Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O1C[CH2:5][CH:4]([O:7][CH:8]([C:10]2[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=2)[CH3:9])[CH2:3][CH2:2]1.Cl.C(N=C=N[CH2:25][CH2:26][CH2:27]N(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:48][CH2:49][C:50]1[C:51]([OH:58])=[N:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56]>ClCCl>[OH:58][C:51]1[C:50]([CH2:49][NH:48][C:14](=[O:15])[C:13]2[CH:17]=[CH:18][C:10]([CH:8]([O:7][C:4]3[CH:5]=[C:26]([CH3:25])[CH:27]=[CH:2][CH:3]=3)[CH3:9])=[CH:11][CH:12]=2)=[C:55]([CH3:56])[CH:54]=[C:53]([CH3:57])[N:52]=1
Reactant: CC(OC1CCOCC1)c1ccc(C(=O)O)cc1
Reactant: Cc1cc(C)c(CN)c(O)n1
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cccc(OC(C)c2ccc(C(=O)NCc3c(C)cc(C)nc3O)cc2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81 %

Procedure:
A mixture of 4-(1-(tetrahydro-2H-pyran-4-yloxy)ethyl)benzoic acid (326 mg, 1.3 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (380 mg, 1.98 mmol), N-hydroxybenzotriazole (267.3 mg, 1.98 mmol) and triethylamine (400 mg, 3.96 mmol) in dichloromethane (50 mL) was stirred for 30 minutes at room temperature. Then to the mixture, 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (200.64 mg, 1.32 mmol) was added. The resultant mixture was stirred at room temperature for 12 hours. Then the mixture was washed with water (30 mL×3). The organic layer was concentrated to give a residue and the residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(1-(m-tolyloxy)ethyl)benzamide (411 mg, 82%). LRMS (M+H+) m/z: calcd 384.2. found 384.
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]5[CH2:34][O:33][CH2:32]5)[CH2:27][C@H:26]4[CH3:35])=[CH:21][N:20]=3)[C:15](=[O:36])[N:14]([CH3:37])[CH:13]=2)=[CH:10][C:9]([F:38])=[CH:8][C:7]=1[N:39]1[CH2:50][CH2:49][N:48]2[C:41](=[CH:42][C:43]3[CH2:44][C:45]([CH3:52])([CH3:51])[CH2:46][C:47]=32)[C:40]1=[O:53])(=O)C.[OH-].[Li+].C1COCC1.C(O)(C)C>O>[F:38][C:9]1[CH:10]=[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]5[CH2:34][O:33][CH2:32]5)[CH2:27][C@H:26]4[CH3:35])=[CH:21][N:20]=3)[C:15](=[O:36])[N:14]([CH3:37])[CH:13]=2)[C:6]([CH2:5][OH:4])=[C:7]([N:39]2[CH2:50][CH2:49][N:48]3[C:47]4[CH2:46][C:45]([CH3:52])([CH3:51])[CH2:44][C:43]=4[CH:42]=[C:41]3[C:40]2=[O:53])[CH:8]=1
Reactant: CC(=O)OCc1c(-c2cc(Nc3ccc(N4CCN(C5COC5)C[C@H]4C)cn3)c(=O)n(C)c2)cc(F)cc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Agent: [Li+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Solvent: C1CCOC1
Product: C[C@@H]1CN(C2COC2)CCN1c1ccc(Nc2cc(-c3cc(F)cc(N4CCn5c(cc6c5CC(C)(C)C6)C4=O)c3CO)cn(C)c2=O)nc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 78.8 %

