Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)[NH2:6].C(N(CC)CC)C.Cl[CH2:24][CH2:25][N:26]=[C:27]=[O:28].C(OCC)(=O)C>C1(C)C=CC=CC=1>[F:1][C:2]([F:14])([F:15])[C:3]1[CH:4]=[C:5]([N:6]2[CH2:24][CH2:25][NH:26][C:27]2=[O:28])[CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=1
Reactant: Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: O=C=NCCCl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: O=C1NCCN1c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 60 °C
Reaction time: 4 h
Yield: 25.5 %

Procedure:
To a solution of 3,5-bis(trifluoromethyl)aniline (21.1 g) and triethylamine (13.9 mL) in toluene (200 ml) was slowly added 2-chloroethyl isocyanate (10.0 g) at 0° C., and the mixture was stirred at 60° C. for 4 hr. To the reaction solution was added ethyl acetate, and the mixture was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (250 ml), sodium hydride (4.0 g) was slowly added at 0° C., and the mixture was stirred at room temperature for 3 hr. To the reaction solution was added ethyl acetate, and the mixture was washed with water and saturated brine, and dried over sodium sulfate. The solvent was concentrated under reduced pressure to give the title compound as a white solid (7.0 g, yield 26%).
Reaction SMILES: [NH2:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4].[C:9]([N:13]=[C:14]=[O:15])([CH3:12])([CH3:11])[CH3:10]>[OH-].[Na+].O1CCCC1>[C:9]([NH:13][C:14]([NH:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:15])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC(C)(C)N=C=O
Reactant: CC(C)[C@H](N)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)[C@H](NC(=O)NC(C)(C)C)C(=O)O
Reaction time: 8 h
Yield: 76.2 %

Procedure:
4.69 g of L-valine was dissolved in 40 ml of a 1N sodium hydroxide aqueous solution, and 5 ml of tetrahydrofuran was added to the solution. While stirring, 4.00 g of tert-butyl isocyanate was added, and the stirring was continued overnight at room temperature. After 10 ml of a 1N sodium hydroxide aqueous solution was added to the reaction mixture, the mixture was washed twice with 50 ml of ethyl acetate and acidified with 6N hydrochloric acid. Then, the reaction mixture was extracted twice with 100 ml of ethyl acetate. The extracts were washed twice with 50 ml of a saturated sodium chloride aqueous solution. After drying over anhydrous sodium sulfate and then concentrating under reduced pressure, recrystallization was carried out from an ethyl acetate-hexane mixture to obtain 6.6 g of N-tert-butylcarbamoyl-L-valine as white crystals.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:25])([C:16]([C:18]1[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=1)=[CH2:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[CH3:26][Si:27]([C:30]#[CH:31])([CH3:29])[CH3:28]>[Pd](Cl)Cl.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.C(N(CC)CC)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:25])([C:16]([C:18]1[CH:23]=[CH:22][C:21]([C:31]#[C:30][Si:27]([CH3:29])([CH3:28])[CH3:26])=[CH:20][CH:19]=1)=[CH2:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: C=C(c1ccc(I)cc1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: C=C(c1ccc(C#C[Si](C)(C)C)cc1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 24 h
Yield: 97.5 %

Procedure:
A mixture of 2-(2,4-difluorophenyl)-3-(4-iodophenyl)-1-(1,2,4-triazol-1-yl)-3-buten-2-ol (7.0 g, 15.5 mmol-see Preparation 20), trimethylsilylacetylene (2.6 ml, 18.5 mmol), cuprous iodide (0.015 g, 0.15 mmol), bis(triphenylphosphine) palladium (II) dichloride (0.21 g, 0.3 mmol) and triethylamine (80 ml) was stirred at room temperature under a nitrogen atmosphere for 24 hours. Volatile materials were removed under reduced pressure and the residue was partitioned between dichloromethane (200 ml) and a solution of ethylenediaminetetraacetic acid (2 g) in water (100 ml). The organic phase was dried (MgSO4) and evaporated under reduced pressure. The crude product was chromatographed on silica by elution with dichloromethanelmethanol (95:5). Fractions containing the desired product were combined and evaporated under reduced pressure to give 2-(2,4-difluorophenyl)-3-(4-[trimethylsilylethynyl]phenyl)-1-(1,2,4-triazol-1-yl)-3-buten-2-ol (6.4 g, 98%) as a yellow foam which was characterised by 1H-N.M.R. spectroscopy, (300 MHz, CDCl3): δ=0.22 (s,9H), 4.57 (d,1H), 4.89 (d,1H), 5.16 (s,1H), 5.26 (d,2H), 6.60-6.80 (m,2H), 7.21 (d,2H), 7.38 (d,2H), 7.42 (m,1H), 7.80 (s,2H) ppm.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[OH:8].[C:12]([O-])([O-])=O.[K+].[K+].O>CO>[CH3:1][C:2]1[CH:3]=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[O:8][CH3:12]
Reactant: O=C([O-])[O-]
Reactant: CC(=O)c1ccc(O)c(C)c1
Agent: [K+]
Solvent: O
Solvent: CO
Product: COc1ccc(C(C)=O)cc1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.1 %

