Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S([O-])([O-])(=O)=O.[Mg+2].[CH:7]1[C:12]([C@@H:13](O)[CH2:14]N)=[CH:11][C:10]([OH:17])=[C:9](O)[CH:8]=1.[C:19]([O:22][CH2:23][CH3:24])(=O)[CH3:20]>[Pt]>[CH2:23]([O:22][C:19]1[CH:20]=[CH:11][C:12]([CH2:7][CH2:8][CH2:9][CH:10]=[O:17])=[CH:13][CH:14]=1)[C:24]1[CH:11]=[CH:12][CH:7]=[CH:8][CH:9]=1
Reactant: CCOC(C)=O
Reactant: NC[C@H](O)c1ccc(O)c(O)c1
Agent: [Pt]
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Product: O=CCCCc1ccc(OCc2ccccc2)cc1

Procedure:
A solution of 4-(4-benzyloxyphenyl)-butanal (52.4 g, 206 mmol) in 150 mL ethyl acetate (1.4M solution) was prepared and set aside. 10% platinum on carbon (3.40 g) was prewetted with ethyl acetate and transferred to the reactor. To this was added magnesium sulfate (60.0 g, 500 mmol), followed by the ethyl acetate solution of (trimethylsilyl)-protected norepinephrine prepared as described in Example 1.
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[Br:26])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].CC1C=CC(S(O)(=O)=O)=CC=1.[I:39]NC(=O)CCC(N)=O>C1COCC1>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[Br:26])[C:9]=1[I:39])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1cc(OCc2ccccc2)c2c(Br)cccc2c1
Reactant: NC(=O)CCC(=O)NI
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1cc(OCc2ccccc2)c2c(Br)cccc2c1I
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.7 %

Procedure:
Carbamate 10 (1.20 g, 2.80 mmol) was dissolved in freshly distilled THF (0.17 M) under Ar and in the absence of light, and TsOH□H2O (53 mg, 0.28 mmol) and N-iodosuccinamide (753 mg, 3.30 mmol) were added. The reaction mixture was allowed to stir at 25° C. for 2 h. After 2 h, the reaction was quenched with the addition saturated aqueous NaHCO3 and diluted with ethyl acetate. The organic layer was washed with saturated aqueous NaCl, dried over Na2SO4, and concentrated under reduced pressure. Flash chromatography (SiO2, 5×16 cm, 5% EtOAc/hexanes elution) provided 11 (1.47 g, 94%) as an orange solid. 1H NMR (CDCl3, 500 MHz) δ 8.16 (s, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.70 (d, J=7.5 Hz, 1H), 7.62 (d, J=7.0 Hz, 2H), 7.39 (t, J=7.2 Hz, 2H), 7.34 (d, J=7.0 Hz, 1H), 7.32 (s, 1H), 7.25-7.22 (m, 2H), 5.28 (s, 2H), 1.58 (s, 9H). 13C NMR (CDCl3, 125 MHz) δ 155.8, 152.4, 139.0, 136.7, 135.9, 132.2, 131.9, 130.0, 128.5, 128.3, 128.0, 127.9, 121.4, 120.2, 120.1, 117.0, 101.9, 81.3, 71.3, 28.3. IR (film) νmax 3378, 2978, 1730, 1225, 1145 cm−1. ESI-TOF HRMS m/z 553.9820 (M+H+, C22H21BrINO3 requires 553.9822).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1.CO[C:24](OC)([CH3:26])[CH3:25].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[N+:11]([C:8]1[CH:7]=[CH:6][C:5]([CH2:4][C@H:3]2[CH2:2][O:1][C:24]([CH3:26])([CH3:25])[N:14]2[C:15]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:21])=[CH:10][CH:9]=1)([O-:13])=[O:12]
Reactant: COC(C)(C)OC
Reactant: CC(C)(C)OC(=O)N[C@H](CO)Cc1ccc([N+](=O)[O-])cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1[C@@H](Cc2ccc([N+](=O)[O-])cc2)COC1(C)C
Temperature: 25 °C
Reaction time: 15 h