Procedure:
A mixture of 124a (59 mg, 0.080 mmol), lithium hydroxide (19 mg, 0.80 mmol), THF (10 mL), i-propanol (8 mL), and water (10 mL) was stirred at room temperature for 1.5 h. It was then concentrated under reduced pressure and the residue was extracted with dichloromethane (2×10 mL). The combined dichloromethane extract was concentrated under reduced pressure. The residue was purified with reverse-phase prep-HPLC to afford 124 (43 mg, 79%). MS: [M+H]+ 682.3. 1H NMR (500 MHz, DMSO-d6) δ 8.58-8.57 (m, 1H), 8.41 (s, 1H), 7.84 (d, J=3.0 Hz, 1H), 7.37-7.31 (m, 3H), 7.22 (d, J=9.5 Hz, 1H), 7.19-7.16 (m, 1H), 6.50 (s, 1H), 4.87 (d, J=2.0 Hz, 1H), 4.57-4.53 (m, 2H), 4.46 (t, J=6.0 Hz, 1H), 4.41 (t, J=6.0 Hz, 1H), 4.31 (d, J=3.0 Hz, 2H), 4.21-4.18 (m, 2H), 4.15-4.10 (m, 1H), 3.88-3.85 (m, 1H), 3.67 (d, J=2.0 Hz, 1H), 3.58 (s, 3H), 3.41-3.37 (m, 2H), 3.10-3.07 (m, 1H), 2.95-2.91 (m, 1H), 2.56 (d, J=1.5 Hz, 2H), 2.41 (s, 2H), 2.32-2.28 (m, 2H), 2.17-2.15 (m, 1H), 1.21 (s, 6H), 0.91 (d, J=6.5 Hz, 3H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28]C(=O)OC(Cl)(Cl)Cl)Cl.[C:37]1([CH:43]([OH:46])[CH2:44][CH3:45])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH:20][C:26](=[O:28])[O:46][CH:43]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:44][CH3:45])=[C:18]([CH3:24])[CH:17]=1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CCC(O)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CCC(OC(=O)Nc1cc(C)c(Oc2ccnc3cc(OC)c(OC)cc23)cc1C)c1ccccc1
Yield: 101.3 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (76 mg, yield 97%).
Reaction SMILES: C1(C[O:8][C:9]2[CH:10]=[C:11]([CH:20]=[CH:21][CH:22]=2)[O:12][CH2:13][CH2:14][O:15][S:16](=[O:19])(=[O:18])[NH2:17])C=CC=CC=1>O1CCCC1.[Pd]>[OH:8][C:9]1[CH:10]=[C:11]([CH:20]=[CH:21][CH:22]=1)[O:12][CH2:13][CH2:14][O:15][S:16](=[O:18])(=[O:19])[NH2:17]
Reactant: NS(=O)(=O)OCCOc1cccc(OCc2ccccc2)c1
Agent: [Pd]
Solvent: C1CCOC1
Product: NS(=O)(=O)OCCOc1cccc(O)c1
Reaction time: 2 h
Yield: 72 %

Procedure:
To a solution of 17.1 g (.053 mole) of sulfamic acid 2-[3-(phenylmethoxy)phenoxy]ethyl ester in 250 ml of tetrahydrofuran was added 0.5 teaspoon of 5% palladium on carbon catalyst and the mixture was hydrogenated in a Parr bottle at 40° C. for 2 hr. The catalyst was removed and a fresh 0.5 teaspoon of 5% palladium on carbon catalyst was added and the mixture was hydrogenated at 40° C. for 19 hr, whereby hydrogen uptake ceased. The catalyst was removed by filtration through Celite® and the solvent was evaporated under reduced pressure to yield 12.3 g of a brown, viscous oil that solidified after standing for five weeks at ambient temperature. The solid was triturated with ethyl ether-petroleum ether into a paste. The solvents were decanted and the paste was dried to yield 8.9 g (72%) a white solid, mp 56°-60° C.
Reaction SMILES: [S-2:1].[Na+].[Na+].C(O)(=O)C.[C:8]([O:12][C:13](=[O:16])[CH2:14]Cl)([CH3:11])([CH3:10])[CH3:9].C([O-])([O-])=O.[K+].[K+].[CH3:23][O:24][C:25](=[O:37])[C:26]1[CH:31]=[CH:30][C:29]([N+]([O-])=O)=[C:28]([CH:35]=O)[CH:27]=1>CN(C=O)C.O>[CH3:23][O:24][C:25]([C:26]1[CH:31]=[CH:30][C:29]2[S:1][C:14]([C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:16])=[CH:35][C:28]=2[CH:27]=1)=[O:37]
Reactant: [S-2]
Reactant: CC(C)(C)OC(=O)CCl
Reactant: COC(=O)c1ccc([N+](=O)[O-])c(C=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1ccc2sc(C(=O)OC(C)(C)C)cc2c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a suspension of sodium sulfide (7.95 g, 102 mmol) in anhydrous DMF (200 mL) at 0° C. were added acetic acid (5.80 mL, 102 mmol) and additional DMF (100 mL). The mixture was allowed to stir at 0° C. for 30 min and chloro-acetic acid tert-butyl ester (14.6 mL, 102 mmol) was added followed by additional DMF (50 mL). The resulting mixture was allowed to stir at 0° C. for 30 min and at rt for 30 min. To this mixture were added K2CO3 (16.4 g, 119 mmol) and 3-formyl-4-nitro-benzoic acid methyl ester (17.68 g, 84.55 mmol) in DMF (30 mL). The resulting mixture was heated at 55° C. for 22 h, cooled to rt and poured into water (1.2 L). The solid formed was filtered, washed with water (300 mL) and crystallized from MeOH to give benzo[b]thiophene-2,5-dicarboxylic acid 2-tert-butyl ester 5-methyl ester as a pale solid. MS (EI): cal'd 237.0 (M-tbutyl+H+) exp 237.1 (M-tbutyl+H+).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[O:8][N:7]=1)=[O:5])[CH3:2].[B-](F)(F)(F)[F:22].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.C1S(=O)(=O)CCC1>O>[F:22][C:10]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[N:7][O:8][C:9]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=1
Reactant: CCOC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)on1
Reactant: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: O
Solvent: O=S1(=O)CCCC1
Product: CCOC(=O)c1noc(-c2ccc(C(F)(F)F)cc2)c1F
Temperature: 120 °C
Reaction time: 0.08 h
Yield: 15.7 %

