O)(OCC)C(OC(=O)c1ccccc1)C(=O)O
Reactant: N=C(N)N
Agent: C=[N+]=[N-]
Agent: CN(N=O)C(=N)N[N+](=O)[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: ClCCl
Product: CCOP(=O)(OCC)C(OC(=O)c1ccccc1)C(=O)OC
Reaction time: 0.17 h

Procedure:
Diazomethane was generated in 3 fire-polished erlenmeyer flasks using ⅓ of each N-methyl-N′-nitro-N-nitrosoguanidine (17.1 g 116. mmol), 5 M sodium hydroxide (200 mL), and diethyl ether (450 mL) at 0° C. by adding the guanidine in small portions with swirling to the other two. After addition was complete, the mixture was allowed to stand at 0° C. for 10 min with occasional swirling. The ethereal was transferred in portions to a suspension of 2-(benzoyloxy)-2-(diethoxyphosphoryl)acetic acid (21.0 g, 66.4 mmol) in dichloromethane (ca. 20 mL) until the solid had all dissolved and a yellow color persisted. The reaction was allowed to rest at 0° C. for 15 min, before bubbling nitrogen through the solution to remove most of the unreacted diazomethane (reaction went almost colorless). The reaction was concentrated to give the 22.0 g (quant.) as a faint yellow oil which was used without purification. 1H-NMR (CDCl3, 500 MHz) δ 1.37 (m, 6H), 3.85 (s, 3H), 4.28 (m, 4H), 5.71 (d, J=16.8, 1H), 7.47 (m, 2H), 7.61 (m, 1H), 8.11 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][C:7]=1[F:8].I[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH2:17]([O:16][C:14](=[O:15])[CH2:13][O:11][CH2:10][CH2:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)[CH3:18]
Reactant: OCCc1ccc(F)c(Cl)c1
Reactant: CCOC(=O)CI
Agent: [Ag+]
Agent: CC(C)(C)c1cccc(C(C)(C)C)n1
Agent: O=S(=O)([O-])C(F)(F)F
Product: CCOC(=O)COCCc1ccc(F)c(Cl)c1

Procedure:
In analogy to the procedure described in example 78.1, 2-(3-chloro-4-fluoro-phenyl)-ethanol was reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridin to give [2-(3-chloro-4-fluoro-phenyl)-ethoxy]-acetic acid ethyl ester as colorless oil. MS: m/e=261.2 [M+H+].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[C:18]([O:23][CH3:24])[CH:17]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:37](=[O:38])[C:36]([C:39](O)=[O:40])=[CH:35][N:34]([CH3:42])[C:33]2=[O:43])=[CH:28][CH:27]=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:39]([C:36]2[C:37](=[O:38])[N:32]([C:29]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=3)[C:33](=[O:43])[N:34]([CH3:42])[CH:35]=2)=[O:40])=[C:18]([O:23][CH3:24])[CH:17]=1
Reactant: COc1cc(Oc2ccnc3cc(OC)c(OC)cc23)ccc1N
Reactant: Cn1cc(C(=O)O)c(=O)n(-c2ccc(F)cc2)c1=O
Product: COc1cc(Oc2ccnc3cc(OC)c(OC)cc23)ccc1NC(=O)c1cn(C)c(=O)n(-c2ccc(F)cc2)c1=O

