Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH:7]=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC1C=CC=C(C)[N+]=1[O-:17].C(OO)(=O)C>C(OCCCC)(=O)C.C(OCC)(=O)C>[CH:1]1([C:7]([OH:17])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cccc(C)[n+]1[O-]
Reactant: O=CC1CCCCC1
Agent: CC(=O)OO
Solvent: CCOC(C)=O
Solvent: CCCCOC(C)=O
Product: O=C(O)C1CCCCC1
Yield: 105 %

Procedure:
To a stirred solution of 5.0 g (44.6 mmol) of cyclohexanecarboxaldehyde in n-butyl acetate (45 mL) cooled in a wet-ice bath (ca. 2° C.) was added 5.5 g (44.6 mmol) of 2,6-dimethylpyridine N-oxide (2,6-lutidine N-oxide). To this solution was then added slowly dropwise 24.6 mL (66.9 mmol) of a 23.0 weight percent solution of peracetic acid in ethyl acetate, at a rate slow enough such that the reaction temperature did not exceed 10° C. (ca. 20 min). After the initial exotherm, the temperature returned to 2° C., and the reaction was maintained at this temperature for an additional 4 hours. The cold reaction solution was then transferred into a separatory funnel, was diluted with n-butyl acetate (50 mL), and was washed with a 1% aqueous solution of sodium thiosulfate (Na2S2O3, 50 mL). The butyl acetate layer was further washed with two portions of water (50 mL each), and the combined water washes were back-extracted with n-butyl acetate (50 mL). The combined butyl acetate layers were extracted with two portions of a 5% aqueous solution of sodium hydroxide (NaOH, 50 mL each). The combined NaOH solutions were acidified to pH=1 with a 10% aqueous solution of hydrochloric acid. The resulting solution was extracted with two portions of dichloromethane (75 mL each), and the extract was dried over anhydrous Na2SO4. The extract was filtered and concentrated in vacuo to give 6.0 g (99%) of cyclohexanecarboxylic acid, containing small levels of unidentified impurities.
Reaction SMILES: I[C:2]1[C:7]([CH:8]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:18])[N:5]=[C:4]2[S:19][C:20]3[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=3[C:3]=12.C(=O)([O-])[O-].[K+].[K+].[F:32][C:33]1[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[C:36]([CH3:43])=[C:37]2[C:42]=1[O:41][CH2:40][CH2:39][CH2:38]2.C(OCC)(=O)C>COCCOC.O.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>[CH3:18][C:6]1[N:5]=[C:4]2[S:19][C:20]3[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=3[C:3]2=[C:2]([C:35]2[C:36]([CH3:43])=[C:37]3[C:42](=[C:33]([F:32])[CH:34]=2)[O:41][CH2:40][CH2:39][CH2:38]3)[C:7]=1[CH:8]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:9]([O:11][CH3:12])=[O:10]
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)cc(F)c2c1CCCO2
Reactant: COC(=O)C(OC(C)(C)C)c1c(C)nc2sc3c(c2c1I)CCCC3
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)C(OC(C)(C)C)c1c(C)nc2sc3c(c2c1-c1cc(F)c2c(c1C)CCCO2)CCCC3
Temperature: 140 °C
Reaction time: 0.5 h
Yield: 56.9 %

