Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4][CH2:5][CH2:6][C:7]1[N:8]=[CH:9][NH:10][CH:11]=1.[N+](C=C(SC)SC)([O-])=O.[N+:21]([CH:24]=[C:25](SC)[NH:26][CH2:27]CSCCC1N=CNC=1)([O-:23])=[O:22].CN>>[N+:21]([CH:24]=[C:25]([NH:26][CH3:27])[NH:1][CH2:2][CH2:3][S:4][CH2:5][CH2:6][C:7]1[N:8]=[CH:9][NH:10][CH:11]=1)([O-:23])=[O:22]
Reactant: NCCSCCc1c[nH]cn1
Reactant: CSC(=C[N+](=O)[O-])NCCSCCc1c[nH]cn1
Agent: CN
Agent: CSC(=C[N+](=O)[O-])SC
Product: CNC(=C[N+](=O)[O-])NCCSCCc1c[nH]cn1

Procedure:
4-[2-(2-Aminoethylthio)ethyl]imidazole (from the dihydrobromide (4.0 g)) is reacted with 1-nitro-2,2-bis-methylthioethylene (2.0 g) by the procedure of Example 8(i) and the resultant 1-nitro-2-methylthio-2-[2-(2-(4-imidazolyl)-ethylthio)ethylamino]ethylene is treated with methylamine according to the procedure of Example 8(ii) to yield the title compound.
Reaction SMILES: [CH3:1][N:2]([CH3:37])[C:3](=[O:36])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14](=O)[CH2:15][C:16](=O)/[CH:17]=[CH:18]/[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=2)=[CH:8][CH:7]=1.Cl.Cl.[NH2:40][NH2:41].CO.C([O-])(O)=O.[Na+]>CCOC(C)=O>[CH3:1][N:2]([CH3:37])[C:3](=[O:36])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]2[NH:41][N:40]=[C:16](/[CH:17]=[CH:18]/[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[CH:21][CH:20]=3)[CH:15]=2)=[CH:8][CH:7]=1
Reactant: CN(C)C(=O)COc1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(OCCN3CCOCC3)cc2)cc1
Reactant: NN
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CN(C)C(=O)COc1ccc(/C=C/c2cc(/C=C/c3ccc(OCCN4CCOCC4)cc3)n[nH]2)cc1
Temperature: 40 °C
Reaction time: 8 h
Yield: 65.7 %

Procedure:
To 2.70 g of N,N-dimethyl-2-[4-[(1E,6E)-7-[4-(2-morpholinoethoxy)phenyl]-3,5-dioxo-hepta-1,6-dienyl]phenoxy]acetamide were added 2.80 g of hydrazine dihydrochloride and 54 mL of methanol, and the mixture was stirred at 40° C. overnight. The reaction mixture was allowed to stand to cool, and poured into 200 mL of a saturated aqueous NaHCO3 solution. To this, 600 mL of AcOEt was added, and the organic layer was separated. The obtained organic layer was washed with saturated brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography (CHCl3/methanol system) to give 1.76 g of the title compound (66% yield).
Reaction SMILES: [F:1][C:2]1[C:7]2[N:8]=[C:9](S)[O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:14])=O>CN(C)C=O>[Cl:14][C:9]1[O:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[C:7]=2[N:8]=1
Reactant: Fc1cccc2oc(S)nc12
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: Fc1cccc2oc(Cl)nc12
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 76.4 %

Procedure:
To a solution of 560 mg (3.31 mmol) 4-fluoro-benzooxazole-2-thiol in 3.6 mL (49.65 mmol) thionyl chloride was added dropwise 60.3 □L N,N-dimethylformamide dry at room temperature. The mixture was stirred at room temperature for 2.5 h. The solvent was removed in vacuo. The crude compound was purified with flash column chromatography on silica eluting with a gradient formed from n-heptane and ethyl acetate to provide 434 mg (76.4%) of the title compound as a white solid. MS(m/e): 171 (M+H+).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH:12]([CH2:23][CH:24]=[CH2:25])[C:13]([NH:15][C@H:16]([C:20]([OH:22])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26](OC(NC(CC=C)C(O)=O)=O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[CH2:26]([O:21][C:20](=[O:22])[C@H:16]([CH:17]([CH3:18])[CH3:19])[NH:15][C:13](=[O:14])[CH:12]([NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:23][CH:24]=[CH2:25])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: C=CCC(NC(=O)OCc1ccccc1)C(=O)O
Reactant: C=CCC(NC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)O)C(C)C
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: C=CCC(NC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)OCc1ccccc1)C(C)C
Reaction time: 19 h

