Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][CH2:5][N:6]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:12]([CH3:13])[C:10](=[O:11])[NH:9][C:7]1=[S:8].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O>[OH:1][CH2:2][CH2:3][O:4][CH2:5][N:6]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:12]([CH3:13])[C:10](=[O:11])[N:9]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:7]1=[S:8]
Reactant: BrCc1ccccc1
Reactant: Cc1c(-c2ccccc2)n(COCCO)c(=S)[nH]c1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1c(-c2ccccc2)n(COCCO)c(=S)n(Cc2ccccc2)c1=O
Yield: 31.4 %

Procedure:
To 2 ml of dimethylformamide, 0.62 g (2.0 mmol) of 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine, 0.26 ml (2.2 mmol) of benzyl bromide and 0.38 ml (2.2 mmol) of ethyldiisopropylamine were added and allowed to react for 5 days at room temperature under nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was adsorbed on a silica gel column and eluted with 1% methanol/chloroform to obtain 0.24 g of the target compound (Yield: 30%).
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][C:8](=[O:13])[CH2:9][C:10](=[O:12])[CH3:11].[CH2:14](Cl)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl>CS(C)=O>[CH2:14]([CH:9]([C:8](=[O:13])[CH3:7])[C:10](=[O:12])[CH3:11])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: ClCc1ccccc1
Reactant: CC(=O)CC(C)=O
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CS(C)=O
Product: CC(=O)C(Cc1ccccc1)C(C)=O
Temperature: 25 °C

Procedure:
To a solution containing 5.5g of potassium tert-butoxide in 50ml of DMSO was added 6.0 g of 2,4-pentanedione followed by 5.0 g of benzyl chloride. The solution was stirred over night at room temperature. 200ml of 1 molar hydrochloric acid was added and the solution was extracted with dichloromethane. The extract was washed 3 times with water and the solvent was evaporated in vacuo. The residue was distilled. Yield 2.9 g, bp 150°-154° C./15 mm.
Reaction SMILES: [Cl:1][CH2:2][C@H:3]([OH:6])[CH2:4][OH:5].[C:7]([Si:11]([CH3:14])([CH3:13])Cl)([CH3:10])([CH3:9])[CH3:8].N1C=CN=C1>CN(C)C=O>[Si:11]([O:5][CH2:4][C@@H:3]([OH:6])[CH2:2][Cl:1])([C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:14])[CH3:13]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OC[C@@H](O)CCl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC[C@@H](O)CCl
Temperature: 0 °C
Yield: 93 %

Procedure:
To N,N-dimethylformamide (40 ml) solution of (R)-(−)-3-chloro-1,2-propanediol (7 g), under ice-cooling and stirring condition, were added tert-butyldimethylchlorosilane (10.6 g) and imidazole (5.2 g), then stirred at a room temperature overnight. Ice-water (120 ml) was added to the reaction mixture, and extracted with ethyl acetate (50 ml) 3 times, the extracts were combined together and washed with an aqueous solution being saturated with sodium chloride, then dried over anhydrous magnesium sulfate. After being filtrated under a reduced pressure, the filtrate was concentrated, there was obtained (R)-(−)-1-(tert-butyldimethylsilanyloxy)-3-chloropropan-2-ol (13.24 g, yield: 92.4%) as colorless liquid product.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH2:11]O)=[N:5][CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O=S(Cl)[Cl:15].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4]([CH2:11][Cl:15])=[N:5][CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccnc(CO)c1OC
Reactant: O=S(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1ccnc(CCl)c1OC
Temperature: 25 °C
Yield: 162.6 %

Procedure:
3,4-Dimethoxy-2-hydroxymethylpyridine (0.34 g, 0.002 mol) was dissolved in CH2Cl2 (8 ml). SOCl2 (0.27 g, 0.00227 mol) in CH2Cl2 (2 ml) was added under stirring at room temperature. After 10 min the mixture was neutralized with NaHCO3 (5 ml). The phases were separated, the CH2Cl2 phase was washed with NaCl-solution, dried over Na2SO4 and evaporated giving the desired product (0.61 g, 88%).
Reaction SMILES: [OH-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1.Br[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18]>C(O)C>[CH2:15]([O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1)[CH2:16][CH:17]([CH3:19])[CH3:18]
Reactant: O=C(O)Cc1ccc(O)cc1
Reactant: CC(C)CCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)CCOc1ccc(CC(=O)O)cc1
Temperature: 25 °C