Procedure:
To a solution of methyl 2-[4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-tert-butoxyacetate (0.075 g; 0.158 mmol) in a mixture of DME-water (3:1) (0.480 mL) were added potassium carbonate (0.066 g; 0.475 mmol), tetrakis(triphenylphosphine)palladium(0) (0.018 g; 0.016 mmol) and 2-(8-fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.069 g; 0.238 mmol). The solution was stirred for 30 min at 140° C. under a microwave irradiation. Ethyl acetate was added to the reaction mixture and the solution was washed with brine. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethylacetate (0-40%) in heptane furnished 0.046 g (57%) of the title compound as a light yellow oil.
Reaction SMILES: Br[C:2]1[S:3][C:4]([CH3:25])=[C:5]([CH2:7][CH2:8][O:9][C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C@H:15]([CH2:19][C:20]([O:22]CC)=[O:21])[CH2:14][CH2:13]3)[N:6]=1.[CH3:26][CH2:27]O.[Li+].[OH-]>C1COCC1.O>[CH:10]([C:26]1[CH:27]=[CH:7][C:5]([C:2]2[S:3][C:4]([CH3:25])=[C:5]([CH2:7][CH2:8][O:9][C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[C@H:15]([CH2:19][C:20]([OH:22])=[O:21])[CH2:14][CH2:13]4)[N:6]=2)=[CH:4][CH:25]=1)([CH3:11])[CH3:18]
Reactant: CCOC(=O)C[C@@H]1CCc2cc(OCCc3nc(Br)sc3C)ccc21
Reactant: CCO
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1sc(-c2ccc(C(C)C)cc2)nc1CCOc1ccc2c(c1)CC[C@H]2CC(=O)O
Reaction time: 24 h
Yield: 66 %

Procedure:
To a solution of Example 174 (305 mg, 0.657 mmol) in a mixture of THF (8 mL), water (8 mL), and EtOH (4 mL), was added LiOH (63 mg, 2.63 mmol). The reaction mixture was vigorously stirred for 24 hours, diluted with water (20 mL), and washed with Et2O (10 mL). The aqueous phase was then acidified to pH ˜1 using 1 N HCl, and then extracted with CH2Cl2 (4×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then purified by silica gel flash chromatography (95:5 CH2Cl2/MeOH) to afford product (189 mg, 66%) as a white solid. (C26H29NO3S): LC-MS, RT 3.95 min., M+H 436.4; 1H NMR (CDCl3): δ 1.25 (s, 3H), 1.28 (s, 3H), 1.70-1.82 (m, 1H), 2.32-2.43 (m, 2H), 2.45 (s, 3H), 2.74-2.98 (m, 4H), 3.18 (t, 2H), 3.47-3.54 (m, 1H), 4.28 (t, 2H), 6.72 (dd, 1H), 6.78 (s, 1H), 7.08 (d, 1H), 7.51 (AB quartet, 4H).
Reaction SMILES: C([Mg]Cl)CCC.[Li]CCCC.Br[C:13]1[CH:14]=[N:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[C:18]([O:23][CH3:24])[CH:17]=2.[F:25][C:26]([F:32])([F:31])[CH2:27][CH2:28][CH:29]=[O:30]>CCOCC.C1(C)C=CC=CC=1>[F:25][C:26]([F:32])([F:31])[CH2:27][CH2:28][CH:29]([C:13]1[CH:14]=[N:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[C:18]([O:23][CH3:24])[CH:17]=2)[OH:30]
Reactant: COc1ccc2cc(Br)cnc2c1
Reactant: O=CCCC(F)(F)F
Agent: CCCC[Mg]Cl
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: COc1ccc2cc(C(O)CCC(F)(F)F)cnc2c1
Temperature: -78 °C
Reaction time: 0.75 h

