Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]1[O:7][C:6]([CH2:8][OH:9])=[CH:5][CH:4]=1.[H][H]>[Ni].C(O)C>[OH:9][CH2:8][CH:6]1[O:7][CH:3]([CH2:2][OH:1])[CH2:4][CH2:5]1
Reactant: [H][H]
Reactant: OCc1ccc(CO)o1
Agent: [Ni]
Solvent: CCO
Product: OCC1CCC(CO)O1

Procedure:
Raney nickel [ethanol was added three times to 50% commercial aqueous Raney nickel suspension (5 mL) from Acros, and decanted] was added to a solution of (5-hydroxymethylfuran-2-yl)methanol (RK-325) (3.46 g, 27 mmol) in absolute ethanol (100 mL), and hydrogenated overnight at room temperature and at a pressure of 2 bar (hydrogen consumption 61 mmol). The reaction mixture was filtered and the filtrate was concentrated under vacuum.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[N:4][C:3]=1[OH:9].[CH3:10][N:11]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:12](Cl)=[O:13].C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[N:4][C:3]=1[O:9][C:12](=[O:13])[N:11]([CH3:10])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: Oc1nncc(Cl)c1Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CN(C(=O)Oc1nncc(Cl)c1Cl)c1ccccc1
Yield: 13.4 %

Procedure:
A solution of 4,5-dichloro-3-hydroxypyridazine (0.49 g, 3.00 mmol), N-methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in tetrahydrofuran (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate:heptane (20:80)) yielding the title compound (0.12 g, 14% yield) as a white solid.
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:12])[C:7](=[O:13])[CH2:6][N:5]([CH:14]([CH3:16])[CH3:15])[C:4]=2[N:3]=1.[NH2:17][C:18]1[CH:19]=[C:20]([S:24]([CH2:27][CH2:28][OH:29])(=[O:26])=[O:25])[CH:21]=[CH:22][CH:23]=1>ClCCl>[OH:29][CH2:28][CH2:27][S:24]([C:20]1[CH:19]=[C:18]([NH:17][C:2]2[N:11]=[CH:10][C:9]3[N:8]([CH3:12])[C:7](=[O:13])[CH2:6][N:5]([CH:14]([CH3:16])[CH3:15])[C:4]=3[N:3]=2)[CH:23]=[CH:22][CH:21]=1)(=[O:25])=[O:26]
Reactant: CC(C)N1CC(=O)N(C)c2cnc(Cl)nc21
Reactant: Nc1cccc(S(=O)(=O)CCO)c1
Solvent: ClCCl
Product: CC(C)N1CC(=O)N(C)c2cnc(Nc3cccc(S(=O)(=O)CCO)c3)nc21
Yield: 85 %

Procedure:
2-Chloro-8-isopropyl-5-methyl-7,8-dihydro-5H-pteridin-6-one (150 mg; 0.623 mmol) and 2-(3-Amino-phenylsulfonyl)-ethanol (120 mg; 0.600 mmol) were heated to 160° C. for 30 minutes. The reaction mixture was then suspended in dichloromethane and ethyl acetate then filtrated to yield 215 mg (0.530 mmol; 85% yield) as yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[O:11][CH3:12].[C:13](O)(=[O:15])[CH3:14].C(OC(=O)C)(=O)C>O>[C:13]([NH:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[O:11][CH3:12])(=[O:15])[CH3:14]
Reactant: COc1ccc([N+](=O)[O-])cc1N
Reactant: CC(=O)O
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: COc1ccc([N+](=O)[O-])cc1NC(C)=O
Temperature: 80 °C
Reaction time: 4 h

Procedure:
504 g (3 mol) of 2-amino-4-nitro-1-methoxybenzene are introduced into 860 ml of acetic acid and 600 ml of water (or the combined main filtrate and first wash filtrate of a previous batch) and the mixture is heated to 80° C. 358 g (3.2 mol) of acetic anhydride are added dropwise in the course of 10 minutes. The mixture is subsequently stirred at 80° C. for 4 hours, and then cooled to room temperature, while stirring, by removing the heating bath and finally to 15° C. The pale yellow needles which have precipitated are filtered off with suction, washed with 300 ml of 60% strength acetic acid and 1500 ml of water in several portions and dried.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.[CH:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH2:21][C:22]#[N:23])=O>O>[O:20]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH:12]=[C:21]1[C:22]#[N:23]
Reactant: N#CCOc1ccccc1C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cc2ccccc2o1
Temperature: 60 °C
Reaction time: 2.5 h
Yield: 43 %

