Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:32])[CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]([C:15](=[O:31])[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]2[CH:24]=[N:25][C:26]([Cl:30])=[CH:27][C:28]=2[CH3:29])[CH:17]=1)[CH3:14].[Li+].[OH-]>C1COCC1>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:15]([N:13]([CH3:14])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][CH2:5][CH2:4][C:3]([OH:32])=[O:2])=[O:31])=[CH:17][C:18]=1[C:23]1[CH:24]=[N:25][C:26]([Cl:30])=[CH:27][C:28]=1[CH3:29]
Reactant: COC(=O)CCCc1ccccc1N(C)C(=O)c1ccc(Cl)c(-c2cnc(Cl)cc2C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1cc(Cl)ncc1-c1cc(C(=O)N(C)c2ccccc2CCCC(=O)O)ccc1Cl
Temperature: 25 °C

Procedure:
4-(2-{[4-Chloro-3-(6-chloro-4-methyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenyl)-butyric acid methyl ester 13-1 (9 mg, 0.019 mmol) was dissolved in THF (0.2 mL) and 1M LiOH (0.15 mL) was added. After 1 hour extra 1N LiOH (0.15 mL) was added and the mixture was stirred at room temperature until LCMS indicated that starting material was completely consumed. The mixture was acidified with 1N HCl until pH ˜5, MeOH was added and purified by prep LCMS to yield 4-(2-{[4-chloro-3-(6-chloro-4-methyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenyl)-butyric acid 14-1. MS [M+H]+: 456.9; tR=7.33 min. (method 2)
Reaction SMILES: [Br:1][C:2]1[CH:19]=[CH:18][C:5]([NH:6][C:7]2[C:8]([C:15]([OH:17])=[O:16])=[CH:9][N:10]([CH3:14])[C:11](=[O:13])[CH:12]=2)=[C:4]([F:20])[CH:3]=1.FC(F)(F)C(O[C:26]1[C:31]([F:32])=[C:30]([F:33])[C:29]([F:34])=[C:28]([F:35])[C:27]=1[F:36])=O.N1C=CC=CC=1>C1COCC1>[Br:1][C:2]1[CH:19]=[CH:18][C:5]([NH:6][C:7]2[C:8]([C:15]([O:17][C:26]3[C:27]([F:36])=[C:28]([F:35])[C:29]([F:34])=[C:30]([F:33])[C:31]=3[F:32])=[O:16])=[CH:9][N:10]([CH3:14])[C:11](=[O:13])[CH:12]=2)=[C:4]([F:20])[CH:3]=1
Reactant: O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
Reactant: Cn1cc(C(=O)O)c(Nc2ccc(Br)cc2F)cc1=O
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: Cn1cc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)c(Nc2ccc(Br)cc2F)cc1=O
Yield: 97 %

Procedure:
4-(4-Bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid and pentafluorophenyl trifluoroacetate were reacted in the presence of pyridine in THF as for example 4, step A. The crude residue was purified by flash chromatography on silica gel (60% EtOAc/Hexane) to give 2,3,4,5,6-pentafluorophenyl 4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate (97%). 1H NMR [400 MHz, (CD3)2SO] δ 9.03 (s, 1H), 8.70 (s, 1H), 7.71 (dd, J=10.6, 2.0 Hz, 1H), 7.49 (dd, J=8.5, 2.0 Hz, 1H), 7.46 (t, J=8.7 Hz, 1H), 5.34 (d, J=1.6 Hz, 1H), 3.49 (s, 3H).
Reaction SMILES: [CH:1]1([NH:7][CH2:8][CH:9]([OH:12])[CH2:10][CH3:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH2:15](Br)[CH3:16].O>O1CCCC1>[CH:1]1([NH:7][CH2:8][CH:9]([O:12][CH2:15][CH3:16])[CH2:10][CH3:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCBr
Reactant: CCC(O)CNC1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(CC)CNC1CCCCC1
Temperature: 60 °C
Reaction time: 1 h
Yield: 45.8 %

