Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O.[CH3:2][C:3]1[C:4]([CH2:15][S:16][C:17]2[NH:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[N:18]=2)=[N:5][CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]([F:14])([F:13])[F:12].C(N)(N)=[O:27].OO.C(N(CC)CC)C.O.O.O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN1CCCC1=O.O>[CH3:2][C:3]1[C:4]([CH2:15][S:16]([C:17]2[NH:18][C:19]3[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=3[N:21]=2)=[O:27])=[N:5][CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]([F:13])([F:12])[F:14]
Reactant: NC(N)=O
Reactant: Cc1c(OCC(F)(F)F)ccnc1CSc1nc2ccccc2[nH]1
Agent: O=S([O-])([O-])=S
Agent: OO
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN1CCCC1=O
Product: Cc1c(OCC(F)(F)F)ccnc1CS(=O)c1nc2ccccc2[nH]1
Temperature: 2.5 °C
Yield: 121.1 %

Procedure:
(i) 40 g (0.108 mole) 2-[[[3-methyl-4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole hydrate was dissolved in 120 ml of 1-methyl-2-pyrrolidone (NMP) at room temperature, then 0.263 g (1.077 mmole) of vanadium(V) oxytriisopropoxide were added and the reaction mixture was cooled to a temperature of from 0 to 5° C. 12.96 g (0.138 mole) of hydrogen peroxide urea adduct were suspended (optionally per partes) and the reaction was carried out at a temperature of from 0 to 10° C. for half an hour and then at a temperature of from 10 to 15° C. until the reaction was completed. At the end of the reaction, 5 ml of triethylamine and a solution of 5.68 g of sodium thiosulphate pentahydrate in 6 ml of water were added. The product was precipitated with water (280 ml at 20±5° C.) and filtered off to obtain 48.3 g of wet lansoprazole.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:6][CH2:7][CH2:8][NH:9][C:10](=[O:45])[C:11]1[CH:16]=[C:15]([F:17])[C:14]([CH2:18][S:19][C:20]2[N:21]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[C:22]([C:25]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][CH3:36])[CH:29]=3)([CH3:27])[CH3:26])=[CH:23][N:24]=2)=[C:13]([Cl:44])[CH:12]=1)[C:3]([OH:5])=[O:4].C([NH:53][C:54](N1C=CC=N1)=[N:55]C(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(CC)CC)C>CO>[Cl:44][C:13]1[CH:12]=[C:11]([CH:16]=[C:15]([F:17])[C:14]=1[CH2:18][S:19][C:20]1[N:21]([C:37]2[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=2)[C:22]([C:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][CH3:36])[CH:29]=2)([CH3:27])[CH3:26])=[CH:23][N:24]=1)[C:10]([NH:9][CH2:8][CH2:7][CH2:6][C@H:2]([NH:1][C:54]([NH2:55])=[NH:53])[C:3]([OH:5])=[O:4])=[O:45]
Reactant: CC(C)(C)OC(=O)N=C(NC(=O)OC(C)(C)C)n1cccn1
Reactant: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(C(=O)NCCC[C@H](N)C(=O)O)cc3Cl)n2-c2ccc(F)cc2)ccc1Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(C(=O)NCCC[C@H](NC(=N)N)C(=O)O)cc3Cl)n2-c2ccc(F)cc2)ccc1Cl
Reaction time: 18 h
Yield: 22.2 %