Procedure:
Aqueous sodium hydroxide solution (2.0 M; 32.9 mL, 65.8 mmol) was added in one portion to a stirred solution of p-hydroxyphenylacetic acid (5.00 g, 32.9 mmol) in ethanol (200 mL) at room temperature. After stirring for 15 min 1-bromo-3-methylbutane (4.97 g, 3.94 mL, 32.9 mmol) was added in one portion and the resulting solution heated at reflux for 12 h. The reaction was cooled to room temperature then evaporated to dryness. The residue was partitioned between dichloromethane (150 mL) and aqueous hydrochloric acid solution (1.0 M; 150 mL). The layers were separated and the aqueous phase was washed with dichloromethane (2×100 mL). The organic extracts were combined, dried (magnesium sulfate) and evaporated to dryness. The resulting white solid residue was used without purification in the preparation of R8782/83/1. LC/MS: 3.30 min; z/e 221, calcd (M−1) 221. 1H NMR (400 MHz: CDCl3): 7.25 (2H), 6.95 (2H), 4.05 (2H), 3.65 (2H), 1.95 (1H), 1.75 (2H), 1.05 (6H). The absolute regiochemistry of the product was unambiguously assigned using an HMBC correlation experiment.
Reaction SMILES: [I-].[CH2:2]([O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]1)=[O:6])[CH3:3].C(=O)([O-])[O-].[K+].[K+].[CH3:19][C:20](=O)[CH2:21][CH3:22]>CCOCC.O>[CH2:2]([O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([CH2:19][C:20]2[CH:22]=[CH:21][C:20]([CH:19]3[C:21]4[CH:22]=[CH:5][CH:7]=[CH:8][C:20]=4[CH2:19][CH2:22][C:21]4[CH:10]=[CH:11][CH:12]=[CH:19][C:20]3=4)=[CH:22][CH:21]=2)[CH2:8]1)=[O:6])[CH3:3]
Reactant: CCC(C)=O
Reactant: CCOC(=O)[C@@H]1CCCNC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CCOCC
Product: CCOC(=O)[C@@H]1CCCN(Cc2ccc(C3c4ccccc4CCc4ccccc43)cc2)C1
Temperature: 50 °C
Yield: 77 %

Procedure:
A mixture of the above iodide (1.80 g, 0.0044 mol), (R)-3-piperidinecarboxylic acid ethyl ester (0.69 g, 0.0044 mol) and anhydrous potassium carbonate (1.82 g, 0.0132 mol) in 2-butanone (30 ml) was heated to 50° C. for 6 h. After cooling, the mixture was diluted with ether (50 ml) and water (50 ml) and the phases were separated. The organic phase was washed with water (30 ml) and dried (MgSO4). The solvent was evaporated in vacuo and the oily residue (2.1 g) was purified by gradient column chromatography on silica gel (40 g) using benzene and ethyl acetate as eluents. The benzene/ethyl acetate (9:1) fraction afforded 1.50 g (77%) of (R)-1-(4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-benzyl)-3-piperidinecarboxylic acid ethyl ester.
Reaction SMILES: [Br:1][C:2]1[C:3]([C:12]([OH:14])=O)=[N:4][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[N:6][CH:7]=1.[CH3:15][NH:16][C:17]([C:19]1[N:20]([CH3:25])[N:21]=[CH:22][C:23]=1[NH2:24])=[O:18]>>[CH3:25][N:20]1[C:19]([C:17](=[O:18])[NH:16][CH3:15])=[C:23]([NH:24][C:12]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([C:8]([OH:11])([CH3:9])[CH3:10])[N:4]=2)=[O:14])[CH:22]=[N:21]1
Reactant: CC(C)(O)c1ncc(Br)c(C(=O)O)n1
Reactant: CNC(=O)c1c(N)cnn1C
Product: CNC(=O)c1c(NC(=O)c2nc(C(C)(C)O)ncc2Br)cnn1C

