Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]([CH2:20][CH3:21])[CH:4]([C:10]1[CH:19]=[CH:18][C:13]2[N:14]=[C:15](N)[S:16][C:12]=2[CH:11]=1)[N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)[CH3:2].[Br:22]C1SC2C=C(C(N3C=CN=C3)C(N(C)C)CC)C=CC=2N=1.CN(C)C(CC)C(C1C=CC2N=C(C(OC)=O)SC=2C=1)N1C=CN=C1.CN(C)C(CC)C(C1C=CC2N=C(N)SC=2C=1)N1C=CN=C1.CN(C)C(CC)C(C1C=CC2N=C(NC(N)=O)SC=2C=1)N1C=CN=C1.C(N(C)C(CC)C(C1C=CC2N=C(NC(=O)C)SC=2C=1)N1C=CN=C1)C.CN(C)C(CC)C(C1C=CC2N=C(C(=N)OC)SC=2C=1)N1C=CN=C1.CN(C)C(CC)C(C1C=CC2N=C(C(N)=O)SC=2C=1)N1C=CN=C1.BrC1SC2C=C(C(N3C=CN=C3)C(N(CC)C)CC)C=CC=2N=1.ClC1SC2C=C(C(N3C=CN=C3)C(N(CC)C)CC)C=CC=2N=1.S1C2C=C(C(N3C=CN=C3)C(N(C)C)CC)C=CC=2N=C1.C(N(C)C(CC)C(C1C=CC2N=C(N)SC=2C=1)N1C=CN=C1)C>>[Br:22][C:15]1[S:16][C:12]2[CH:11]=[C:10]([CH:4]([N:5]3[CH:9]=[CH:8][N:7]=[CH:6]3)[CH:3]([CH2:20][CH3:21])[CH2:1][CH3:2])[CH:19]=[CH:18][C:13]=2[N:14]=1
Reactant: CCC(C(c1ccc2nc(Br)sc2c1)n1ccnc1)N(C)C
Reactant: CCC(CC)C(c1ccc2nc(N)sc2c1)n1ccnc1
Agent: CCC(C(c1ccc2nc(Br)sc2c1)n1ccnc1)N(C)CC
Agent: CCC(C(c1ccc2nc(C(=N)OC)sc2c1)n1ccnc1)N(C)C
Agent: CCC(C(c1ccc2nc(C(=O)OC)sc2c1)n1ccnc1)N(C)C
Product: CCC(CC)C(c1ccc2nc(Br)sc2c1)n1ccnc1

Procedure:
6-(2-Ethyl-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-amine; 1-(2-Bromobenzo[d]thiazol-6-yl)-1-(1H-imidazol-1-yl)-N,N-dimethylbutan-2-amine; Methyl 6-(2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazole-2-carboxylate; 6-(2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-amine: 1-(6-(2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)urea; N-(6-(2-(ethyl(methyl)amino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)acetamide; Methyl 6-(2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazole-2-carbimidate; 6-(2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazole-2-carboxamide; 1-(2-Bromobenzo[d]thiazol-6-yl)-N-ethyl-1-(1H-imidazol-1-yl)-N-methylbutan-2-amine; 1-(2-Chlorobenzo[d]thiazol-6-yl)-N-ethyl-1-(1H-imidazol-1-yl)-N-methylbutan-2-amine; 1-(Benzo[d]thiazol-6-yl)-1-(1H-imidazol-1-yl)-N,N-dimethylbutan-2-amine; and 6-(2-(ethyl(methyl)amino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-amine.
Reaction SMILES: [CH:1]1([O:32][P:33]([OH:36])([OH:35])=[O:34])[CH:6]([O:7][P:8]([OH:11])([OH:10])=[O:9])[CH:5]([O:12][P:13]([OH:16])([OH:15])=[O:14])[CH:4]([O:17][P:18]([OH:21])([OH:20])=[O:19])[CH:3]([O:22][P:23]([OH:26])([OH:25])=[O:24])[CH:2]1[O:27][P:28]([OH:31])([OH:30])=[O:29]>O>[C@@H:3]1([O:22][P:23]([OH:26])([OH:25])=[O:24])[C@@H:4]([O:17][P:18]([OH:20])([OH:21])=[O:19])[C@H:5]([O:12][P:13]([OH:15])([OH:16])=[O:14])[C@@H:6]([O:7][P:8]([OH:11])([OH:10])=[O:9])[C@@H:1]([O:32][P:33]([OH:36])([OH:35])=[O:34])[C@H:2]1[O:27][P:28]([OH:30])([OH:31])=[O:29]
Reactant: O=P(O)(O)OC1C(OP(=O)(O)O)C(OP(=O)(O)O)C(OP(=O)(O)O)C(OP(=O)(O)O)C1OP(=O)(O)O
Solvent: O
Product: O=P(O)(O)O[C@H]1[C@H](OP(=O)(O)O)[C@@H](OP(=O)(O)O)[C@H](OP(=O)(O)O)[C@@H](OP(=O)(O)O)[C@H]1OP(=O)(O)O
Reaction time: 0.5 h