Procedure:
N-(N-Benzyloxycarbonyl-2-Amino-4-Pentenoyl)-L-Valine Benzxyl Ester (4) To a cooled (0-5° C.) solution of 24 mg (0.096 mmol) N-(N-benzyloxycarbonyl-2-amino-4-pentenoic acid (3), 36 mg (0.096 mmol) valine benzyl ester p-toluenesulfonyl salt, and 11 μL (0.096 mmol) N-methylmorpholine in 2 mL CH2Cl2 was added 14 mg (0.101 mmol) HOBt and 21 mg (0.101 mmol) DCC and the mixture was stirred for 19 h. The solution was filtered and the filtrate diluted with 10 mL CH2Cl2 and washed with two 10-mL portions of 0.5 N HCl, with two 10-mL portions of saturated aqueous NaHCO3, and with 10 mL brine. The organic phase was dried (MgSO4) and concentrated. The crude product was applied to a silica gel column (1×15 cm) and elution with 5% MeOH in CH2Cl2 gave pure N-(N-benzyloxycarbonyl-2-amino-4-Pentenoyl)-L-valine benzyl ester (4) as a colorless oil: yield 35 mg (83%); 1H NMR (CDCl3) δ0.80-0.90 (m, 6H); 2.14-2.20 (m, 1H); 2.49-2.56 (m, 2H); 4.20-4.32 (M, 1H); 4.55-4.60 (m, 1H0; 5.07-5.30 (M, 6H); 5.65-5.83 (m, 1H); 6.42-6.49 (m, 1H); 7.30-7.34 (m, 10H); mass spectrum (CI, methane) m/z 439 (M+H)+, 225.
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[N:7]([C:15]([O:17][CH2:18][CH:19]2[CH2:21][CH2:20]2)=[O:16])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2].CC1(C)OB([C:29]2[CH:30]=[N:31][N:32](C(OC(C)(C)C)=O)[CH:33]=2)OC1(C)C.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:29]3[CH:30]=[N:31][NH:32][CH:33]=3)=[CH:11][CH:12]=2)[N:7]([C:15]([O:17][CH2:18][CH:19]2[CH2:21][CH2:20]2)=[O:16])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2]
Reactant: CC(=O)N1c2ccc(Br)cc2N(C(=O)OCC2CC2)C[C@@H]1C
Reactant: CC(C)(C)OC(=O)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(=O)N1c2ccc(-c3cn[nH]c3)cc2N(C(=O)OCC2CC2)C[C@@H]1C
Temperature: 100 °C
Reaction time: 8 h
Yield: 41.5 %

Procedure:
A 100-mL round-bottom flask was purged with nitrogen and charged with cyclopropylmethyl (3S)-4-acetyl-7-bromo-3-methyl-1,2,3,4-tetrahydroquinoxaline-1-carboxylate (1 g, 2.72 mmol), tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-carboxylate (953 mg, 3.24 mmol), sodium carbonate (573 mg, 5.41 mmol), [1,1′bis(diphenylphosphino) ferrocene]dichloropalladium(II) dichloromethane complex (265 mg, 0.326 mmol), 1,4-dioxane (9 mL), and water (3 mL). The resulting mixture was stirred overnight at 100° C. After cooling to room temperature, the reaction mixture was poured into water (20 mL). The aqueous layer was separated and extracted with ethyl acetate (4×40 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1:1, ethyl acetate/petroleum ether) to afford cyclopropylmethyl (3S)-4-acetyl-3-methyl-7-(1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinoxaline-1-carboxylate (400 mg, 41%) of as a yellow solid. MS (ESI, pos. ion) m/z 355 [M+H]+.
Reaction SMILES: [H-].[Na+].C[N:4](C=O)C.[CH2:8]([O:10][C:11]([C:13]1[NH:14][C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:17]=1)=[O:12])[CH3:9].[N+](C1C=C([N+]([O-])=O)C=CC=1ON)([O-])=O>O>[CH2:8]([O:10][C:11]([C:13]1[N:14]([NH2:4])[C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:17]=1)=[O:12])[CH3:9]
Reactant: CN(C)C=O
Reactant: CCOC(=O)c1ccc(C(=O)OCC)[nH]1
Agent: NOc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)c1ccc(C(=O)OCC)n1N
Reaction time: 1 h