Procedure:
BuMgCl (0.16 mL of a 2 M solution in ether, 0.32 mmol) was added to 1 mL of toluene at −10° C. n-BuLi (0.26 mL of a 2.5 M solution in hexanes, 0.64 mmol) was added dropwise and the reaction mixture was allowed to age at −10° C. for 45 min. A solution of 3-bromo-7-methoxyquinoline (200 mg,) in 1 mL of toluene was added at −20° C. After 1 h, the reaction mixture was cooled to −78° C. and 4,4,4-trifluorobutyraldehyde (0.16 mL, 1 mmol) was added and the reaction mixture was slowly allowed to warm to ambient temperature. The procedure was repeated proportionally using 440 mg (1.8 mmol) of 3-bromo-7-methoxyquinoline. The two reactions were combined and partitioned between water and hexanes-EtOAc. The organic phase was concentrated and purified by flash chromatography on silica gel (25% to 66% EtOAc/hexanes) to provide the title compound as a racemic mixture. 1H NMR (500 MHz, CD2Cl2): δ (ppm) 8.71 (d, J=2.1 Hz, 1H), 8.06 (s, 1H), 7.70 (d, J=8.9 Hz, 1H), 7.35 (d, J=2.1 Hz, 1H), 7.21 (dd, J=8.9, 2.2 Hz, 1H), 4.93 (m, 1H), 3.93 (s, 3H), 2.33 (m, 2H).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1CCO.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([B:18]2[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]2)[CH:15]=[CH:14][C:13]=1[OH:27].[Br:28]C1C=CC(O)=C(OC)C=1>>[Br:28][C:4]1[S:5][CH:6]=[C:2]([CH2:1][O:27][C:13]2[CH:14]=[CH:15][C:16]([B:18]3[O:19][C:20]([CH3:26])([CH3:25])[C:21]([CH3:23])([CH3:24])[O:22]3)=[CH:17][C:12]=2[O:11][CH3:10])[N:3]=1
Reactant: COc1cc(Br)ccc1O
Reactant: Cc1ncsc1CCO
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1O
Product: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1OCc1csc(Br)n1

Procedure:
The title compound was prepared by substituting Example 652A for 2-(4-methylthiazol-5-yl)-ethanol and 2-methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol for 4-bromo-2-methoxyphenol, respectively, in Example 630A. MS (ESI) m/e 426 (M+H)+; 1H NMR (300 MHz, DMSO-d.6 □ 7.77 (s, 1H), 7.25 (dd, J=8.1, 1.4 Hz, 1H), 7.15 (d, J=1.4 Hz, 1H), 7.09 (d, J=8.1 Hz, 1H), 5.15 (s, 2H), 3.77 (s, 3H), 1.28 (s, 12H).
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]([OH:8])=O.[NH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C[Si](C)(C)N[Si](C)(C)C>C(Cl)(Cl)Cl>[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]([N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)=[O:8]
Reactant: C1CNCCN1
Reactant: O=C(O)C1CCCO1
Agent: C[Si](C)(C)N[Si](C)(C)C
Solvent: ClC(Cl)Cl
Product: O=C(C1CCCO1)N1CCNCC1
Temperature: 110 °C
Reaction time: 5 h
Yield: 92.8 %

Procedure:
In a 100 ml round-bottom flask, tetrahydrofuran-2-carboxylic acid (3.48 grams, 30 mmole), piperazine (5.16 grams, 60 mmole) and 1,1,1,3,3,3-hexamethyldisilazane (4.83 grams, 30 mmole) were added, stirred under a nitrogen atmosphere and heated to 110° C. After 5 hours, the completion of the reaction was detected by thin-layer chromatography (TLC). After cooling to room temperature, the product was dissolved in chloroform, washed with a sodium hydrogen carbonate solution once and with water once. The organic layer was dried with anhydrous sodium sulfate, filtered, and applied suction to obtain 5.13 grams of Compound 3.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][Cl:5].[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7]1.CCN(CC)CC>O1CCOCC1>[Cl:5][CH2:4][CH2:3][CH2:2][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7]1
Reactant: c1ccc2c(c1)CCN2
Reactant: ClCCCBr
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: ClCCCN1CCc2ccccc21
Temperature: 70 °C
Reaction time: 15 h
Yield: 45.4 %