Procedure:
The product was obtained starting from 5-bromo-2-(2-hydroxypropan-2-yl)pyrimidine-4-carboxylic acid (150 mg, 0.575 mmol) and 4-amino-2-methyl-2H-pyrazole-3-carboxylic acid methylamide (106 mg, 0.69 mmol) according to the method described in example 64, step 6 after purification by silica gel chromatography using a heptane/ethyl acetate gradient as light brown waxy solid (31 mg, 13%).
Reaction SMILES: FC(F)(F)S([O-])(=O)=O.[CH2:9]([C@@:12]1([CH3:37])[CH2:17][C@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)[C@@H:15]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[N+:14]2[C@@H:32]([CH2:35][CH3:36])[CH2:33][O:34][C:13]1=2)[CH:10]=[CH2:11].[CH2:38]([S-:40])[CH3:39].[Na+]>CN(C=O)C>[CH2:9]([C@@:12]1([CH3:37])[CH2:17][C@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)[C@@H:15]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[N:14]([C@@H:32]([CH2:35][CH3:36])[CH2:33][S:40][CH2:38][CH3:39])[C:13]1=[O:34])[CH:10]=[CH2:11]
Reactant: C=CC[C@@]1(C)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)[N+]2=C1OC[C@@H]2CC
Reactant: CC[S-]
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CC[C@@]1(C)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@@H](CC)CSCC)C1=O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of (3S,5S,6R,8S)-8-allyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-8-methyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium trifluoromethanesulfonate (86 mg, 0.15 mmol; Example 339, Step A) in DMF (0.74 ml) was added sodium ethanethiolate (38 mg, 0.45 mmol). After being stirred at 25° C. for 1.5 h, the reaction was quenched (sat. aq. NH4Cl), extracted (2×EtOAc), and washed (2×brine). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by chromatography on silica gel (12 g SiO2, 10% and 20% EtOAc/hex) provided the title compound as a colorless liquid.
Reaction SMILES: O=[C:2]([CH2:8][C:9](OC)=O)[CH2:3][C:4](OC)=O.BrC[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1CBr.C[O-].[Na+]>C1COCC1.CO>[CH2:2]1[C:8]2=[CH:9][CH:19]=[CH:20][CH:15]=[CH:16][C:17]2=[CH:18][CH:4]=[CH:3]1
Reactant: COC(=O)CC(=O)CC(=O)OC
Reactant: BrCc1ccccc1CBr
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: C1=CC=C2CC=CC=C2C=C1

Procedure:
Accordingly, compounds of formula (Ca) are prepared, as set forth above in REACTION SCHEME 2B, by first combining a pentane-3-dioate, e.g. dimethyl 3-oxopentanedioate shown, with a 1,2-bismethyl aromatic having a suitable leaving group on each methyl group, e.g., 1,2-bis(bromomethyl)benzene, in a mixed protic/aprotic solvent medium, e.g., THF-MeOH, and a metal alkoxide, e.g., sodium methoxide. The metal alkoxide can be added as such or made in situ via careful addition (e.g., at low temperature) of the appropriate metal to at least the protic solvent, preferably prior to combination with the remaining reactants. The intermediate benzo[7]annulene product so formed can be optionally isolated and may contain one or two carboxy ester groups depending on the reaction conditions, e.g., methyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate, as shown above. The intermediate, dimethyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate, is subjected to basic hydrolysis (saponification) conditions followed by acidification to give compounds of formula (Ca).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:9](O)=[CH:8][C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:6][C:5]=2[O:4][N:3]=1.P(Cl)(Cl)([Cl:20])=O>>[Cl:20][C:9]1[CH:8]=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:6]=[C:5]2[O:4][N:3]=[C:2]([CH3:1])[C:10]=12
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1noc2nc(-c3ccccc3)cc(O)c12
Product: Cc1noc2nc(-c3ccccc3)cc(Cl)c12

Procedure:
6.8 g. of 3-methyl-6-phenylisoxazolo[5,4-b]pyridin-4-ol (0.03 mol.) are refluxed in 60 ml. of phosphorous oxychloride for 3 hours. the excess phosphorous oxychloride is removed in vacuo and the oily residue is treated with ice water. The compound becomes solid. The compound is extracted with chloroform, washed with an aqueous sodium carbonate solution (10%) and again with water. Evaporation of the dried (Na2SO4) and charcoal treated chloroform extract provides 6.3 g. (86%) of 4-chloro-3-methyl-6-phenylisoxazolo[5,4-b]-pyridine which is recrystallized from ligroin and melts at 130°-131°.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5]([OH:17])=[CH:6][C:7]2[S:11][C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][C:8]=2[CH:16]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:26](I)[CH2:27][CH3:28]>C(C(C)=O)C>[CH2:1]([O:3][C:4]1[C:5]([O:17][CH2:26][CH2:27][CH3:28])=[CH:6][C:7]2[S:11][C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][C:8]=2[CH:16]=1)[CH3:2]
Reactant: CCCI
Reactant: CCOc1cc2cc(C(=O)OC)sc2cc1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCOc1cc2sc(C(=O)OC)cc2cc1OCC

