Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(N1[C@@H](C2C=CC=CC=2)[C@H](C(O)=O)OC1(C)C)=O)(C)(C)C.[C:24]([O:28][C:29]([N:31]1[C@@H:35]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C@H:34]([C:42]([O:44]CC)=[O:43])[O:33][C:32]1([CH2:49][CH3:50])[CH2:47][CH3:48])=[O:30])([CH3:27])([CH3:26])[CH3:25]>>[C:24]([O:28][C:29]([N:31]1[C@@H:35]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C@H:34]([C:42]([OH:44])=[O:43])[O:33][C:32]1([CH2:49][CH3:50])[CH2:47][CH3:48])=[O:30])([CH3:27])([CH3:26])[CH3:25]
Reactant: CCOC(=O)[C@@H]1OC(CC)(CC)N(C(=O)OC(C)(C)C)[C@H]1c1ccccc1
Agent: CC(C)(C)OC(=O)N1[C@@H](c2ccccc2)[C@H](C(=O)O)OC1(C)C
Product: CCC1(CC)O[C@@H](C(=O)O)[C@H](c2ccccc2)N1C(=O)OC(C)(C)C
Yield: 79.8 %

Procedure:
(4S,5R)-3-tert-Butoxycarbonyl-2,2-diethyl-4-phenyl-5-oxazolidinecarboxylic acid may be obtained under the conditions described in Example 6 for the preparation of (4S,5R)-3-tert-butoxycarbonyl-2,2-dimethyl-4-phenyl-5-oxazolidinecarboxylic acid. Thus, starting with 2.3 g of ethyl (4S,5R)-3-tert-butoxycarbonyl-2,2-diethyl-4-phenyl-5-oxazolidinecarboxylate, 1.7 g of (4S,5R)-3-tert-butoxycarbonyl-2,2-diethyl-4-phenyl-5-oxazolidinecarboxylic acid is obtained in the form of white crystals, melting point 185° C.
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]2[CH2:6][CH2:7][C:4]=2[CH:3]=1.[CH3:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[CH2:16])=[CH:13][CH:12]=1.C(N(CCCC)CCCC)CCC.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[CH3:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[CH:16][C:2]2[CH:9]=[CH:8][C:5]3[CH:6]=[CH:7][C:4]=3[CH:3]=2)=[CH:13][CH:12]=1
Reactant: Brc1ccc2c(c1)CC2
Reactant: C=Cc1ccc(C)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Solvent: CCCCN(CCCC)CCCC
Product: Cc1ccc(C=Cc2ccc3c(c2)C=C3)cc1

Procedure:
A solution of 3.0 g 4-bromobenzocyclobutane, 1.9 g 4-methylstyrene, 3.0 g tri-n-butylamine, 150 mg tri-o-tolylphosphine, 36 mg palladium (II) acetate, and 10 ml of acetonitrile is stirred at reflux under nitrogen for 4 hours. The reaction mixture is poured into 60 ml of 10 percent HCl. The product is isolated by filtration, dried, recrystallized from ethanol, and isolated. About 2.9 g of monomer is prepared.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=2[Cl:16])=[CH:4][CH:3]=1.[OH:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=2)[CH2:20][CH2:19]1>>[Cl:16][C:10]1[CH:11]=[C:12]([NH:15][C:28](=[O:29])[C:27]2[CH:31]=[CH:32][C:24]([N:21]3[CH2:22][CH2:23][CH:18]([OH:17])[CH2:19][CH2:20]3)=[CH:25][CH:26]=2)[CH:13]=[CH:14][C:9]=1[NH:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:28](=[O:29])[C:27]2[CH:26]=[CH:25][C:24]([N:21]3[CH2:22][CH2:23][CH:18]([OH:17])[CH2:19][CH2:20]3)=[CH:32][CH:31]=2)=[CH:7][CH:6]=1
Reactant: O=C(O)c1ccc(N2CCC(O)CC2)cc1
Reactant: Nc1ccc(Nc2ccc(N)cc2Cl)cc1
Product: O=C(Nc1ccc(Nc2ccc(NC(=O)c3ccc(N4CCC(O)CC4)cc3)cc2Cl)cc1)c1ccc(N2CCC(O)CC2)cc1

