Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(C)C=CC(S([Cl:10])(=O)=O)=CC=1.[NH2:12][C:13]1[C:17]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]([F:31])([F:30])[F:29])=S)=[CH:16][S:15][CH:14]=1.[OH-].[Na+]>C1COCC1.O>[ClH:10].[F:29][C:28]([F:31])([F:30])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][C:19]1[NH:18][C:17]2=[CH:16][S:15][CH:14]=[C:13]2[N:12]=1
Reactant: Nc1cscc1NC(=S)Nc1ccccc1C(F)(F)F
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cl
Product: FC(F)(F)c1ccccc1Nc1nc2cscc2[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 165.3 mg of p-toluenesulfonyl chloride in 5 ml of THF was added dropwise to a mixture prepared from a solution of 250 mg of N-(3-amino-4-thienyl)-N′-(2-trifluoromethylphenyl)thiourea in 15 ml of THF and a solution of 77.8 mg of NaOH in 3 ml of water. After stirring at room temperature for 2 hours, the solvent was distilled off, and the residue was admixed with water and extracted with ethyl acetate. After the washing, the organic phase was dried over sodium sulfate, the solvent was distilled off and the residue was purified by column chromatography on silica gel using a mixture of 20 parts by volume of ethyl acetate, 10 parts by volume of n-heptane and 3 parts by volume of glacial acetic acid. After the solvent of the fraction which had been identified by the LC-MS technique had been distilled off, the residue was dissolved in a little ethyl acetate, made strongly acidic using a solution of hydrogen chloride gas in diethyl ether, and the crystals were filtered off after having been left to stand overnight.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH:12]=[O:13])=[CH:5][N:6]2[CH3:11].[Mn]([O-])(=O)(=O)=[O:15].[K+]>CC(C)=O>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([C:12]([OH:15])=[O:13])=[CH:5][N:6]2[CH3:11]
Reactant: Cn1cc(C=O)c2c(F)cccc21
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Cn1cc(C(=O)O)c2c(F)cccc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 58 %

Procedure:
In acetone (95 ml) was dissolved 4-fluoro-1-methylindole-3-carbaldehyde (1.43 g, 8.08 mmol), followed by the addition of potassium permanganate (a 0.2M aqueous solution, 62.0 ml, 12.4 mmol) in portions at room temperature. After the reaction mixture was stirred at room temperature for 16 hours, the precipitate was filtered off through Celite. The filtrate was distilled under reduced pressure to remove the solvent. The residue was acidified with 1N HCl. The crystals thus precipitated were collected by filtration under reduced pressure, washed with water, and dried under reduced pressure to give 4-fluoro-1-methylindole-3-carboxylic acid (0.91 g, 58%) as a brown solid.
Reaction SMILES: [OH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([CH2:11][C:12](O)=[O:13])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[C:18](O)(=O)C.[CH3:22][OH:23]>CC#N>[CH3:22][O:23][C:12](=[O:13])[CH2:11][C:5]1[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([O:1][CH3:18])=[C:3]([N+:15]([O-:17])=[O:16])[CH:4]=1
Reactant: O=C(O)Cc1cc([N+](=O)[O-])c(O)c([N+](=O)[O-])c1
Reactant: CO
Reactant: CC(=O)O
Solvent: CC#N
Product: COC(=O)Cc1cc([N+](=O)[O-])c(OC)c([N+](=O)[O-])c1
Reaction time: 2 h

Procedure:
A solution of TMSCHCN2 (1.0 M) was added to 4.28 g (17.3 mmol) of (4-hydroxy-3,5-dinitro-phenyl)-acetic acid in 63 mL of MeCN and 7 mL of MeOH. After 2 h, 0.8 mL of acetic acid was added. After stirring an additional 30 min, the solution was concentrated and partitioned between saturated NaHCO3 and EtOAc. The organic portion was washed with brine, dried with Na2SO4, filtered, and concentrated to provide (4-methoxy-3,5-dinitro-phenyl)-acetic acid methyl ester (3.22 g).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[Cl:13]N1C(=O)CCC1=O>C(O)(=O)C>[Cl:13][C:5]1[S:1][C:2]([O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:3][CH:4]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCOC(=O)COc1cccs1
Solvent: CC(=O)O
Product: CCOC(=O)COc1ccc(Cl)s1
Reaction time: 1.5 h
Yield: 96.6 %