Procedure:
1.0 g PYY acetate (0.247 mmol) is dissolved in 100 mL water and with vigorous stirring, 11.5 mL of the phytate solution of Example 1 is added (a molar ratio of PYY:phytate=1:1). After another 30 min of stirring, the precipitate is filtered and washed 4 times with water. The final product is lyophilized.
Reaction SMILES: [NH2:1][C:2]1[C:11]([N+:12]([O-])=O)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]>O1CCCC1.[Pd]>[NH2:1][C:2]1[C:11]([NH2:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1N
Agent: [Pd]
Solvent: C1CCOC1
Product: COC(=O)c1cccc(N)c1N
Temperature: 25 °C
Reaction time: 4 h
Yield: 99.3 %

Procedure:
To a solution of methyl 2-amino-3-nitrobenzoate (29.6 g, 151 mmol) in tetrahydrofuran (containing stabilizer; 500 mL) was added palladium on carbon (3.0 g), and the mixture was purged with hydrogen and stirred under balloon pressure hydrogen at room temperature for 4 hr. The catalyst was removed by filtration, and the filtrate was concentrated in vacuo. The residual solid was washed with diethyl ether-n-hexane to give the title compound (25.0 g, 150 mmol, >99%) as a pale yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[CH3:10].Cl.[NH2:12][OH:13]>CO>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[N:12][OH:13])=[CH:4][C:3]=1[CH3:10]
Reactant: NO
Reactant: Cc1cc(C=O)ccc1Br
Agent: Cl
Solvent: CO
Product: Cc1cc(C=NO)ccc1Br
Yield: 64.7 %

Procedure:
A solution of 4-bromo-3-methylbenzaldehyde (D80) (1 g; 0.005 mol) in methanol (20 ml) was treated with hydroxylamine hydrochloride (700 mg, 0.01 mol) and the mixture stood at room temperature over a weekend. The solvent was evaporated under reduced pressure and the residual solid was partitioned between saturated K2CO3 solution and ethyl acetate. The organic phase was dried (Na2SO4), concentrated in vacuo and the residue purified by chromatography on silica gel eluting with 60-80 petroleum-ether and ethyl acetate, to afford the title compound as a pale pink powder (693 mg, 20%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-])=O)=[CH:5][C:4]=1[C:12](=[O:14])[CH3:13]>CO.[Pd]>[NH2:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([C:12](=[O:14])[CH3:13])[CH:5]=1
Reactant: COc1ccc([N+](=O)[O-])cc1C(C)=O
Agent: [Pd]
Solvent: CO
Product: COc1ccc(N)cc1C(C)=O
Yield: 84.1 %