Procedure:
A mixture of tert-butyl N-[(1S)-2-hydroxy-1-(4-nitrobenzyl)ethyl]carbamate (22.3 g), 2,2-dimethoxypropane (46.3 ml), p-toluenesulfonic acid monohydrate (1.43 g) and dichloromethane (200 ml) was stirred at room temperature for 15 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with isopropyl ether to give tert-butyl (S)-4-(4-nitrobenzyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (16.9 g) as a pale yellow powder.
Reaction SMILES: [OH:1][C:2]1[C:9]([O:10][CH3:11])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].Br[CH:13]([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.O>[CH:4]([C:3]1[CH:6]=[CH:7][CH:8]=[C:9]([O:10][CH3:11])[C:2]=1[O:1][CH:13]([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:5]
Reactant: COc1cccc(C=O)c1O
Reactant: CCOC(=O)C(C)Br
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)C(C)Oc1c(C=O)cccc1OC
Temperature: 70 °C
Reaction time: 5 h
Yield: 104.2 %

Procedure:
A mixture of 2-hydroxy-3-methoxybenzaldehyde (3.04 g), ethyl 2-bromopropionate (5.85 g), and potassium carbonate (4.14 g) in dimethylsulfoxide (20 ml) was stirred at 70° C. for 5 hours. The mixture was diluted with water, neutralized with 1N hydrochloric acid, and was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated. The crude product (0.93 g) was purified on a silica gel column (60 g) eluting with a mixed solvent of n-hexane and toluene (from 6:1 to 5:1) to give ethyl 2-(2-formyl-6-methoxyphenoxy)-propionate (5.25 g).
Reaction SMILES: [CH:1]([C:3]1[S:7][C:6]([C:8]([NH2:10])=[O:9])=[CH:5][CH:4]=1)=O.FC(F)(F)C([NH:15]OC(=O)C(F)(F)F)=O.N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([C:3]1[S:7][C:6]([C:8]([NH2:10])=[O:9])=[CH:5][CH:4]=1)#[N:15]
Reactant: O=C(NOC(=O)C(F)(F)F)C(F)(F)F
Reactant: NC(=O)c1ccc(C=O)s1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: N#Cc1ccc(C(N)=O)s1
Yield: 39.5 %

Procedure:
5-Formyl-2-thiophenecarboxylic acid (2.64 g) (synthesized in accordance with the method described in Tetrahedron, 41, 3803 (1985)) was dissolved in tetrahydrofuran (30 ml), and N,N-dimethylformamide (3 drops) was added. Oxalyl chloride (2.2 ml) was added dropwise at room temperature, and the mixture was stirred for 2 hours. The reaction mixture was concentrated under reduced pressure and the concentrate was dissolved in ethyl acetate (50 ml). The resulting solution was added dropwise to a mixture of 25% aqueous ammonia (50 ml) and ethyl acetate (200 ml) with stirring under ice-cooling. The resulting mixture was stirred at room temperature, and then the organic layer was collected. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and concentrated under reduced pressure to give 5-formyl-2-thiophenecarboxamide (1.77 g). A mixture of 5-formyl-2- thiophenecarboxamide (1.55 g), N,O- bis(trifluoroacetyl)hydroxyamine (3.5 g), pyridine (2 ml) and toluene (110 ml) was stirred under reflux for 1 hour, and then cooled, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 5-cyano-2-thiophenecarboxamide (0.6 g).
Reaction SMILES: [CH2:1]([NH:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[C:9]([NH2:22])[N:8]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C1C(=O)N([Br:30])C(=O)C1>C(Cl)(Cl)Cl.C(Cl)Cl>[Br:30][C:12]1[N:13]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[C:14]2[C:10]([N:11]=1)=[C:9]([NH2:22])[N:8]=[C:7]([NH:6][CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[N:15]=2
Reactant: O=C1CCC(=O)N1Br
Reactant: CCCCCNc1nc(N)c2ncn(C3CCCCO3)c2n1
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: CCCCCNc1nc(N)c2nc(Br)n(C3CCCCO3)c2n1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of N2-pentyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2,6-diamine (543 mg) in dry chloroform (4.6 mL) was cooled to 0° C. and NBS (334 mg) was added. The mixture was stirred at room temperature for 10 mins. The reaction was taken up in DCM (30 mL) and was washed with water (30 mL). The organics were separated, dried using a hydrophobic frit and concentrated in vacuo to give the title compound as a viscous brown residue (627 mg) which was used crude in the next step.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])C.[NH2:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:12])[CH3:11].C(O)=O>>[CH:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:3]
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)[C@H](N)C(=O)O
Solvent: O=CO
Product: CC(C)[C@H](NC=O)C(=O)O
Temperature: 25 °C