Procedure:
To a stirred solution of 1-(3-methyl-4-hydroxylphenyl)ethanone (15.02 g, 100 mmol) in MeOH was added K2CO3 (41.5 g, 300 mmol), and Mel (28.4 g, 200 mmol). The reaction mixture was stirred at room temperature for 2 hours. Another 56.7 g of Mel was added, and the reaction mixture was stirred for an additional 2 hours. Water (50 ml) was added, and the product was extracted with 600 ml of EtOAc. The organic layer was washed with brine (250 ml), and dried with Na2SO4, and the solvent was removed in vacuo to give the title compound (10.2 g, 62%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[CH2:18][CH2:17][CH2:16]2.C(N(C(C)C)CC)(C)C>O1CCOCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[CH2:18][CH2:17][CH2:16]3)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Reactant: Nc1ccc2c(c1)CCC2
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: O=[N+]([O-])c1cnc(Cl)nc1Nc1ccc2c(c1)CCC2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 2,4-dichloro-5-nitropyrimidine (5.0 g, 25.8 mmol) in dioxane (35 mL) was added a solution of 5-aminoindane (3.43 g, 25.8 mmol) in dioxane (9 mL) and diisopropylethyl amine (4.5 mL, 25.8 mmol). The mixture was stirred at 25° C. for 1 hr and then concentrated to a residue to provide crude (2-chloro-5-nitro-pyrimidin-4-yl)-indan-5-yl-amine, (1).
Reaction SMILES: Cl.[NH:2]1[C:12]2[C:13]3[C:4]([CH2:5][NH:6][CH2:7][C:8]=3[CH:9]=[CH:10][CH:11]=2)=[CH:3]1.[C:14](OC(=O)C)(=[O:16])[CH3:15]>N1C=CC=CC=1>[C:14]([N:6]1[CH2:5][C:4]2=[CH:3][NH:2][C:12]3[C:13]2=[C:8]([CH:9]=[CH:10][CH:11]=3)[CH2:7]1)(=[O:16])[CH3:15]
Reactant: CC(=O)OC(C)=O
Reactant: c1cc2c3c(c[nH]c3c1)CNC2
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)N1Cc2cccc3[nH]cc(c23)C1

Procedure:
A mixture of 1,3,4,5-tetrahydropyrrolo[4,3,2-de]isoquinoline hydrochoride (9.8 g), described in Example 5, in 30 ml of pyridine and 10 ml of acetic anhydride is heated at 50°C for 2 hr. The excess anhydride is destroyed by the addition of water. The mixture is poured into cold 5% HCl. The resulting precipitate is collected and recrstallized from ethanol to give 4-acetyl-1,3,4,5 -tetrahydropyrrolo[4,3,2-de]isoquinoline, mp 205°-206°C.
Reaction SMILES: C([O-])(O)=O.[Na+].Br[CH2:7][CH:8](OC)OC.Br.[Cl:14][C:15]1[N:20]=[C:19]([NH2:21])[CH:18]=[N:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>O.CCCCCC.C(OC(=O)C)C.CC(O)C>[Cl:14][C:15]1[N:20]2[CH:7]=[CH:8][N:21]=[C:19]2[CH:18]=[N:17][CH:16]=1
Reactant: COC(CBr)OC
Reactant: Nc1cncc(Cl)n1
Agent: Br
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Solvent: CCCCCC
Product: Clc1cncc2nccn12
Reaction time: 0.08 h
Yield: 25.3 %