Procedure:
A mixture of ethyl-5-(4-(trifluoromethyl)phenyl)isoxazole-3-carboxylate (0.96 g, 3.37 mmol), Selectfluor (1.25 g, 3.53 mmol), and tetramethylene sulfone (7.5 g, 62.5 mmol) was heated to 120° C. for 8 hours. After cooling to room temperature, the reaction mixture was diluted with water, stirred for 5 minutes and the resulting white crystals were collected, washed with water and purified by silica gel chromatography eluting with dichloromethane to obtain the title compound (147 mg, 0.53 mmol).
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:26])=[C:4]([C:23](=[O:25])[CH3:24])[C:5]([OH:22])=[C:6]([O:10][CH2:11][CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH3:14])[C:7]=1[O:8][CH3:9].[Br:27][CH2:28][CH2:29]Br>>[Br:27][CH2:28][CH2:29][O:22][C:5]1[C:6]([O:10][CH2:11][CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH3:14])=[C:7]([O:8][CH3:9])[C:2]([Cl:1])=[C:3]([CH3:26])[C:4]=1[C:23](=[O:25])[CH3:24]
Reactant: COc1c(Cl)c(C)c(C(C)=O)c(O)c1OCCC(C)c1ccc(F)cc1
Reactant: BrCCBr
Product: COc1c(Cl)c(C)c(C(C)=O)c(OCCBr)c1OCCC(C)c1ccc(F)cc1

Procedure:
Example 7c (511 mg, 1.34 mmol) was reacted with 1,2-dibromoethane (20.0 eq.) as described under General Procedure F to afford the title compound (641 mg, quantitative yield) as a light brown oil. 1H NMR (300 MHz, CDCl3) δ 7.20-7.15 (m, 2H), 7.01-6.96 (m, 2H), 4.26 (t, J=6.2 Hz, 2H), 3.96 (t, J=6.6 Hz, 2H), 3.84 (s, 3H), 3.49 (t, J=6.2 Hz, 2H), 2.99 (m, 1H), 2.50 (s, 3H), 2.19 (s, 3H), 2.07-2.01 (m, 2H), 1.30 (d, J=6.9 Hz, 3H). MS (ES+) m/z 487.3 (M+H+).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:9][C:10]([CH2:12][C:13]1[C:14]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22](OC)=[O:23])[C:15]=2[S:16][CH:17]=1)=O)C.C(OCC)(=O)C.O>C1COCC1>[OH:23][CH2:22][C:18]1[C:15]2[S:16][CH:17]=[C:13]([CH2:12][CH2:10][OH:9])[C:14]=2[CH:21]=[CH:20][CH:19]=1
Reactant: CCOC(=O)Cc1csc2c(C(=O)OC)cccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OCCc1csc2c(CO)cccc12
Reaction time: 0.17 h
Yield: 97.5 %