Procedure:
This compound was synthesized using 4-(6,7-dimethoxyquinolin-4-yloxy)-2-methoxy-phenylamine and 3-(4-fluorophenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid using the procedure for example 1. LCMS m/z=573 (M+1); 1H NMR (CDCl3) δ: 11 (s, 1H), 8.61 (s, 1H), 8.54 (d, 1H, J=9 Hz), 8.49 (d, 1H, J=5 Hz), 7.55 (s, 1H), 7.42 (s, 1H), 7.26-7.23 (m, 4H), 6.81 (dd, 1H, J=3, 9 Hz), 6.74 (d, 1H, J=3 Hz), 6.5 (d, 1H, J=5 Hz), 4.05 (s, 6H), 3.84 (s, 3H), 3.61 (s, 3H).
Reaction SMILES: [N:1]([C:4]1[C:13]2[C:8](=[N:9][C:10]([CH3:14])=[CH:11][CH:12]=2)[N:7]=[CH:6][C:5]=1[C:15]([O:17]CC)=[O:16])=[N+:2]=[N-:3]>[OH-].[Na+]>[N:1]([C:4]1[C:13]2[C:8](=[N:9][C:10]([CH3:14])=[CH:11][CH:12]=2)[N:7]=[CH:6][C:5]=1[C:15]([OH:17])=[O:16])=[N+:2]=[N-:3]
Reactant: CCOC(=O)c1cnc2nc(C)ccc2c1N=[N+]=[N-]
Agent: [Na+]
Agent: [OH-]
Product: Cc1ccc2c(N=[N+]=[N-])c(C(=O)O)cnc2n1

Procedure:
4-Azido-3-carbethoxy-7-methyl-1,8-naphthyridine (2.4 g; 0.008 M) was suspended in 10% aq. NaOH (60 ml) and the mixture stirred at ambient temperatures until all the ester had reacted. The insoluble material was removed by filtration and redissolved in H2O. The pH of the solution was adjusted to 3.5 with 5 M HCl and the resulting precipitate (1.3 g; 71%) filtered off, washed with H2O and dried over P2O5 in vacuo, m.p. 198° C. (explosive dec. on rapid heating), (Found: N, 29.66%; C10H7N5O2.1/2H2O requires N, 29.41%), m/e 201 (M+--N2 ; 95%), 159 (100%) νmax (KBr) 3430 (br), 2430 (br), 2150, 2060-1800 (br), 1705, 1605, 1560, 1475, 1375, 1260, 1230, 1202, 920, 810 cm-1, δ [(CD3)2SO] 2.72 (s) (CH3), 7.62 (d), 8.62 (d), 9.29 (s) (heterocyclic protons), CO2H* diffuse low-field resonance, *exchangeable with D2O.
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:22]=[CH:21][C:11]([CH2:12][O:13]C(=O)CCCCBr)=[CH:10][CH:9]=1.[OH-].[Na+]>CO>[OH:13][CH2:12][C:11]1[CH:10]=[CH:9][C:8]([N:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C:2]2=[O:1])=[CH:22][CH:21]=1
Reactant: O=C(CCCCBr)OCc1ccc(N2CCCCC2=O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C1CCCCN1c1ccc(CO)cc1
Reaction time: 0.33 h

Procedure:
The oxo-piperdinyl intermediate from Step 2 (2 g, 5.43 mmol) was dissolved in MeOH and treated with 1N NaOH (20 mL). The reaction was stirred for 20 minutes. The reaction mixture was concentrated in vacuo. The resulting oil was partitioned between H2O and EtOAc. The layers were separated and the organic layer was dried (MgSO4), filtered and concentrated to give the title compound as an off-white solid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=[O:7])[CH3:2].[C:12]([NH2:16])(=[O:15])[CH2:13]O>>[CH2:1]([O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]1[NH:16][C:12](=[O:15])[CH2:13][O:7]1)[CH3:2]
Reactant: CCOc1ccccc1C=O
Reactant: NC(=O)CO
Product: CCOc1ccccc1C1NC(=O)CO1

Procedure:
prepared by reaction of 2-ethoxybenzaldehyde with glycolamide; LC-MS: tR=0.75 min; [M+H]+=207.97.
Reaction SMILES: [C:1]([NH:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[NH2:2].C([O:18][CH:19](O)[C:20](OCC1C=CC=CC=1)=[O:21])C1C=CC=CC=1.[N+](C1C=C(C=CC=1)CN1C(=O)C(=O)N(CC(O)=O)C1=C)([O-])=O>>[OH:21][CH:20]1[N:4]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:1](=[O:3])[NH:2][C:19]1=[O:18]
Reactant: CCOC(=O)CNC(N)=O
Reactant: O=C(OCc1ccccc1)C(O)OCc1ccccc1
Agent: C=C1N(CC(=O)O)C(=O)C(=O)N1Cc1cccc([N+](=O)[O-])c1
Product: CCOC(=O)CN1C(=O)NC(=O)C1O