Procedure:
NaHCO3 (4.215 g, 50.1736 mmol) and IPA (40 mL) were added to a mixture of 2-bromo-1,1-dimethoxy-ethane (6.37 mL, 10.8066 mmol), 40% HBr (475 mL, 2.3157 mmol) and 2 drops of water previously refluxed for 1 hr. The reaction mixture was stirred for 5 mins and filtered. To the filtrate was added 6-chloro-pyrazin-2-ylamine (1 g, 7.7190 mmol) and the resulting mixture was refluxed for overnight. The reaction was monitored by TLC (50% ethylacetate in hexane). The reaction mixture was neutralized with Na2CO3 and partitioned between ethylacetate and water. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. Purification by column chromatography on silica gel (1-2% MeOH in CHCl3) afforded 300 mg of the product (25.31% yield).
Reaction SMILES: [CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([OH:12])[CH2:9][C@H:8]1[CH2:13][C:14]1[CH:15]=[N:16][CH:17]=[N:18][CH:19]=1)=[O:6])[CH:2]=[CH2:3].C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>ClCCl>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][S:28]([CH3:27])(=[O:30])=[O:29])[CH2:9][C@H:8]1[CH2:13][C:14]1[CH:15]=[N:16][CH:17]=[N:18][CH:19]=1)=[O:6])[CH:2]=[CH2:3]
Reactant: CS(=O)(=O)Cl
Reactant: C=CCOC(=O)N1C[C@H](O)C[C@H]1Cc1cncnc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1Cc1cncnc1
Temperature: 0 °C
Yield: 92.6 %

Procedure:
Under nitrogen atmosphere to a solution of (2R,4R)-1-allyloxycarbonyl-4-hydroxy-2-(pyrimidin-5-ylmethyl)pyrrolidine (21.0 g) in dichloromethane (105 ml) were added triethylamine (16.1 g) firstly and methanesulfonyl chloride (13.7 g) secondly at 5° to 10° C. After the reaction mixture was stirred for an hour at the same temperature, dichloromethane (50 ml) and ice-water (150 ml) were added thereto, and then the solution was stirred vigorously for twenty minutes. The organic layer was separated and washed with 1N-hydrochloric acid (100 ml), 1N-sodium hydroxide (200 ml), and brine (200 ml). The organic layer was dried over magnesium sulfate and evaporated under reduced pressure to give (2R,4R)-1-allyloxycarbonyl-4-methanesulfonyloxy-2-(pyrimidin-5-ylmethyl) pyrrolidine (25.2 g) as an oil.
Reaction SMILES: Cl.Cl.[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([CH3:6])([CH3:5])[CH3:4].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([CH2:32][O:33][C:34]2[CH:42]=[CH:41][C:37]([C:38](O)=[O:39])=[CH:36][CH:35]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>O.CN(C)C=O.C(N(CC)CC)C>[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][N:16]([C:38]([C:37]2[CH:36]=[CH:35][C:34]([O:33][CH2:32][CH:29]3[CH2:28][CH2:27][N:26]([C:24]([O:23][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:25])[CH2:31][CH2:30]3)=[CH:42][CH:41]=2)=[O:39])[CH2:15][CH2:14]1)([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)OC(=O)N1CCC(COc2ccc(C(=O)O)cc2)CC1
Reactant: CC(C)(C)c1ccccc1N1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(COc2ccc(C(=O)N3CCN(c4ccccc4C(C)(C)C)CC3)cc2)CC1
Temperature: 25 °C
Yield: 87 %

Procedure:
A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (1.0 g), 4-{[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy}benzoic acid obtained in Reference Example 6 (1.41 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (824 mg), 1-hydroxy-1H-benzotriazole monohydrate (659 mg), triethylamine (1.53 mL), and N,N-dimethylformamide (10 mL) was stirred at room temperature for over-night. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (NH-silica gel, 10:90-0:100 hexane/ethyl acetate) to provide the title compound (1.6 g, 87%) as crystals.
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[CH2:29]([O:36][C:37]1[C:38]([NH:45][C:46]2[S:47][CH:48]=[C:49]([CH3:51])[N:50]=2)=[N:39][CH:40]=[C:41]([CH:44]=1)[CH:42]=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C1COCC1>[CH2:29]([O:36][C:37]1[C:38]([NH:45][C:46]2[S:47][CH:48]=[C:49]([CH3:51])[N:50]=2)=[N:39][CH:40]=[C:41]([CH:42]=[CH:2][O:3][CH3:4])[CH:44]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: Cc1csc(Nc2ncc(C=O)cc2OCc2ccccc2)n1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COC=Cc1cnc(Nc2nc(C)cs2)c(OCc2ccccc2)c1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 70.7 %