Procedure:
A solution of 1-(2-methoxy-5-nitro-phenyl)-ethanone (350 mg, 1.8 mmol) in methanol (20 ml) was hydrogenated over 10% Pd—C (70 mg) at atmospheric pressure until no further absorption of gas took place. The reaction mixture was then filtered over celite and the filtrate concentrated under reduced pressure to give 1-(5-amino-2-methoxy-phenyl)-ethanone (250 mg, 85%) as a solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](S(C)(=O)=O)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31].[F:32][C:33]([F:37])([F:36])[CH2:34][NH2:35]>>[F:32][C:33]([F:37])([F:36])[CH2:34][NH:35][C:16]1[N:17]=[C:18]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[CH3:26])[C:13]2[CH:12]=[CH:11][C:10](=[O:31])[N:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])[C:14]=2[N:15]=1
Reactant: Cc1cc(F)ccc1-c1nc(S(C)(=O)=O)nc2c1ccc(=O)n2-c1c(F)cccc1F
Reactant: NCC(F)(F)F
Product: Cc1cc(F)ccc1-c1nc(NCC(F)(F)F)nc2c1ccc(=O)n2-c1c(F)cccc1F

Procedure:
The product of Example 48 (300 mg, 0.67 mmol) and trifluoroethylamine (300 mg, 3 mmol) were dissolved in THE (10 ml) and sealed in a vial under Ar. The mixture was heated in an oil bath to 60° for 4 days. The solvents were removed in vacuo, and the residue was flash chromatographed with 60-90% CH2Cl2/hexane. Recrystallization from CH2Cl2/hexane gave the title compound as a white crystalline solid. mp 195-196°, LC MS m/z=465(MH+) Retention time=2.38 min.
Reaction SMILES: [C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].O[N:10]1[C:14](=[O:15])[CH2:13][CH2:12][C:11]1=[O:16]>C1COCC1>[C:1]([O:8][N:10]1[C:14](=[O:15])[CH2:13][CH2:12][C:11]1=[O:16])(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCC(=O)O
Reactant: O=C1CCC(=O)N1O
Solvent: C1CCOC1
Product: CCCCCC(=O)ON1C(=O)CCC1=O
Reaction time: 5 h
Yield: 87.1 %

Procedure:
To a solution of 55.2 g (0.475 mol) of hexanoic acid and 60.161 g (0.523 mol) of N-hydroxy succinimide in 600 mL THF, 107.855 g (0.523 mol) of DCCl was added. The mixture was cooled with an ice-water bath and stirred for 5 h. The dicyclohexyl urea (DCU) precipitate was removed by filtration, and the THF solvent was removed by vacuum rotary evaporation. The yellow oil residue was dissolved again in 600 mL hexane followed by another vacuum filtration to remove the excess dicyclohexyl urea (DCU). The filtrate was then concentrated under vacuum evaporation yield a white solid, which was vacuum dried at ambient temperature to give 88.187 g (87.07%) of N-hexanoyloxy succinimide. IR (KBr): 1816 cm−1 (ν(C═O) of ester), 1745-1786 cm−1 (ν(C═O) of imide). 1H-NMR (DMSO-d6, ppm): 0.86 (3H, —CH3), 1.31 (4H, —(CH2)2CH3), 1.62 (2H, CH2CH2COO—), 2.64 (2H, —CH2COO—), 2.80 (4H, —COCH2CH2CO—).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]=1[OH:14])([O-])=O>CO.[Pd]>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[CH:12][CH:13]=[C:4]([NH2:1])[C:5]=1[OH:14]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1O
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cccc(N)c1O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of methyl 3-nitrosalicylate (26.6 mmol) in MeOH (50 mL) is treated with Pd/C (10%, 500 mg) and stirred at RT under a hydrogen atmosphere (1 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification.
Reaction SMILES: C([NH:4][C:5]1[CH:14]=[C:13]2[C:8]([NH:9][C:10](=[O:22])[C:11](=[O:21])[N:12]2[CH2:15][C:16]([O:18]CC)=[O:17])=[CH:7][CH:6]=1)(=O)C.[N+:23]([O-])([O-:25])=[O:24].[K+]>S(=O)(=O)(O)O>[NH2:4][C:5]1[CH:14]=[C:13]2[C:8]([NH:9][C:10](=[O:22])[C:11](=[O:21])[N:12]2[CH2:15][C:16]([OH:18])=[O:17])=[CH:7][C:6]=1[N+:23]([O-:25])=[O:24]
Reactant: CCOC(=O)Cn1c(=O)c(=O)[nH]c2ccc(NC(C)=O)cc21
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: Nc1cc2c(cc1[N+](=O)[O-])[nH]c(=O)c(=O)n2CC(=O)O
Temperature: 0 °C
Yield: 69.3 %