Procedure:
Acetic anhydride (4 mL, 0.04 mol) was added dropwise to a solution of L-Valine (1 g, 8.35 mmol) in formic acid (12 mL, 0.32 mol) while stirring on ice. The mixture was then warmed up to RT and kept stirring for 24 hours before the solvent was removed by rotary evaporation under high vacuum. The formyl-valine was recrystallized from ethyl acetate and the desired product was obtained as a white solid. Yield: 0.78 g (64%) 1HNMR (500 MHz, [D6]Acetone, 25° C., TMS): δ=8.22 (s, 1H), 7.41 (b, 1H), 4.50 (m, 1H), 2.22 (m, 1H), 0.98 (m, 6H).
Reaction SMILES: O[CH:2]=[C:3]1[C:8](=[O:9])[C:7]([CH3:11])([CH3:10])[CH2:6][C:5]([CH3:13])([CH3:12])[CH2:4]1.Cl.[NH2:15]O>C(O)C.O>[CH3:12][C:5]1([CH3:13])[CH2:4][C:3]2[CH:2]=[N:15][O:9][C:8]=2[C:7]([CH3:11])([CH3:10])[CH2:6]1
Reactant: NO
Reactant: CC1(C)CC(=CO)C(=O)C(C)(C)C1
Agent: Cl
Solvent: CCO
Solvent: O
Product: CC1(C)Cc2cnoc2C(C)(C)C1
Temperature: 110 °C
Yield: 88.3 %

Procedure:
Under a nitrogen atmosphere and with stirring, a solution of 16 (140 mg, 0.77 mmol) in ethanol (19.1 mL) was added to a solution of hydroxylamine hydrochloride (7.98 mmol, 555 mg, 10.4 eq) in water (980 μL) at room temperature. The mixture was heated to 110° C. and stirred at reflux for 1 hour. After heating, the reaction mixture was diluted with water (10 mL) and the aqueous layer was extracted with methylene chloride/ethyl ether (1:2, 3×10 mL). The organic layers were then combined and washed with saturated aqueous sodium bicarbonate solution (1×12 mL) and brine (2×12 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to give 17 as a yellow oil (122 mg, 0.68 mmol, 89%). The material was used in the next reaction without further purification: 1H NMR (CDCl3) δ 8.00 (1H, s), 2.24 (2H, s), 1.60 (2H, s), 1.34 (6H, s), 1.03 (6H, s); 13C NMR (CDCl3) δ 173.2, 150.0, 110.4, 52.4, 34.4, 32.6, 32.4, 29.7, 29.3. MS: No molecular ion peak is observed by ESI+ and EI methods.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:41][CH:42]([C:48]#[N:49])[C:43]([O:45][CH2:46][CH3:47])=[O:44]>C1COCC1>[C:48]([CH:42]([NH:41][C:7](=[O:9])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)[C:43]([O:45][CH2:46][CH3:47])=[O:44])#[N:49]
Reactant: CCOC(=O)C(N)C#N
Reactant: O=C(O)c1ccccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C(C#N)NC(=O)c1ccccn1
Temperature: 25 °C
Reaction time: 6 h
Yield: 30 %

Procedure:
To a solution of picolinic acid (1.23 g, 10 mmol), EDC.HCl (1.91 g, 10 mmol) and HOBT (1.35 g, 10 mmol) in THF (80 mL) was added DIPEA (3.6 g, 30 mmol) at ambient temperature. The reaction mixture was maintained at the same temperature for 1 hr at which time a solution of ethyl 2-amino-2-cyanoacetate (1.28 g, 10 mmol) in THF (5 mL) was added. The reaction mixture was stirred at ambient temperature for additional 6 hr. It was then concentrated, and the residue was purified by silica gel column chromatography (5:1 PE/EtOAc) to give ethyl 2-cyano-2-(picolinamido)acetate (0.7 g, 30%) as yellow solid.
Reaction SMILES: [CH:1]1([CH2:7][NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[Cl:18][C:19]1[N:24]=[C:23](Cl)[C:22]([N+:26]([O-:28])=[O:27])=[CH:21][N:20]=1>ClCCl>[Cl:18][C:19]1[N:24]=[C:23]([NH:8][CH2:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:22]([N+:26]([O-:28])=[O:27])=[CH:21][N:20]=1
Reactant: NCC1CCCCC1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=[N+]([O-])c1cnc(Cl)nc1NCC1CCCCC1
Yield: 25.6 %