Procedure:
N-Cyclohexyl-N-(2-hydroxybutyl)amine (3 g) is dissolved in tetrahydrofuran (50 ml), and thereto is added with stirring sodium hydride (60% oily dispersion, 2.1 g) under ice-cooling, and the mixture is heated with stirring at 60° C. for one hour. To the reaction mixture is added dropwise with stirring ethyl bromide (2.1 g) under ice-cooling, and the mixture is stirred at room temperature for 4 hours. Water is added to the reaction mixture, and the mixture is extracted with ethyl acetate. The extract is concentrated under reduced pressure to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol:aqueous ammonia=100:10:1) to give N-cyclohexyl-N-(2-ethoxybutyl)amine(1.6 g) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]=[CH:9][C:10]([NH:12][C@H:13]([C:16]([O:18]C)=[O:17])[CH2:14][OH:15])=[O:11].[OH-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]=[CH:9][C:10]([NH:12][C@H:13]([C:16]([OH:18])=[O:17])[CH2:14][OH:15])=[O:11]
Reactant: COC(=O)[C@H](CO)NC(=O)C=Cc1ccccc1F
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(C=Cc1ccccc1F)N[C@@H](CO)C(=O)O
Yield: 72.9 %

Procedure:
The same procedures as in Example 64 were carried out from the compound obtained in Example 54 (4.2 g), 1 mol/L of an aqueous sodium hydroxide solution (39 mL), and methanol (390 mL), to give the captioned compound (2.9 g, 73%) as crystals.
Reaction SMILES: [NH2:1][C:2]([C@@H:4]1[C:8]([CH3:10])([CH3:9])[CH2:7][CH2:6][N:5]1C(OCC1C=CC=CC=1)=O)=[O:3]>CO.[Pd]>[CH3:9][C:8]1([CH3:10])[CH2:7][CH2:6][NH:5][C@@H:4]1[C:2]([NH2:1])=[O:3]
Reactant: CC1(C)CCN(C(=O)OCc2ccccc2)[C@@H]1C(N)=O
Agent: [Pd]
Solvent: CO
Product: CC1(C)CCN[C@@H]1C(N)=O
Reaction time: 5 h
Yield: 102.6 %

Procedure:
In a 200 ml flask was dissolved phenylmethyl (2S)-2-(aminocarbonyl)-3,3-dimethyl-1-pyrrolidinecarboxylate (0.0192 mol, 5.3 g) in 80 ml methanol at 20° C. 10% Pd/C (Degussa type, 0.53 g) was added and the mixture was stirred for 5 hr under atmospheric H2. The catalyst was filtered and the reaction was concentrated yielding 2.8 g (quantitative) of 3,3-dimethyl-L-prolinamide as a white solid. LCMS (ESI+)=143 m/z (MH+). 1H NMR (400 MHz, CDCl3)— rotomers δ 7.20 (bs, 1H), 6.20 (bs, 1H), 3.32 (s, 1H), 3.05-3.01 (m, 2H), 2.50 (bs, 1H), 1.67-1.62 (m, 2H), 1.23 (s, 3H), 0.97 (s, 3H). [α]D +1.2° (c=0.5, methanol)
Reaction SMILES: [CH3:1][O:2][C:3]([C@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]1[S:14]([C:17]1[CH:22]=[CH:21][C:20]([O:23]CC2C=CC=CC=2)=[CH:19][CH:18]=1)(=[O:16])=[O:15])=[O:4]>C(O)C.[Pd]>[CH3:1][O:2][C:3]([C@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]1[S:14]([C:17]1[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=1)(=[O:16])=[O:15])=[O:4]
Reactant: COC(=O)[C@H]1Cc2ccccc2N1S(=O)(=O)c1ccc(OCc2ccccc2)cc1
Agent: [Pd]
Solvent: CCO
Product: COC(=O)[C@H]1Cc2ccccc2N1S(=O)(=O)c1ccc(O)cc1
Reaction time: 18.5 h
Yield: 55.3 %