Procedure:
57.5 g (0.19 mol) of 7-acetamido-1-(ethoxycarbonylmethyl)-2,3(1H,4H)-quinoxalinedione were dissolved in 575 ml of concentrated sulfuric acid. The solution was cooled to 0° C., and 19.0 g (0.19 mol) of potassium nitrate were added a little at a time. The cooling was then removed and the mixture was stirred until the reaction was complete and was then poured into 2 l of ice-water and heated on a water bath for 2 h. The pH was then adjusted with aqueous ammonia solution to about 4-5, and the precipitate was filtered off with suction. The filtrate was concentrated under reduced pressure, and the residue was purified by chromatography on silica gel (mobile phase: methanol/tetrahydrofuran/water==5:4:1+2.5% glacial acetic acid). The resulting product was combined with the first precipitate to yield 36.9 g (70%) of product.
Reaction SMILES: [CH3:1][OH:2].[Na].C[O-].[Na+].[Br:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12](Br)[CH:13]=1>CN(C=O)C>[Br:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([O:2][CH3:1])[CH:13]=1
Reactant: Brc1cncc(Br)c1
Reactant: CO
Agent: C[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CN(C)C=O
Product: COc1cncc(Br)c1
Temperature: 70 °C
Yield: 62 %

Procedure:
A solution of methanol (180 mL) was treated with sodium spheres (4.7 g, 0.20 mol) portionwise, evaporated to dryness, azeotroped with toluene (100 mL), and then concentrated under reduced pressure. The sodium methoxide in dry DMF (130 mL) was treated with 3,5-dibromopyridine (32 g, 135 mmol), from Avocado Chemicals. After heating at 70° C. for 4 hours, the mixture was poured onto ice/water (300 g) and filtered. The filter cake was dried under reduced pressure to provide the title compound (15.6 g, 62% yield). MS (DCI/NH3) m/z 188/190 (M+H)+.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:13]=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)[CH2:8][CH2:7]1)=[O:5])C.O[Li].O>C1COCC1.O.CO>[CH3:19][O:18][C:15]1[N:14]=[N:13][C:12]([N:9]2[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]2)=[CH:17][CH:16]=1
Reactant: CCOC(=O)C1CCN(c2ccc(OC)nn2)CC1
Agent: [Li]O
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(N2CCC(C(=O)O)CC2)nn1
Reaction time: 8 h
Yield: 51.7 %

Procedure:
To a stirred solution 1-(6-methoxy-pyridazin-3-yl)-piperidine-4-carboxylic acid ethyl ester (3.20 g, 12.06 mmol) in THF (40 mL), H2O (40 mL) and MeOH (4 mL) was added LiOH.H2O (600 mg, 14.3 mmol). Stirring was continued overnight at RT before the organic solvent were removed under vacuo. The pH of the was adjusted to 5 with acetic acid, and the product extracted with EtOAc, dried over Na2SO4. The resulting solid was suspended in heptane, filtered off, washed with cold Et2O to give 1.48 g (61%) of 1-(6-methoxy-pyridazin-3-yl)-piperidine-4-carboxylic acid. ES-MS m/e: 236.2 (M−H+)
Reaction SMILES: O[C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.O.[OH-].[Na+].P(Cl)(Cl)([Cl:16])=O>>[Cl:16][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Oc1nc2ccccc2[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Clc1nc2ccccc2[nH]1
Reaction time: 6 h