Procedure:
A solution of 0.42 g. of methyl 5-ethoxy-6-hydroxybenzothiophene-2-carboxylate, 0.25 g. of potassium carbonate, a catalytic amount of potassium iodide, and 0.31 g. of propyl iodide in methyl ethyl ketone was heated to reflux for 48 hours. The hot solution was filtered and the filtrate was evaporated in vacuo to provide the desired subtitle intermediate which was used in the subsequent reaction without purification.
Reaction SMILES: [CH:1]([CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]1(=[O:27])[O:26][C:24](=[O:25])[CH2:23][O:22][CH2:21]1>ClCCl>[CH:1]([CH:14]1[CH2:19][CH2:18][N:17]([C:24](=[O:25])[CH2:23][O:22][CH2:21][C:20]([OH:27])=[O:26])[CH2:16][CH2:15]1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1COCC(=O)O1
Reactant: c1ccc(C(c2ccccc2)C2CCNCC2)cc1
Solvent: ClCCl
Product: O=C(O)COCC(=O)N1CCC(C(c2ccccc2)c2ccccc2)CC1

Procedure:
In a similar operation, 5.0 grams (20 millimoles) of 4-benzhydrylpiperidine in 140 milliliters of dichloromethane was reacted with 2.3 grams (20 millimoles) of diglycolic anhydride in 200 milliliters of dichloromethan to obtain the desired [2-(4-benzhydrylpiperidino)-2-oxoethoxy]acetic acid product as a white solid which after purifying with ethyl acetate-hexane mixture had a m.p. of 139.5°-141° C.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[O:9]([C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[CH3:26])[C:20]([NH2:22])=[O:21])[Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]>C(Cl)(Cl)(Cl)Cl>[O:9]([C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[CH2:26][Br:1])[C:20]([NH2:22])=[O:21])[Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:11])[CH3:12]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(C(N)=O)cc1O[Si](C)(C)C(C)(C)C
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)[Si](C)(C)Oc1cc(C(N)=O)ccc1CBr
Reaction time: 0.17 h
Yield: 81.7 %

Procedure:
N-Bromosuccinimide (NBS) (0.507 g, 2.85 mmol) was added to a solution of 3-t-butyldimethylsiloxy-4-methyl benzamide (Compound 7.1) in 30 mL CCl4. The mixture was irradiated with a 275 W sunlamp (Sears, #34-7105) at 60° C. Each irradiation took 10 minutes followed by 10 minutes to let the lamp cool down. It took 2 hours of irradiation over a period of 4 hours to complete the reaction. After the solvent was removed at reduced pressure, the residue was subjected to flash silica gel chromatography to yield the product as a white solid (0146 g, y=81.7%). 1H NMR (CDCl3) δ0.318(s,6H), 1.05(s,9H), 4.51(s,2H), 6.10(b,2H), 7.25(d,J=7.8 Hz,1H), 7.32(s,1H), 7.39(d,J=7.9 Hz,1H); 13 C NMR (CDCl3) δ-4.08, 18.28, 25.76, 27.87, 117.99, 118.07, 119.49, 131.23, 132.54, 134.97, 168.46.
Reaction SMILES: O.[CH:2]1[N:6]=[CH:5][N:4]2[C@H:7]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=3[F:18])[CH2:8][CH2:9][C:3]=12.C([O:23]O)(C)(C)C>[Fe](Cl)(Cl)Cl.N1C=CC=CC=1>[F:18][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:10]=1[C@H:7]1[N:4]2[CH:5]=[N:6][CH:2]=[C:3]2[C:9](=[O:23])[CH2:8]1)[C:14]#[N:15]
Reactant: CC(C)(C)OO
Reactant: N#Cc1ccc([C@@H]2CCc3cncn32)c(F)c1
Agent: Cl[Fe](Cl)Cl
Solvent: O
Solvent: c1ccncc1
Product: N#Cc1ccc([C@@H]2CC(=O)c3cncn32)c(F)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 23.6 %