Procedure:
To a suspension of the title B compound, (R)-1-(4-benzyloxy-benzenesulfonyl)-2,3-dihydro-1H-indole-2-carboxylic acid methyl ester (3.00 g, 7.1 mmol) in ethanol (200 mL) under nitrogen is added 10% palladium on carbon (0.3 g). The resulting mixture is hydrogenated at 46 psi for 18.5 hours at room temperature. The mixture is filtered through celite by vacuum filtration. The filtrate is concentrated in vacuo to give 1.31 g of (R)-1-(4-hydroxy-benzene-sulfonyl)-2,3-dihydro-1H-indole-2-carboxylic acid methyl ester which is used without further purification: [M+1]+=334.22, [M−1]−=332.16.
Reaction SMILES: [NH:1]=[C:2]([NH:16][CH2:17][NH:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=1)(=[O:21])=[O:20])[CH2:3][CH2:4][C@@H:5]1[NH:10][CH2:9][CH2:8][N:7]([CH2:11][C:12]([OH:14])=[O:13])[C:6]1=[O:15].S(Cl)(Cl)=O.[CH3:33]O>>[CH3:33][O:13][C:12](=[O:14])[CH2:11][N:7]1[CH2:8][CH2:9][NH:10][C@@H:5]([CH2:4][CH2:3][C:2]([NH:16][CH2:17][NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)(=[O:20])=[O:21])=[NH:1])[C:6]1=[O:15]
Reactant: Cc1ccc(S(=O)(=O)NCNC(=N)CC[C@@H]2NCCN(CC(=O)O)C2=O)cc1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)CN1CCN[C@@H](CCC(=N)NCNS(=O)(=O)c2ccc(C)cc2)C1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
A solution of the compound of Example 15 (198 mg) in MeOH at 0° C., was treated with excess thionyl chloride (20 eq). The mixture was stirred at room temperature overnight and evaporated to give the title compound (100% yield).
Reaction SMILES: [C:1]([C:3]1[C:4]([NH:19][C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][C:30]=2[CH3:31])[C:23]([NH:25][O:26][CH3:27])=[O:24])=[N:5][C:6](S(C)=O)=[N:7][C:8]=1[N:9]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH3:10])#[N:2].[CH3:32][N:33]1[CH2:39][CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1>C1COCC1>[C:1]([C:3]1[C:4]([NH:19][C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][C:30]=2[CH3:31])[C:23]([NH:25][O:26][CH3:27])=[O:24])=[N:5][C:6]([N:36]2[CH2:37][CH2:38][CH2:39][N:33]([CH3:32])[CH2:34][CH2:35]2)=[N:7][C:8]=1[N:9]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH3:10])#[N:2]
Reactant: CONC(=O)c1ccc(C)c(Nc2nc(S(C)=O)nc(N(C)CC(C)(C)C)c2C#N)c1
Reactant: CN1CCCNCC1
Solvent: C1CCOC1
Product: CONC(=O)c1ccc(C)c(Nc2nc(N3CCCN(C)CC3)nc(N(C)CC(C)(C)C)c2C#N)c1

Procedure:
3-{5-Cyano-6-[(2,2-dimethyl-propyl)-methyl-amino]-2-methanesulfinyl-pyrimidin-4-ylamino}-N-methoxy-4-methyl-benzamide (40 mg) and 1-methyl-homopiperazine (0.05 mL) in THF (0.5 mL) were heated in sealed tube at 75° C. for overnight. After the solvent was removed in vacuo, the residue was purified by silica gel column chromatography to afford the product (6.8 mg). MS (m/z): 495 (M+H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[C:5](=O)[NH:6][NH:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16](=[O:27])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]([F:26])([F:25])[F:24])[CH2:12][CH2:11]1)=[S:9])[CH3:2].CS(O)(=O)=O>C1(C)C=CC=CC=1.CN1CCCC1=O>[CH2:1]([O:3][C:4]([C:5]1[S:9][C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:27])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]([F:26])([F:25])[F:24])[CH2:12][CH2:11]2)=[N:7][N:6]=1)=[O:29])[CH3:2]
Reactant: CCOC(=O)C(=O)NNC(=S)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1
Agent: CS(=O)(=O)O
Solvent: CN1CCCC1=O
Solvent: Cc1ccccc1
Product: CCOC(=O)c1nnc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)s1
Yield: 68 %

