Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH:2]1[CH2:5][N:4]([CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][C:8]([O:10][CH3:11])=[O:9])[C:3]1=[O:18].C[Si](C([Si](C)(C)C)C(N)=O)(C)C.ClC(Cl)C([O:35][N:36]=[C:37]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:38](O)=[O:39])=O.P(Cl)(Cl)(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[OH:35][N:36]=[C:37]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:38]([NH:1][CH:2]1[CH2:5][N:4]([CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][C:8]([O:10][CH3:11])=[O:9])[C:3]1=[O:18])=[O:39]
Reactant: COC(=O)CC(c1ccccc1)N1CC(N)C1=O
Reactant: O=C(O)C(=NOC(=O)C(Cl)Cl)c1ccccc1
Agent: C[Si](C)(C)C(C(N)=O)[Si](C)(C)C
Agent: ClP(Cl)(Cl)(Cl)Cl
Agent: O=C([O-])O
Solvent: ClCCl
Product: COC(=O)CC(c1ccccc1)N1CC(NC(=O)C(=NO)c2ccccc2)C1=O
Reaction time: 0.25 h
Yield: 35.7 %

Procedure:
3-Amino-1-(2-methoxycarbonyl-1-phenylethyl)-2-azetidinone (1.3 g.) was added to methylene chloride (30 ml.), and then bis(trimethylsilyl)acetamide (3.05 g.) was added thereto. To the solution, there was dropwise added methylene chloride (30 ml.) solution containing 2-(2,2-dichloroacetoxyimino)-2-phenylacetic acid (1.9 g.) and phosphorus pentachloride (1.7 g.) at -40° to -35° C. in the course of 5 minutes. The mixture was stirred at the same temperature for 15 minutes and additionally stirred at 5° C. for 15 minutes. An aqueous sodium bicarbonate was added to the reaction mixture and the mixture was stirred at ambient temperature for 5 minutes. The methylene chloride layer was separated from the mixture, washed with dilute hydrochloric acid, an aqueous sodium bicarbonate and water in turn, and then dried over magnesium sulfate. The solvent was removed by distillation under reduce pressure to give a residue, which was subjected to column chromatography on silica gel (100 g.). Elution was carried out with chloroform and the fractions containing a desired compound were collected. The solvent was distilled off from the eluate under reduced pressure to give crystals of 3-(2-hydroxyimino-2-phenylacetamido)-1-(2-methoxycarbonyl-1-phenylethyl)-2-azetidinone (0.74 g.).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:2]=1.[C:14]([NH:21][CH2:22][C:23](O)=[O:24])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]>>[C:17]([O:16][C:14](=[O:15])[NH:21][CH2:22][C:23](=[O:24])[N:11]1[CH2:12][CH2:13][N:8]([CH2:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:9][CH2:10]1)([CH3:20])([CH3:18])[CH3:19]
Reactant: c1cncc(CN2CCNCC2)c1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Product: CC(C)(C)OC(=O)NCC(=O)N1CCN(Cc2cccnc2)CC1