Procedure:
A 250 mL round-bottomed flask was charged with (methoxymethyl)triphenylphosphonium chloride (6.8 g, 20 mmol), THF (40 mL) and cooled to −78° C. under nitrogen. Butyllithium (8.0 ml, 20 mmol) was slowly added and stirred for 30 min at 0° C. The reaction was cooled to −78° C. and 5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)nicotinaldehyde (2.6 g, 8.0 mmol) dissolved in THF (10 mL) was added slowly and stirred at −78° C. and slowly warmed to ambient temperature. After stirring for 2 hours the reaction was partitioned between EtOAc and water. The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified on a silica gel column (15 to 25% EtOAc/hexanes) to afford the title compound (2.0 g, 71% yield) as a pale yellow foam (about a 1:1 mixture of E and Z isomers). Mass spectrum (apci) m/z=354.1 (M+H).
Reaction SMILES: [CH:1]1([NH:4][CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[O:15][N:14]=[C:13]([CH:16]([CH3:18])[CH3:17])[N:12]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[F:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[N:29]1[CH:33]=[N:32][CH:31]=[N:30]1)[C:23](O)=[O:24]>>[CH:1]1([N:4]([CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[O:15][N:14]=[C:13]([CH:16]([CH3:18])[CH3:17])[N:12]=3)[CH2:7][CH2:6]2)[C:23](=[O:24])[C:22]2[CH:26]=[CH:27][C:28]([N:29]3[CH:33]=[N:32][CH:31]=[N:30]3)=[C:20]([F:19])[CH:21]=2)[CH2:2][CH2:3]1
Reactant: O=C(O)c1ccc(-n2cncn2)c(F)c1
Reactant: CC(C)c1noc(N2CCC(NC3CC3)CC2)n1
Product: CC(C)c1noc(N2CCC(N(C(=O)c3ccc(-n4cncn4)c(F)c3)C3CC3)CC2)n1

Procedure:
The title compound is prepared from cyclopropyl-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-amine and 3-fluoro-4-[1,2,4]triazol-1-yl-benzoic acid following a procedure analogous to that described in Example 90. LC (method 19): tR=3.84 min; Mass spectrum (ESI+): m/z=440 [M+H]+.
Reaction SMILES: [C:1](=[N:9][OH:10])([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:11](Cl)(=[O:15])[O:12][CH2:13][CH3:14]>C(Cl)(Cl)Cl>[CH2:13]([O:12][C:11]([O:10][N:9]=[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[NH2:8])=[O:15])[CH3:14]
Reactant: NC(=NO)c1ccccc1
Reactant: CCOC(=O)Cl
Solvent: ClC(Cl)Cl
Product: CCOC(=O)ON=C(N)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95 %

Procedure:
To a solution of benzamide oxime (25.0 g, 184 mmol) in chloroform (250 ml) was added dropwise a solution of ethyl chlorocarbonate (8.79 ml, 92.0 mmol) in chloroform (60 ml), and the mixture was stirred at room temperature for 3 hours. Insolubles were filtered off, and then the filtrate was concentrated. The residue was recrystallized from a mixed solvent of ethanol and water to yield 18.2 g (94.8%) of the desired product.
Reaction SMILES: [CH3:1][C:2]([CH3:28])=[CH:3][CH2:4][CH2:5]/[C:6](/[CH3:27])=[CH:7]/[CH2:8][CH2:9]/[C:10](/[CH3:26])=[CH:11]/[CH2:12][CH2:13][C:14]1([CH3:25])[O:19][C:18]2[CH:20]=[CH:21][C:22]([OH:24])=[CH:23][C:17]=2[CH2:16][CH2:15]1.[CH3:29]CCCCC.C(OC(=O)C)C>>[CH3:29][C:20]1[C:18]2[O:19][C@@:14]([CH2:13][CH2:12]/[CH:11]=[C:10](/[CH2:9][CH2:8]/[CH:7]=[C:6](/[CH2:5][CH2:4][CH:3]=[C:2]([CH3:28])[CH3:1])\[CH3:27])\[CH3:26])([CH3:25])[CH2:15][CH2:16][C:17]=2[CH:23]=[C:22]([OH:24])[CH:21]=1
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CCC1(C)CCc2cc(O)ccc2O1
Reactant: CCCCCC
Solvent: CCOC(C)=O
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/CC[C@]1(C)CCc2cc(O)cc(C)c2O1