Procedure:
A solution of (S)-2-amino-5-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)pentanoic acid (268 mg, 0.40 mmol), N,N′-di-Boc-1H-pyrazole-1-carboxamidine (135 mg, 0.44 mmol) and triethylamine (175 μL, 1.19 mmol) in MeOH (10 mL) was stirred at 25° C. for 18 h. The reaction mixture was concentrated and reconstituted in EtOAc. The organic layer was washed with 1N HCl (3×5 mL), sat. aq. NaHCO3 (5 mL), dried over Na2SO4 and concentrated to a colorless oil. To the oil was added 4N HCl in Dioxane (10 mL) at 25° C. and stirred for 18 h. Upon completion, the reaction mixture was concentrated and purified by flash chromatography (MeOH/DCM, 0-20%) to give the title product (64 mg, 28% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.91 (t, J=5.2 Hz, 1H), 7.76 (s, 1H), 7.61 (dd, J=10.1, 1.0 Hz, 1H), 7.50-7.10 (br s, 4H), 7.45 (d, J=6.6 Hz, 2H), 7.21 (d, J=8.3 Hz, 1H), 7.17 (s, 1H), 6.95 (t, J=8.4 Hz, 2H), 6.58-6.43 (m, 4H), 4.06 (s, 2H), 3.77 (d, J=4.6 Hz, 1H), 3.67 (s, 3H), 3.23 (s, 2H), 1.71-1.59 (m, 2H), 1.58-1.46 (m, 2H), 1.46 (s, 6H). MS (EI) m/z 719 (MH+).
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:20])OCC(Cl)(Cl)Cl)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.F[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[N:32]=[C:31]([N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[S:30][N:29]=1.C(N(C(C)C)CC)(C)C.CS(C)=O>O>[C:23]1([C:28]2[N:32]=[C:31]([N:33]3[CH2:38][CH2:37][N:36]([C:13]([NH:12][C:9]4[CH:8]=[CH:7][C:6]([N:1]5[CH:5]=[CH:4][CH:3]=[N:2]5)=[CH:11][CH:10]=4)=[O:20])[CH2:35][CH2:34]3)[S:30][N:29]=2)[CH:22]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(Nc1ccc(-n2cccn2)cc1)OCC(Cl)(Cl)Cl
Reactant: Fc1ccccc1-c1nsc(N2CCNCC2)n1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: O=C(Nc1ccc(-n2cccn2)cc1)N1CCN(c2nc(-c3ccccc3)ns2)CC1

Procedure:
A solution of 2,2,2-trichloroethyl [4-(1H-pyrazol-1-yl)phenyl]carbamate (200 mg, 0.598 mmol), 1-[3-(2-fluorophenyl)-1,2,4-thiadiazol-5-yl]piperazine (147 mg, 0.598 mmol), diisopropylethylamine (0.208 ml, 1.20 mmol) and dimethyl sulfoxide (4 ml) was stirred at 70° C. for 24 hours, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) to give the desired product as a solid. The solid was recrystallized from ethyl acetate to give 63.7 mg (24.7%) of the desired product as a solid.
Reaction SMILES: [ClH:1].[NH2:2][CH2:3][C:4]([O:6]CC)=O.[C:9]1([Mg]Br)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[ClH:1].[C:9]1([C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)([OH:6])[CH2:3][NH2:2])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CCOC(=O)CN
Reactant: Br[Mg]c1ccccc1
Agent: Cl
Product: NCC(O)(c1ccccc1)c1ccccc1

Procedure:
Treatment of ethyl glycinate hydrochloride (4.5 g) with phenylmagnesium bromide (from 0.39 mole each of bromobenzene and magnesium), as discussed by A. McKenzie and G. O. Wills J. Chem. Soc. 1925, 127, 283 (and references cited therein), affords the title compound (mp 191°-193° C.).
Reaction SMILES: [F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[OH:12].C([O-])([O-])=O.[K+].[K+].Br[CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26].CCCCCC.C(OCC)(=O)C>CC(C)=O>[F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:12][CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26]
Reactant: Oc1ccc2ccccc2c1F
Reactant: CC(C)(C)OC(=O)NCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC(C)(C)OC(=O)NCCOc1ccc2ccccc2c1F
Yield: 65 %