Procedure:
NaH (60% in mineral oil, 154.3 mg, 3.86 mmol) was rinsed with hexanes (5 ml), then anhydrous DMF (10 ml) was added, to this suspension 406B (0.68 g, 3.22 mmol) was added portionwise at 0° C., and the mixture was stirred for 1 h from 0° C. to rt. O-(2,4-dinitro-phenyl)-hydroxylamine (705.6 mg, 3.54 mmol) was added in two portions at 0° C., the reaction mixture was stirred at rt overnight. Water (50 ml) was added, the mixture was extracted with EtOAc (3×25 ml), the combined organic layer was washed with water (4×20 ml) and brine (1×20 ml), dried and concentrated. The residue was purified by silica gel flash column chromatography to give 406C (480 mg, 66%) as a yellow solid (25% EtOAc—hexanes).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([N:14]3[CH2:19][CH2:18][N:17]([S:20]([CH2:23][C@H:24]([CH:29]([CH3:31])[CH3:30])[C:25]([NH:27][OH:28])=[O:26])(=[O:22])=[O:21])[CH2:16][CH2:15]3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1.[C:32](C1C=CC(C2C=NC(N3CCN(S(C[C@H](C(C)C)C(O)=O)(=O)=O)CC3)=NC=2)=CC=1)#[N:33]>>[C:32]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([N:14]3[CH2:19][CH2:18][N:17]([S:20]([CH2:23][C@H:24]([CH:29]([CH3:30])[CH3:31])[C:25]([NH:27][OH:28])=[O:26])(=[O:21])=[O:22])[CH2:16][CH2:15]3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1)#[N:33]
Reactant: CC(C)[C@@H](CS(=O)(=O)N1CCN(c2ncc(-c3ccc(F)cc3)cn2)CC1)C(=O)NO
Reactant: CC(C)[C@@H](CS(=O)(=O)N1CCN(c2ncc(-c3ccc(C#N)cc3)cn2)CC1)C(=O)O
Product: CC(C)[C@@H](CS(=O)(=O)N1CCN(c2ncc(-c3ccc(C#N)cc3)cn2)CC1)C(=O)NO
Yield: 53 %

Procedure:
Prepared according to the method for the preparation of 2-(R)-{4-[5-(4-fluorophenyl)pyrimidin-2-yl]piperazine-1-sulfonylmethyl}-N-hydroxy-3-methylbutyramide, from 2-(R)-{4-[5-(4-Cyanophenyl)pyrimidin-2-yl]piperazine-1-sulfonylmethyl}-3-methylbutyric acid (0.070 g), to provide the title compound as a white solid (0.039 g, 53%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C@@H:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][S:25]([N:28]1[CH2:33][CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH2:30][CH2:29]1)(=[O:27])=[O:26]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C@@H:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:31]4[CH2:32][CH2:33][N:28]([S:25]([CH3:24])(=[O:27])=[O:26])[CH2:29][CH:30]=4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC1(C)OB(C2=CCN(S(C)(=O)=O)CC2)OC1(C)C
Reactant: CC(C)(C)OC(=O)N1CCC([C@H]2Cc3cc(Cl)ncc3O2)CC1
Product: CC(C)(C)OC(=O)N1CCC([C@H]2Cc3cc(C4=CCN(S(C)(=O)=O)CC4)ncc3O2)CC1