Procedure:
The title compound is synthesized by condensation of 1-Pyridin-3-ylmethyl-piperazine and N-Boc-glycine analogously to the preparation of Example 2 as a colorless solid; ES-MS: M+H=335.3; HPLC: AtRet=3.93 min.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7](Br)[N:6]=1)=[O:4].C(Cl)Cl.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C([O-])([O-])=O.[Cs+].[Cs+].[OH-].[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:11][C:10]1[C:5]([C:3]([OH:2])=[O:4])=[N:6][C:7]([C:24]2[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=2)=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=1
Reactant: COC(=O)c1nc(Br)c(C(F)(F)F)cc1N
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Solvent: ClCCl
Product: Cn1cc(-c2nc(C(=O)O)c(N)cc2C(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (500 mg, 1.672 mmol), PdCl2(dppf).CH2Cl2 adduct (205 mg, 0.251 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (383 mg, 1.839 mmol) and Cs2CO3 (6.69 ml, 6.69 mmol) in THF (12 ml) under N2, was heated using microwave radiation at 150° C. for 10 minutes. 2M NaOH (5 ml) was added and the mixture was stirred at RT overnight. The mixture was filtered through Celite® (filter material) and the organic solvent was removed. The resulting aqueous layer was washed with EtOAc and acidified to pH1. The product was extracted with DCM and concentrated in vacuo to afford the title compound;
Reaction SMILES: [CH3:1][C@@:2]12[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[C@H:14]1[C@@H:5]([C:6]3[CH:7]=[CH:8][C:9]([OH:20])=[CH:10][C:11]=3[CH2:12][CH2:13]1)[CH2:4][CH2:3]2.N1C=CN=C1.[C:26]([Si:30]([CH3:33])([CH3:32])Cl)([CH3:29])([CH3:28])[CH3:27]>CN(C=O)C>[Si:30]([O:20][C:9]1[CH:8]=[CH:7][C:6]2[C@@H:5]3[C@H:14]([C@H:15]4[C@@:2]([CH2:3][CH2:4]3)([CH3:1])[C:18](=[O:19])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]=2[CH:10]=1)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:33])[CH3:32]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CCC2=O
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reaction time: 18 h
Yield: 98.8 %

Procedure:
To a solution of estrone (18, 8.10 g, 30.0 mmol) in DMF (25 mL) were added imidazole (3.07 g, 45 mmol) and tert-butyldimethylchlorosilane (5.42 g, 36 mmol) at room temperature. The reaction mixture was stirred for 18 h and then quenched with H2O (100 mL). The precipitate was collected by filtration and washed with H2O to afford 11.4 g of 50 (99% yield), m.p. 171°-172° C.
Reaction SMILES: C([O-])(=O)C.[NH4+].[CH2:6]([N:13]1[CH2:18][CH2:17][C:16](=O)[C:15]([CH2:21][CH3:22])([CH3:20])[CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C([BH3-])#[N:24].[Na+]>CO>[NH2:24][CH:16]1[CH2:17][CH2:18][N:13]([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:14][C:15]1([CH2:21][CH3:22])[CH3:20]
Reactant: [BH3-]C#N
Reactant: CCC1(C)CN(Cc2ccccc2)CCC1=O
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: CCC1(C)CN(Cc2ccccc2)CCC1N
Temperature: 0 °C
Reaction time: 3 h

Procedure:
Ammonium acetate (2.5 g, 32.46 mmol) was added to the stirred solution of 1-benzyl-3-ethyl-3-methyl-4-piperidinone (0.9 g, 3.9 mmol) in methanol (20 ml) and stirring was continued for 3 hr at ambient temperature. The resulting mixture was cooled at 0° C. and sodium cyanoborohydride (0.2 g, 3.1 mmol) was added to it. Cooling was removed after 10 min. and resulting mixture was stirred for 6 hr at ambient temperature. The reaction mixture was concentrated to dryness, triturated with water, acidified with conc. HCl (pH 3˜4) and extracted with ethyl acetate to remove impurities. The aqueous layer was basified with 1 M sodium hydroxide solution (pH10) and extracted with ethyl acetate. Ethyl acetate extract was dried (Na2SO4) and concentrated to dryness to furnish 4-amino-1-benzyl-3-ethyl-3-methylpiperidine. Yield 0.6 g (66%), C15H24N2, m/z 233 (M+1).
Reaction SMILES: [Br:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.OS(O)(=O)=O.[CH3:16]O>C(=O)(O)[O-].[Na+]>[Br:1][C:2]1[C:3]([C:8]([O:10][CH3:16])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1ncccc1Br
Reactant: CO
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: COC(=O)c1ncccc1Br