Procedure:
Ethyl N-carbamoylaminoacetate was made to react with benzyl 2-benzyloxy-2-hydroxyacetate in the same manner as mentioned in Example 8 paragraph (1) to give ethyl 5-hydroxy-2,4-dioxoimidazolidine-1-acetate.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([N+:11]([O-:13])=[O:12])[CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10].CS(C)=O.[C-:18]#[N:19].[Na+].C(OCC)(=O)C>O.CCCCCC>[C:18]([CH2:2][C:3]1[CH:4]=[C:5]([N+:11]([O-:13])=[O:12])[CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])#[N:19]
Reactant: [C-]#N
Reactant: CCc1ccc([N+](=O)[O-])cc1CCl
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Solvent: O
Product: CCc1ccc([N+](=O)[O-])cc1CC#N
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a mixture of 3-chloromethyl-4-ethylnitrobenzene (4.0 g) and dimethyl sulfoxide (50 ml), sodium cyanide (982 mg) was added. The reaction mixture was stirred at room temperature for 3 h and then ethyl acetate, n-hexane and water were added. The organic layer was washed with a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the titled compound quantitatively.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[H-].[Na+].[CH3:19]I.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH3:19])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
Reactant: Cc1cc(Nc2cc(Br)cn(C)c2=O)n[nH]1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(Nc2cc(Br)cn(C)c2=O)nn1C
Yield: 33.7 %

Procedure:
A solution of 5-bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one 112a (2.8 g, 9.9 mmol) in anhydrous DMF (10 mL) was treated with 60% dispersion of NaH in mineral oil (0.5 g, 13 mmol) while stirring under nitrogen. After effervescence the reaction was stirred for an additional 30 minutes. At this time the reaction was treated with MeI (0.98 g, 7 mmol) and continued to stir under nitrogen for 2 hours. Water (50 mL) was added slowly and the mixture was filtered and then concentrated. The residue was purified by flash column chromatography eluting with petroleum ether/ethyl acetate to afford 142a (0.7 g, 24%), which was used directly without further purification. LCMS: (M+H)+ 297.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]=[C:12]=[S:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:15][NH:16][O:17][CH2:18][C:19]([OH:21])=[O:20].C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([N:16]([CH3:15])[O:17][CH2:18][C:19]([OH:21])=[O:20])=[S:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CNOCC(=O)O
Reactant: CC(C)(C)c1ccc(N=C=S)cc1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CN(OCC(=O)O)C(=S)Nc1ccc(C(C)(C)C)cc1
Yield: 100.4 %

Procedure:
A mixture of 4-tert-butylphenyl-isothiocyanate (10.8 g), N-methyl aminooxy acetic acid hydrochloride (8.0 g), triethylamine (14 g) and chloroform (300 mL) was heated at reflux for three hours, then evaporated to dryness. The residue was treated with 2N HCl (300 mL) and the mixture was stirred for fifteen minutes. The solid was collected by filtration, washed with water and dried to give (16.8 g) of [[[[(4-tert-butylphenyl)amino]thioxomethyl]methylamino]oxy]acetic acid. 1H-NMR (DMSO-d6; 300 Mhz) δ13.5 (br s, 1H), 10.48 (s, 1H), 7.48-7.32 (m, 4H), 4.62 (s, 2H), 3.52 (s, 3H), and 1.28 ppm (s, 9H). The acid (14.8 g) was dissolved in benzene (200 mL). Phosphorus pentachloride (10.4 g) was added in portions. The mixture was heated at reflux for one half hour then evaporated to dryness. The residue was dissolved in ethyl acetate (600 mL) and washed with sodium bicarbonate saturated solution (2×400 mL) then with water (400 mL). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was chromatographed on silica gel (40% methylene chloride in hexane). The title compound (9.1 g) was obtained as a solid, m.p. 168-170° C. Mass spectrum (El, M.+) m/z 276. 1H-NMR (DMSO-d6; 400 MHz) δ7.45 (d, 2H), 7.09 (d, 2H), 5.06 (s, 2H), 3.68 (s, 3H), and 1.30 ppm (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:12])[NH:5][C:6]2=[O:11].[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]N)=[CH:16][CH:15]=1>C(O)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:12])[N:5]([CH2:18][C:17]1[CH:20]=[CH:21][C:14]([F:13])=[CH:15][CH:16]=1)[C:6]2=[O:11]
Reactant: O=C1NC(=O)c2c(Cl)cccc21
Reactant: NCc1ccc(F)cc1
Solvent: CC(=O)O
Product: O=C1c2cccc(Cl)c2C(=O)N1Cc1ccc(F)cc1
Temperature: 150 °C
Yield: 88.8 %