Procedure:
To a solution of 1-bromo-3-chloropropane (1.98 g, 12.6 mmol) and indoline (500 mg, 4.20 mmol) in 1,4-dioxane (6.0 mL) was added Et3N (2.12 g, 21.0 mmol) at 20° C. The reaction mixture was then stirred for 15 h at 70° C. The reaction mixture was cooled to 20° C. and quenched by addition of H2O. The product was extracted with Et2O. The organic solution was then washed with H2O and brine, dried over MgSO4, filtered and concentrated in vacuo. 1-(3-Chloro-1-propyl)indoline (373 mg, 45%) was isolated by flash chromatography on a silica gel column by elution with EtOAc/Hexanes a pale yellow oil. 1H NMR (CDCl3, 300 MHz) δ2.07 (qu, 2H, J=6.2 Hz), 2.97 (t, 2H, J=8.2 Hz), 3.24 (t, 2H, J=6.6 Hz), 3.35 (t, 2H, J=8.3 Hz), 3.68 (t, 2H, J=6.2 Hz), 6.50-6.56 (m, 1H), 6.66 (t, 1H, J=6.6 Hz), 7.04-7.10 (m, 2H) ppm.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([CH:19]2[CH2:21][CH2:20]2)[C:13]=1[C:14]([O:16]CC)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N(C(OC(C)(C)C)=O)C1SC=C(C2CC2)C=1C(OCC)=O)=O)(C)(C)C.[OH-].[K+]>CO.O>[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([CH:19]2[CH2:20][CH2:21]2)[C:13]=1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)c1c(C2CC2)csc1NC(=O)OC(C)(C)C
Agent: CCOC(=O)c1c(C2CC2)csc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)Nc1scc(C2CC2)c1C(=O)O
Temperature: 60 °C
Yield: 170.4 %

Procedure:
To a stirred mixture of ethyl 2-t-butoxycarbonylamino-4-cyclopropylthiophene-3-carboxylate (2.7 g, 8.7 mmol) and ethyl 2-bis(t-butoxycarbonyl)amino-4-cyclopropylthiophene-3-carboxylate (4.5 g, 10.9 mmol) in methanol (150 ml), a solution of potassium hydroxide (5.3 g, 95 mmol) in water (55 ml) was added. After heating at 60° C. for 6 h, the mixture was concentrated in vacuo and the residue taken up in water (50 ml) followed by acidification (pH=5) with acetic acid under cooling on ice. The precipitate was filtered off and recrystallized from ethyl acetate/ petroleum ether to afford (4.2 g, 70%) of 2-t-butoxycarbonylamino-4-cyclopropylthiophene-3-carboxylic acid. M.p. 175°-176° C. 1H-NMR (CDCl3, δ): 0.6 (m, 2H), 0.9 (m, 2H), 1.55 (s, 9H), 2.35 (m, 1H), 6.2 (s, 1H), 10.15 (s, 1H).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C@@H:11]([N:18]1[N:22]=[N:21][CH:20]=[N:19]1)[C@H:12]1[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]1.[CH2:23](N(CC)CC)[CH3:24].ICC>C(#N)C.C(OCC)(=O)C>[CH2:23]([N:14]1[CH2:15][CH2:16][CH2:17][C@H:12]([C@@H:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[N:18]2[N:22]=[N:21][CH:20]=[N:19]2)[CH2:13]1)[CH3:24]
Reactant: CCN(CC)CC
Reactant: c1ccc2cc([C@H]([C@H]3CCCNC3)n3ncnn3)ccc2c1
Solvent: CCI
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCN1CCC[C@H]([C@@H](c2ccc3ccccc3c2)n2ncnn2)C1
Temperature: 40 °C

Procedure:
(3S)-3-[(S)-naphthalen-2-yl(2H-tetrazol-2-yl)methyl]piperidine (2.0 mmol) from Example 2 was dissolved in acetonitrile and the solution was treated with triethylamine (3.0 mmol) at room temperature. To this solution was added iodoethane in acetonitrile slowly and the solution was warmed up to 40° C. After the completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed with 5% aq NaOH, water, brine, and dried over MgSO4. After concentration, the crude product was purified by flash column chromatography with a 10% Methanol in dichloromethane to afford (3S)-1-ethyl-3-[(S)-naphthalen-2-yl(2H-tetrazol-2-yl)methyl]piperidine.