Procedure:
To a solution of 3-bromopyridine-2-carboxylic acid (CAS number 30683-23-9; 2.0 g, 9.90 mmol) in methanol (15 ml) was added concentrated H2SO4 (3 ml) and the reaction mixture was refluxed for 2 hours. The reaction was diluted with a saturated solution of sodium bicarbonate and extracted with ethyl acetate (3×75 ml). The organics were washed with water (50 ml), brine (20 ml), dried over sodium sulfate and concentrated in vacuo to afford the title compound.
Reaction SMILES: [CH:1]1([C:10]([O:12][CH3:13])=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O1CCCC1>[CH2:24]([C:1]1([C:10]([O:12][CH3:13])=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)C1CCc2ccccc21
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)C1(Cc2ccccc2)CCc2ccccc21
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 78.9 %

Procedure:
To a −78° C. tetrahydrofuran solution containing methyl indane-1-carboxylate (2.10 g, 11.9 mmol) from Step A, was added a 1M tetrahydrofuran solution of NaHMDS (23.8 mL, 23.8 mmol). The mixture was stirred at −78° C. for 30 minutes. Benzyl bromide (1.49 mL, 12.5 mmol) was added and the reaction was warmed to 0° C. and stirred for 90 minutes. The reaction was quenched with aqueous sodium bicarbonate and then extracted into EtOAc (3×50 mL) and the combined organic washings were dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc) to afford of methyl 1-benzylindane-1-carboxylate (2.5 g, 79%) as a partially pure oil that was taken to the next step.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:6][CH2:5]1.[C:23]12[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=1)[NH:28]C(=O)[O:26][C:24]2=O.C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1.CN(C=O)C>[NH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:23]=1[C:24]([N:2]([CH3:1])[CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:6][CH2:5]1)=[O:26]
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Reactant: CNCC1CCN(C(c2ccccc2)c2ccccc2)CC1
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(CC1CCN(C(c2ccccc2)c2ccccc2)CC1)C(=O)c1ccccc1N
Yield: 65.9 %

Procedure:
Step 3): A solution of 4-(N-methylamino)methyl-1-diphenylmethylpiperidine (1.8 g, 6.0 mmol), isatoic anhydride (0.9 g, 5.5 mmol) and 4-dimethylaminopyridine (0.74 g) in DMF (25 ml) was stirred at room temperature for 2 hours. The reaction mixture was poured into 1% NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate and hexane) to give 2-amino-N-methyl-N-[(1-diphenylmethylpiperidin-4-yl)methyl]benzamide (1.5 g, 67%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-])=O)=[CH:4][CH:3]=1.[BH4-].[Na+].C(=O)([O-])[O-].[K+].[K+]>O.CCOC(C)=O.C(O)(C)(C)C>[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([NH2:9])=[CH:4][CH:3]=1
Reactant: Nc1nc(Cl)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [BH4-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Solvent: O
Product: Nc1ccc(Cl)nc1N
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a mixture of ethyl acetate (450 mL) and tert-butanol (50 mL), 6-chloro-3-nitropyridin-2-amine (CAS 27048-04-0) (15 g, 86.42 mmol), stannous chloride dehydrate (CAS 10025-69-1) (97.5 g, 432.1 mmol) were added. The resulting mixture was stirred at 60° C. for 1 hour. Sodiumborohydride (1.63 g, 43.21 mmol) was added and the mixture was stirred further at 60° C. for another 3 h. The mixture was cooled and stripped from the EtOAc on the rotavapor. The resulting residue was diluted with water (350 mL) and neutralized to pH=9-10 by addition of an aqueous solution of potassium carbonate. The resulting mixture was extracted with EtOAc (3×250 mL), dried over Na2SO4 and evaporated. The residue was stirred for 72 hours in a mixture of EtOAc/heptane 1/1. The precipitate was filtered and dried in vacuum for 2 hours. The intermediate 1-1 was collected as a greenish powder (9.32 g, 75%). m/z=144 (M+H)+.
Reaction SMILES: [CH2:1]([C:3]1([OH:8])[CH2:7][CH2:6][CH2:5][CH2:4]1)[CH3:2].CN1CCCC1=O.N12CCCN=C1CCCCC2.[Br:27][CH2:28][C:29](Br)=[O:30]>C(OCC)(=O)C.O>[Br:27][CH2:28][C:29]([O:8][C:3]1([CH2:1][CH3:2])[CH2:7][CH2:6][CH2:5][CH2:4]1)=[O:30]
Reactant: CCC1(O)CCCC1
Reactant: O=C(Br)CBr
Solvent: O
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCOC(C)=O
Product: CCC1(OC(=O)CBr)CCCC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 88.2 %