Procedure:
Potassium carbonate (65.2 g) was added to a DMF solution (500 ml) of (2-formylphenyl)oxyacetonitrile (38 g), which was stirred at 60° C. for 2.5 hours. Water was added to the reaction mixture, which was extracted with diethyl ether. The organic layer was washed with water and a saturated aqueous sodium chloride solution, then dried and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=10/1) to obtain the entitled compound (14.5 g).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](SC)[C:5]([C:12]#[N:13])=[C:4]([S:14][CH2:15][C:16]2[N:17]=[C:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[S:19][CH:20]=2)[N:3]=1.[OH:28][CH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.[Cl-].[NH4+].C(OCC)(=O)C>CC(C)=O>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([N:32]2[CH2:33][CH2:34][CH:29]([OH:28])[CH2:30][CH2:31]2)[C:5]([C:12]#[N:13])=[C:4]([S:14][CH2:15][C:16]2[N:17]=[C:18]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=3)[S:19][CH:20]=2)[N:3]=1
Reactant: CSc1c(C#N)c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c1C#N
Reactant: OC1CCNCC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: N#Cc1c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1N1CCC(O)CC1

Procedure:
100 mg (0.23 mmol) of 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-(methyl-thio)pyridine-3,5-dicarbonitrile and 1000 mg (9.89 mmol) of 4-hydroxypiperidine are combined in 2 ml of acetone and stirred under reflux for 8 h. The mixture is then added to a mixture of semiconcentrated aqueous ammonium chloride solution and ethyl acetate. After vigorous mixing, the organic phase is separated off, washed with saturated sodium chloride solution, dried over magnesium sulfate and filtered off using a glass frit, and the solvent is removed on a rotary evaporator. The residue is purified initially by column chromatography on silica gel 60 (mobile phase: gradient toluene/ethyl acetate 3:1→1:1) and then by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). The title compound in obtained as a white powder.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([S:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH:5]=[CH:4][C:3]=1[N+:16]([O-:18])=[O:17].[CH3:19][O:20][C:21]([N:23]=[C:24]=[S:25])=[O:22].[S-]C#N.[K+].COC(Cl)=O>CC(C)=O>[CH3:19][O:20][C:21]([NH:23][C:24](=[S:25])[NH:1][C:2]1[CH:7]=[C:6]([S:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH:5]=[CH:4][C:3]=1[N+:16]([O-:18])=[O:17])=[O:22]
Reactant: COC(=O)N=C=S
Reactant: Nc1cc(S(=O)c2ccccc2)ccc1[N+](=O)[O-]
Agent: COC(=O)Cl
Agent: N#C[S-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)NC(=S)Nc1cc(S(=O)c2ccccc2)ccc1[N+](=O)[O-]

Procedure:
A suspension of 5.2 g. of 1-amino-5-phenylsulfinyl-2-nitrobenzene in 50 ml. of acetone is treated at 20°-25° C with a solution of 100 ml. of methoxycarbonyl isothiocyanate (made from 0.125 mol. (each) of potassium thiocyanate and methylchloroformate) in acetone. After several days, the solvent is stripped off under vacuum and the residue triturated with ether. Recrystallization of the crude product from methanol-chloroform yields 1-(3-methoxycarbonyl-2-thioureido)-5-phenylsulfinyl-2-nitrobenzene.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][NH:5][C@@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.C([O-])(O)=O.[Na+].Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].C(=O)=O>O.C1(C)C=CC=CC=1>[C:16]([N:5]1[CH2:6][C@H:2]([OH:1])[CH2:3][C@@H:4]1[C:7]([OH:9])=[O:8])([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]
Reactant: O=C(O)[C@H]1C[C@@H](O)CN1
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: O=C=O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: O=C(O)[C@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1
Reaction time: 16 h
Yield: 96 %