Procedure:
Compound 826 was prepared according to the procedure described in Scheme IV from N1-(4-aminophenyl)-2-chlorobenzene-1,4-diamine and 4-(4-hydroxypiperidin-1-yl)benzoic acid. [M+H]+ calcd for C36H38ClN5O4: 640.26; found 640.12.
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6]2[N:15]=[CH:14][C:13]3[C:8](=[CH:9][C:10]([C:17]([O:19]C)=[O:18])=[CH:11][C:12]=3[F:16])[N:7]=2)[CH2:3][CH2:2]1.[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[CH:1]1([CH2:4][NH:5][C:6]2[N:15]=[CH:14][C:13]3[C:8](=[CH:9][C:10]([C:17]([OH:19])=[O:18])=[CH:11][C:12]=3[F:16])[N:7]=2)[CH2:2][CH2:3]1
Reactant: COC(=O)c1cc(F)c2cnc(NCC3CC3)nc2c1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cc(F)c2cnc(NCC3CC3)nc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of methyl 2-(cyclopropylmethylamino)-5-fluoro-quinazoline-7-carboxylate (40 mg, 0.15 mmol) in THF (1.3 mL) and water (0.4 mL) was treated with LiOH (10.4 mg, 0.44 mmol) and stirred at ambient temperature for 1 h. The mixture was acidified with 1M aqueous citric acid and the resulting precipitate collected via centrifugation, washed with water, and then dried under high vacuum to afford 2-(cyclopropylmethylamino)-5-fluoroquinazoline-7-carboxylic acid as a yellow solid which was used without further purification.
Reaction SMILES: C([O:8][CH2:9][C@H:10]1[O:14][C:13](=[O:15])[N:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[OH:8][CH2:9][C@H:10]1[O:14][C:13](=[O:15])[N:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[CH2:11]1
Reactant: CC(C)(C)OC(=O)NN1C[C@@H](COCc2ccccc2)OC1=O
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CC(C)(C)OC(=O)NN1C[C@@H](CO)OC1=O
Reaction time: 5 h
Yield: 72 %

Procedure:
A solution of (S)-tert-butyl 5-(benzyloxymethyl)-2-oxooxazolidin-3-ylcarbamate (1.537 g, 4.77 mmol) in ethanol (25 mL), with 10% Pd/C (0.761 g, 0.715 mmol), was hydrogenated for 18 h at 40 psi. Conversion was about 40%. Catalyst was filtered away and replaced with fresh 10% Pd/C (0.254 g, 0.238 mmol); ammonium formate (0.752 g, 11.92 mmol) was added and the reaction was refluxed, under nitrogen, while stirring for 5 h. Conversion was complete. Catalyst was filtered away and the solvent evaporated. The residue was triturated with hot diisopropyl ether/MeOH (10:1) and left to precipitate on standing at r.t., The title compound was obtained as a white solid (802 mg, 3.45 mmol). Yield=72%.
Reaction SMILES: [ClH:1].C(OC([NH:9][C:10]1[CH:11]=[C:12]([CH2:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([NH:25][C:26]([C:28]3[S:38][C:37]4[N:39]5[C:30](=[CH:31][N:32]=[C:33]5[CH:34]=[CH:35][CH:36]=4)[CH:29]=3)=[O:27])[CH2:21][CH2:20]2)[CH:13]=[CH:14][CH:15]=1)=O)(C)(C)C>C(O)C>[ClH:1].[ClH:1].[ClH:1].[NH2:9][C:10]1[CH:11]=[C:12]([CH2:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([NH:25][C:26]([C:28]3[S:38][C:37]4[N:39]5[C:30](=[CH:31][N:32]=[C:33]5[CH:34]=[CH:35][CH:36]=4)[CH:29]=3)=[O:27])[CH2:21][CH2:20]2)[CH:13]=[CH:14][CH:15]=1
Reactant: CC(C)(C)OC(=O)Nc1cccc(CCCN2CCC(NC(=O)C3=Cc4cnc5cccc(n45)S3)CC2)c1
Agent: Cl
Solvent: CCO
Product: Nc1cccc(CCCN2CCC(NC(=O)C3=Cc4cnc5cccc(n45)S3)CC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 66 %