Procedure:
Subsequently, a mixed solution containing 14.00 g of 1-ethylcyclopentanol, 220 mL of N-methylpyrrolidone (NMP) and 28.00 g of 1,8-diazabicylco[5,4,0]undec-7-ene (DBU) was cooled in an ice bath, and 61.87 g of bromoacetyl bromide was added dropwise. The mixture was stirred at room temperature for 5 hours, and the reaction solution was cooled in an ice bath. The reaction was then stopped by adding dropwise distilled water, and the reaction solution was diluted with 800 mL of ethyl acetate and washed with 500 mL of distilled water four times. The organic layer was concentrated and purified by column chromatography to obtain 25.43 g of (1-ethyl)cyclopentyl bromoacetate. Also, tert-butyl bromoacetate was obtained in the same manner as above except for changing 1-ethylcyclopentanol to tert-butanol.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH:10]2[S:15][CH2:14][CH2:13][CH2:12][S:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])(CC)C.Br[CH2:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O1CCCC1>[C:1]1([CH2:7][CH2:8][CH2:9][C:10]2([CH2:22][CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[S:11][CH2:12][CH2:13][CH2:14][S:15]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(CCCC2SCCCS2)cc1
Reactant: BrCCCc1ccccc1
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Product: c1ccc(CCCC2(CCCc3ccccc3)SCCCS2)cc1
Temperature: -25 °C
Reaction time: 0.33 h

Procedure:
A solution of 1.0 g (4.2 mmol) of 2-(3-phenylpropyl)-1,3-dithiane in 25 ml of dry tetrahydrofuran was cooled to -78° C., and treated with 3.23 ml (4.2 mmol) of secbutyllithium. The resulting solution was stirred at -25° C. for 20 min, recooled to -78° C., and treated with 0.64 ml (4.2 mmol) of 1-bromo-3-phenylpropane. After being stirred at -78° C. for 15 min, the solution was allowed to stir overnight at ambient temperature. The solution was partitioned between ether and aqueous ammonium chloride, and the organic layer was washed sequentially with water, 1 M sodium bisulfite, and saturated brine, dried over MgSO4, and concentrated in vacuo to give the desired compound. 1H NMR (CDCl3) δ 65-1.9 (m, 9H), 2.18 (m, 1H), 2.55-2.75 (m, 6H), 2.78 (t, J=8 Hz, 1H), 3.40 (t, J=6 Hz, 1H), 7.1-7.35 (m, 10H). Mass spectrum (M+H)+ =357.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:30])[CH2:5][CH2:6][C:7]1[N:8]([C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=2[CH3:29])[C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)[CH3:2].[N-:31]=[N+:32]=[N-:33].[Na+].[Cl-].[NH4+].Cl>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:30])[CH2:5][CH2:6][C:7]1[N:8]([C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=2[CH3:29])[C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:31]=[N:32][NH:33][N:19]=3)=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)[CH3:2]
Reactant: CCOC(=O)CCc1ccc(-c2ccc(C#N)cc2)n1-c1ccc(C(N)=O)cc1C
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1ccc(-c2ccc(-c3nn[nH]n3)cc2)n1-c1ccc(C(N)=O)cc1C
Temperature: 100 °C
Reaction time: 16 h
Yield: 48.8 %