Procedure:
A mixture of 4-chloro-isoindole-1,3-dione (2.75 g, 15 mmol) and 4-fluorobenzylamine (1.88 g, 15 mmol) in glacial acetic acid (10 mL) was heated at 150° C. in microwave for 30 mins. After cooled to room temperature, the reaction mixture was poured into ice water and the white precipitates were collected. Recrystallization with EtOH provided the title compound (3.86 g, 89%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[C:4]([CH3:25])[C:3]=1[CH3:26].[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:32]5[CH:33]=[N:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=5)[C:3]([CH3:26])=[C:4]([CH3:25])[CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1
Reactant: COc1ccc(B(O)O)cn1
Reactant: Cc1cc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc(Cl)c1C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: COc1ccc(-c2nc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)cc(C)c2C)cn1
Temperature: 80 °C
Reaction time: 8 h
Yield: 88.2 %

Procedure:
A solution of N-(6-chloro-4,5-dimethylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (38 mg, 0.1 mmol) in DME (1 mL) was added to a reaction tube containing 6-methoxypyridin-3-ylboronic acid (46 mg, 0.15 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol). Saturated Na2CO3 solution was added (100 μL) and the reaction was stirred at 80° C. overnight. The reaction was filtered, concentrated and purified by column chromatography (0-50% ethyl acetate in hexanes) to obtain 40 mg (44%) of a clear oil. ESI-MS m/z calc. 453.4. found 454.3 (M+1)+. Retention times: 2.06 minutes. H NMR (400 MHz, DMSO) 8.76 (s, 1H), 8.19 (d, J=2.4 Hz, 1H), 7.82 (s, 1H), 7.74 (dd, J=2.4, 8.5 Hz, 1H), 7.55 (d, J=1.3 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 7.33 (dd, J=1.5, 8.3 Hz, 1H), 6.87 (d, J=8.5 Hz, 1H), 3.88 (s, 3H), 2.31 (s, 3H), 2.13 (s, 3H), 1.51-1.49 (m, 2H), 1.18-1.15 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[I:13]N1C(=O)CCC1=O.O>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][C:12]=1[I:13]
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: O=C1CCC(=O)N1I
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1ccc(N)c(I)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.4 %

Procedure:
To a solution of ethyl 4-aminobenzoate (13.0 g) in DMF (33 mL) is added a solution of N-iodosuccinimide (18.6 g) in DMF (39 mL). The reaction is stirred at room temperature overnight. The mixture is poured into 800 mL water. The resulting solid is collected and dried to yield 20.7 g (90%) of the titled compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[C:11](=[O:13])[N:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:9]2)([O-])=O>C1C=CC=CC=1.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[C:11](=[O:13])[N:10]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH2:9]2
Reactant: O=C1c2c(cccc2[N+](=O)[O-])CN1c1ccccc1
Agent: [Pd]
Solvent: c1ccccc1
Product: Nc1cccc2c1C(=O)N(c1ccccc1)C2
Yield: 96.4 %

Procedure:
7-Nitro-2-phenyl-2,3-dihydro-isoindol-1-one (0.19 g) obtained in Example 25 was catalytically reduced in the presence of 10% palladium/carbon (0.18 mg) in benzene (250 ml). The reaction solution was filtered, and concentrated under reduced pressure. The resulting residue was purified by recrystallization (ethanol) to obtain 7-amino-2-phenyl-2,3-dihydro-isoindol-1-one as a pale yellow powdery substance (0.16 g, yield: 96.4%).
Reaction SMILES: CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[F:22][C:23]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:24]=1[NH2:25].[Br:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41](O)=[O:42]>CN(C=O)C>[Br:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41]([NH:25][C:24]1[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=1[F:22])=[O:42]
Reactant: Nc1ccc(F)cc1F
Reactant: O=C(O)CCCCCCCCCBr
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: O=C(CCCCCCCCCBr)Nc1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 15 h
Yield: 44.8 %