Procedure:
Concentrated hydrochloric aicd (1.5 ml) was added to N-[1-[3-(3-tert-butoxycarbonylaminophenyl)propan-1-yl]piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide (392 mg, 0.735 mmol) and the mixture was stirred at room temperature for 1 hour. Ethanol was added to the mixture to give N-[1-[3-(3-aminophenyl)propan-1-yl]piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide trihydrochloride as orange crystals (265 mg, 66%), which were collected by filtration and washed with ethanol.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:19]=[C:18]([CH2:20][C:21]([NH:23][CH:24]([C:37]([O:39][CH2:40][CH2:41][CH3:42])=[O:38])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:22])[CH:17]=[CH:16][C:5]=1[C:6]([O:8]CC1C=CC=CC=1)=[O:7])[CH3:2]>C(O)CC>[CH2:1]([O:3][C:4]1[CH:19]=[C:18]([CH2:20][C:21]([NH:23][CH:24]([C:37]([O:39][CH2:40][CH2:41][CH3:42])=[O:38])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:22])[CH:17]=[CH:16][C:5]=1[C:6]([OH:8])=[O:7])[CH3:2]
Reactant: CCCOC(=O)C(NC(=O)Cc1ccc(C(=O)OCc2ccccc2)c(OCC)c1)c1ccccc1N1CCCCC1
Solvent: CCCO
Product: CCCOC(=O)C(NC(=O)Cc1ccc(C(=O)O)c(OCC)c1)c1ccccc1N1CCCCC1

Procedure:
Prepared analogously to Example 40 by catalytic hydrogenation of benzyl 2-ethoxy-4-[N-(α-n-propoxycarbonyl-2-piperidino-benzyl)-aminocarbonylmethyl]-benzoate in n-propanol.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][C:4]([C:7](=[CH2:18])[C:8]([O:10]CC2C=CC=CC=2)=[O:9])=[N:3]1>[Pd].CO>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([CH:7]([CH3:18])[C:8]([OH:10])=[O:9])=[N:3]1
Reactant: C=C(C(=O)OCc1ccccc1)c1ccn(C)n1
Agent: [Pd]
Solvent: CO
Product: CC(C(=O)O)c1ccn(C)n1
Reaction time: 8 h
Yield: 76.7 %

Procedure:
To 0.10 mg (0.093 mmol) of 10% palladium on carbon was added a solution of (0.23 g, 0.93 mmol) of benzyl 2-(1-methyl-1H-pyrazol-3-yl)acrylate prepared in step C above in 6 mL of methanol. The resulting suspension was stirred under an atmosphere of hydrogen (1 atmosphere) overnight. The residue was filtered through a pad of Celite® and the pad was washed with cold methanol. The combined filtrates were evaporated under reduced pressure to yield the title compound as an off-white gum (0.11 g, 76%). LC-MS: m/z (ES) 155 (MH)+.
Reaction SMILES: [C:1]1([C:7]2[O:11][C:10]([C:12]([NH:14][C:15]3[CH:16]=[C:17]([CH2:21][C:22]([OH:24])=O)[CH:18]=[CH:19][CH:20]=3)=[O:13])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH4+:25].[OH-]>>[C:22]([CH2:21][C:17]1[CH:16]=[C:15]([NH:14][C:12]([C:10]2[O:11][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:8][CH:9]=2)=[O:13])[CH:20]=[CH:19][CH:18]=1)(=[O:24])[NH2:25]
Reactant: [NH4+]
Reactant: O=C(O)Cc1cccc(NC(=O)c2ccc(-c3ccccc3)o2)c1
Agent: [OH-]
Product: NC(=O)Cc1cccc(NC(=O)c2ccc(-c3ccccc3)o2)c1

Procedure:
The carboxylic acid (10) (50 mg, 0.15 mmol) was coupled to NH4OH (0.01 ml, 0.15 mmol) using Method C. The crude compound was purified by column chromatography, eluting with a stepped gradient of 80-100% EtOAc in heptane to give the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([OH:15])=O)=[CH:9]2)([O-:3])=[O:2].[NH2:16][C@@H:17]([CH2:26][S:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[CH2:18][O:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][S:27][CH2:26][C@H:17]([NH:16][C:13]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[CH:7][CH:6]=[CH:5][C:4]=3[N+:1]([O-:3])=[O:2])=[O:15])[CH2:18][O:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:34][CH:33]=1
Reactant: O=C(O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Reactant: COc1ccc(CSC[C@H](N)COC(=O)C(C)(C)C)cc1
Agent: O=C([O-])O
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COc1ccc(CSC[C@@H](COC(=O)C(C)(C)C)NC(=O)c2cc3cccc([N+](=O)[O-])c3[nH]2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.4 %

