Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[Ru:2](Cl)[C:3]1[CH2:10][CH2:9][CH:8]=[CH:7]CCC=1.[CH3:12][Si:13](C1([Na])C=CC=C1)([CH3:15])[CH3:14].[CH:22]1([Na])[CH:26]=[CH:25][CH:24]=[CH:23]1>O1CCCC1>[CH3:12][Si:13]([Ru:2]([CH:3]1[CH:10]=[CH:9][CH:8]=[CH:7]1)[CH:22]1[CH:26]=[CH:25][CH:24]=[CH:23]1)([CH3:15])[CH3:14]
Reactant: C[Si](C)(C)C1([Na])C=CC=C1
Reactant: [Na]C1C=CC=C1
Reactant: Cl[Ru](Cl)C1=CCCC=CCC1
Solvent: C1CCOC1
Product: C[Si](C)(C)[Ru](C1C=CC=C1)C1C=CC=C1
Temperature: -78 °C
Reaction time: 3 h
Yield: 4.3 %

Procedure:
Further separately, 5 g of dichloro(1,5-cyclooctadienyl)ruthenium was dissolved in 200 ml of well dried tetrahydrofuran in a 500 ml flask whose inside had been substituted by nitrogen. This solution was cooled to −78° C., and the above tetrahydrofuran solution of trimethylsilyl cyclopentadienyl sodium and the above tetrahydrofuran solution of cyclopentadienyl sodium were added dropwise to the solution at the same time in a stream of nitrogen over 1 hour. The resulting solution was stirred at −78° C. for 3 hours and heated to room temperature under agitation over 12 hours. After the resulting solution was let pass through a neutral alumina column in an argon gas atmosphere to be purified and concentrated, it was separated and purified by a neutral alumina column again to obtain 0.23 g of trimethylsilyl cyclopentadienyl(cyclopentadienyl)ruthenium (yield rate of 4.3%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[OH:22].Cl[C:24]1[N:29]=[C:28]([O:30][CH:31]([C:33]([O:35][CH3:36])=[O:34])[CH3:32])[CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:18])([F:19])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[O:22][C:24]1[N:29]=[C:28]([O:30][CH:31]([CH3:32])[C:33]([O:35][CH3:36])=[O:34])[CH:27]=[CH:26][N:25]=1
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(O)c(Cl)cc2F)c1=O
Reactant: COC(=O)C(C)Oc1ccnc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)Oc1ccnc(Oc2cc(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)c(F)cc2Cl)n1
Temperature: 80 °C
Reaction time: 2 h
Yield: 49.3 %

Procedure:
339 mg of 2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenol and 217 mg of 2-chloro-4-[1-(methoxycarbonyl)ethoxy]pyrimidine were dissolved in 2 ml of N,N-dimethylformamide, to this solution was added 150 mg of potassium carbonate, and the mixture was stirred for 2 hours at 80° C. The reaction solution was cooled to room temperature, then, this reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 256 mg of methyl 2-([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}pyrimidin-4-yl]oxy)propionate [present compound 1-2].
Reaction SMILES: [C:1]1(=[O:8])[O:7][C:5](=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH:9](=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH2:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1(C)C(C)=CC=CC=1>[CH2:9]([N:24]1[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:2]([C:1]([OH:7])=[O:8])[CH2:3][CH2:4][C:5]1=[O:6])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C1CCCC(=O)O1
Reactant: O=Cc1ccccc1
Reactant: NCc1ccccc1
Solvent: Cc1ccccc1C
Product: O=C(O)C1CCC(=O)N(Cc2ccccc2)C1c1ccccc1
Temperature: 0 °C
Yield: 69 %

Procedure:
11.4 g (0.10 mole) of glutaric anhydride and 19.5 g (0.10 mole of Schiff base, prepared from benzaldehyde and benzylamine, are refluxed in 300 ml of xylene at 140° C. for 10 hr. After cooling to 0° C. the solid is collected, washed with xylene and ether: 24.7 g (80%) of acid. Recrystallization from acetone-ether gave 21.3 g (69%) of title compound mp 171°-4° C. EXAMPLE 16
Reaction SMILES: [CH3:1][N:2]1[C:10](=[O:11])[C:9]2[N:8](CC=C)[C:7]([C:15]#[N:16])=[N:6][C:5]=2[N:4]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:3]1=[O:22].N1CCOCC1.CS(C)=O>C1COCC1.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>[CH3:1][N:2]1[C:10](=[O:11])[C:9]2[NH:8][C:7]([C:15]#[N:16])=[N:6][C:5]=2[N:4]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:3]1=[O:22]
Reactant: C=CCn1c(C#N)nc2c1c(=O)n(C)c(=O)n2CCCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CS(C)=O
Solvent: C1COCCN1
Product: CCCCCn1c(=O)n(C)c(=O)c2[nH]c(C#N)nc21
Reaction time: 2.5 h
Yield: 17.8 %