Procedure:
A solution of 2-hydroxy benzimidazole (40.2 g) in 93 ml phosphorus oxychloride is heated to reflux under stirring for 6 hours. After achievement of the reaction the solution is let to revert to -10° C. and hydrolysed with 100 g crushed ice and 100 ml iced water. They are slowly added 249 ml sodium hydroxide 10N to get a neutral pH value. The precipitated product is filtered, washed with the minimal amount of water. The crystals are taken up in hot ethanol. After cooling, the alcoholic juice are filtered and concentrated to dryness.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]2[CH2:8][C:9]3[C:21]4[NH:20][C:19]5[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=5)[C:13]=4[C:12]4[C:22](=[O:25])[NH:23][CH2:24][C:11]=4[C:10]=3[C:4]=2[CH:3]=1.C[Si]([C:30]#[CH:31])(C)C.C(N(CC)CC)C.CO>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[C:30]([C:2]1[CH:7]=[CH:6][C:5]2[CH2:8][C:9]3[C:21]4[NH:20][C:19]5[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=5)[C:13]=4[C:12]4[C:22](=[O:25])[NH:23][CH2:24][C:11]=4[C:10]=3[C:4]=2[CH:3]=1)#[CH:31]
Reactant: C#C[Si](C)(C)C
Reactant: O=C1NCc2c3c(c4[nH]c5ccccc5c4c21)Cc1ccc(Br)cc1-3
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C#Cc1ccc2c(c1)-c1c3c(c4c([nH]c5ccccc54)c1C2)C(=O)NC3
Temperature: 25 °C
Reaction time: 24 h
Yield: 8.2 %

Procedure:
To a solution of 3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7-(7H)one (Compound I-9) (435 mg, 1.1 mmol), trimethylsilylacetylene (0.47 ml, 3.3 mmol) and triethylamine (1.0 mL) in DMF (11 mL) was added bis(triphenylphosphine)palladium(II)chloride (17 mg). The solution was heated in a sealed reaction tube at 100°-110° C. for 24 h. The mixture was cooled to ambient temperature, filtered through a pad of celite then the solvent concentrated at reduced pressure. The product was dissolved in DMF (8 mL), MeOH (8 mL) cesium fluoride (370 mg, 2.4 mmol) added and the mixture stirred at ambient temperature 24 h. The solvent was concentrated at reduced pressure to give a dark solid. Purification by column chromatography (silica gel, EtOAc:MeOH; 10:1, Rf=0.53) give 30 mg of a tan solid. The compound was further purified by preparative TLC (silica gel, EtOAc:hexane; 3:1) to give Compound I-36 as a tan solid, mp>300° C. 1H NMR (DMSO-d6, 300 MHz): d 4.2 (s, 2H), 5.0 (s, 2H), 7.38-7.46 (m, 3H), 7.58-7.75 (m,4H), 8.15 (s, 1H), 8.63 (s, 1H), 9.42 (d, 1H, J=9Hz), 12.19 (s, 1H); MS m/e=335 (m+).
Reaction SMILES: CO[CH:3](OC)[C:4](=[N:7][OH:8])[C:5]#[N:6].[OH:11][CH2:12][CH2:13][NH:14][NH2:15].O.[S:17](=[O:21])(=[O:20])([OH:19])[OH:18]>CO>[S:17]([OH:21])([OH:20])(=[O:19])=[O:18].[NH2:6][C:5]1[N:14]([CH2:13][CH2:12][OH:11])[N:15]=[CH:3][C:4]=1[N:7]=[O:8]
Reactant: NNCCO
Reactant: COC(OC)C(C#N)=NO
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CO
Product: Nc1c(N=O)cnn1CCO
Temperature: 66.5 °C
Yield: 88.1 %