Procedure:
To a solution of 1-fluoronaphthalen-2-ol (0.162 g, 1.0 mmol) and K2CO3 (0.300 g, 2.0 mmol) in acetone was added tert-butyl (2-bromoethyl)carbamate (0.336 g, 1.5 mmol). The resulting mixture was heated at reflux overnight. After TLC control (n-hexane/ethyl acetate 6:4) showed the disappearance of 1-fluoronaphthalen-2-ol, solvent was evaporated in vacuo and the residue was dissolved in 15 mL of ethyl acetate and washed with water (3×5 mL), brine (10 mL) and dried over Na2SO4. The evaporation of solvent afforded tert-butyl {2-[(1-fluoronaphthalen-2-yl)oxy]ethyl}carbamate as a white solid (65% yield) which was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]3[CH2:23][CH:22]([CH2:24][S:25][C:26]4[N:30]=[CH:29][NH:28][N:27]=4)[O:21][C:20]3=[O:31])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C[O:33]C1C=CC(C2C=CC(S(NC(CC3OC3)C(OC)=O)(=O)=O)=CC=2)=CC=1.CCN(CC)CC>C1C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]([S:15]([NH:18][CH:19]([CH2:23][CH:22]([OH:33])[CH2:24][S:25][C:26]3[N:30]=[CH:29][NH:28][N:27]=3)[C:20]([OH:21])=[O:31])(=[O:16])=[O:17])=[CH:13][CH:14]=2)=[CH:5][CH:4]=1
Reactant: COC(=O)C(CC1CO1)NS(=O)(=O)c1ccc(-c2ccc(OC)cc2)cc1
Reactant: COc1ccc(-c2ccc(S(=O)(=O)NC3CC(CSc4nc[nH]n4)OC3=O)cc2)cc1
Solvent: c1ccccc1
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc(-c2ccc(S(=O)(=O)NC(CC(O)CSc3nc[nH]n3)C(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-[(4′-Methoxy[1,1′-biphenyl]-4-yl)sulfonyl]amino-2-oxo-5-[(1H-1,2,4-triazol-3-ylthio)methyl]-tetrahydrofuran: To a solution of methyl 2-[(4′-methoxy[1,1′-biphenyl]-4-yl)sulfonyl]amino-4,5-epoxypentanoate 1d (0.7 g, 1.79 mmol) in benzene (6 mL) and Et3N (0.33 mL, 2.3 mmol) at room temperature is added slowly 1H-1,2,4-mercaptotriazole (0.47 g, 4.48 mmol). The reaction mixture is stirred overnight at room temperature. Diluted with water, the mixture is extracted three times with EtOAc. The combined EtOAc layer is washed with water, brine, dried over MgSO4 and concentrated to an oil which is purified by column chromatography eluting with hexane/EtOAc (1:1) to give the desired product.
Reaction SMILES: Br[C:2]1[C:3](=[O:20])[O:4][C:5]([CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:6][C:7]=1[OH:8].[C:21]([O:30][CH3:31])(=[O:29])[C:22]1[C:23](=[CH:25][CH:26]=[CH:27][CH:28]=1)[SH:24].N1CCCCC1>ClCCl>[OH:8][C:7]1[CH2:6][C:5]([CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:4][C:3](=[O:20])[C:2]=1[S:24][C:23]1[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=1[C:21]([O:30][CH3:31])=[O:29]
Reactant: COC(=O)c1ccccc1S
Reactant: CC(C)CCC1(c2ccccc2)CC(O)=C(Br)C(=O)O1
Solvent: ClCCl
Solvent: C1CCNCC1
Product: COC(=O)c1ccccc1SC1=C(O)CC(CCC(C)C)(c2ccccc2)OC1=O

Procedure:
The title compound was prepared as described in General Method 6 from 1.9 mmol of 3-bromo-5,6-dihydro-4-hydroxy-6-(3-methylbutyl)-6-phenyl-2H-pyran-2-one (prepared in example CCC), 2.2 mmol of methyl thiosalicylate and 2.1 mmol of piperidine in 30 mL of dichloromethane. The crude product was chromatographed on silica gel, eluting first with chloroform and then with 5% methanol in chloroform, to give the title compound (m.p. 115°-116° C.). 1H NMR (DMSO-d6) δ 0.80 (m, 6 H), 1.0 (m, 1 H), 1.17 (m, 1 H), 1.43 (m, 1 H), 1.96 (m, 2 H), 3.4 (2 H+H2O), 3.81 (s, 3 H), 6.02 (bd, 1 H), 6.88 (t, 1 H), 7.05 (t, 1 H), 7.42 (m, 5 H), 7.80 (dd, 1 H).
Reaction SMILES: C(OC([N:8]1[CH2:26][CH2:25][C@@H:11]2[N:12]([CH3:24])[C:13]3[C:14]([C:20]([F:23])([F:22])[F:21])=[CH:15][C:16](Br)=[CH:17][C:18]=3[C@@H:10]2[CH2:9]1)=O)(C)(C)C.[CH3:27][O:28][C:29]1[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=1[NH2:31]>>[O:28]([C:29]1[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=1[NH:31][C:16]1[CH:15]=[C:14]([C:20]([F:22])([F:23])[F:21])[C:13]2[N:12]([CH3:24])[C@H:11]3[CH2:25][CH2:26][NH:8][CH2:9][C@H:10]3[C:18]=2[CH:17]=1)[CH3:27]
Reactant: COc1ccccc1N
Reactant: CN1c2c(cc(Br)cc2C(F)(F)F)[C@@H]2CN(C(=O)OC(C)(C)C)CC[C@@H]21
Product: COc1ccccc1Nc1cc2c(c(C(F)(F)F)c1)N(C)[C@H]1CCNC[C@@H]21