Procedure:
7-Nitro-1H-indole-2-carboxylic acid (8.2 g, 22.7 mmol) prepared in Step A and 2,2-dimethyl-propionic acid (R)-2-amino-3-(4-methoxy-benzylsulfanyl)-propyl ester (13.2 g, 27.2 mmol) prepared in Preparation 31 were dissolved in N,N-dimethylformamide (100 mL). EDC (6.6 g, 25.0 mmol) and HOBT (4.6 g, 25.0 mmol) were added thereto, and the mixture was stirred for 8 h at room temperature. Saturated aqueous sodium bicarbonate solution was added to the mixture to quench the reaction. The reaction mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered, and distilled under reduced pressure. The residue was purified by column chromatography to give the title compound (8.1 g, Yield 71%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15](Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]#[CH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C=O
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: C#C[C@@H]1CCCN1C(=O)OC(C)(C)C

Procedure:
A solution of (2S)-N-(tert-butoxycarbonyl)-2-formylpyrrolidine (4.0 g, 20 mmole), carbon tetrabromide (6.67 g, 20.1 mmole) and triphenylphosphine (5.26 g, 20.1 mmole) in methylene chloride (100 mL) was stirred at ambient temperature under a nitrogen atmosphere for 24 hours. The mixture was concentrated, then purified by chromatography, using (1:1) ethyl acetate:hexane as eluant to provide the desired product as an oil. The product was dissolved in dry tetrahydrofuran (50 mL) and cooled to −78° C. A solution of n-butyllithium (50.25 mL, 20.1 mmole, 2.5 M solution in hexanes) was added and the mixture was stirred at −78° C. for 1 h. The material was quenched with water (20 mL) and extracted with ethyl acetate (3×50 mL). The combined extracts were dried (K2CO3), concentrated and purified by chromatography, using (1:1) ethyl acetate:hexane as eluant to provide (3.10 g, 91%) of a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][C:9]=2[F:17])=[CH:4][CH:3]=1.Br[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25]([NH:28][C@@H:29]([CH3:32])[CH2:30][OH:31])(=[O:27])=[O:26].C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>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].CS(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:19]3[C:20]([S:25]([NH:28][C@@H:29]([CH3:32])[CH2:30][OH:31])(=[O:27])=[O:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:10][C:9]=2[F:17])=[CH:4][CH:3]=1
Reactant: C[C@@H](CO)NS(=O)(=O)c1ccccc1Br
Reactant: Nc1ccc(-c2ccc(B(O)O)cc2F)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CS(C)=O
Solvent: ClCCl
Product: C[C@@H](CO)NS(=O)(=O)c1ccccc1-c1ccc(-c2ccc(N)nc2)c(F)c1
Temperature: 80 °C

Procedure:
A mixture of (4-(6-aminopyridin-3-yl)-3-fluorophenyl)boronic acid (100 mg, 0.43 mmol), (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide (160 mg, 0.54 mmol), Pd(dppf)Cl2.CH2Cl2 (18 mg, 0.022 mmol), K2CO3 (340 mg, 2.4 mmol), and DMSO (3 mL) was sparged with nitrogen, then the reaction vessel was sealed and heated at 80° Celsius for 16 hours. The mixture was cooled to rt, then filtered, and subjected to HPLC purification to provide the title compound. MS (CI): mass calcd. for C20H20FN3O3S, 401.12; m/z found, 402.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.31-7.93 (m, 5H), 7.72-7.57 (m, 3H), 7.42-7.25 (m, 4H), 7.11-7.04 (d, J=9.2, 1H), 3.34-3.25 (s, 1H), 3.18-3.00 (m, 2H), 1.00-0.91 (d, J=6.5, 3H).
Reaction SMILES: CC(C(OC)=O)=C.COCC(O)C.CC(=O)CC(C)(O)C.CCCCCCCCOC(CCC1C=C([N:41]2[N:49]=[C:48]3[C:43]([CH:44]=[CH:45][CH:46]=[CH:47]3)=[N:42]2)C(O)=C(C(C)(C)C)C=1)=O.CCC(C1C=C(N2N=C3C(C=CC=C3)=N2)C(O)=C(C(CC)(C)C)C=1)(C)C.CC(CC(C1C=CC(O)=C(N2N=C3C(C=CC=C3)=N2)C=1)(C)C)(C)C>>[NH:42]1[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:48]=2[N:49]=[N:41]1
Reactant: CCCCCCCCOC(=O)CCc1cc(-n2nc3ccccc3n2)c(O)c(C(C)(C)C)c1
Agent: C=C(C)C(=O)OC
Agent: CC(C)(C)CC(C)(C)c1ccc(O)c(-n2nc3ccccc3n2)c1
Agent: CCC(C)(C)c1cc(-n2nc3ccccc3n2)c(O)c(C(C)(C)CC)c1
Solvent: CC(=O)CC(C)(C)O
Solvent: COCC(C)O
Product: c1ccc2[nH]nnc2c1
Reaction time: 0.17 h