Procedure:
To a flask having an inner volume of 25 ml and equipped with a stirring device, a thermometer and a reflux condenser were charged 1.47 g (10.0 mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of 98.1% by weight synthesized in the same manner as in Example 1, 0.84 g (10.5 mmol) of 2-hydroxyethylhydrazine with a purity of 95% by weight, 0.54 ml of water, 10 ml of methanol and 1.18 g (12.0 mmol) of conc. sulfuric acid, and the mixture was reacted under reflux (66 to 67° C.) for 3 hours. After completion of the reaction, when the reaction mixture was analyzed by high performance liquid chromatography (absolute calibration curve method), it was found that 2.24 g of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrogen sulfate (Reaction yield: 88.2%) had been formed.
Reaction SMILES: [O:1]=[C:2]1[CH2:18][CH2:17][CH2:16][O:15][C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1>[Co].C(O)(C)C>[OH:1][CH:2]1[CH2:18][CH2:17][CH2:16][O:15][C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=C1CCCCCCCCCCC(=O)OCCC1
Agent: [Co]
Solvent: CC(C)O
Product: O=C1CCCCCCCCCCC(O)CCCO1
Yield: 95.2 %

Procedure:
480 g (1.89 mol) of 12-oxo-15-pentadecanolide (VI) are mixed with 1,000 g of isopropanol and hydrogenated in an autoclave with addition of 9.6 g of Raney cobalt under a hydrogen pressure of 100 bar at 135° C. After the solvent has been stripped off, distillation of the residue gives 460 g (1.80 mol) of 12-hydroxy-15-pentadecanolide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:7][CH:8]=1.C1(=O)O[C:16](=[O:17])[C:15]2=[CH:19][CH:20]=[CH:21][CH:22]=[C:14]12>C([O-])(=O)C.[Na+]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][CH:8]=1)[CH:9]=[C:10]1[C:19]2[C:15](=[CH:14][CH:22]=[CH:21][CH:20]=2)[C:16](=[O:17])[O:12]1
Reactant: COc1cccc(CC(=O)O)c1
Reactant: O=C1OC(=O)c2ccccc21
Agent: CC(=O)[O-]
Agent: [Na+]
Product: COc1cccc(C=C2OC(=O)c3ccccc32)c1
Temperature: 240 °C
Yield: 69.7 %

Procedure:
A mixture of 15 g (89 mmol) of m-methoxyphenyl acetic acid, 13.2 g (89 mmol) of phthalic anhydride and 246 mg (2.9 mmol) of sodium acetate was heated to 240° C. for 6 hours and water was continuously removed from the reaction. The solid formed in the reaction flask on cooling. This was recrystallized from absolute ethanol to obtain 15.6 g (62 mmol, 69%) of 1 as yellow powder.
Reaction SMILES: [C:1]1([CH:7]([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(C1C=CC(C)=CC=1)C.O=O>>[CH3:9][C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[CH2:8]
Reactant: CC(C)c1ccccc1
Agent: O=O
Solvent: CCc1ccc(C)cc1
Product: C=C(C)c1ccccc1

Procedure:
This example illustrates the dehydrogenation of cumene and p-ethyltoluene using a diluent comprising steam and nitrogen. Three and three-tenths of the catalyst prepared in Example I, ground to 18 to 40 mesh, was employed in the reactor described in Example I. Initially p-ethyltoluene was flowed into the reactor at 0.38 liquid hourly space velocity, 11:1 diluent to p-ethyltoluene ratio (8:1 steam and 3:1 nitrogen) at 588° C. yielding a relatively poor conversion and selectivity. The catalyst was decoked with 5% oxygen and nitrogen for about 1 hr. Cumene was then run at 0.38 liquid hourly space velocity, 11:1 diluent ratio (8:1 steam and 3:1 nitrogen) at 588° C. providing 40% conversion to alphamethylstyrene and 88% selectivity. The feed was then switched from cumene to p-ethyltoluene using the same diluent dilution and conditions providing 22% conversion to p-methylstyrene and 93% selectivity. Conditions were then changed to 0.72 liquid hourly space velocity, 10:1 diluent ratio for the p-ethyltoluene (8:1 steam and 2:1 nitrogen) at 598° C. yielding 40% conversion and 92% selectivity to p-methylstyrene.
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][C@@H:8]2[O:12][CH2:11][C@@H:10]([S:13]C(=O)C)[CH2:9]2)=[CH:4][CH:3]=1.C[O-].[Na+].CO>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH:8]2[O:12][CH2:11][CH:10]([SH:13])[CH2:9]2)=[CH:17][CH:18]=1
Reactant: CC(=O)S[C@@H]1CO[C@@H](COc2ccc(F)cc2)C1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: Fc1ccc(OCC2CC(S)CO2)cc1
Yield: 52.4 %