Procedure:
The title compound was prepared by following the general coupling procedure as a yellow solid (22 mg, 61%) from (4aS,9bR)-8-bromo-5-methyl-6-trifluoromethyl-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester (Example 45, 41 mg, 0.095 mmol) and 2-methoxyaniline (37 mg, 0.30 mmol). 1H NMR (CDCl3, 300 MHz) δ (ppm) 1.82–2.00 (m, 2H), 2.58–2.80 (m, 3H), 2.80–3.00 (m, 5H), 3.07 (dd, J=12.9, 5.9 Hz, 1H), 3.15–3.25 (m, 1H), 3.45–3.55 (m, 1H), 3.91 (s, 3H), 5.97 (s, 1H), 6.75–6.90 (m, 3H), 6.99 (dd, J=1.6, 7.5 Hz, 1H), 7.09 (d, J=1.8 Hz, 1H).
Reaction SMILES: [NH:1]1[C:5]2[CH2:6][CH2:7][CH:8]([CH2:10][C:11]([OH:13])=[O:12])[CH2:9][C:4]=2[N:3]=[CH:2]1.S(Cl)(Cl)=O.[CH2:18](O)[CH3:19]>>[CH2:18]([O:12][C:11](=[O:13])[CH2:10][CH:8]1[CH2:7][CH2:6][C:5]2[NH:1][CH:2]=[N:3][C:4]=2[CH2:9]1)[CH3:19]
Reactant: CCO
Reactant: O=C(O)CC1CCc2[nH]cnc2C1
Solvent: O=S(Cl)Cl
Product: CCOC(=O)CC1CCc2[nH]cnc2C1
Reaction time: 0.5 h

Procedure:
A mixture of 4,5,6,7-tetrahydro-1H-benzimidazole-5-acetic acid (2.2 g, 10 mmol) and ethanol (40 ml) was placed on an ice-bath and thionylchloride (1.78 g, 15 mmol) was added dropwise. When addition was complete, the mixture was stirred for 30 minutes and then heated at reflux for 5 hours. The solvent was evaporated and the residue was re-evaporated with acetonitrile and then stirred with acetonitrile (40 ml) and triethylamine (1.5 ml). The resulting mixture was filtered and the solid was discarded. From the filtrate the solvent was evaporated to give crude 4,5,6,7-tetrahydro-1H-benzimidazole-5-acetic acid ethyl ester. This ester was dissolved in acetonitrile (40 ml) and triethylamine (1.5 ml, 11 mmol) was added followed by portionwise addition of triphenylmethylchloride (2.8 g, 10 mmol). When addition was complete the mixture was stirred overnight at ambient temperature. The mixture was filtered and from the filtrate the solvent was evaporated. The residue was dissolved in ethyl acetate (25 ml) and left for crystallisation. The solid formed was isolated and discarded and from the filtrate the solvent was evaporated. The residue was dissolved in THF (40 ml) and the mixture was placed under an atmosphere of nitrogen. 1 N Lithiumaluminium hydride in THF (6 ml, 6 mmol) was added dropwise. When addition was complete the mixture was stirred at ambient temperature for 3 hours. The mixture was quenched with small amounts of water and 4 N Sodium hydroxide and ethyl acetate was added (50 ml). The solid was removed by filtration and the filtrate was dried (magnesium sulphate). The solvent was evaporated to give a residue that was crystallised from ethyl acetatete (20 ml). This afforded 1.3 g (32%) of 2-(1(3)-triphenylmethyl-4,5,6,7-tetrahydro-1H-benzimidazol-5-yl)ethanol.
Reaction SMILES: B.C1COCC1.[Cl:7][C:8]1[S:12][CH:11]=[C:10]([C:13]#[N:14])[CH:9]=1.Cl.O.CO>C1COCC1>[ClH:7].[Cl:7][C:8]1[S:12][CH:11]=[C:10]([CH2:13][NH2:14])[CH:9]=1
Reactant: N#Cc1csc(Cl)c1
Agent: B
Agent: Cl
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: NCc1csc(Cl)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 312.2 %