Procedure:
To a solution of ethyl 2-thienyloxyacetate (1.1 g, 5.9 mmol) in acetic acid (15 mL) is added N-chlorosuccinimide (0.78 g, 5.9 mmol). The solution is stirred for 1.5 hour. After this time the solution is concentrated. The resulting oil is dissolved in ether and washed with 1N NaOH, water and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated under vacuum. The title compound (1.26 g, 5.7 mmol) is obtained as an oil. 1H NMR (CDCl3, 300 MHz) δ6.52 (d, 1H), 6.06 (d, 1H), 4.60 (s, 2H), 4.24 (q, 2H), 1.31 (t, 3H).
Reaction SMILES: O=[C:2]1[CH2:6][S:5][CH2:4][CH:3]1[C:7]([O:9][CH3:10])=[O:8].[CH3:11][CH:12]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:13]([C:15]1[CH:16]=C(O)[CH:18]=[C:19]([CH:21]=1)[OH:20])[CH3:14].Cl>C(O)C>[OH:20][C:19]1[C:18]2[C:2]3[CH2:6][S:5][CH2:4][C:3]=3[C:7](=[O:8])[O:9][C:10]=2[CH:16]=[C:15]([CH:13]([CH:12]([CH3:11])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH3:14])[CH:21]=1
Reactant: COC(=O)C1CSCC1=O
Reactant: CCCCCC(C)C(C)c1cc(O)cc(O)c1
Agent: Cl
Solvent: CCO
Product: CCCCCC(C)C(C)c1cc(O)c2c3c(c(=O)oc2c1)CSC3
Reaction time: 72 h

Procedure:
A solution of 20 g. (0.125 mole) of the methyl 4-oxo-2,3,4,5-tetrahydrothiophene-3-carboxylate prepared in A and 32 g. (0.135 mole) of 5-(3-methyl-2-octyl)resorcinol in 200 ml. of absolute ethanol was cooled in an ice-salt bath and saturated with anhydrous hydrogen chloride. The reaction mixture was allowed to stand at room temperature for 72 hours and the solid which formed was removed by filtration. Recrystallization from ethanol gave 16 g. (37%) m.p. 165°-166°C. The structure was confirmed by the IR and NMR spectra.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:9]([N:11]2[CH2:16][CH2:15][C@@H:14]([C:17](O)=[O:18])[CH2:13][C@@H:12]2[C:20]([NH:22][CH2:23][CH2:24][N:25]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[O:34][CH3:35])[CH3:26])=[O:21])=[O:10])[CH:5]=[CH:6][CH:7]=1.[CH2:42]([NH:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:9]([N:11]2[CH2:16][CH2:15][C@@H:14]([C:17]([N:49]([CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[O:18])[CH2:13][C@@H:12]2[C:20]([NH:22][CH2:23][CH2:24][N:25]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[O:34][CH3:35])[CH3:26])=[O:21])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccccc1CN(C)CCNC(=O)[C@H]1C[C@H](C(=O)O)CCN1C(=O)N(c1ccccc1)c1cccc(Cl)c1
Reactant: c1ccc(CNCc2ccccc2)cc1
Product: COc1ccccc1CN(C)CCNC(=O)[C@H]1C[C@H](C(=O)N(Cc2ccccc2)Cc2ccccc2)CCN1C(=O)N(c1ccccc1)c1cccc(Cl)c1
Yield: 32.9 %

Procedure:
According to the procedure given in Example 2, Step E, 0.051 g of trans 1-(N-(3-chlorophenyl)-N-(phenyl)-aminocarbonyl)-2-(RS)-(2-(N-(2-methoxybenzyl)-N-methylamino)ethylaminocarbonyl)-piperidine-4-(RS)-carboxylic acid and 0.035 g of dibenzylamine gave 22 mg (33%) of an oil.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]([NH:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=2)=[O:12])(=[O:9])=[O:8])=[CH:4][CH:3]=1.[Li+].[OH-]>CO.C(#N)C>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]([NH:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=2)=[O:12])(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc(NC(=O)NS(=O)(=O)c2ccc(Cl)s2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CC#N
Solvent: CO
Product: O=C(Nc1ccc(C(=O)O)cc1)NS(=O)(=O)c1ccc(Cl)s1
Temperature: 25 °C
Reaction time: 21 h
Yield: 127.5 %