Procedure:
WSC (990 mg, 5.2 mmols) and HOBt (698 mg, 5.2 mmols) were added to a DMF (10 ml) solution of 2,4-difluoroaniline (1.29 g, 10 mmols) and 10-bromodecanoic acid (1.18 g, 4.7 mmols), and stirred at room temperature for 15 hours. The reaction mixture was extracted with ether. The organic layer was washed with water, 1 N HCl, an aqueous saturated solution of sodium hydrogencarbonate and saturated saline in that order, and dried with anhydrous magnesium sulfate, and the solvent was evaporated. Then, the residue was purified through silica gel column chromatography (developer: hexane/acetone=10/1), and the resulting crystals were recrystallized from ether-hexane to obtain 763 mg (yield: 45%) of 10-bromo-N-(2,4-difluorophenyl)decanamide as colorless needle-like crystals.
Reaction SMILES: [F:1][C:2]([C:33]([F:48])([F:47])[C:34]([F:46])([F:45])[C:35]([F:44])([F:43])[C:36]([F:42])([F:41])[C:37]([F:40])([F:39])[F:38])=[CH:3][CH2:4][N:5]([CH3:32])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C@@H:11]1[CH2:28][C:27]2[CH:26]=[C:25]([OH:29])[CH:24]=[CH:23][C:22]=2[C@@H:21]2[C@@H:12]1[C@H:13]1[C@@:17]([CH2:19][C@@H:20]2[F:30])([CH3:18])[C:16](=[O:31])[CH2:15][CH2:14]1.[BH4-].[Na+]>CO>[F:1][C:2]([C:33]([F:47])([F:48])[C:34]([F:45])([F:46])[C:35]([F:43])([F:44])[C:36]([F:41])([F:42])[C:37]([F:40])([F:39])[F:38])=[CH:3][CH2:4][N:5]([CH3:32])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C@@H:11]1[CH2:28][C:27]2[CH:26]=[C:25]([OH:29])[CH:24]=[CH:23][C:22]=2[C@@H:21]2[C@@H:12]1[C@H:13]1[C@@:17]([CH2:19][C@@H:20]2[F:30])([CH3:18])[C@@H:16]([OH:31])[CH2:15][CH2:14]1
Reactant: CN(CC=C(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CCC(=O)[C@@]1(C)C[C@@H]2F
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CN(CC=C(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 13.3 %

Procedure:
2.4 g of 7α-{5-[(3,4,4,5,5,6,6,7,7,8,8,8-dodecafluor-oct-2-enyl)-methyl-amino]-pentyl}-11β-fluoro-3-hydroxy-estra-1,3,5(10)-trien-17-one is dissolved in 15 ml of methanol and carefully mixed with 222 mg of sodium borohydride. After 15 minutes of stirring at room temperature, the batch is added to saturated common salt solution, extracted with methylene chloride, dried on magnesium sulfate and concentrated by evaporation in a vacuum. After the crude product is chromatographed on silica gel with ethyl acetate as an eluant, 319 mg of 7α-{5-[(3,4,4,5,5,6,6,7,7,8,8,8-dodecafluor-oct-2-enyl)-methyl-amino]-pentyl}-11β-fluor-estra-1,3,5(10)-triene-3,17β-diol is obtained as a foam, [α]D=+37° (c=0.5 in CHCl3).
Reaction SMILES: C(OC([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:12]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Br:30])[CH:25]=3)[C:11]=2[N:10]=[CH:9]1)=O)(C)(C)C>CN(C=O)C.[C-]#N.[C-]#N.[Zn+2]>[C:20]([O:19][C:17]([N:13]1[CH2:14][CH2:15][C:16]2[NH:8][CH:9]=[N:10][C:11]=2[CH:12]1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Br:30])[CH:25]=1)=[O:18])([CH3:23])([CH3:21])[CH3:22]
Reactant: CC(C)(C)OC(=O)N1CCc2c(ncn2C(=O)OC(C)(C)C)C1c1cccc(Br)c1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCc2[nH]cnc2C1c1cccc(Br)c1