Procedure:
To 25 mL vial which contained 3-[1-(4-carbamoyl-2-methyl-phenyl)-5-(4-cyano-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (26A) (50 mg, 0.12 mmoL) in DMF (4 mL) was added sodium azide (40 mg, 0.6 mmoL) and ammonium chloride (40 mg, 0.8 mmoL) at rt. The vial was sealed and the reaction mixture was heated to 100° C. and stirred for 16 h. The reaction mixture was cooled to rt and poured into 30 mL ice-water solution. The aqueous solution was acidified with aq HCl (1 N) to pH=1-2, the solid which formed was filtered out, washed with water (25 mL), dried over air to afford the desired compound 3-{1-(4-Carbamoyl-2-methyl-phenyl)-5-[4-(2H-tetrazol-5-yl)-phenyl]-1H-pyrrol-2-yl}-propionic acid ethyl ester (26B) (27 mg, 50% yield).
Reaction SMILES: [NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:2][C:3]([NH:5][C@H:6]([C:8]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12](O)=[O:13])=[O:9])[CH3:7])=[O:4].[N+:28](C1C=CC=CC=1NCC(O)=O)([O-])=O.OS([O-])=O.[Na+].[OH-].[Na+]>CO>[NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:2][C:3]([NH:5][C@H:6]([C:8]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12]([NH2:28])=[O:13])=[O:9])[CH3:7])=[O:4]
Reactant: O=C(O)CNc1ccccc1[N+](=O)[O-]
Reactant: C[C@H](NC(=O)CNC(=O)OCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
Agent: O=S([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C[C@H](NC(=O)CNC(=O)OCc1ccccc1)C(=O)N1CCC[C@H]1C(N)=O

Procedure:
Z-Gly-Ala-Pro-2-nitrophenylglycine (SEQ ID NO:13) amide (0.025 mmol) in MeOH (12.5 ml) was added to 80 mM NaHSO3 (12.5 ml) and pH was adjsuted to 9.5 with 5N NaOH. The reaction mixture was purged with N2 for 15 min and subsequently photolyzed under nitrogen cover at a distance of 20 cm from the SP 200 lamp through Pyrex. The photolysis was followed by extraction of samples at 0, 30, 60 and 120 min. Each sample was analyzed using HPLC system-5 and the results compared with those from the 0 min sample as well as with the results from the CPD-Y hydrolysis and the transpeptidation mixture. Purification and identification were performed as previously described.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[CH:5]=[C:4]([CH3:16])[N:3]=1.[Cl:17][C:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[CH:20][N:19]=1>>[Cl:17][C:18]1[CH:23]=[C:22]([C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=3)[CH:5]=[C:4]([CH3:16])[N:3]=2)[CH:21]=[CH:20][N:19]=1
Reactant: Cc1cc(-c2ccc(Cl)c(Cl)c2)nc(Cl)n1
Reactant: OB(O)c1ccnc(Cl)c1
Product: Cc1cc(-c2ccc(Cl)c(Cl)c2)nc(-c2ccnc(Cl)c2)n1

Procedure:
The title compound was prepared from 2-chloro-4-(3,4-dichloro-phenyl)-6-methyl-pyrimidine (example A.41) (0.4 g, 1.46 mmol) and commercially available 2-chloro-pyridine-4-boronic acid (0.3 g, 1.9 mmol) according to the general procedure IVb. Obtained as a light brown solid (0.15 g, 29%). MS (ISP) 350.2 [(M+H)+]; mp 155° C.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[CH:8]=[CH:7][C:6]3[O:12][CH2:13][CH2:14][NH:15][C:5]=3[C:4]=2[N:3]=1.CCN(CC)CC.[C:23](Cl)(=[O:25])[CH3:24]>C(Cl)Cl>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[CH:8]=[CH:7][C:6]3[O:12][CH2:13][CH2:14][N:15]([C:23](=[O:25])[CH3:24])[C:5]=3[C:4]=2[N:3]=1
Reactant: CC(=O)Cl
Reactant: Cc1ccc2ccc3c(c2n1)NCCO3
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N1CCOc2ccc3ccc(C)nc3c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.2 %