Procedure:
Oxo-{N′-[4-(2-trifluoromethylbenzoyl)piperazine-1-carbothioyl]hydrazino}-acetic acid ethyl ester (2.88 g, 6.56 mmol) was dissolved in a mixture of 50 mL of toluene and 10 mL of N-methyl-2-pyrrolidone. Methanesulfonic acid (0.723 mL, 11.15 mmol) was then added dropwise over 5 minutes to the stirred solution. The mixture was refluxed for 1.5 hours, then evaporated to 10 mL, and then 20 mL of water was added. The pH of the solution was adjusted to 8 by saturated NaHCO3. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography to give the title compound in 68% yield (1.84 g). 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J=7.8 Hz, 1H), 7.64 (dd, J=7.5, 7.5 Hz, 1H), 7.60 (dd, J=7.5, 7.5 Hz, 1H), 7.35 (d, J=7.3 Hz, 1H), 4.44 (q, J=7.1 Hz, 2H), 4.06-4.11 (m, 1H), 3.86-3.91 (m, 1H), 3.56-3.77 (m, 4H), 3.35 (t, J=5.4 Hz, 2H), 1.41 (t, J=7.1 Hz, 3H). MS (ES+) m/z 415.5 (M+1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-])=O)=[CH:28][CH:27]=1)[CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([C:16](=[O:24])[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[Ca+2].[Cl-]>C(O)(=O)C.[Zn]>[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1)[CH2:9][N:10]1[CH2:11][CH2:12][CH:13]([C:16](=[O:24])[C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)[CH2:14][CH2:15]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccc([N+](=O)[O-])cc1)CN1CCC(C(=O)c2ccc(F)cc2)CC1
Agent: [Ca+2]
Agent: [Cl-]
Agent: [Zn]
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N[C@H](Cc1ccc(N)cc1)CN1CCC(C(=O)c2ccc(F)cc2)CC1
Temperature: 0 °C
Reaction time: 0.58 h

Procedure:
To a solution of [(R)-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-(4-nitro-benzyl)-ethyl]-carbamic acid tert-butyl ester (1.41 g, 2.90 mmol) in acetic acid (11 ml), cooled to 0° C., is added an aqueous solution of calcium chloride (4 ml, 0.47M) and zinc dust (3.9 g, 59.6 mmol). The reaction mixture is stirred at 0° C. for 35 minutes and then filtered through a celite plug. The filtrate is evaporated and the residue dissolved in water and extracted into dichloromethane. The dichloromethane is evaporated and the residue disolved in water and basified with aqueous sodium bicarbonate solution and extracted into dichloromethane. The dichloromethane is dried over magnesium sulphate and evaporated to afford {(R)-1-(4-amino-benzyl)-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl}-carbamic acid tert-butyl ester, [MH]+456.5.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C:10](=[CH:11][C:12]3[C:17]2=[N:16][C:15]([Cl:22])=[C:14]([O:23][CH2:24][CH3:25])[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.C(=O)(O)[O-].[Na+]>>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([Cl:22])=[C:14]([O:23][CH2:24][CH3:25])[CH:13]=3)[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: CCOc1cc2cc3n(c2nc1Cl)[C@H](C)CN(C(=O)OC(C)(C)C)C3
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: CCOc1cc2c(nc1Cl)N1[C@H](C2)CN(C(=O)OC(C)(C)C)C[C@H]1C
Yield: 96.8 %