Procedure:
4-(3-Bromophenyl)-6,7-dihydro-4H-imidazo[4,5-c]pyridine-1,5-dicarboxylic acid di-tert-butyl ester (0.879 g, 1.83 mmol) and Zn(CN)2 (0.323 g, 2.75 mmol) were stirred in anh. DMF (30 mL) at 80° C. under Ar for 72 h. The solution was concentrated in vacuo, partitioned between CHCl3 and sat. NaHCO3 soln, dried (MgSO4), filtered, and concentrated to yield the title compound without further purification.
Reaction SMILES: [Cu:1].[Cr:2]([O-:6])([O-:5])(=[O:4])=[O:3].[Cr:7]([O-:10])([O-:9])=[O:8]>>[Cr:2]([O-:6])([O-:5])(=[O:4])=[O:3].[Cu+2:1].[Cr:7]([O-:10])([O-:9])=[O:8].[Cu+2:1]
Reactant: [Cu]
Agent: O=[Cr](=O)([O-])[O-]
Agent: O=[Cr]([O-])[O-]
Product: [Cu+2]

Procedure:
A passivating film 46 is then formed on top of the deposited copper layer 44 by depositing one of either a chromate or chromite on the deposited copper layer and forming a respective copper chromate or copper chromite composition. The passivating layer deposition could be formed by passing the wafer through a heating oven and depositing the chromite or chromate onto the deposited copper layer 44. It is also possible to use other techniques, even a wet technique. The semiconductor wafer and associated layers are then passed to a mechanical tool 48 for performing chemical mechanical polishing on the wafer 31. The wafer 31 is carried by wafer carrier 49 and placed face-down on a polishing pad 50 so that the wafer surface to be polished rests against the surface of the polishing pad 50. Various drive mechanisms 52 provide the rotation and movement of a wafer 31 relative to the polishing pad 50. The polishing pad can rotate in operation.
Reaction SMILES: C1(P([N:15]=[N+:16]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2.[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH:36]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][C:68]=1[Cl:73])[N:37]1[CH:42]2[CH2:43][CH2:44][CH:38]1[CH2:39][C:40]([C:46]1[N:51]=[C:50]([CH2:52][NH:53]C(NCCNC(=O)OC(C)(C)C)=O)[CH:49]=[CH:48][CH:47]=1)([OH:45])[CH2:41]2>>[N:53]([CH2:52][C:50]1[N:51]=[C:46]([C:40]2([OH:45])[CH2:39][CH:38]3[N:37]([CH:36]([C:67]4[CH:72]=[CH:71][CH:70]=[CH:69][C:68]=4[Cl:73])[C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=4[Cl:29])[CH:42]([CH2:43][CH2:44]3)[CH2:41]2)[CH:47]=[CH:48][CH:49]=1)=[N+:15]=[N-:16]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)NCCNC(=O)NCc1cccc(C2(O)CC3CCC(C2)N3C(c2ccccc2Cl)c2ccccc2Cl)n1
Solvent: C1CCC2=NCCCN2CC1
Product: [N-]=[N+]=NCc1cccc(C2(O)CC3CCC(C2)N3C(c2ccccc2Cl)c2ccccc2Cl)n1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Add diphenylphosphoryl azide (272 mg, 0.99 mmol) and 1,8-diazabicyclo-[5,4,0]undec-7-ene (150 mg, 0.99 mmol) to the product from Step 4 (404 mg, 0.86 mmol) at 0° C., stir for 20 min., warm to RT then stir at 50° C. for 1 h. Cool to RT and stir overnight. Quench the reaction with H2O and saturated aqueous NH4Cl , extract with CH2Cl2, dry and concentrate. Purify the residue by column chromatography to give the desired compound.