Procedure:
A coating solution was prepared containing 7 grams (g) of Elvacite 2041 PMMA, 79 g of 1-methoxy-2-propanol, 14 g of diacetone alcohol, 0.85 g of Tinuvin 384, 0.43 g of Tinuvin 328, 0.22 g of Cyasorb 5411, and 2 drops of BYK 331 surfactant. Thus, the solution contains 7% PMMA by total weight and 10% Tinuvin 384, 5% Tinuvin 328, and 2.5% Cyasorb 5411 based on solids. This solution was applied by flow coating onto 7 mil (177.8 μm) polycarbonate films 10 inches (25.4 cm) wide and 15 inches (38.1 cm) long, the solvent was flashed at 50° C. for 10 minutes, and the coated film was baked for 1 hour at 100° C. The top 5 inches (12.7 cm) of the films was discarded.
Reaction SMILES: Cl.C[O:3][C:4](=[O:33])[C@H:5]([CH2:29][CH2:30][S:31][CH3:32])[NH:6][C:7](=[O:28])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][NH:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:10][C:9]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O.[OH-].[Li+]>C1COCC1.O>[N:18]1[CH:19]=[CH:20][CH:21]=[C:16]([NH:15][CH2:14][C:11]2[CH:12]=[CH:13][C:8]([C:7]([NH:6][C@H:5]([C:4]([OH:33])=[O:3])[CH2:29][CH2:30][S:31][CH3:32])=[O:28])=[C:9]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:10]=2)[CH:17]=1
Reactant: COC(=O)[C@H](CCSC)NC(=O)c1ccc(CNc2cccnc2)cc1-c1ccccc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CSCC[C@H](NC(=O)c1ccc(CNc2cccnc2)cc1-c1ccccc1)C(=O)O
Reaction time: 0.5 h
Yield: 56 %

Procedure:
To a solution of [4-(pyrid-3-ylaminomethyl)-2-phenylbenzoyl]methionine methyl ester hydrochloride (72 mg, 0.16 mmol) in THF (3 mL) was added a solution of lithium hydroxide hydrate (13 mg, 0.32 mmol) in water (1 mL) and the reaction mixture was stirred for 30 minutes. The THF was evaporated in vacuo and the residue was taken up in aqueous 3N HCl. The solution was concentrated and the residue was purified by preparative HPLC (70% acetonitrile-0.1% aqueous trifluoroacetic acid) to give [4-(pyrid-3-ylaminomethyl)-2-phenylbenzoyl]methionine (39 mg, 50%). 1H NMR (300 MHz., DMSO-d6) δ 8.48 (d, 1H), 8.17 (m, 1H), 7.97 (m, 1H), 7.56 (m, 2H), 7.29-7.44 (m, 7H), 4.51 (bd, 2H), 4.48 (ddd, 1H), 2.24 (m, 2H), 1.99 (s, 3H), 1.85 (m, 2H). MS (CI NH3) m/e 436 (M+H)+, 418, 319, 287, 194, 165. Anal calcd for C24H25N3O3S (+1.26 TFA): C, 55.00; H, 4.57; N, 7.25. Found: C, 54.97; H, 4.58; N, 7.33.
Reaction SMILES: [NH2:1][C:2]1[C:3]([OH:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:9](Cl)([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>C(Cl)Cl>[OH:8][C:3]1[C:2]([NH:1][C:9](=[O:10])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:7][CH:6]=[CH:5][N:4]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: Nc1cccnc1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(Nc1cccnc1O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.9 %