Procedure:
Cyclohexylmethylamine (3.11 g) and N,N-diisopropylethylamine (6.2 ml) were dissolved into 45 ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine (4.85 g) in dichloromethane (30 ml) at 0° C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 20 min. Purification was conducted by a column chromatography to obtain a bright-yellow sheet-like solid (1.73 g) in a yield of 26%. ESI-MS (m/z, %) 272 (M−H)+. 1H NMR (400 MHz, CDCl3): δ 9.03 (s, 1H), 8.48 (s, 1H), 3.52 (m, 2H), 1.78-1.64 (m, 7H), 1.33-1.14 (m, 4H), 1.08-1.00 (m, 2H).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])[C:11]([Cl:19])=[CH:10][C:9]=1[NH:20][C:21](=[O:38])[CH2:22][C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([CH3:37])[CH:32]=2)[CH:26]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:19][C:11]1[C:12]([NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])=[CH:13][C:8]2[N:7]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]4[CH:36]=[CH:35][N:34]=[C:33]([CH3:37])[CH:32]=4)[CH:26]=3)[CH2:22][C:21](=[O:38])[NH:20][C:9]=2[CH:10]=1
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(Cl)c(NCC(C)C)cc3NC(=O)OC(C)(C)C)c2)ccn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(-c2cccc(C3=Nc4cc(NCC(C)C)c(Cl)cc4NC(=O)C3)c2)ccn1

Procedure:
The title compound was prepared from (4-chloro-5-isobutylamino-2-{3-[3-(2-methyl-pyridin-4-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M72) (0.47 g, 0.85 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (313 mg, 85%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21](Cl)=[O:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:24][C:25]([F:35])([F:34])[C@H:26]([OH:33])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].CC1C=CN=C(N)C=1C.C(N(CC)CC)C>C(Cl)Cl>[F:24][C:25]([F:34])([F:35])[C@H:26]([O:33][C:21]([C:18]1[CH:19]=[CH:20][C:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][CH:11]=2)=[CH:16][CH:17]=1)=[O:22])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: O=C(Cl)c1ccc(-c2ccc(OCc3ccccc3)cc2)cc1
Reactant: CCCCCC[C@@H](O)C(F)(F)F
Agent: Cc1ccnc(N)c1C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCC[C@@H](OC(=O)c1ccc(-c2ccc(OCc3ccccc3)cc2)cc1)C(F)(F)F
Temperature: 0 °C

Procedure:
To a solution of 4-benzyloxybiphenyl-4'-carboxylic acid chloride (1.23 g) in methylene chloride (10 ml) was added by little and little under ice-cooling a solution of (R)-(+)-1,1,1-trifluoro-2-octanol (0.96 g) ([α]D22.5 =+20.1, optical purity 96.3%ee), dimethyl-aminopyridine (0.55 g) and triethylamine (0.48 g) in methylene chloride (20 ml). The mixture was left to stand over-night at room temperature in order to complete the reaction before the mixture obtained was poured in ice-water.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([NH2:11])[CH:8]=[C:4]([C:5]([O-:7])=O)[C:3]=1[C:12]([O-:14])=[O:13].[Na+].[Na+].[CH3:17][C:18]1=[C:19]([CH3:25])[C:20]([O:22][C:23]1=[O:24])=O>O.C1(C)C=CC=CC=1>[CH3:25][C:19]1[C:20](=[O:22])[N:1]([C:2]2[CH:10]=[C:9]([N:11]3[C:5](=[O:7])[C:4]([CH3:8])=[C:3]([CH3:2])[C:12]3=[O:13])[CH:8]=[C:4]3[C:5]([O:14][C:12](=[O:13])[C:3]=23)=[O:7])[C:23](=[O:24])[C:18]=1[CH3:17]
Reactant: Nc1cc(N)c(C(=O)[O-])c(C(=O)[O-])c1
Reactant: CC1=C(C)C(=O)OC1=O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC1=C(C)C(=O)N(c2cc3c(c(N4C(=O)C(C)=C(C)C4=O)c2)C(=O)OC3=O)C1=O
Temperature: 100 °C
Yield: 115.7 %