Procedure:
To a solution of 9-methyl-2,3-dihydro-1H-[1,4]oxazino[2,3-h]quinoline (200 mg, 1.0 mmol) and NEt3 (304 mg, 3.0 mmol) in DCM (5 mL) was added acetyl chloride (157 mg, 2.0 mmol) at room temperature. After stirring at room temperature for 1 h, the mixture was washed with water (10 mL×3). The organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to give the title compound (170 mg) as a yellow solid. MS (ESI): m/z 243 [M+H]+.
Reaction SMILES: [N+]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-])=O)[CH:5]=1)([O-])=O.[C:13](Cl)(=[O:17])[C:14]([CH3:16])=[CH2:15]>O1CCOCC1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:13]([C:9]1[CH:8]=[CH:7][C:6]([NH:10][C:13](=[O:17])[C:14]([CH3:16])=[CH2:15])=[CH:5][CH:4]=1)(=[O:17])[CH2:14][CH3:15]
Reactant: O=[N+]([O-])c1cccc([N+](=O)[O-])c1
Reactant: C=C(C)C(=O)Cl
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: C1COCCO1
Product: C=C(C)C(=O)Nc1ccc(C(=O)CC)cc1
Reaction time: 0.5 h

Procedure:
A small amount of m-dinitrobenzene and copper(II) acetate were added whereupon a solution of 124.5 g of methacrylyl chloride (1 mole) in 125 ml of dioxan were added dropwise. The temperature was kept at 20°-25° C. Stirring was then continued for 30 min whilst slowly heating until reflux. Light yellow needles were sucked off, washed with ether, and dried under vacuum.
Reaction SMILES: [CH:1]1([NH:6][C:7](=[O:20])[NH:8][CH:9]([C:11]2[S:15][C:14]([C:16]([O:18]C)=[O:17])=[CH:13][CH:12]=2)[CH3:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].Cl>O1CCCC1.CO>[CH:1]1([NH:6][C:7](=[O:20])[NH:8][CH:9]([C:11]2[S:15][C:14]([C:16]([OH:18])=[O:17])=[CH:13][CH:12]=2)[CH3:10])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COC(=O)c1ccc(C(C)NC(=O)NC2CCCC2)s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(NC(=O)NC1CCCC1)c1ccc(C(=O)O)s1
Temperature: 40 °C

Procedure:
To a solution of methyl 5-(1-(3-cyclopentylureido)ethyl)thiophene-2-carboxylate obtained from step 1 in tetrahydrofuran (1 mL) and methanol (0.5 mL) was added 1.0 M aqueous NaOH (0.5 mL) and the reaction solution was heated to 40° C. for 8 hours. The reaction was neutralized with the addition of 1M aqueous HCl (0.5 mL) and the solution was evaporated to dryness to afford 5-(1-(3-cyclopentylureido)ethyl)thiophene-2-carboxylic acid. LC-MS: (FA) ES+ 283.
Reaction SMILES: [CH:1]1(/[CH:6]=[C:7](/B2OC(C)(C)C(C)(C)O2)\[CH2:8][OH:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:19][N:20]([CH:22]=[N:23][S:24]([C:27]1[S:28][C:29](Br)=[CH:30][CH:31]=1)(=[O:26])=[O:25])[CH3:21].[F-].[Cs+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:21][N:20]([CH:22]=[N:23][S:24]([C:27]1[S:28][C:29](/[C:7](/[CH2:8][OH:9])=[CH:6]\[CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[CH:30][CH:31]=1)(=[O:26])=[O:25])[CH3:19]
Reactant: CN(C)C=NS(=O)(=O)c1ccc(Br)s1
Reactant: CC1(C)OB(/C(=C/C2CCCC2)CO)OC1(C)C
Agent: [Pd]
Agent: [Cs+]
Agent: [F-]
Product: CN(C)C=NS(=O)(=O)c1ccc(/C(=C\C2CCCC2)CO)s1