Procedure:
To a solution of 3-aminopyridin-2-ol (8.05 g, 73.0 mmol) in DCM (20 mL) was added CbzCl (13.2 mL, 93.0 mmol) and Na2CO3 (18.0 g, 170 mmol). The mixture was stirred at room temperature overnight. Ethyl acetate (500 mL) was added and the mixture was washed with NaHCO3 (50 mL). The organic phase was dried over MgSO4, filtered and concentrated. The crude product was purified by combi-flash (ISCO, 40 g silica, MeOH/DCM from 3% to 5%, UV254) to afford benzyl (2-hydroxypyridin-3-yl)carbamate (16.2 g, 90% yield): MS (ES) m/z 245 (M+H).
Reaction SMILES: C(OC([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][N:26]([C:35]4[CH:39]=[CH:38][O:37][N:36]=4)[C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28])[O:22][C:21]3=[O:40])=[CH:16][C:15]=2[F:41])[CH2:10]1)=O)(C)(C)C.Cl>ClCCl.C(O)C>[NH2:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][N:26]([C:35]4[CH:39]=[CH:38][O:37][N:36]=4)[C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:32])[Cl:33])=[O:28])[O:22][C:21]3=[O:40])=[CH:16][C:15]=2[F:41])[CH2:10]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCN(c2ccc(N3C[C@H](CN(C(=O)OCC(Cl)(Cl)Cl)c4ccon4)OC3=O)cc2F)C1
Agent: Cl
Solvent: CCO
Solvent: ClCCl
Product: N[C@H]1CCN(c2ccc(N3C[C@H](CN(C(=O)OCC(Cl)(Cl)Cl)c4ccon4)OC3=O)cc2F)C1
Temperature: 25 °C
Reaction time: 5 h
Yield: 110.8 %

Procedure:
3-(4-(3(S)-(t-Butoxycarbonyl)aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one (1.03 g, 1.62 mM) was dissolved in dichloromethane (5 ml) under nitrogen and treated with a solution of hydrogen chloride in ethanol (3.8 M, 25 ml). After stirring 5 hours at ambient temperature, solvent was removed, and the residue evaporated repeatedly with portions of dichloromethane to give the hydrochloride salt of the desired product as a white foam (962 mg ). NMR (DMSO-d6) δ: 2.02 (hextet, 1H); 2.25 (hextet, 1H); 3.26 (dd, 1H); 3.42 (m overlapped by solvent, ˜1H); 3.53 (m, 2H); 3.84 (dd overlapping m, 2H); 4.15 (m, 2H); 4.35 (dd, 1H); 4.97 (d, 1H); 5.02 (m, 1H); 5.08 (d, 1H); 6.77 (t, 1H); 6.88 (d, 1H); 7.12 (dd, 1H); 7.39 (dd, 1H); 8.48 (br, 3H); 8.91 (d, 1H). (+1 proton for HCl salt). MS (ESP): 536 (MH+) for C20H21Cl3FN5O5
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][CH:14]([C:16]2[NH:20][C:19]3[CH:21]=[CH:22][C:23]([Cl:25])=[CH:24][C:18]=3[N:17]=2)[CH3:15])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].[NH2:26][CH2:27][CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]1.C(N(C(C)C)CC)(C)C.ClCl>CS(C)=O>[NH2:26][CH2:27][CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][N:31]([C:4]([C:3]2[CH:7]=[CH:8][C:9]([C:11]([NH:13][CH:14]([C:16]3[NH:20][C:19]4[CH:21]=[CH:22][C:23]([Cl:25])=[CH:24][C:18]=4[N:17]=3)[CH3:15])=[O:12])=[CH:10][C:2]=2[Cl:1])=[O:5])[CH2:30]1
Reactant: NCCC1CCCNC1
Reactant: CC(NC(=O)c1ccc(C(=O)O)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1
Agent: ClCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(NC(=O)c1ccc(C(=O)N2CCCC(CCN)C2)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 1d from rac.-2-chloro-4-{N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]aminocarbonyl}benzoic acid, rac.-3-(2-aminoethyl)piperidine, PFTU, and diisopropylethylamine in DMSO at ambient temperature. HPLC-MS results: retention time: 3.88 minutes; C24H27Cl2N5O2 (488.42); mass spectrum: (M−H)−=487/489/491 (chlorine isotope).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25]2[CH:26]=[C:27]3[C:36](=[CH:37][CH:38]=2)[C:35](C(O)=O)=[CH:34][C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]3=2)=[C:17]2[C:12]=1[CH:13]=[CH:14][CH:15]=[CH:16]2.N#N.CO.O>N1C2C(=CC=CC=2)C=CC=1.[Cr]([O-])([O-])=O.[Cu+2]>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:18]([C:25]2[CH:26]=[C:27]3[C:36](=[CH:37][CH:38]=2)[CH:35]=[CH:34][C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]3=2)=[C:19]2[C:24]=1[CH:23]=[CH:22][CH:21]=[CH:20]2
Reactant: O=C(O)c1cc2ccccc2c2cc(-c3c4ccccc4c(-c4ccc5ccccc5c4)c4ccccc34)ccc12
Agent: O=[Cr]([O-])[O-]
Agent: [Cu+2]
Agent: N#N
Solvent: CO
Solvent: O
Solvent: c1ccc2ncccc2c1
Product: c1ccc2cc(-c3c4ccccc4c(-c4ccc5ccc6ccccc6c5c4)c4ccccc34)ccc2c1