Procedure:
To a 500 mL round-bottomed flask equipped with a water condensor is added (S)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (6.0 g, 26.3 mmol) and pyridine (32.6 mL). To the solution is added iron(III) chloride (0.21 g, 1.32 mmol and tert-butyl hydroperoxide (10.9 mL, 79 mmol). The reaction is heated to reflux and stirred for 5 hours. The reaction is allowed to cool to room temperature and is then filtered through celite. The collect filtrate is concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (XBridge, C8 H2O (0.1% NH4OH)/CH3CN) to give 1.5 g of the entitled product. MS (m+1)=242.1; LCMS condition B, retention time=0.97 min; 1H NMR (400 MHz, CDCl3) δ ppm 3.12 (dd, 1H), 3.80 (dd, 1H), 6.04 (dd, 1H), 7.14 (t, 1H), 7.48-7.57 (m, 2H), 7.61 s, 1H, 7.72 s, 1H.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:9].O=O>CO>[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:4]1(=[O:9])[CH:5]=[CH:6][C:1](=[O:7])[CH:2]=[CH:3]1
Reactant: O=S(=O)(O)O
Agent: O=O
Solvent: Oc1ccccc1
Solvent: CO
Product: O=C1C=CC(=O)C=C1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
Twenty milligrams of the inactive complex obtained as described in Example 1, 100 milligrams of phenol and one cubic centimeter of methanol were added to a 1/2 ounce bottle. The complex was insoluble in the methanol. Two microliter portions of concentrated sulfuric acid were added until 10 microliters were in the bottle. The insoluble complex went into solution with the methanol and acid when the mixture was heated with steam at 100° C. An oxidation was run with the solution formed by charging 100 microliters of said solution into a micro reactor, heating to 65° C., and charging 500 pounds per square inch gauge oxygen pressure. After oxidizing for 60 minutes, 29.6 percent conversion of phenol to benzoquinone was obtained.
Reaction SMILES: [CH3:1][NH2:2].[C:3]1([S:9]([C:12]2[C:13]([S:23][CH3:24])=[N:14][N:15]3[C:20](Cl)=[CH:19][C:18]([CH3:22])=[N:17][C:16]=23)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>CCO.CN(C=O)C>[C:3]1([S:9]([C:12]2[C:13]([S:23][CH3:24])=[N:14][N:15]3[C:20]([NH:2][CH3:1])=[CH:19][C:18]([CH3:22])=[N:17][C:16]=23)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CN
Reactant: CSc1nn2c(Cl)cc(C)nc2c1S(=O)(=O)c1ccccc1
Solvent: CCO
Solvent: CN(C)C=O
Product: CNc1cc(C)nc2c(S(=O)(=O)c3ccccc3)c(SC)nn12
Temperature: 25 °C
Reaction time: 2 h
Yield: 60 %

Procedure:
10 ml of a 33% solution of methylamine in EtOH was added to a solution of 0.3 g (0.85 mmol) of 3-benzenesulphonyl-7-chloro-5-methyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidine in 5 ml of DMF and stirred at RT for 2 hrs. The reaction solution was evaporated in a high vacuum and the residue was partitioned between 2N NaOH and CH2Cl2. The aqueous phase was extracted three times with CH2Cl2, and the combined organic phases were dried (MgSO4), filtered and evaporated. Subsequent chromatography (SiO2,CH2Cl2/AcOEt 15:1) and crystallization from EtOH yielded 0.18 g (60%) of (3-benzenesulphonyl 5-methyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-yl)-methyl-amine as colorless crystals, m.p. >230°.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]2[N:18]([CH2:19][CH3:20])[N:17]=[N:16][C:8]=2[C:9](OCC)=[N:10][C:11]=1[CH3:12])=[O:5])[CH3:2].[CH2:21]([NH2:25])[CH2:22][CH2:23][CH3:24]>>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[N:18]([CH2:19][CH3:20])[N:17]=[N:16][C:8]=2[C:9]([NH:25][CH2:21][CH2:22][CH2:23][CH3:24])=[N:10][C:11]=1[CH3:12])=[O:5])[CH3:2]
Reactant: CCCCN
Reactant: CCOC(=O)c1c(C)nc(OCC)c2nnn(CC)c12
Product: CCCCNc1nc(C)c(C(=O)OCC)c2c1nnn2CC
Yield: 78 %