Procedure:
Under a nitrogen stream, to a solution (38 mL) of lithium aluminum hydride (0.74 g, 19.5 mmol) in THF was added a solution (30 mL) of methyl 3-ethoxycarbonylmethyl-benzo[b]thiophene-7-carboxylate (2.7 g, 9.7 mmol) in THF at 0° C., and the resultant solution was stirred for 10 minutes at the same temperature. To the solution was further added lithium aluminum hydride (0.74 g, 19.5 mmol) at 0° C., and the resultant solution was stirred for 10 minutes at the same temperature. Ethyl acetate was added to the solution, and then water (5.2 mL) was added thereto at 0° C. The temperature of the resultant solution was raised to room temperature, and then the solution was stirred for 10 minutes. The reaction mixture was filtered through Celite. Solvent was then removed by distillation under reduced pressure. The resulting residue was treated by addition of ethyl acetate and n-hexane (1:2), to thereby obtain the titled compound (1.97 g, 98%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH3:14])([CH3:13])[C:10](=[O:15])[C:9]=2[C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:29][C:30]1[CH:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]=1>CN(C=O)C>[CH3:14][C:11]1([CH3:13])[C:10](=[O:15])[C:9]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:29][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=3)=[CH:7][CH:6]=2)[O:12]1
Reactant: ClCc1ccc2ccccc2n1
Reactant: CC1(C)OC(c2ccc(O)cc2)=C(c2ccncc2)C1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC1(C)OC(c2ccc(OCc3ccc4ccccc4n3)cc2)=C(c2ccncc2)C1=O
Reaction time: 0.5 h
Yield: 0.1 %

Procedure:
To a room temperature solution of 5-(4-hydroxyphenyl)-2,2-dimethyl-4-(pyridin-4-yl)furan-3(2H)-one (280 mg, 0.9 mol) in DMF (5 mL), K2CO3 (413 mg, 2.98 mol) was added and the reaction mixture was stirred for 30 min. 2-Chloro methyl quinoline (235 mg, 1.09 mol) was then added to the reaction and stirring was continued for 2 h at 85° C. The reaction mixture was then quenched with cold water and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water, dried over Na2SO4 and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 2,2-dimethyl-4-(pyridin-4-yl)-5-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (240 mg, 57%) as a solid. 1H NMR (509 MHz, d6-DMSO): δ 8.58-8.54 (m, 2 H), 8.42 (d, J=7.8 Hz, 1 H), 8.04-7.98 (m, 2 H), 7.80 (t, J=7.6 Hz, 1H), 7.68 (d, J=7.4 Hz, 1 H), 7.64 (t, J=7.6 Hz, 1 H), 7.58 (d, J=7.4 Hz, 2 H), 7.30-7.24 (m, 2 H), 7.19 (d, J=7.2 Hz, 2 H), 5.43 (s, 2 H), 1.50 (s, 6 H). MS: M+H; m/z=423.0. HPLC: 96%, (Condition-I).
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[CH2:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[O:3]1.[N+:14]([O-])([OH:16])=[O:15].O>S(=O)(=O)(O)O>[N+:14]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[O:3][C:2]([CH3:13])([CH3:1])[CH2:11][C:10]2=[O:12])([O-:16])=[O:15]
Reactant: CC1(C)CC(=O)c2ccccc2O1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Solvent: O
Product: CC1(C)CC(=O)c2cc([N+](=O)[O-])ccc2O1
Temperature: 0 °C

Procedure:
2,2-Dimethylchroman-4-one (4 g, 23.2 mmol) was added portionwise over 10 minutes to 7 ml of concentrated sulfuric acid at 0°-5° C., then cooled in an acetone-ice bath as concentrated nitric acid (s.g. 1.5, 90%, 1.4 ml) in 3 ml concentrated sulfuric acid was added dropwise over 20 minutes. The resulting mixture was poured into 100 ml ice and water and extracted 2×50 ml ethyl acetate. The organic layers were combined, washed 4×50 ml water and then brine, dried over magnesium sulfate, stripped to solids (5.3 g) and chromatographed on 500 g silica gel, gradiently eluting with 20:1, 15:1, 10:1 and finally 5:1 hexane:diethyl ether to yield title product as a white solid, 2.1 g (39%); tlc Rf 0.3 (1:1 diethyl ether:hexane); m/e 221(P+), 206, 166, 120.