Procedure:
To a pre-cooled (ice-water bath) solution of BH3.THF (3.4 eq, 11.8 mL) was added a solution of 5-chlorothiophene-3-carbonitrile (0.5 g, 3.48 mmol) in THF (11.5 ml). The reaction mixture was stirred for 4 hours at room temperature and subsequently 6 N HCl (17 ml) was added slowly followed by H2O/MeOH (17/114 mL). The reaction mixture was stirred overnight. Removal of the volatiles afforded the title product (1.0 g) as an off-white solid.
Reaction SMILES: [CH:1]([C@H:4]1[C:9]([O:10]C)=[N:8][C@@:7]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(C)[C:6]([O:20][CH3:21])=[N:5]1)([CH3:3])[CH3:2].Cl.[CH2:23](OCC)C>>[CH:1]([C@@:4]1([CH3:23])[C:9](=[O:10])[NH:8][C@H:7]([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:6]([O:20][CH3:21])=[N:5]1)([CH3:2])[CH3:3]
Reactant: CCOCC
Reactant: COC1=N[C@](C)(Cc2ccccc2)C(OC)=N[C@H]1C(C)C
Agent: Cl
Product: COC1=N[C@@](C)(C(C)C)C(=O)N[C@@H]1Cc1ccccc1
Reaction time: 2 h
Yield: 69 %

Procedure:
1.44 g of (2S,5R)-2,5-dihydro-2-isopropyl-3,6-dimethoxy-5-benzyl-5-methylpyrazine in 30 ml of diethyl ether were treated at room temperature with 25 ml of 0.2N HCl in diethyl ether. After 2 h, the mixture was evaporated in vacuo. Distillation of the residue gave 0.94 g (69%) of crude (2S,5R)-2,5-dihydro-2-isopropyl-6-methoxy-5-benzyl-methyl-pyrazin-3-one, boiling point 170° C./0.005 Torr.
Reaction SMILES: [CH:1]1([S:4][CH2:5][CH2:6][CH2:7][OH:8])[CH2:3][CH2:2]1.C(Br)(Br)(Br)[Br:10].[C:14]1([P:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.ClCCl>CCCCC>[Br:10][CH2:7][CH2:6][CH2:5][S:4][CH:1]1[CH2:3][CH2:2]1.[CH:30]1[CH:31]=[CH:32][C:27]([P:20]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:8])=[CH:28][CH:29]=1
Reactant: OCCCSC1CC1
Reactant: BrC(Br)(Br)Br
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCCCC
Product: BrCCCSC1CC1
Product: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reaction time: 4 h
Yield: 188.4 %