Procedure:
2.8 g. of 4-ethoxy-1-ethyl-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine-7-carboxylic acid ethyl ester is treated for 14 hours with 10 ml. of n-butylamine at reflux temperature. The excess butylamine is distilled off and the residue of 4-butylamino-1-ethyl-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine-7-carboxylic acid ethyl ester is recrystallized from petroleum ether, yield 78%, m.p. 85°-87°.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][NH:8]2)=[CH:4][CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].ClC(Cl)C>C(O)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)[CH2:6][CH2:7]2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: Brc1ccc2c(c1)NCC2
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: CC(C)(C)OC(=O)N1CCC(N2CCc3ccc(Br)cc32)CC1
Reaction time: 8 h
Yield: 64 %

Procedure:
Triacetoxylated sodium borohydride (11.7 g) was added to a mixture of 6- bromoindoline (8.3 g), 1-(t-butoxycarbonyl)-4-piperidone (10 g, [CAS Registry No. 7909-07-3]), acetic acid (14.9 g) and dichloroethane (200 ml) followed by stirring overnight. Then the reaction solution was concentrated under reduced pressure, and the pH value thereof was adjusted to 9 with ethyl acetate, an 8 N aqueous solution of sodium hydroxide and water and the layers were separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate system) to give the title compound (10.3 g) (yield: 64%).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][CH3:15])[CH2:10][C:11]([OH:13])=O)=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[CH2:20]([NH:23][CH2:24][CH2:25][CH3:26])[CH2:21][CH3:22]>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][CH3:15])[CH2:10][C:11]([N:23]([CH2:24][CH2:25][CH3:26])[CH2:20][CH2:21][CH3:22])=[O:13])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2]
Reactant: CCN(CC(=O)O)c1ccc(C#N)c(C(F)(F)F)c1
Reactant: CCCNCCC
Product: CCCN(CCC)C(=O)CN(CC)c1ccc(C#N)c(C(F)(F)F)c1

Procedure:
Synthesized as described in example 3 using N-[4-cyano-3-(trifluoromethyl)phenyl]-N-ethylglycine and dipropylamine: 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J=9.0 Hz, 1H), 6.76 (d, J=2.5 Hz, 1H), 6.65 (dd, J=8.8, 2.5 Hz, 1H), 4.14 (s, 2H), 3.51 (m, 2H), 3.31 (t, J=7.5 Hz, 2H), 3.25 (t, J=6.7 Hz, 2H), 1.63 (m, 4H), 1.25 (t, J=7.1 Hz, 3H), 1.00 (t, J=7.3 Hz, 3H), 0.88 (t, J=7.4 Hz, 3H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=1.[Mg].[CH3:10][N:11]1[C:15](=[O:16])[CH2:14][CH2:13][C:12]1=[O:17].S(=O)(=O)(O)O>C1C=CC=CC=1.C(OCC)C>[OH:16][C:15]1([C:2]2[CH:3]=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=2)[N:11]([CH3:10])[C:12](=[O:17])[CH2:13][CH2:14]1
Reactant: CN1C(=O)CCC1=O
Reactant: Cc1cccc(Br)c1
Agent: O=S(=O)(O)O
Agent: [Mg]
Solvent: c1ccccc1
Solvent: CCOCC
Product: Cc1cccc(C2(O)CCC(=O)N2C)c1
Reaction time: 8 h

Procedure:
To a Grignard prepared from 27.3g (0.16 mole) of 3-bromotoluene and 3.7 g. (0.16 mole) of magnesium turnings in 100 ml. of dry diethylether, there is added dropwise over a period of about 10 minutes 12.2 g. (0.11 mole) of N-methylsuccinimide in 100 ml. of dry benzene. The resulting mixture is stirred and refluxed for about 4 hours and then allowed to stand overnight at room temperature. Stirring is resumed and 40 ml. of 50% sulfuric acid is added dropwise at such a rate to maintain a gentle reflux. After an additional 0.5 hours, the water layer is separated and washed twice with 50 ml. of benzene. The organic layers are combined and washed with 50 ml. of sodium carbonate and then twice more with 50 ml. of water. The resulting layer is dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The resulting residue is crystallized from methylene chloride/hexane to give 5-hydroxy-1-methyl-5-(m-tolyl) pyrrolidone; m.p. 128°-130°C.