Procedure:
49 g (94 mmol) of 6-(10-naphth-2-ylanthracen-9-yl)phenanthrene-9-carboxylic acid are suspended in 250 ml of quinoline, the suspension is saturated with N2, 11.8 g (38 mmol) of copper chromite are added, and the mixture is heated at the boil for 8 h. The mixture is subsequently poured into 1 l of MeOH/water, and the black solid is filtered off with suction, washed with MeOH and subjected to Soxhlet extraction with CHCl3. Removal of the solvent leaves a greyish solid, which is recrystallised four times from chlorobenzene and sublimed twice in vacuo (p=1×10−5 mbar, T=360° C.). The yield is 32 g (71%) with a purity>99.9%.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][C:11](=[O:15])[NH:12][C:13]=2[CH3:14])=[CH:4][CH:3]=1.Cl[CH2:17][C:18](=[O:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O>[CH2:17]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:9][CH2:10][C:11](=[O:15])[NH:12][C:13]=2[CH3:14])=[CH:6][CH:7]=1)[C:18]([CH3:19])=[O:20]
Reactant: CC(=O)CCl
Reactant: CC1=C(c2ccc(O)cc2)CCC(=O)N1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(=O)COc1ccc(C2=C(C)NC(=O)CC2)cc1

Procedure:
A mixture of 3,4-dihydro-5-(4-hydroxyphenyl)-6-methyl-2(1H)-pyridinone (0.94 g), chloroacetone (0.43 g) and potassium carbonate (0.64 g), with a catalytic amount of potassium iodide, was stirred and heated under reflux in acetone (80 ml) for 16 hr. The solvent was evaporated and the residue partitioned between water and ethyl acetate. The organic layer was dried (MgSO4) and evaporated to give 3,4-dihydro-5-(4-acetonyloxyphenyl)-6-methyl-2(1H)-pyridinone as a solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[NH2:12][CH:13]1[CH2:20][C:16]2([CH2:19][O:18][CH2:17]2)[N:15]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:14]1.CCN(CC)CC>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:12][CH:13]2[CH2:20][C:16]3([CH2:17][O:18][CH2:19]3)[N:15]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:14]2)=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1
Reactant: O=[N+]([O-])c1cc(Cl)ccc1F
Reactant: CC(C)(C)OC(=O)N1CC(N)CC12COC2
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(Nc2ccc(Cl)cc2[N+](=O)[O-])CC12COC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.1 %

Procedure:
A mixture of 4-chloro-1-fluoro-2-nitrobenzene (264 mg, 1.50 mmol), tert-butyl 7-amino-2-oxa-5-azaspiro[3.4]octane-5-carboxylate (343 mg, 1.50 mmol) and NEt3 (0.44 mL, 3.12 mmol) in 10 mL of tetrahydrofuran was stirred at room temperature overnight and then heated under reflux for 5 hours. The resulting mixture was concentrated in vacuo and the residue was purified by flash column (eluting with 0-5% MeOH in DCM) to afford tert-butyl 7-[(4-chloro-2-nitrophenyl)amino]-2-oxa-5-azaspiro[3.4]octane-5-carboxylate (438 mg, yield: 76.1%) as an orange solid.