Procedure:
To a suspension of 3-(cyclopropylthio)propan-1-ol (1.68 g, 12.7 mmol) and CBr4 (5.06 g, 15.2 mmol) in pentane (13 ml) was added triphenylphosphine (4.00 g, 15.2 mmol) portionwise under icecooling. Dichloromethane (7 ml) was added and the suspension was stirred for 4 hours. The reaction mixture was filtered and washed with pentane. The obtained solution was concentrated in vacuo. The title compound was obtained as a mixture with TPPO as brown semisolid (6.66 g). The material was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[C:8]([C:15]([O:17][CH3:18])=[O:16])=[N:7][C:6]=1[C:19]([O:21][CH3:22])=[O:20])=[O:4]>C(O)C.[Pd]>[CH3:1][O:2][C:3]([CH:5]1[CH:6]([C:19]([O:21][CH3:22])=[O:20])[NH:7][CH:8]([C:15]([O:17][CH3:18])=[O:16])[CH:9]([C:11]([O:13][CH3:14])=[O:12])[NH:10]1)=[O:4]
Reactant: COC(=O)c1nc(C(=O)OC)c(C(=O)OC)nc1C(=O)OC
Agent: [Pd]
Solvent: CCO
Product: COC(=O)C1NC(C(=O)OC)C(C(=O)OC)NC1C(=O)OC

Procedure:
A solution of tetrakis-methoxycarbonylpyrazine (5.3 g, 16.9 mmol) (prepared in accordance with J. Org. Chem. 37 (19), p2963 (1972)) in 800 ml of dry ethanol, was hydrogenated at 50 bar in the presence of 10 g 5% palladium on charcoal at 80° C. for 16 hours. After cooling, the solution was filtered and evaporated to give slightly yellow crystals. Yield: 4.8 g (90%) , mp. 162°-163° C. (Lit. 162°-163° C.). NMR confirmed the structure.
Reaction SMILES: [CH:1](=[N:9]O)[C:2]1[C:3](=[CH:5][CH:6]=CC=1)O.[N+:11]([C:14]1[CH:15]=[N:16][NH:17][CH:18]=1)([O-:13])=[O:12].C(=O)([O-])[O-].[Cs+].[Cs+].BrC1C=NC=CC=1>[Cu]=O.CN(C=O)C.C(OCC)(=O)C>[N+:11]([C:14]1[CH:15]=[N:16][N:17]([C:2]2[CH:1]=[N:9][CH:6]=[CH:5][CH:3]=2)[CH:18]=1)([O-:13])=[O:12]
Reactant: O=[N+]([O-])c1cn[nH]c1
Reactant: ON=Cc1ccccc1O
Agent: O=[Cu]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: Brc1cccnc1
Product: O=[N+]([O-])c1cnn(-c2cccnc2)c1
Temperature: 130 °C
Reaction time: 8 h

Procedure:
A flask which had been baked out and filled with argon was initially charged with 8.3 g (56.6 mmol) of copper oxide, 31.9 g (228 mmol) of salicylaldoxime, 200 g (1.71 mol) of 4-nitro-1H-pyrazole and 597 g (1.83 mol) of caesium carbonate. The flask was repeatedly evacuated and filled with argon. 218 g (800 mmol) of 3-bromopyridine and 1 l of DMF which had been degassed on a rotary evaporator were added. The reaction mixture was stirred at 130° C. overnight, cooled and filtered, and the DMF was removed on a rotary evaporator. The substance was dissolved in 1 l of ethyl acetate, and extracted with 2 l of H2O. The water phase was extracted twice with 500 ml of ethyl acetate. Filtration of the aqueous phase gave a green solid. 1 l of ethyl acetate and 100 ml of DMF were added thereto, and the mixture was heated to 50° C. Cooling was followed by filtration through Hyflo and washing with 500 ml of ethyl acetate. The filtrate was washed with 300 ml of water and 300 ml of saturated NaCl solution, dried over Na2SO4, filtered and concentrated. The solid was suspended in 100 ml of ethyl acetate, filtered and washed with ethyl acetate and methyl tert-butyl ether, and the beige solid (45 g) was dried on a rotary evaporator.
Reaction SMILES: [C:1](O)(=[O:3])[CH3:2].P(=O)(O)(O)O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[CH2:23]([C:25]1[C:29]([C:30]2[NH:31][C:32]3[C:37]([CH:38]=2)=[CH:36][CH:35]=[CH:34][CH:33]=3)=[C:28]([CH3:39])[O:27][N:26]=1)[CH3:24]>C(#N)C.CCOCC>[C:1]([C:38]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][C:30]=1[C:29]1[C:25]([CH2:23][CH3:24])=[N:26][O:27][C:28]=1[CH3:39])(=[O:3])[CH3:2]
Reactant: CC(=O)O
Reactant: CCc1noc(C)c1-c1cc2ccccc2[nH]1
Agent: O=P(O)(O)O
Solvent: CC#N
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: CCOCC
Product: CCc1noc(C)c1-c1[nH]c2ccccc2c1C(C)=O
Reaction time: 0.25 h