Procedure:
To a solution of 0.30 g (0.82 mmol) (R)-6-chloro-7-ethoxy-4-methyl-3,4-dihydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 6 mL acetic acid 0.26 g (4.10 mmol) sodium cyanoborohydride was added. After 1 h the reaction was poured into 10% aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography over silica gel with ethyl acetate:n-hexane (1:2) as eluant to yield the product as a light yellow oil (96.8%).
Reaction SMILES: [NH2:1][CH2:2][C:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)([OH:5])[CH3:4].[CH:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:20]([NH:1][CH2:2][C:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)([OH:5])[CH3:4])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=Cc1ccccc1
Reactant: CC(O)(CN)c1ccc(OCc2ccccc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(O)(CNCc1ccccc1)c1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 62.8 %

Procedure:
A mixture of 1-amino-2-(4-benzyloxy-phenyl)-propan-2-ol (1.26 g; 4.9 mmol), benzaldehyde (0.55 mL; 5.4 mmol), and p-toluenesulfonic acid (0.04 g; 0.24 mmol) in toluene (30 mL) was heated under reflux in a Dean-Stark apparatus, overnight. Subsequently, the mixture was cooled to RT and the solvent was removed in vacuo. The residue was suspended in MeOH (30 mL), cooled to −15° C., and treated with NaBH4 (0.74 g; 19.6 mmol), portionwise. After the addition was complete the mixture was warmed to RT and stirred for one hour. Subsequently, the MeOH was removed in vacuo. The residue was partitioned between Et2O and 5% aqueous NaHCO3. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O:hexanes 2:1) to give 1-benzylamino-2-(4-benzyloxy-phenyl)-propan-2-ol (1.07 g).
Reaction SMILES: [CH2:1]([N:4]1[C:8]([C:9]2[CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[S:12][CH:13]=2)=[CH:7][CH:6]=[N:5]1)[CH2:2][CH3:3].C1C(=O)N([Cl:25])C(=O)C1>C1COCC1>[Cl:25][C:7]1[CH:6]=[N:5][N:4]([CH2:1][CH2:2][CH3:3])[C:8]=1[C:9]1[CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[S:12][CH:13]=1
Reactant: CCCn1nccc1-c1csc(C(=O)OC)c1
Reactant: O=C1CCC(=O)N1Cl
Solvent: C1CCOC1
Product: CCCn1ncc(Cl)c1-c1csc(C(=O)OC)c1
Temperature: 70 °C
Reaction time: 2 h
Yield: 69.9 %

Procedure:
A mixture of methyl 4-(1-propyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (250 mg, 1.0 mmol) and NCS (200 mg, 1.5 mmol) in THF (5 mL) was heated to 70° C. in a sealed tube. After 2 h, the reaction mixture was concentrated and purified via column chromatography (silica, 10% EtOAc/Hexane) affording the title compound (199 mg, 70%) as a white solid: LC-MS (ES) m/z 285 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[CH2:4][C@@H:5]([NH2:20])[C:6]1[CH:11]=[CH:10][C:9]([NH:12]C(OC(C)(C)C)=O)=[CH:8][CH:7]=1.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][C:3](=[O:21])[CH2:4][C@@H:5]([NH:20][C:22](=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[CH:10][CH:11]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: COC(=O)C[C@@H](N)c1ccc(NC(=O)OC(C)(C)C)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)C[C@@H](NC(=O)c1ccccc1)c1ccc(N)cc1
Temperature: 25 °C
Reaction time: 2.25 h