Procedure:
According to method 20b was used (Z)-3-cyclopentyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-prop-2-en-1-ol (678 mg, 2.69 mmol), 5-bromo-thiophene-2-sulfonic acid dimethylaminomethyleneamide (799 mg, 2.69 mmol), caesium fluoride ( 817 mg, 5.38 mmol) and tetrakis-(triphenylphosphin)-palladium(0) (155 mg, 0.135 mmol) to give 538 mg purified product. MS (m/e): 343.0 (M+H).
Reaction SMILES: C1(C)C=CC(S(O[CH2:11][Si@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)(=O)=O)=CC=1.[CH2:26]([Si@H:31]1[CH2:36][CH2:35][C@H:34]([CH2:37][Mg]Br)[CH2:33][CH2:32]1)[CH2:27][CH2:28][CH2:29][CH3:30].C1(C)C=CC(S(OC[C@H]2CC[C@H](C3C=CC(F)=CC=3)CC2)(=O)=O)=CC=1.C([Si@H]1CC[C@H](C[Mg]Br)CC1)CC>>[F:24][C:21]1[CH:20]=[CH:19][C:18]([C@H:15]2[CH2:14][CH2:13][Si@H:12]([CH2:11][CH2:37][C@H:34]3[CH2:35][CH2:36][Si@H:31]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:32][CH2:33]3)[CH2:17][CH2:16]2)=[CH:23][CH:22]=1
Reactant: Cc1ccc(S(=O)(=O)OC[Si@H]2CC[C@H](c3ccc(F)cc3)CC2)cc1
Reactant: CCCCC[Si@H]1CC[C@H](C[Mg]Br)CC1
Agent: CCC[Si@H]1CC[C@H](C[Mg]Br)CC1
Agent: Cc1ccc(S(=O)(=O)OC[C@H]2CC[C@H](c3ccc(F)cc3)CC2)cc1
Product: CCCCC[Si@H]1CC[C@H](CC[Si@H]2CC[C@H](c3ccc(F)cc3)CC2)CC1

Procedure:
The preparation was conducted in the same manner as in Example 22, except that 18.9 g (50 mmol) of (trans-4-(p-fluorophenyl)-1-silacyclohexyl)methyl p-toluenesulfonate and (trans-4-n-pentyl-4-silacyclohexyl)methylmagnesium bromide were used instead of 18.1 g (50 mmol) of (trans-4-(p-fluorophenyl) cyclohexyl)methyl p-toluenesulfonate and (trans-4-n-propyl4-silacyclohexyl)methylmagnesium bromide.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:22][CH3:23])=[C:10]([N:13]3[CH2:18][C@H:17]([CH3:19])[N:16]([CH3:20])[C@H:15]([CH3:21])[CH2:14]3)[CH:11]=2)[CH2:6][CH2:5]1)(=O)C.C([O-])([O-])=O.[K+].[K+]>Cl>[CH3:23][O:22][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][C:10]=1[N:13]1[CH2:14][C@H:15]([CH3:21])[N:16]([CH3:20])[C@H:17]([CH3:19])[CH2:18]1)[NH:4][CH2:5][CH2:6]2
Reactant: COc1cc2c(cc1N1C[C@@H](C)N(C)[C@@H](C)C1)N(C(C)=O)CC2
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1cc2c(cc1N1C[C@@H](C)N(C)[C@@H](C)C1)NCC2
Yield: 101.7 %

Procedure:
A stirred solution of D2 (1.6 g, 5 mmole) in 2M HCl acid (50 ml) was heated under reflux for 2 h, then the solution was allowed to cool, basified with K2CO3 and extracted with DCM. The extract was dried (Na2SO4) and concentrated under vacuum to afford the title compound as a pale orange solid (1.4 g, 100%).