Procedure:
The title compound is prepared from (R)-4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 1-methanesulfonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2,3,6-tetrahydro-pyridine following a procedure analogous to that described for Intermediate 10. LC (method 3): tR=1.10 min; Mass spectrum (ESI+): m/z=464 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].CN1CCCC1=O.[Cl:23][C:24]1[C:29](F)=[C:28]([C:31]([F:34])([F:33])[F:32])[CH:27]=[CH:26][N:25]=1>O>[Cl:23][C:24]1[C:29]([O:9][C:4]2[CH:3]=[C:2]([Br:1])[CH:7]=[C:6]([Br:8])[CH:5]=2)=[C:28]([C:31]([F:32])([F:33])[F:34])[CH:27]=[CH:26][N:25]=1
Reactant: Fc1c(C(F)(F)F)ccnc1Cl
Reactant: Oc1cc(Br)cc(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN1CCCC1=O
Product: FC(F)(F)c1ccnc(Cl)c1Oc1cc(Br)cc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a round bottom flask charged with 3,5-dibromophenol (1.16 g, 4.61 mmol) and potassium carbonate (1.27 g, 9.22 mmol) was added N-methylpyrrolidinone (10 mL). To this suspension under N2 was added 2-chloro-3-fluoro-4-(trifluoromethyl)pyridine (0.920 g, 4.61 mmol) and the reaction mixture was placed in an oil bath at 120° C. After 30 minutes, the reaction mixture was allowed to cool to room temperature. Water (50 mL) was added and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (3×50 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on a pre-packed silica gel Redi Sep 120 gram column, eluting with 0-75% CH2Cl2 in hexanes to afford the title compound. 1H NMR (CDCl3) δ 8.53 (d, J=5.0 Hz, 1H), 7.62 (d, J=5.0 Hz, 1H), 7.44-7.42 (m, 1H), 6.92-6.88 (m, 2H). LRMS (M+1)=431.5.
Reaction SMILES: CO[C:3]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)=[C:4]([C:7]#[N:8])[C:5]#[N:6].Cl.[CH:19]([NH:22][NH2:23])([CH3:21])[CH3:20].C(N(CC)CC)C>C(O)C>[NH2:6][C:5]1[N:22]([CH:19]([CH3:21])[CH3:20])[N:23]=[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:4]=1[C:7]#[N:8]
Reactant: COC(=C(C#N)C#N)c1cccc([N+](=O)[O-])c1
Reactant: CC(C)NN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC(C)n1nc(-c2cccc([N+](=O)[O-])c2)c(C#N)c1N
Yield: 78.6 %

Procedure:
Compound 25 (5 g, 21.8 mmol), isopropylhydrazine hydrochloride (2.41 g, 21.8 mmol) (purchased from Ryan Scientific) and triethylamine (6.40 mL, 46.0 mmol) were allowed to react in ethanol (145 mL) at room temperature for 1 hr. After concentrating the reaction mixture, it was purified by silica chromatography using a chloroform/methanol solvent system (methanol gradient increased with time from 0-10%). The relevant fractions were concentrated in vacuo to yield a yellow powder (4.65 g, 79% yield): 1H NMR (400 MHz, DMSO) δ 8.59 (s, 1H), 8.24 (m, 2H), 7.78 (t, J=8.2, 1H), 6.82 (br, 2H), 4.53 (hept, J =6.5, 1H), 1.36 (d, J=6.5, 6H). 13C NMR (100 MHz, DMSO) δ 153.04, 148.76, 146.98, 133.97, 132.22, 131.19, 123.80, 120.37, 116.28, 70.74, 48.64, 22.02; [M+H]+ calculated for C13H11N5O2 272.1, found 272.3.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[S:9][CH2:8][CH2:7][N:6]3C(=O)[C:11](=[O:14])[C:12]([CH:13]=1)=[C:5]23.[OH-:16].[Na+].OO.Cl>O>[Br:1][C:2]1[CH:3]=[C:4]2[S:9][CH2:8][CH2:7][NH:6][C:5]2=[C:12]([C:11]([OH:14])=[O:16])[CH:13]=1
Reactant: O=C1C(=O)N2CCSc3cc(Br)cc1c32
Reactant: [OH-]
Agent: Cl
Agent: OO
Agent: [Na+]
Solvent: O
Product: O=C(O)c1cc(Br)cc2c1NCCS2
Reaction time: 0.5 h
Yield: 92.3 %

Procedure:
To a suspension of 8-bromo-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzothiazine-5,6-dione (4.6 g) in water (50 ml) was added 2N sodium hydroxide solution (30 ml) and dissolved. To the solution was added 30% hydrogen peroxide solution (4 ml) at 15° C. After stirring for 30 minutes, the mixture was brought to slightly acidic by the addition of concentrated hydrochloric acid. The resulting crystals were collected by filtration, washed with water and dried to give the title compound (4.1 g, 92.3%) which was recrystallized from ethanol as pale yellow needles, mp 205°-206° C. (decompd.).
Reaction SMILES: [CH2:1]([NH:4][C:5]1[N:10]=[C:9]([NH:11][CH2:12][CH:13]=[CH2:14])[N:8]=[C:7](Cl)[N:6]=1)[CH:2]=[CH2:3].[CH3:16][C:17]1([CH3:28])[CH2:22][CH:21]([CH2:23][CH2:24][NH2:25])[CH2:20][C:19]([CH3:27])([CH3:26])[NH:18]1>C1(C)C(C)=CC=CC=1>[CH2:1]([NH:4][C:5]1[N:10]=[C:9]([NH:11][CH2:12][CH:13]=[CH2:14])[N:8]=[C:7]([NH:25][CH2:24][CH2:23][CH:21]2[CH2:22][C:17]([CH3:28])([CH3:16])[NH:18][C:19]([CH3:27])([CH3:26])[CH2:20]2)[N:6]=1)[CH:2]=[CH2:3]
Reactant: CC1(C)CC(CCN)CC(C)(C)N1
Reactant: C=CCNc1nc(Cl)nc(NCC=C)n1
Solvent: Cc1ccccc1C
Product: C=CCNc1nc(NCC=C)nc(NCCC2CC(C)(C)NC(C)(C)C2)n1