Procedure:
Cis-4-hydroxy-D-proline 8 (10.0 g, 76.3 mmol) was dissolved in H2O (165 mL) containing NaHCO3 (16.0 g, 190 mmol). Benzyl chloroformate (12.5 mL, 15.0 g, 87.7 mmol) in toluene (40 mL) was added to this stirring solution at room temperature over 30 minutes using a dropping funnel. The reaction was stirred for 16 h. By this time, CO2 evolution had ceased, and the two phases were separated. Excess benzyl chloroformate was removed from the aqueous layer by washing with ether (3×50 mL). The aqueous phase was cooled in an ice bath and acidified to pH2 with concentrated HCl, causing precipitation of the oily product. This oil was extracted from the aqueous layer by repeated washings with ethyl acetate (5×50 mL). Further acidification of the aqueous layer produced no more precipitate, indicating the extraction was complete. The combined organic layers were washed with brine, dried (MgSO4), and concentrated to a colorless viscous oil, which crystallized upon standing at room temperature to provide 19.42 g (96%) of N-CBZ-cis-4-hydroxy-D-proline: mp 110°-111° C. (lit. 19 mp 110.5°-111.5° C.); [α]25d +24.4° (c 1.0, CHCl3) ]lit. 19 [α25D +26.3° (c 1.0, CHCl3)].
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16](N(CC)CC)C.COC(ON=C(C#N)C(N)=O)=O>C(Cl)(Cl)Cl.C(#N)C>[CH3:16][O:14][C:13](=[O:15])[CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]
Reactant: O=C(O)CNC(=O)OCc1ccccc1
Reactant: CCN(CC)CC
Agent: COC(=O)ON=C(C#N)C(N)=O
Solvent: CC#N
Solvent: ClC(Cl)Cl
Product: COC(=O)CNC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of N-benzyloxycarbonylglycine (1.05 g) and triethylamine (0.7 ml) in chloroform (10 ml) and acetonitrile (5 ml), 2-methoxycarbonyloxyimino-2-cyanoacetic acid amide (0.85 g) is added, and the resulting mixture is stirred at room temperature for 1 hour and allowed to stand over night. The reaction mixture is treated as in Example A to give N-benzyloxycarbonylglycine methyl ester (1.1 g) as an oil.
Reaction SMILES: [CH2:1]([OH:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[H-].[Na+].[N+](C1C=CC([O:25][C:26](=O)[O:27][CH2:28][N:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][N:44]4[CH2:49][CH2:48][N:47]([C:50]5[C:58]6[CH:57]=[CH:56][S:55][C:54]=6[CH:53]=[CH:52][CH:51]=5)[CH2:46][CH2:45]4)[CH:37]=3)[CH:32]=[CH:31][C:30]2=[O:59])=CC=1)([O-])=O.O>C1COCC1>[CH2:1]([O:13][C:26](=[O:25])[O:27][CH2:28][N:29]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][N:44]3[CH2:49][CH2:48][N:47]([C:50]4[C:58]5[CH:57]=[CH:56][S:55][C:54]=5[CH:53]=[CH:52][CH:51]=4)[CH2:46][CH2:45]3)[CH:37]=2)[CH:32]=[CH:31][C:30]1=[O:59])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCO
Reactant: O=C(OCn1c(=O)ccc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc21)Oc1ccc([N+](=O)[O-])cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCCCCCCCOC(=O)OCn1c(=O)ccc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc21
Reaction time: 1 h
Yield: 39.5 %

Procedure:
1-Dodecanol (0.10 g) was dissolved in anhydrous THF (5 ml) under a nitrogen atmosphere and sodium hydride (about 55% oil) (25 mg) was added under ice-cooling with stirring. The reaction mixture was stirred at room temperature for 30 min under a nitrogen atmosphere, and then the mixture was ice-cooled. To the mixture was added a solution (5 ml) of carbonic acid 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-2-oxo-2H-quinolin-1-ylmethyl ester 4-nitrophenyl ester obtained in Example 133 (0.33 g) in anhydrous THF using a cannula. Under a nitrogen atmosphere, the reaction mixture was stirred with ice-cooling for 2 hr, and at room temperature for 1 hr. Water was added to the reaction mixture to discontinue the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated by filtration. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1) to give the title compound (0.14 g) as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[O:6][C@@H:7]([C@:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][NH:12]1)[C:8]([OH:10])=[O:9].[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41](Cl)=[O:42])=[CH:36][CH:35]=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[O:6][C@@H:7]([C@:11]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][N:12]1[C:41](=[O:42])[CH2:40][C:37]1[CH:38]=[CH:39][C:34]([O:33][CH3:32])=[CH:35][CH:36]=1)[C:8]([OH:10])=[O:9]
Reactant: COc1ccc(CC(=O)Cl)cc1
Reactant: COc1cc(OC)cc(O[C@H](C(=O)O)[C@@]2(c3ccccc3)NCCc3ccccc32)c1
Product: COc1ccc(CC(=O)N2CCc3ccccc3[C@@]2(c2ccccc2)[C@H](Oc2cc(OC)cc(OC)c2)C(=O)O)cc1
Yield: 60.9 %

Procedure:
(±)-(S*)-(3,5-dimethoxy-phenoxy)-{(1S*)-2-[2-(4-methoxy-phenyl)-acetyl]-1-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-yl}-acetic acid (74 mg) is prepared in analogy to Example 5 starting from (±)-(S*)-(3,5-dimethoxy-phenoxy)-((1S*)-1-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)-acetic acid (90 mg, 0.214 mmol, Example 1) and 4-methoxyphenylacetyl chloride (49 μl, 0.321 mmol). LC-MS2: tR=5.25 min, [M+1]+=568.43, [M−1]−=566.51.