Procedure:
7.20 g (0.039 mol) of disodium 3,5-diaminophthalate, dissolved in 200 ml of water, are added to a solution of 8.82 g (0.078 mol) of dimethylmaleic anhydride in 80 ml of toluene. This mixture is boiled under reflux for 1 hour. It is then evaporated to dryness in a rotary evaporator, the residue is dissolved, at 90° C., in 100 ml of N,N-dimethylacetamide and 50 ml of water and the solution is rendered acid to Congo Blue with 10% strength hydrochloric acid. After cooling, the slurry-like mixture is filtered and the residue is rinsed with acetone and then dried in vacuo at 80° C. The dry residue is then suspended in 100 ml of acetic anhydride and this mixture is warmed to about 100° C. for 1 hour. It is then evaporated to dryness and the residue is recrystallised from 1,2-dichlorobenzene. 8.9 g (69% of theory) of 3,5-bis-(dimethylmaleimidyl)-phthalic anhydride are obtained; colour: light brownish; melting point 298° C. (decomposition).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH:4]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=1)[CH2:5][CH:6]=[CH2:7].C(=O)(O)[O-].[Na+].[C:20]1([S:26](Cl)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(OCC)(=O)C.O>[Cl:14][C:10]1[CH:9]=[C:8]([CH:4]([CH2:5][CH:6]=[CH2:7])[CH2:3][N:2]([CH3:1])[S:26]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)(=[O:28])=[O:27])[CH:13]=[CH:12][CH:11]=1
Reactant: C=CCC(CNC)c1cccc(Cl)c1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: C=CCC(CN(C)S(=O)(=O)c1ccccc1)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.9 %

Procedure:
N-Methyl-(2-(3-chlorophenyl)pent-4-enyl)amine (202 mg, 1.03 mmol) was dissolved in 10 mL of ethyl acetate. A solution of sodium bicarbonate (766 mg, 10.3 mmol) in water (10 mL) was added followed by benzenesulfonyl chloride (363 mg, 4.06 mmol), and the heterogeneous mixture was stirred overnight at room temperature. The mixture was extracted with 5 mL of ethyl acetate followed by an additional 2×15 mL of ethyl acetate. The combined organic layers were dried over sodium sulfate, decanted, and evaporated. The residue was purified by flash column chromatography on silica gel, eluting with 10-20% ethyl ether in hexane to give 223 mg the title compound. 1NMR (400 MHz, CDCl3): δ 7.72 (d, 2H, J=8 Hz), 7.58 (tt, 1H, J=8, 1 Hz), 7.50 (t, 2H, J=8 Hz), 7.24 (d, 1H, J=8 Hz), 7.20 (dt, 1H, J=8, 1 Hz), 7.14 (t, 1H, J=1 Hz), 7.10 (dt, 1H, J=8, 1 Hz), 5.63 (ddt, 1H, J=17, 10, 7 Hz), 5.00 (dm, 1H, J=17 Hz),4.97 (dm, 1H, J=10 Hz) 3.42-3.34 (m, 1H), 3.00-2.90 (m, 2H), 2.61 (s, 3H), 2.56 (dtm, 1H, J=14, 6 Hz), 2.36 (dtm, 1H, J=14, 7 Hz). Mass spectrum (NH3 /CI): m/z=350 (M+1).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH3:14][C:15]([CH3:27])=[CH:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH2:23].F[P-](F)(F)(F)(F)F.N1([P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>O1CCCC1>[CH3:14][C:15]([CH3:27])=[CH:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH:23][C:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)=[O:13]
Reactant: O=C(O)c1ccc2ncccc2c1
Reactant: CC(C)=CCOc1cccc(CN)c1
Agent: CN(C)[P+](N(C)C)(N(C)C)n1nnc2ccccc21
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)=CCOc1cccc(CNC(=O)c2ccc3ncccc3c2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 80.1 %

Procedure:
6-Quinolinecarboxylic acid (100 mg, 0.577 mmol), 3-(3-methyl-2-butenyloxy)-benzylamine described in Preparation Example 134 (112 mg, 0.635 mmol), benzotriazol-1-yl-tris(dimethylamino)phosphonium hexafluorophosphate (306 mg, 0.693 mmol) and triethylamine (0.12 mL, 0.87 mmol) were dissolved in tetrahydrofuran (5 mL), and the solution was stirred at room temperature for 3 hours. The solvent was evaporated in vacuo, the obtained residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=4:1), and the title compound (153 mg, 80.1%) was obtained as a white solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[C:19]([Cl:21])[N:18]=[N:17][C:16]=2Cl)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[NH2:24][NH2:25]>CCO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[C:19]([Cl:21])[N:18]=[N:17][C:16]=2[NH:24][NH2:25])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2cc(Cl)nnc2Cl)CC1
Reactant: NN
Solvent: CCO
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(Nc2cc(Cl)nnc2NN)CC1
Temperature: 70 °C
Reaction time: 16 h