Procedure:
A solution of (R)-3-amino-3-[4-(tert-butoxycarbonylamino)phenyl]-propanoic acid methyl ester [3.0 g, Reference Example 7(c)] in dimethylformamide (50 ml), was treated with benzoyl chloride (1.24 ml) and triethylamine (1.56 ml). After stirring at ambient temperature for 2.25 hours, the mixture was evaporated to dryness and the resultant solid washed with water before being fried in vacuo. The resulting white solid (3.8 g) was dissolved in dichloromethane (70 ml) and the solution was treated with trifluoracetic acid (20 ml). After stirring at ambient temperature for 45 minutes, the reaction mixture was evaporated. The residue was treated with toluene (70 ml), concentrated to dryness and the resultant material treated with dichloromethane (200 ml). The resultant suspension was treated with saturated aqueous potassium carbonate solution (20 ml) with stirring at ambient temperature for 5 minutes. The organic layer was separated, dried over magnesium sulphate, and then evaporated to give the title compound as a white foam (2.0 g).
Reaction SMILES: [C:1]([OH:15])(=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH:12][CH3:13].C(O)(=O)CCCCCCCCCCC=C>>[C:1]([OH:15])(=[O:14])[CH:2]=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CC=CCCCCCCCCCC(=O)O
Agent: C=CCCCCCCCCCCC(=O)O
Product: CCCCCCCCCCC=CC(=O)O

Procedure:
11-tridecenoic acid; 12-tridecenoic acid;
Reaction SMILES: [CH:1](Br)=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[Mg].[Cl-].[NH4+]>O1CCCC1.[Br-].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.[Ni+2].[Br-]>[CH2:1]=[CH:2]/[CH:3]=[CH:4]/[CH:5]=[CH:6]/[CH2:7][CH2:1][CH2:2][CH2:3][CH3:4]
Reactant: CCCCCC=CBr
Agent: [Ni+2]
Agent: [Br-]
Agent: [Cl-]
Solvent: C1CCOC1
Product: C=C/C=C/C=C/CCCCC
Reaction time: 1 h

Procedure:
100 millimoles of magnesium 1-heptenyl bromide (mixture of two isomers Z and E in a ratio by weight of 50% and 50%) are added to a solution of 50 millimoles of (E)-1,3-butadiene butyl sulphide and 3.25 millimoles of nickel (2+) bis(triphenylphosphine) bromide in 200 ml of tetrahydrofuran. The reaction is allowed to proceed, without the reaction medium being cooled, until the starting materials have disappeared completely. The mixture is then hydrolysed with 100 ml of a saturated ammonium chloride solution or another saturated aqueous salt solution. The mixture is stirred for one hour. It is then decanted and the organic phase is recovered. The reaction medium is then washed a second time with the saturated aqueous salt solution and the organic phase is recovered. The organic phase is dried over anhydrous magnesium sulphate and the solvent is removed by evaporation under reduced pressure (20 mmHg) and at a temperature of 30° C. A mixture of (3E,5Z)-1,3,5-undecatriene (I) and (3E,5E)-1,3,5-undecatriene (II) is obtained. This mixture is distilled in the presence of an antioxidant under reduced pressure (0.05 mmHg) and at a temperature of 35° C. in order to obtain a pure mixture of compounds of the formulae I and II.
Reaction SMILES: C[Al](C)C.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:30][CH2:31][CH2:32][O:33][CH2:34][C@H:35]([OH:40])[C:36](OC)=[O:37])([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.O>[Si:13]([O:30][CH2:31][CH2:32][O:33][CH2:34][C@H:35]([OH:40])[C:36]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([Cl:5])=[CH:11][N:10]=1)=[O:37])([C:26]([CH3:29])([CH3:27])[CH3:28])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: COC(=O)[C@@H](O)COCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: Nc1ccc(Cl)cn1
Agent: C[Al](C)C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)[Si](OCCOC[C@H](O)C(=O)Nc1ccc(Cl)cn1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 61.3 %