Procedure:
18.05 g (0.08 mole) of 2,4-bis-allylamino-6-chloro-1,3,5-triazine and 14.74 g (0.08 mole) of 2-(2,2,6,6-tetramethylpiperid-4-yl)-ethylamine in 130 ml of xylene are heated at reflux temperature for 4 hours, while stirring. 3.5 g (0.088 mole) of finely powdered sodium hydroxides are then added to the reaction mixture in 4 portions over a period of 4 hours, and the mixture is kept at reflux temperature overnight. The reaction mixture is then freed from the precipitated sodium chloride by filtration while hot, the xylene is completely removed by vacuum distillation, and the residue is recrystallised from n-pentane. The 2,4-bis-allylamino-6-[2-(2,2,6,6-tetramethylpiperid-4-yl)-ethylamino]-1,3,5-triazine thus obtained has a melting point of 74°-75° (stabiliser No. 14).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:35][C:36]1[CH:45]=[CH:44][CH:43]=[C:42]2[C:37]=1[CH2:38][CH2:39][NH:40][CH2:41]2.N1C=CC=CC=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23]([N:40]4[CH2:39][CH2:38][C:37]5[C:42](=[CH:43][CH:44]=[CH:45][C:36]=5[Cl:35])[CH2:41]4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(n2cc(-c3cnc(N)c(B4OC(C)(C)C(C)(C)O4)c3)cn2)CC1
Reactant: Clc1cccc2c1CCNC2
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(n2cc(-c3cnc(N)c(N4CCc5c(Cl)cccc5C4)c3)cn2)CC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A mixture of 4-{4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB4) (245 mg, 0.517 mmol), 5-chloro-1,2,3,4-tetrahydroisoquinoline (175 mg, 1.03 mmol), cupric acetate (94.8 mg, 0.517 mmol), pyridine (84 μL, 1.0 mmol), 4 Å molecular sieves (139 mg, 264 mg/mmol SM), and DCM (9 mL, 100 mmol) was stirred at rt under an atmosphere of air for 3 d. The mixture was diluted with DCM (50 ml), washed with EDTA solution (2%, 3×50 ml), water (3×50 ml) and brine (50 ml), dried over MgSO4, filtered, and concentrated in vacuo to give a dark black oil that was purified by MDPS to give the title compound as a brown solid. 1H NMR (400 MHz, CDCl3): δ=1.48 (s, 9H), 1.88-1.99 (m, 2H), 2.12-2.19 (m, 2H), 2.84-2.98 (m, 2H), 3.04 (t, J=6.0 Hz, 2H), 3.36 (t, J=6.0 Hz, 2H), 4.16 (s, 2H), 4.22-4.36 (m, 3H), 7.02 (d, J=7.6 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.50 (s, 1H), 7.62 (s, 1H), 7.66 (s, 1H), 7.69 (s, 1H). MS(ES+): m/z=508.77/511.16 (52/20) [MH+]. HPLC: tR=3.00 min (ZQ2, polar—5 min).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:13]#[C:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][C:5]([OH:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[N+:19]([O-])([OH:21])=[O:20].O>C(O)(=O)C>[Cl:1][C:2]1[C:3]([C:13]#[C:14][Si:15]([CH3:16])([CH3:18])[CH3:17])=[C:4]([N+:19]([O-:21])=[O:20])[C:5]([OH:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: O=[N+]([O-])O
Reactant: COC(=O)c1cc(Cl)c(C#C[Si](C)(C)C)cc1O
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)c1cc(Cl)c(C#C[Si](C)(C)C)c([N+](=O)[O-])c1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.3 %