Procedure:
1-Methyl-2,6-dioxo-3-pentyl-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purine-8-carbonitrile (0.17 g, 0.56 mmol) and morpholine (0.6 ml, 6.7 mmol) were dissolved in THF (5 ml) containing DMSO (0.5 ml). The flask containing the solution was placed under vacuum and the air replaced with nitrogen (×3). Tetrakis(triphenylphosphine)palladium (0) (0.13 g, 0.11 mmol) was added and the solution stirred for 2.5 h. The solution was separated between ethyl acetate (20 ml) and 2N hydrochloric acid (10 ml) and the organics isolated and washed with brine (3×10 ml). The organics were then washed with 2N sodium hydroxide solution (2×10 ml) and the aqueous acidified with 2N hydrochloric acid and extracted with ethyl acetate (2×10 ml). The organics were isolated, dried (MgSO4) and concentrated to yield the title compound (0.026 g, 18%). NMR; δH (400 MHz, CDCl3) 0.92 (t, 3H, J=7 Hz), 1.32-1.43 (m, 4H), 1.79 (m, 2H), 3.54 (s, 3H), 4.15 (t, 2H, J=7.5 Hz), 14.35 (br. s, 1H); m/z 262 [MH+]
Reaction SMILES: [I-].I[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.BrC1C=CC=CC=1.[C:16]([O:20][CH2:21][CH3:22])(=[O:19])[CH:17]=[CH2:18]>ClC1C=CC=CC=1>[C:16]([O:20][CH2:21][CH3:22])(=[O:19])[CH:17]=[CH:18][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Ic1ccccc1
Reactant: C=CC(=O)OCC
Agent: [I-]
Solvent: Brc1ccccc1
Solvent: Clc1ccccc1
Product: CCOC(=O)C=Cc1ccccc1

Procedure:
More specifically, we have found that chlorobenzene reacts with ethyl acrylate to form ethyl cinnamate in relatively high yield by reacting the chlorobenzene with iodide and/or bromide ion to form a mixture of chlorobenzene, iodobenzene and/or bromobenzene, then reacting the mixture with ethyl acrylate in the presence of a catalyst to form ethyl cinnamate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1.N1C=CC=CC=1.CS([Cl:33])(=O)=O>ClCCl>[Cl:33][C:7]1[CH:6]=[C:5]([O:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: COc1cc(OS(C)(=O)=O)cc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1cc(Cl)cc(OS(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 37.7 %

Procedure:
To a 0° C. solution of 3-chloro-5-methoxy-phenol (Scheme #4, K) (16.62 g, 104.80 mmol) and pyridine (12.8 mL, 157.20 mmol) in dichloromethane (150 mL) was added methanesulfonyl chloride (8.9 mL, 115.28 mmol). The reaction was warmed to room temperature and stirred 24 hours. The dichloromethane was removed under reduced pressure and the crude material partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was washed 1N hydrochloric acid (4×), aqueous saturated sodium chloride (1×), saturated potassium carbonate (3×), aqueous saturated sodium chloride (1×), dried over magnesium sulfate, and solvent removed under reduced pressure. The crude solid was crystallized overnight from dichloromethane (50 mL) and crystals filtered off, washed with dichloromethane, and placed under high vacuum to give the title compound (9.35 g, 38%). 1H NMR (300 MHz, DMSO-d6) δ 7.09 (t, J=2.0 Hz, 1 H), 7.05 (t, J=1.9 Hz, 1 H), 6.93 (t, J=2.1 Hz, 1 H), 3.82 (s, 3 H), 3.42 (s, 3 H); MS (APCI+) m/z 237 [M+1]+; tR=2.28 min.
Reaction SMILES: [NH:1]([C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[CH:6]=[CH:5][N:4]=1)[NH2:2].[C:19](OCC)(OCC)(OCC)[CH2:20][CH3:21]>>[CH2:20]([C:21]1[N:4]2[CH:5]=[CH:6][C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=3)=[N:8][C:3]2=[N:1][N:2]=1)[CH3:19]
Reactant: NNc1nccc(-c2cccc(C(F)(F)F)c2)n1
Reactant: CCOC(CC)(OCC)OCC
Product: CCc1nnc2nc(-c3cccc(C(F)(F)F)c3)ccn12