Procedure:
Trimethylaluminium (2M in toluene) (4.97 mL, 9.94 mmol) was added carefully to 5-chloropyridin-2-amine (1.277 g, 9.94 mmol) in toluene (10 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 15 minutes. (S)-Methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (Intermediate AB3) (2 g, 4.97 mmol) in toluene (2 mL) was added. The reaction was heated to 120° C. for 2 hours in the microwave reactor. The reaction mixture was allowed to cool. The residue was neutralised with citric acid (1M, aq) and then diluted with water and extracted with EtOAc. The combined organics were dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane to afford the product (1.52 g, 61.3%). 1H NMR (400 MHz, CDCl3) δ 1.04 (9H, s), 3.63-3.68 (3H, m), 3.79-3.83 (2H, m), 3.85 (2H, d), 4.33 (1H, q), 7.34-7.46 (6H, m), 7.63-7.69 (5H, m), 8.18-8.25 (2H, m), 9.19 (1H, s); m/z (ES+) (M+H)+=499.55; HPLC tR=3.43 min.
Reaction SMILES: [CH:1]1([C:6]#[N:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:9][CH2:10][OH:11]>>[CH:1]1([C:6](=[NH:7])[O:11][CH2:10][CH3:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCO
Reactant: N#CC1CCCC1
Agent: Cl
Product: CCOC(=N)C1CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of cyclopentanecarbonitrile (10.0 g, 105.1 mmol) in EtOH (7 mL) was treated with HCl (4.0 M in dioxane, 105 mL, 3.02 mol) and the mixture stirred at rt overnight. After this time, nitrogen gas was passed through the mixture and the mixture was concentrated. The residue was treated with ether and reconcentrated. The residue was again suspended in ether and filtered to afford the title compound (16.0 g, crude) as a white solid. MW=141.21. 1H NMR (CDCl3, 500 MHz) δ 4.79-4.46 (m, 2H), 3.43-3.23 (m, 1H), 2.76 (s, 1H), 2.20-2.00 (m, 2H), 1.86-1.63 (m, 6H), 1.55-1.40 (m, 3H); APCI MS m/z 142 [M+H]+.
Reaction SMILES: [OH:1][CH:2]([CH:26]1[CH2:31][C:30]([CH3:33])([CH3:32])[NH:29][C:28]([CH3:35])([CH3:34])[CH2:27]1)[CH2:3][NH:4][C:5]1[N:10]=[C:9]([NH:11][CH2:12][CH:13]([CH:15]2[CH2:20][C:19]([CH3:22])([CH3:21])[NH:18][C:17]([CH3:24])([CH3:23])[CH2:16]2)[OH:14])[N:8]=[C:7](Cl)[N:6]=1.[CH2:36]([NH2:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.N>>[OH:1][CH:2]([CH:26]1[CH2:31][C:30]([CH3:33])([CH3:32])[NH:29][C:28]([CH3:35])([CH3:34])[CH2:27]1)[CH2:3][NH:4][C:5]1[N:10]=[C:9]([NH:11][CH2:12][CH:13]([CH:15]2[CH2:20][C:19]([CH3:22])([CH3:21])[NH:18][C:17]([CH3:24])([CH3:23])[CH2:16]2)[OH:14])[N:8]=[C:7]([NH:43][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:6]=1
Reactant: CC1(C)CC(C(O)CNc2nc(Cl)nc(NCC(O)C3CC(C)(C)NC(C)(C)C3)n2)CC(C)(C)N1
Reactant: NCc1ccccc1
Agent: N
Product: CC1(C)CC(C(O)CNc2nc(NCc3ccccc3)nc(NCC(O)C3CC(C)(C)NC(C)(C)C3)n2)CC(C)(C)N1

Procedure:
2,4-Bis{2-hydroxy-N-(2,2,6,6-tetramethyl-4-piperidyl)ethylamino}-6-chloro-1,3,5-triazine (5.0 g) was reacted with benzylamine (25.0 g) for 8 hours and 30 minutes at 150°-160° C. The reaction mixture was poured into an aqueous ammonia solution, extracted with chloroform and dried over anhydrous potassium carbonate and chloroform was distilled off. The resulting residue was treated with silica gel chromatography (eluent=ethyl acetate:triethylamine:ethanol=10:12:3) to yield crystals, which were recrystallized from cyclohexane to afford the desired product as white crystals melting at 88° C.