Procedure:
The title compound is prepared by the procedure of Example 16 using 0.943 g of product from Example 35, 0.86 ml of 25% sodium methoxide/methyl alcohol and 12 ml of tetrahydrofuran to give 0.417 g of the desired product.
Reaction SMILES: [NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][SH:4].[OH-].[Na+].[CH:10]1([CH2:13]Br)[CH2:12][CH2:11]1.Cl>C(O)C>[CH:10]1([CH2:13][S:4][CH2:3][C@@H:2]([C:5]([OH:7])=[O:6])[NH2:1])[CH2:12][CH2:11]1
Reactant: BrCC1CC1
Reactant: N[C@@H](CS)C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: N[C@@H](CSCC1CC1)C(=O)O
Temperature: 27.5 °C
Reaction time: 18 h
Yield: 88.6 %

Procedure:
To a suspension of L-cysteine (100 g) in ethanol (850 mL) under nitrogen was added over 40 min a solution of sodium hydroxide (2.0 eq., 64.6 g) in ethanol (650 mL) (the sodium hydroxide solution was maintained below 40° C. during its preparation, 3 hours for complete dissolution). After the addition, cyclopropylmethyl bromide (1.1 eq., 122.5 g) was added over 20 minutes while maintaining the temperature at 25-30° C. with a cold bath. The resulting white slurry was stirred for another 18 hours and then quenched by adding 2N HCl (0.73 eq., 300 mL) over 20 minutes. The thick suspension was concentrated (100 mbars, 52° C. bath) to about 400 mL (1.5L ethanol/water distilled) and then water (750 mL) was added. The pH (9.6) was adjusted to pH 6.5 with 2N HCl and the mixture was stirred at 4° C. for 2 hours and then filtered. The cake was washed five times with water (100 mL) and then dried in vacuum to afford S-cyclopropylmethyl-L-cysteine (128.2 g, 88.6% yield).
Reaction SMILES: [CH:1]1([N:7]([CH2:25][CH:26]2[CH2:28][CH2:27]2)[C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=3)=[O:15])[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C(Cl)Cl.O=[Mn]=O>[CH:1]1([N:7]([CH2:25][CH:26]2[CH2:28][CH2:27]2)[C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]=[O:24])=[CH:19][CH:18]=3)=[O:15])[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Nc1ccc(CO)cc1)c1cc(N(CC2CC2)C2CCCCC2)ncn1
Agent: O=[Mn]=O
Solvent: ClCCl
Product: O=Cc1ccc(NC(=O)c2cc(N(CC3CC3)C3CCCCC3)ncn2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 92.7 %

Procedure:
A solution of 6-[cyclohexyl(cyclopropylmethyl)amino]-N-[4-(hydroxymethyl)phenyl]pyrimidine-4-carboxamide (Intermediate 23, 990 mg; 2.60 mmol) in DCM (100 ml) was treated with MnO2 (2262 mg; 26.0 mmol) and the reaction mixture was stirred at room temperature for 18 hours the mixture was filtered through celite and the solvent was removed under vacuum affording a the title compound as a yellow solid (912 mg; 79%), which was used without further purification for the following steps.