Procedure:
A mixture of 1.50 g. of 2-hydrazino-4-(m-trifluoromethylphenyl)pyrimidine and 25 ml. of triethyl orthopropionate is refluxed for 8 hours. On cooling the desired compound is obtained by filtration, m.p. 223°-224° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[O:6][B:5]([OH:7])[C:4]2[CH:8]=[CH:9][C:10]([CH3:12])=[CH:11][C:3]1=2.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C1C(=O)N([Br:39])C(=O)C1.O>C(Cl)(Cl)(Cl)Cl>[Br:39][CH2:12][C:10]1[CH:9]=[CH:8][C:4]2[B:5]([OH:7])[O:6][C:2]([CH3:13])([CH3:1])[C:3]=2[CH:11]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc2c(c1)C(C)(C)OB2O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: CC1(C)OB(O)c2ccc(CBr)cc21
Temperature: 25 °C
Yield: 62.2 %

Procedure:
To a solution of 3,3,5-trimethylbenzo[c][1,2]oxaborol-1(3H)-ol (5.0 g, 28.4 mmol) in CCl4 (50 mL) at rt was added benzoyl peroxide (0.7 g, 2.8 mmol) followed by NBS (5.0 g, 28.4 mmol). The reaction mixture was refluxed overnight, cooled to rt and treated with water. The aqueous layer was extracted with EA (20 mL×3). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give the product (4.5 g, yield 62%) as yellow oil. MS: 255 & 257 [M+H]+.
Reaction SMILES: CC([O-])(C)C.[K+].Cl.[NH2:8][OH:9].[CH2:10]([C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([CH3:20])[N:19]=1)[C:15]#[N:16])[CH3:11]>CO>[CH2:10]([C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([CH3:20])[N:19]=1)[C:15]([NH:8][OH:9])=[NH:16])[CH3:11]
Reactant: CCc1cc(C#N)cc(C)n1
Reactant: NO
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CO
Product: CCc1cc(C(=N)NO)cc(C)n1
Yield: 108.3 %

Procedure:
At 0° C., KOtBu (1.81 g, 16.2 mmol) is carefully added to methanol (25 mL). Hydroxylamine hydrochloride (963 mg, 13.9 mmol) is then added to this solution. The suspension is stirred for 30 min before 2-ethyl-6-methyl-isonicotinonitrile (675 mg, 4.62 mmol) is added. The mixture is refluxed for 1 h, the solvent is evaporated. The residue is dissolved in water, extracted three times with EA. The org. extracts are dried over MgSO4, filtered, evaporated and dried under HV to give 2-ethyl-N-hydroxy-6-methyl-isonicotinamidine (897 mg) as a white powder, LC-MS: tR=0.31 min, [M+1]+=180.32.
Reaction SMILES: [NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:2]([C:20]([OH:22])=O)[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].[NH2:30][C@H:31]([C:37]([NH:39][C@H:40]([C:45]([NH2:47])=[O:46])[CH2:41][CH2:42][S:43][CH3:44])=[O:38])[CH2:32][CH2:33][CH:34](C)C.Cl.[CH:49]1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1>>[NH:1]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[C@@H:2]([C:20]([NH:30][C@H:31]([C:37]([NH:39][C@H:40]([C:45]([NH2:47])=[O:46])[CH2:41][CH2:42][S:43][CH3:44])=[O:38])[CH2:32][CH:33]([CH3:34])[CH3:49])=[O:22])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:13]=[CH:14][C:15]([CH3:16])=[CH:17][CH:18]=1)(=[O:10])=[O:11]
Reactant: Cc1ccc(S(=O)(=O)NC(=N)NCCC[C@@H](NC(=O)OC(C)(C)C)C(=O)O)cc1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CSCC[C@H](NC(=O)[C@@H](N)CCC(C)C)C(N)=O
Agent: Cl
Agent: On1nnc2ccccc21
Product: CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCCNC(=N)NS(=O)(=O)c1ccc(C)cc1)NC(=O)OC(C)(C)C)C(N)=O
Yield: 54 %