Procedure:
A solution of methyl 5-chloro-2-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate (540 g, 1.9 mol) in acetic acid (3.7 L) was heated at 55-59° C. The heating was discontinued and the reaction mixture was flushed with nitrogen and treated with a solution of nitric acid (120 mL, 2.9 mol) in acetic acid (200 mL, 3.6 mol) over 30 minutes. The reaction temperature reached 98.9° C. The resulting solution was stirred for 30 minutes at which time the temperature went from 98.9 to 87.5° C. The reaction was cooled to room temperature and treated with crushed ice (3.5 kg) in one portion. The reaction mixture temperature dropped to −12° C. The reaction mixture was treated with water (3.5 kg) and and stirred at room temperature for 1 hour. The product was filtered, rinsed with water (2 L), and dried on the filter under vacuum overnight to give the desired product (450 g, 72%) as a yellow solid. HPLC 92.9% pure @ 220 nm. LCMS for C13H15ClNO5Si (M+H)+: m/z=328.0; Found: 327.9; 1H NMR (300 MHz, DMSO-d6): δ 11.2 (br s, 1 H), 8.00 (s, 1 H), 3.89 (s, 3 H), 0.23 (s, 9 H).
Reaction SMILES: [CH:1]([N:4]([CH:26]([CH3:28])[CH3:27])[C:5](=[O:25])[CH:6]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)[CH:7]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:8][C:9]([O:11]C)=[O:10])([CH3:3])[CH3:2].O.[OH-].[Na+].Cl>CCO>[CH:26]([N:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:25])[CH:6]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)[CH:7]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:8][C:9]([OH:11])=[O:10])([CH3:27])[CH3:28]
Reactant: COC(=O)CC(c1ccccc1)C(C(=O)N(C(C)C)C(C)C)c1cccnc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C)N(C(=O)C(c1cccnc1)C(CC(=O)O)c1ccccc1)C(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of methyl 5-(diisopropylamino)-5-oxo-3-phenyl-4-pyridin-3-ylpentanoate (Diastereomer 2, 1.095 g, 2.863 mmol) in EtOH (13 mL) was added water (15 mL) followed by 1 N aqueous NaOH (5.725 mL). The reaction mixture was stirred at room temperature. After 24 h, 1N HCl (5.725 mL) was added. The mixture was then extracted with CH2Cl2 (4×). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to give a light yellow solid.
Reaction SMILES: [CH:1]([CH:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:2].ClCC=CC1C=CC=CC=1.C(N(CC)CC)C.[F:28][C:29]([F:48])([C:33]([F:47])([F:46])[C:34]([F:45])([F:44])[C:35]([F:43])([F:42])[C:36]([F:41])([F:40])[CH:37]([F:39])[F:38])[C:30](Cl)=[O:31]>C(OCC)C>[CH:1]([CH:3]([O:10][C:30](=[O:31])[C:29]([F:28])([F:48])[C:33]([F:46])([F:47])[C:34]([F:44])([F:45])[C:35]([F:42])([F:43])[C:36]([F:40])([F:41])[CH:37]([F:38])[F:39])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:2]
Reactant: C=CC(O)c1ccccc1
Reactant: O=C(Cl)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)F
Agent: ClCC=Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: C=CC(OC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)F)c1ccccc1
Temperature: 0 °C
Yield: 44 %

Procedure:
100 ml of diethyl ether, 40.2 g (0.3 mol) of vinylbenzylalcohol (synthesized by the method described in "Polymer", 14 330 (1973) from chloromethylstyrene (meta: para=about 6: about 4); b.p.=69° to 73° C./0.4 mm Hg), 30.3 g (0.3 mol) of triethylamine, and 0.5 g of 2,6-di-tbutylphenol were charged into a 300-ml three-necked flask equipped with a stirrer, a reflux condenser, and a calcium chloride tube, and the mixture was then cooled with ice-water. 109.4 g (0.3 mol) of the 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-n-heptanoic acid chloride synthesized above was cooled with ice and was added to the mixture dropwise, with stirring. Next the mixture was stirred for 2 hours at room temperature, after which it was stirred for 1 hour under reflux. Then, after cooling, the deposited triethylamine hydrochloride was filtered off, the filtrate was washed twice with water, then with an aqueous sodium carbonate solution, and then it was dried over anhydrous sodium carbonate. Distillation was carried out twice to purify the dried filtrate, thus giving 61.0 g (yield: 44.0%; b.p.: 106 to 116° C./0.9 mm Hg; d: 1.47) of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-n-heptanoic acid vinylbenzyl ester.