Procedure:
Tocotrienol isomers were derived from tocotrienol rich fraction of palm oil received from First Tech International Ltd., Hong Kong and was fractionated using silica gel column chromatography with n-hexane/ethylacetate (gradient elution) as a mobile phase to yield pure δ-tocotrienol.
Reaction SMILES: C(OC([N:7]1[C@H:11]([CH:12]([OH:21])[C:13]2[S:17][C:16]3=[CH:18][N:19]=[CH:20][N:15]3[CH:14]=2)[CH2:10][C@H:9]([S:22][C:23]2[C@H:24]([CH3:40])[C@@H:25]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:26]3[C:27]=2[C:28]([O:30]CC=C)=[O:29])[CH2:8]1)=O)C=C.CNC1C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[OH:38][C@@H:36]([C@H:35]1[C:34](=[O:39])[N:26]2[C:27]([C:28]([OH:30])=[O:29])=[C:23]([S:22][C@H:9]3[CH2:10][C@@H:11]([CH:12]([OH:21])[C:13]4[S:17][C:16]5=[CH:18][N:19]=[CH:20][N:15]5[CH:14]=4)[NH:7][CH2:8]3)[C@H:24]([CH3:40])[C@H:25]12)[CH3:37]
Reactant: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](C(O)c3cn4cncc4s3)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CNc1ccccc1
Solvent: CN(C)C=O
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](C(O)c4cn5cncc5s4)C3)[C@H](C)[C@H]12
Yield: 10.9 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (8.4 mg) is added to a solution of 40.6 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate (stereoisomer A) and 0.045 ml of N-methylaniline in 1. 0 ml of DMF, and the mixture is stirred in an argon atmosphere at room temperature for 35 min. DMF is removed by evaporation under reduced pressure, 3 ml of distilled water is added to the residue, and the mixture is extracted three times with 5 ml of ethyl acetate while removing insolubles. The aqueous layer is concentrated under reduced pressure to distil-off ethyl acetate, and the concentrate is then purified by column chromatography on Cosmosil 40C18-PREP (water-methanol) to give 3.5 mg of the title compound as a colorless flocculent material.
Reaction SMILES: [C:1](=[O:4])([O-:3])[O-:2].[Na+:5].[Na+].[C:7](=O)([OH:9])[O-:8].[OH-].[Na+]>>[OH-:2].[Na+:5].[C:7]([O-:9])(=[O:8])[C:1]([O-:3])=[O:4].[Na+:5].[Na+:5]
Reactant: O=C([O-])O
Reactant: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Product: O=C([O-])C(=O)[O-]

Procedure:
Causticisation with lime slurry then converts the sodium carbonate and bicarbonate to sodium hydroxide. The recovery of sodium hydroxide from the effluent results in soda savings of approximately 0.6 tonne/tonne of sodium oxalate. It is estimated that this will result in savings of over 5600 tonnes per annum at the Worsley Alumina refinery alone.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[N:9]=[CH:10][C:11]([NH2:20])=[N:12][C:13]=1[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[Br:21]N1C(=O)CCC1=O>CS(C)=O.O>[Br:21][C:10]1[C:11]([NH2:20])=[N:12][C:13]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[C:8]([C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[F:1])[N:9]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Nc1cnc(-c2ccncc2F)c(-c2cccnc2)n1
Solvent: O
Solvent: CS(C)=O
Product: Nc1nc(-c2cccnc2)c(-c2ccncc2F)nc1Br
Temperature: 25 °C
Reaction time: 5 h
Yield: 30.9 %

Procedure:
To a 0° C. stirred solution of 5-(3-fluoropyridin-4-yl)-6-pyridin-3-ylpyrazin-2-amine (Example 115) (1.10 g, 4.11 mmol) in a mixture of DMSO (13 mL) and water (0.34 mL), was added N-bromosuccinimide (0.77 g, 4.32 mmol) in portions. After stirring for 5 h at room temperature, the mixture was poured into water, the precipitate collected by filtration, washed with water and dried to give the title compound as a green solid (0.44 g, 31%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([N+:16]([O-:18])=[O:17])[C:14]=1F)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.Cl.[CH3:20][N:21]([CH3:25])[CH2:22][CH2:23][SH:24].C([Li])CCC.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([N+:16]([O-:18])=[O:17])[C:14]=1[S:24][CH2:23][CH2:22][N:21]([CH3:25])[CH3:20])[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1
Reactant: CN(C)CCS
Reactant: O=[N+]([O-])c1c(F)c(Cl)cc2c1[nH]c1cnccc12
Agent: Cl
Agent: [Li]CCCC
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)CCSc1c(Cl)cc2c([nH]c3cnccc32)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 84 %