Procedure:
Condensation of BocDArg(Tos)OH (2.14 g.) and HLeu-MetNH2 hydrochloride salt (Example 1, 1.49 g.) using dicyclohexylcarbodiimide and 1-hydroxybenzotriazole gave BocDArg(Tos)-Leu-MetNH2 in 54% yield. De-t-butoxycarbonylation of BocDArg(Tos)-Leu-MetNH2 (1.7 g.) using hydrogen chloride in dioxane gave HDArg(Tos)-Leu-MetNH2 in 45% yield.
Reaction SMILES: [NH2:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[O:13][C:14]([F:17])([F:16])[F:15])[C:3]=1[C:18]([OH:20])=O.Cl.C(N=C=NCCCN(C)C)C.[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>ClCCl>[NH2:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[O:13][C:14]([F:15])([F:16])[F:17])[C:3]=1[C:18]([N:43]1[CH2:42][CH2:41][N:40]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[F:33])[CH2:45][CH2:44]1)=[O:20]
Reactant: Nc1onc(-c2ccccc2OC(F)(F)F)c1C(=O)O
Reactant: Fc1ccccc1N1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: Nc1onc(-c2ccccc2OC(F)(F)F)c1C(=O)N1CCN(c2ccccc2F)CC1
Yield: 69.6 %

Procedure:
In a similar manner as described in Example 1, by using dichloromethane (30 mL), 5-amino-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-carboxylic acid (530 mg, 1.84 mmol), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (388 mg, 2.02 mmol) and 1-(2-fluorophenyl)piperazine (332 mg, 1.84 mmol), a white solid required compound (576 mg, 1.28 mmol, 70%) was obtained.
Reaction SMILES: [C:1]1([CH:7]=[N:8][N:9]2[CH2:13][CH2:12][NH:11][C:10]2=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C=NN2[CH2:27][CH2:26][N:25]([CH2:28]CCCI)[C:24]2=O)C=CC=CC=1.[H-].[Na+].CN(CCCl)C>CN(C)C=O.O>[C:1]1([CH:7]=[N:8][N:9]2[CH2:13][CH2:12][N:11]([CH2:27][CH2:26][N:25]([CH3:28])[CH3:24])[C:10]2=[O:14])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1NCCN1N=Cc1ccccc1
Reactant: O=C1N(CCCCI)CCN1N=Cc1ccccc1
Agent: CN(C)CCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)CCN1CCN(N=Cc2ccccc2)C1=O
Temperature: 25 °C

Procedure:
A solution of 1-phenylmethyleneamino-2-imidazolidinone (prepared as described in Part II of Example A (14.4 g, 0.076 mole) in dry dimethylformamide (338 ml) is stirred and treated portionwise over a 3 minute period with sodium hydride (60% dispersion in mineral oil) (3.0 g, 0.023 mole). During the addition, a nitrogen sweep is maintained. After the addition is complete, the reaction is heated on a steam bath for 15 minutes and then chilled to ambient temperature. The nitrogen sweep is discontinued and the reaction mixture is treated all at once with dimethylaminoethyl chloride (17.66 g, 0.16 mole), prepared as described in Part I herein. The reaction is stirred at ambient temperature for 15 minutes and then heated at 80° to 90° C. for 3 hours. The reaction is filtered hot, and the filtrate is chilled and concentrated under reduced pressure to leave an oily residue. The residue is treated with 300 ml of water and extracted with 3×300 ml portions of chloroform. The extracts are combined and dried over anhydrous MgSO4. The extract is filtered and the filtrate is concentrated under reduced pressure to leave a tan-colored semi-solid. The semi-solid is triturated with anhydrous ether to give the 1-phenylmethyleneamino-3-[2-(dimethylamino)ethyl]-2-imidazolidinone, weighing 6.17 g.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]3[CH2:11][CH2:12][CH:13]([C:15]([OH:17])=O)[CH2:14][C:9]=3[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:18][NH:19][CH2:20][CH2:21][CH2:22][CH3:23]>>[CH2:20]([N:19]([CH3:18])[C:15]([CH:13]1[CH2:12][CH2:11][C:10]2[C:3]3[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=3[S:8][C:9]=2[CH2:14]1)=[O:17])[CH2:21][CH2:22][CH3:23]
Reactant: O=C(O)C1CCc2c(sc3ncnc(Cl)c23)C1
Reactant: CCCCNC
Product: CCCCN(C)C(=O)C1CCc2c(sc3ncnc(Cl)c23)C1