Procedure:
4-(3,6-Dichloro-pyridazin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (9.73 g; 28.03 mmol) was dissolved in 20 ml EtOH and treated with Hydrazine Hydrate (14.03 g; 280.33 mmol). It was stirred at 70° C. for 16 hours. Two peaks with product mass detected via HPLC-MS. The reaction mixture was extracted with aqueous NaHCO3 solution and DCM. The organic phase was dried and evaporated to dryness. The crude product was purified by using reversed phase chromatography under acid conditions.
Reaction SMILES: Br[CH2:2]C(=O)CC(C1C=CC=CC=1)C.[Br:14][CH2:15][C:16](=[O:28])[CH:17](C)[CH2:18][C:19]1[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][C:20]=1[CH3:26]>>[Br:14][CH2:15][C:16](=[O:28])[CH2:17][CH:18]([C:19]1[C:20]([CH3:26])=[CH:21][CH:22]=[CH:23][C:24]=1[CH3:25])[CH3:2]
Reactant: Cc1cccc(C)c1CC(C)C(=O)CBr
Reactant: CC(CC(=O)CBr)c1ccccc1
Product: Cc1cccc(C)c1C(C)CC(=O)CBr

Procedure:
According to the same method the compounds 1-bromo-4-phenyl-2-pentanone and 1-bromo-4-(2,6-dimethylphenyl)-3-methyl-2-butanone were prepared.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].ClCCl.[C:19](Cl)(=[O:21])[CH3:20].C(=O)([O-])[O-].[Na+].[Na+]>O>[CH3:10][CH:9]([CH3:11])[C:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:19](=[O:21])[CH3:20])=[C:3]([N+:13]([O-:15])=[O:14])[CH:4]=1)=[O:12]
Reactant: CC(C)C(=O)c1ccc(N)c([N+](=O)[O-])c1
Reactant: CC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CC(=O)Nc1ccc(C(=O)C(C)C)cc1[N+](=O)[O-]
Reaction time: 0.25 h
Yield: 100 %

Procedure:
To a stirred and cooled mixture (ice bath, 0° C.) of 30 parts of 1-(4-amino-3-nitrophenyl)-2-methyl-1-propanone and 390 parts of dichloromethane were added dropwise 33 parts of acetyl chloride. Upon complete addition, the reaction mixture was stirred for 12 hours at room temperature. The whole was poured into water and after the addition of sodium carbonate, stirring was continued for 15 minutes. The separated organic layer was dried, filtered and evaporated, yielding 36 parts (100%) of N-[4-(2-methyl-1-oxopropyl)-2-nitrophenyl]acetamide (interm. 14).
Reaction SMILES: [CH2:1]([CH:8]1[C:14](=[O:15])[N:13]2[CH:9]1[CH2:10][C:11](Cl)([S:26]([CH2:28][CH3:29])=[O:27])[CH:12]2[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N12CCCCC1C=NCCC2>C(OCC)(=O)C>[CH2:1]([CH:8]1[C:14](=[O:15])[N:13]2[CH:9]1[CH2:10][C:11]([S:26]([CH2:28][CH3:29])=[O:27])=[C:12]2[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCS(=O)C1(Cl)CC2C(Cc3ccccc3)C(=O)N2C1C(=O)OCc1ccccc1
Agent: C1=NCCCN2CCCCC12
Solvent: CCOC(C)=O
Product: CCS(=O)C1=C(C(=O)OCc2ccccc2)N2C(=O)C(Cc3ccccc3)C2C1
Reaction time: 0.25 h
Yield: 87.1 %

Procedure:
A solution of benzyl 6-benzyl-3-chloro-3-ethylsulphinyl-7-oxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (79) (0.020 g) in ethyl acetate (2 ml) was treated with 1,5-diazabicyclo[5.4.0]undec-5-ene (0.0069 g). It was stirred for 15 mins. at room temperature and then the solution was washed with brine and dried over sodium sulphate. Concentration of the solution gave benzyl 6-benzyl-3-ethylsulphinyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (80) (0.016 g) as a colourless gum; νmax (CHCl3) 2990, 1790, 1725 and 1590 cm-1 ; λmax (ethanol) 308 nm; τ(CDCl3) 2.5-2.9 (10H, m, phenyls), 4.66 and 4.82 (2H, ABq J 12 Hz, OCH2), 5.99 (1H, ddd J 10, 8 and 3 Hz, C5-H), 6.39 (1H, ddd J 9 6 and 3 Hz, C6-H), 6.6-7.2 (4H, m, C4-H2 and C8-H2), 7.20 (2H, q J 71/2 Hz, SCH2) and 8.76 (3H, t J 71/2 Hz, CH3); (M+ at m/e 409.1333 C23H23NO4S requires 409.1348).