Procedure:
To a suspension of methyl 4-({[(5-chloro-2-thienyl)sulfonyl]amino}carbonylamino)benzoate (56 mg, 0.15 mmol) in methanol (1 mL) and acetonitrile (1 mL) was added 1N LiOH (0.16 mL, 0.16 mmol). The resulting solution was stirred at room temp for 21 hr, then an additional 0.32 mL 1N LiOH was added and the reaction was stirred at 40° C. for another 21 hr til complete. Concentration in vacuo gave crude 4-({[(5-chloro-2-thienyl)sulfonyl]amino}carbonylamino)benzoic acid (69 mg). ES-MS (M+H)+=361.
Reaction SMILES: [F:1][C:2]([F:41])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([CH2:34][CH:35]([OH:40])[C:36]([F:39])([F:38])[F:37])[C:15]2[CH:16]=[C:17]([CH:31]=[CH:32][CH:33]=2)[O:18][CH2:19][C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([O:25]CC)=[O:24])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:5])[F:4].[OH-].[Li+].Cl>O.O1CCCC1>[F:1][C:2]([F:41])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([CH2:34][CH:35]([OH:40])[C:36]([F:37])([F:38])[F:39])[C:15]2[CH:16]=[C:17]([CH:31]=[CH:32][CH:33]=2)[O:18][CH2:19][C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([OH:25])=[O:24])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:4])[F:5]
Reactant: CCOC(=O)c1cccc(COc2cccc(N(Cc3cccc(OC(F)(F)C(F)F)c3)CC(O)C(F)(F)F)c2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cccc(COc2cccc(N(Cc3cccc(OC(F)(F)C(F)F)c3)CC(O)C(F)(F)F)c2)c1
Yield: 24.9 %

Procedure:
A solution of ethyl 3-[[3-[[[3-(1,1,2,2-tetrafluoroethoxy) phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]phenoxy]methyl]benzoate (22.1 mg, 0.04 mmol) and lithium hydroxide (5 mg, 0.12 mmol) in water (1 mL) and tetrahydrofuran (0.5 mL) was heated at 80° C. for 16 h. The reaction mixture was added to 6 N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated. The residue was purified by reverse phase HPLC eluting with 10% to 90% acetonitrile in water to afford 5.6 mg (19%) of the desired benzoic acid product as a brown oil. HRMS calcd. for C26H23F7NO5: 562.1464 [M+H]+, found: 562.1418. 1H NMR (acetone-d6) δ3.64 (dd, 1H), 3.95 (m, 1H), 4.45-4.50 (m, 1H), 4.80 (s, 2H), 5.12 (s, 2H), 6.27-6.63 (m, 4-H), 7.06-7.27 (m, 4-H), 7.41 (t, 1H), 7.50 (t, 1H), 7.66 (d, 1H), 7.99 (d, 1H), 8.10 (s, 1H).
Reaction SMILES: [CH:1]([C:3]1[CH:52]=[CH:51][C:6]([C:7]([O:9][CH2:10][O:11][C:12]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([CH2:23][C:24]([NH:37][C:38]([O:40][CH2:41][C:42]3[O:43][C:44]4[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=4[CH:46]=3)=[O:39])([C:26](=[O:36])[NH:27][CH:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH3:29])[CH3:25])=[CH:15]2)=[O:13])=[O:8])=[CH:5][CH:4]=1)=O.[OH:53][CH2:54][CH2:55][N:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1.C(O)(=O)C.C(Cl)(Cl)[Cl:67]>>[ClH:67].[ClH:67].[OH:53][CH2:54][CH2:55][N:56]1[CH2:61][CH2:60][N:59]([CH2:1][C:3]2[CH:52]=[CH:51][C:6]([C:7]([O:9][CH2:10][O:11][C:12]([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16]([CH2:23][C:24]([NH:37][C:38]([O:40][CH2:41][C:42]4[O:43][C:44]5[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=5[CH:46]=4)=[O:39])([C:26](=[O:36])[NH:27][CH:28]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH3:29])[CH3:25])=[CH:15]3)=[O:13])=[O:8])=[CH:5][CH:4]=2)[CH2:58][CH2:57]1
Reactant: ClC(Cl)Cl
Reactant: OCCN1CCNCC1
Reactant: CC(NC(=O)C(C)(Cc1cn(C(=O)OCOC(=O)c2ccc(C=O)cc2)c2ccccc12)NC(=O)OCc1cc2ccccc2o1)c1ccccc1
Solvent: CC(=O)O
Product: CC(NC(=O)C(C)(Cc1cn(C(=O)OCOC(=O)c2ccc(CN3CCN(CCO)CC3)cc2)c2ccccc12)NC(=O)OCc1cc2ccccc2o1)c1ccccc1
Product: Cl
Reaction time: 0.5 h
Yield: 69 %