Procedure:
300 mg (1.12 mmol) (RS)-4-chloro-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-7-carboxylic acid (prepared according to intermediate example 31b) were transformed in analogy to example 3 using N-methylbutan-1-amine to give after working up and purification 249 mg (66%) of the title compound.
Reaction SMILES: C(O[CH:4]=[C:5]([C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=O)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.[N+:18]([CH2:21][C:22](=O)[CH3:23])([O-:20])=[O:19].C([O-])(=O)C.[Na+].C([O-])(=O)C.[NH4+:34]>C(O)C>[CH3:23][C:22]1[N:34]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:21]=1[N+:18]([O-:20])=[O:19]
Reactant: [NH4+]
Reactant: CC(=O)C[N+](=O)[O-]
Reactant: CCOC=C(C(=O)OCC)C(=O)C(=O)OCC
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cc([N+](=O)[O-])c(C)nc1C(=O)OCC
Temperature: -10 °C
Reaction time: 16 h
Yield: 18.2 %

Procedure:
Diethyl ethoxymethyleneoxalacetate (150.4 g, 0.616 mol, 1 eq) is dissolved in 300 mL absolute ethanol under a nitrogen atmosphere and the mixture is cooled to -10° C. in an ice/acetone bath. Unpurified 1-nitro-2-propanone (prepared by the method of D. Baker and S. Putt, Synthesis, 1978, 478-9, assumed to be 63.448 g, 0.616 mol) dissolved in 1.00 mL absolute ethanol is then added to the stirred solution. Sodium acetate (101.06 g, 1.232 mol) is then added in portions so that the temperature of the reaction remains below 10° C., followed by the addition of ammonium acetate (94.6 g, 1.232 g). The reaction mixture is allowed to warm to room temperature and is then stirred for 16 hours. The mixture is filtered through two pads of silica gel which are then eluted with methylene chloride. The filtrate is concentrated in vacuo to a thick dark oil which is chromatographed using hexanes as eluant, yielding the product in an 18.2% yield (31.4 g), having a melting point 90°-91.5° C.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[C:8]([Br:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.S([O-])([O-])(=O)=O.[Na+].[Na+].O.[C:19]1(C)[CH:24]=CC(S(O)(=O)=O)=C[CH:20]=1.C(OC=CC)C>C(Cl)(Cl)Cl.O>[Br:10][C:8]1[CH:9]=[C:2]2[C:3]([CH:4]=[C:19]([CH3:24])[CH:20]=[N:1]2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: Nc1cc(Br)ccc1C=O
Agent: CC=COCC
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: Cc1cnc2cc(Br)ccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.8 %

Procedure:
A 1 L round bottom flask fitted with a stirbar, a Dean-Stark trap for solvents heavier than water, and a condenser was charged with 2-amino-4-bromobenzaldehyde (20 g, 100 mmol), sodium sulfate (71.0 g, 500 mmol), and p-toluenesulfonic acid monohydrate (4.75 g, 25.00 mmol). The solids were taken up in anhydrous chloroform (498 mL) and the suspension treated with 1-ethoxyprop-1-ene (14.39 mL, 130 mmol). The mixture was then heated to reflux with stirring overnight. The reaction mixture was cooled to room temperature and transferred to a 2 L separatory funnel. The solution was extracted twice with 200 mL saturated aq sodium bicarbonate and once with 200 mL water. The organic layer was isolated and the aqueous layers were combined and re-extracted twice with an additional 100 mL dichloromethane. The organics were then pooled, dried over sodium sulfate, filtered, and concentrated to a residue. The residue was purified by flash chromatography (0.2-1.9% methanol:dichloromethane). Fractions containing the desired material were pooled and concentrated to afford the title compound as a bright orange solid (5.603 g, 25.2 mmol, 25% yield). MS(ES)+ m/e 221.8 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][O:8][C:9](=[O:29])[C@@H:10]2[CH2:14][C:13](=[O:15])[CH2:12][N:11]2[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:17])=[CH:5][CH:4]=1.[BH4-].[Na+]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9](=[O:29])[C@@H:10]2[CH2:14][C@H:13]([OH:15])[CH2:12][N:11]2[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:17])=[CH:30][CH:31]=1.[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9](=[O:29])[C@@H:10]2[CH2:14][C@@H:13]([OH:15])[CH2:12][N:11]2[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:17])=[CH:30][CH:31]=1
Reactant: COc1ccc(COC(=O)[C@@H]2CC(=O)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: COc1ccc(COC(=O)[C@@H]2C[C@@H](O)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)cc1
Product: COc1ccc(COC(=O)[C@@H]2C[C@H](O)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)cc1
Reaction time: 0.5 h