Procedure:
A 25 ml round-bottom flask with magnetic stirrer was charged with 6-chloro-7-fluoro-8-nitro-9H-β-carboline (98 mg, 0.37 mmol) in 2 ml of anhydrous DMF. A second 10 ml round-bottom flask with magnetic stirrer was charged with 2-dimethylamino-ethanethiol hydrochloride (100 mg, 0.70 mmol) in 2 ml anhydrous DMF. To the resulting suspension was added n-butyllithium (0.43 ml of 1.6 M solution in hexanes, 0.69 mmol) via syringe and the mixture was stirred for 5 min at RT. Next, the thioanion solution was added via syringe to 6-chloro-7-fluoro-8-nitro-9H-β-carboline, and the resulting red solution was stirred at RT for 30 min. The reaction mixture was slowly added to a 5:1 mixture of H2O/saturated aqueous sodium bicarbonate (30 ml) and allowed to sit at RT for several hours. The resulting precipitated solid was collected via suction filtration and air-dried to afford 109 mg of [2-(6-chloro-8-nitro-9H-β-carbolin-7-ylsulfanyl)-ethyl]-dimethyl-amine as an orange solid (83%).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([S:12][CH:13]([CH2:15][CH3:16])[CH3:14])[N:7]=1)=O)C.[Li+].[BH4-].O>C1COCC1>[CH:13]([S:12][C:8]1[N:7]=[C:6]([CH2:4][OH:3])[CH:11]=[CH:10][CH:9]=1)([CH2:15][CH3:16])[CH3:14]
Reactant: CCOC(=O)c1cccc(SC(C)CC)n1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CCC(C)Sc1cccc(CO)n1
Temperature: 40 °C
Reaction time: 1 h
Yield: 89.9 %

Procedure:
6-sec-Butylsulfanyl-pyridine-2-carboxylic acid ethyl ester (0.17 g, 0.71 mmol) obtained in Step A was dissolved in anhydrous THF (3 mL). 2.0 M LiBH4 solution (0.5 mL, 1.0 mmol) was added thereto, and the mixture was stirred at 40° C. for 1 hour. After the termination of the reaction, the reactant was cooled to room temperature. The reactant was added with water and then extracted with EtOAc. The organic layer was separated, dried with MgSO4, and concentrated under reduced pressure to obtain the title compound (0.126 g, 90%).
Reaction SMILES: [C:1]([C:4]1[O:5][CH:6]=[CH:7][CH:8]=1)(=[O:3])[CH3:2].[F:9][C:10]([F:23])([F:22])[C:11]([F:21])([F:20])[C:12]([F:19])([F:18])[C:13](OCC)=[O:14]>>[F:18][C:12]([F:19])([C:11]([F:20])([F:21])[C:10]([F:9])([F:22])[F:23])[C:13](=[O:14])[CH2:2][C:1]([C:4]1[O:5][CH:6]=[CH:7][CH:8]=1)=[O:3]
Reactant: CC(=O)c1ccco1
Reactant: CCOC(=O)C(F)(F)C(F)(F)C(F)(F)F
Product: O=C(CC(=O)C(F)(F)C(F)(F)C(F)(F)F)c1ccco1

Procedure:
The compound was synthesized according to example 1 using 2-acetylfuran and ethyl heptafluorobutyrate as starting materials. 1H NMR (CDCl3): 6.54 (s, 1 H); 6.65 (dd, 1 H, J=1.6 & 3.6 Hz); 7.37 (dd, 1 H, J=0.6 & 3.6 Hz); 7.70 (dd, 1 H, J=0.6 & 1.6 Hz). IR (film): 1616 (C═O); 1231 (C—F).
Reaction SMILES: C1OCC2C1=CC=CC=2.ON1[C:15](=[O:16])[C:14]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]2[C:12]1=[O:21].[N]=O>C(#N)C>[CH:12](=[O:21])[C:13]1[C:14](=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH:15]=[O:16]
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: [N]=O
Agent: c1ccc2c(c1)COC2
Solvent: CC#N
Product: O=Cc1ccccc1C=O
Yield: 94 %

Procedure:
To a mixture of 10 mmol of phthalan (isocoumaran), 1 mmol of N-hydroxyphthalimide, and 5 ml of acetonitrile was introduced 120 mmol of nitrogen monoxide, and the resultant mixture was stirred at 60° C. for 8 hours. Isolation of products in the reaction mixture by column chromatography on a silica gel revealed that phthalan was converted, at a rate of 99%, into phthalaldehyde (yield: 94%).