Procedure:
NaHB(OAc)3 (0.423 g, 1.996 mmol, 1.4 eq.) was added in three equal portions in 10 minutes to a cloudy solution of compound 19 (1.0 g, 1.43 mmol), N-hydroxyethylpiperazine (0.192 mL, 1.57 mmol, 1.1 eq.) and acetic acid (0.179 mL, 3.14 mmol, 2.2 eq.) in dry chloroform (20 mL) under N2 in an ice bath. The reaction was stirred in ice bath for 30 minutes and at room temperature overnight to give a white suspension. The reaction was worked up as above to give compound 20d as a white foam (0.804 g, 69%).
Reaction SMILES: C([O:3][C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:21])=[C:17]([F:20])[CH:18]=3)[C:13]([C:22]#[N:23])=[CH:12]2)=[CH:7][C:6]=1[OH:24])C.O1CCCC1.[OH-].[Li+].Cl>O.C(O)C>[C:22]([C:13]1[C:14]2[C:19](=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)[N:11]([C:8]2[CH:9]=[CH:10][C:5]([C:4]([OH:25])=[O:3])=[C:6]([OH:24])[CH:7]=2)[CH:12]=1)#[N:23]
Reactant: CCOC(=O)c1ccc(-n2cc(C#N)c3cc(F)c(F)cc32)cc1O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: N#Cc1cn(-c2ccc(C(=O)O)c(O)c2)c2cc(F)c(F)cc12
Temperature: 25 °C
Reaction time: 26 h
Yield: 88.3 %

Procedure:
To a solution of 4-(3-cyano-5,6-difluoroindol-1-yl)-2-hydroxybenzoic acid ethyl ester (0.074 g) in a mixed solvent of tetrahydrofuran (3.0 mL) and ethanol (0.75 mL) were added 0.1 g/mL aqueous lithium hydroxide solution (0.62 mL) and water (1.0 mL), and this mixture was stirred at room temperature for 26 hours. To this reaction mixture was added 2 mol/L hydrochloric acid (5 mL), this organic solvent was removed under reduced pressure. This resulting mixture was extracted with ethyl acetate, this organic layer was washed with water, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure to give the title compounds (0.06 g).
Reaction SMILES: C[O:2][C:3](=[O:23])[C@@H:4]([NH:9][C:10]([O:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2)=[O:11])[C:5]([CH3:8])([CH3:7])[CH3:6].O.[OH-].[Li+]>C1COCC1.CO.O>[C:13]12([O:12][C:10]([NH:9][C@@H:4]([C:5]([CH3:8])([CH3:7])[CH3:6])[C:3]([OH:23])=[O:2])=[O:11])[CH2:14][CH:15]3[CH2:16][CH:17]([CH2:18][CH:19]([CH2:21]3)[CH2:20]1)[CH2:22]2
Reactant: COC(=O)[C@@H](NC(=O)OC12CC3CC(CC(C3)C1)C2)C(C)(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CC(C)(C)[C@H](NC(=O)OC12CC3CC(CC(C3)C1)C2)C(=O)O
Temperature: 25 °C
Reaction time: 5 h
Yield: 85.1 %

Procedure:
To a solution of (S)-2-(Adamantan-1-yloxycarbonylamino)-3,3-dimethyl-butyric acid methyl ester (358 mg, 1.107 mmol) in THF (4 mL) and MeOH (4 mL) was added a pre-made solution of lithium hydroxide monohydrate (93 mg, 2.214 mmol) in water (4.00 mL). The cloudy white solution was stirred at rt for 5 hrs. The volatiles were removed, and the reaction mixture was diluted with dilute citric acid solution and extracted with EtOAc (3×10 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated to obtain a white solid (291.4 mg, 85%) as product. The crude material was used without further purification.
Reaction SMILES: [C:1]1([CH:7]2[O:12][CH2:11][CH2:10][NH:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[CH2:18][C:19](Cl)=[O:20].C(N(CC)CC)C>ClCCl>[C:1]1([CH:7]2[O:12][CH2:11][CH2:10][N:9]([C:19](=[O:20])[CH2:18][C:14]3[S:13][CH:17]=[CH:16][CH:15]=3)[CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(C2CNCCO2)cc1
Reactant: O=C(Cl)Cc1cccs1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Cc1cccs1)N1CCOC(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 6 h
Yield: 88.9 %

Procedure:
A solution of 2-phenylmorpholine (326 mg, 2 mmol) in dry dichloromethane (6 mL) is cooled in an ice bath, and thiophen-2-yl-acetyl chloride (401.5 mg, 2.5 mmol, 1.25 eq) and triethylamine (417 μL, 3 mmol, 1.5 eq) are added. After stirring for 6 hours at room temperature the reaction mixture is diluted with dichloromethane (10 mL). The organic solution is subsequently washed with 1 M KHSO4, 5% NaHCO3 and brine. After drying over Na2SO4, dichloromethane is removed in vacuo and the crude material is purified by flash chromatography (silicagel, ethyl acetate/toluene 1:3). The fractions containing 1-(2-phenylmorpholin-4-yl)-2-(thiophen-2-yl)ethan-1-one are collected and the solvent is removed in vacuo to give 511 mg of colorless oil.