Procedure:
To a mixture of 0.77 milliliters (13.45 m mole) of acetic acid and 0.17 grams (1.47 m mole) of 85% phosphoric acid in 10 milliliters of acetonitrile is added, at room temperature, 1.9 milliliters (13.45 m mole) of trifluoroacetic acid anhydride. The mixture is stirred for 15 minutes and then treated by dropwise addition with 1.0 grams (4.42 m mole) of 2-(3-ethyl-5-methyl-isoxazolyl)-indole in 10 milliliters acetonitrile. The mixture is stirred for 31/2 hours at room temperature and then poured onto water and extracted with ether. The ether extracts are dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting oil is filtered through silica gel using 10% methanol/methylene chloride. The solvent is evaporated, and the oil obtained is dissolved in ether. The solution is washed with 10% sodium bicarbonate solution, decolorized with charcoal, dried over magnesium sulfate and evaporated in vacuo. The resulting oil crystallizes upon treatment with ether to give 3-acetyl-2-(3-ethyl-5-methyl-4 -isoxazolyl)-indole, m.p. 170°-171°.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.Br[C:10]([CH3:16])([CH3:15])[C:11]([O:13][CH3:14])=[O:12].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:14][O:13][C:11](=[O:12])[CH:10]([CH3:16])[CH2:15][N:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]1=[O:8]
Reactant: O=c1cc(Br)cc[nH]1
Reactant: COC(=O)C(C)(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)C(C)Cn1ccc(Br)cc1=O
Temperature: 60 °C
Reaction time: 3 h

Procedure:
A mixture of 4-bromo-1H-pyridin-2-one (0.50 g), methyl 2-bromoisobutyrate (0.45 mL), and potassium carbonate (0.68 g) in dimethylformamide (5 mL) was stirred at 60° C. for 3 h. After cooling to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 70:30->50:50) to afford the title compound. Yield: 0.53 g (67% of theory); Mass spectrum (ESI+): m/z=274/276 (Br) [M+H]+. Additionally 2-(4-bromo-pyridin-2-yloxy)-2-methyl-propionic acid methyl ester was obtained {Yield: 0.15 g; Mass spectrum (ESI+): m/z=274/276 (Br) [M+H]+}
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH:11]1[CH2:16][CH2:15][S:14](=[O:18])(=[O:17])[NH:13][C:12]1=O.[BH4-].[Na+].C1COCC1.FC(F)(F)C(O)=O>CO>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH:11]1[CH2:16][CH2:15][S:14](=[O:18])(=[O:17])[NH:13][CH2:12]1
Reactant: O=C1NS(=O)(=O)CCC1c1ccc([N+](=O)[O-])cc1F
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(C2CCS(=O)(=O)NC2)c(F)c1
Temperature: 0 °C

Procedure:
4-(2-Fluoro-4-nitrophenyl)dihydro-2H-1,2-thiazin-3(4H)-one 1,1-dioxide (2.43 g, 8.44 mmol) and sodium borohydride (3.83 g, 101.3 mmol) are placed under nitrogen and dry THF (70 ml) added. To the ice cooled suspension is added trifluoroacetic acid (7.8 ml, 101.3 mmol) over 5 min. After stirring for 16 hr additional trifluoroacetic acid (20.0 ml, 260 mmol) is added followed by methanol (20 ml). The solution is evaporated and the residue dissolved in ethyl acetate (150 ml) and washed with sodium bicarbonate solution (3×100 ml) and brine (50 ml). Evaporation gives a yellow gum which is chromatographed over silica gel (90 g) eluting with 1-3% methanol-chloroform. The title compound is obtained as a gum (1.99 g, 86%): Calcd for C10H11FN2O4S: C, 43.79; H, 4.04; N, 10.21. Found: C, 43.72; H, 4.07; N, 10.11.