Procedure:
650 mg of 1-(p-nitrobenzyloxycarbonyl)-4-oxo-L-proline p-methoxybenzyl ester was dissolved in 45 ml of ethanol, and 86 mg of sodium borohydride was added thereto in two divided portions at room temperature. After 30 minutes, the reaction mixture was concentrated under reduced pressure at 30° C. or below, and the concentrate was diluted with ethyl acetate, washed with water, dried over sodium sulfate and distilled off to remove the solvent. The residue was purified by silica gel column chromatography to obtain cis-1-(p-nitrobenzyloxycarbonyl)-4-hydroxy-L-proline p-methoxybenzyl ester (450 mg) and trans-1-(p-nitrobenzyloxycarbonyl)-4-hydroxy-L-proline p-methoxybenzyl ester (190 mg).
Reaction SMILES: CCOCC.[CH2:6]([Li:10])[CH2:7][CH2:8][CH3:9].BrC1C2[C:16](=[CH:17][C:18]3[O:24][CH2:23][O:22]C=3C=2)[N:15]=[CH:14][CH:13]=1.O1CCCC1>CCCCCC>[CH2:23]1[O:24][C:18]2[CH:17]=[C:16]3[C:7]([C:6]([Li:10])=[CH:13][CH:14]=[N:15]3)=[CH:8][C:9]=2[O:22]1
Reactant: [Li]CCCC
Reactant: Brc1ccnc2cc3c(cc12)OCO3
Solvent: CCCCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: [Li]c1ccnc2cc3c(cc12)OCO3

Procedure:
To 250 ml. of anhydrous ether was added 19.3 ml. of a 1.45M solution of n-butyllithium in hexane. The resulting solution was cooled to -68°. Thereafter, there was added 6.55 g. of 4-bromo-6,7-methylenedioxyquinoline dissolved in 200 ml. of anhydrous tetrahydrofuran over a period of 30 minutes with stirring and under a nitrogen atmosphere to afford 6,7-methylenedioxy-4-quinolyllithium. Stirring of the mixture was continued at the same temperature for 30 minutes followed by the addition of a solution of 2.15 g. of a mixture of epimeric, racemic 4,5-erythro-5-ethylquinuclidine-2ξ-carboxaldehydes in 250 ml. of ether over a period of one hour. The reaction mixture was stirred at -70° under a nitrogen atmosphere overnight. After quenching with water, the mixture was allowed to warm to room temperature and subsequently was concentrated under reduced pressure. The residue was dissolved in ether. The ethereal solution was washed with water, dried over sodium sulfate and evaporated to dryness to give 6.54 g. of an oil. Chromatography on neutral alumina (Woelm, activity I) with ethyl acetate yielded 2.97 g. of a yellow solid. Subsequent elution with methanol yielded 3.37 g. of a brown oil. This was chromatographed on silica gel preparative plates (20 × 20 × 0.2 cm) with ethyl acetate-triethylamine (97:3) as the solvent mixture. The plates were developed three times. Elution of the lowest major band with methanolchloroform and crystallization of the eluate (510 mg.) from acetone gave racemic 6',7'-methylenedioxy-dihydrocinchonidine, m.p. 232°-233°. Elution of the next higher band with methanolchloroform and crystallization of the eluate (597 mg.) from acetone gave racemic 6',7'-methylenedioxydihydrocinchonine, m.p. 234°-235°.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:13])[CH3:12])[CH:5]=1)([OH:3])=[O:2].[Si](C=[N+]=[N-])(C)(C)[CH3:15]>CO.C1C=CC=CC=1>[CH3:15][O:2][C:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:13])[CH3:12])[CH:5]=1)=[O:3]
Reactant: CC(=O)Nc1cc(C(=O)O)ccn1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: c1ccccc1
Product: COC(=O)c1ccnc(NC(C)=O)c1

Procedure:
4-Carboxy-2-acetylaminopyridine (3.4 g, 19 mmol) was dissolved in methanol/benzene (100 mL, 1:1). TMS-diazomethane was added (1M, Aldrich) with cooling until the yellow color just persisted, then the solvent was removed under reduced pressure. The product was purified by silica gel column chromatography (50/50 hexane/ethyl acetate) and 3.0 g of product was recovered.