Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[NH:9][C:8](=[O:19])[NH:7][C:6]=1[CH2:20][O:21][CH3:22])=[O:4].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Cl[C:34]([O:36][C:37]1[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=1)=[O:35]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[N:9]([C:34]([O:36][C:37]2[CH:38]=[CH:39][C:40]([N+:43]([O-:45])=[O:44])=[CH:41][CH:42]=2)=[O:35])[C:8](=[O:19])[NH:7][C:6]=1[CH2:20][O:21][CH3:22])=[O:4]
Reactant: COCC1=C(C(=O)OC)C(c2ccc(F)c(F)c2)NC(=O)N1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COCC1=C(C(=O)OC)C(c2ccc(F)c(F)c2)N(C(=O)Oc2ccc([N+](=O)[O-])cc2)C(=O)N1
Reaction time: 0.17 h

Procedure:
To a solution of (+)-5-methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro-2-oxo-6-(3,4-difluorophenyl)-pyrimidine (1.98 g, 6.34 mmol) in anhydrous THF (20 mL) at −78° C. under argon atmosphere, a solution of lithium hexamethyldisilazide in THF (1M, 18.0 mL, 18.0 mmol) was added over 2-3 min. and the mixture was stirred for 10 min. This solution was added over 6 min., via a cannula, to a stirred solution of 4-nitrophenyl chloroformate (4.47 g, 22.2 mmol) in THF (20 mL) at −78° C. Stirring was continued for 10 min. and the mixture was poured onto ice (50 g) and extracted with chloroform (2×50 mL). The combined extracts were dried (sodium sulfate) and the solvent was evaporated. The residue was purified by flash column chromatography (hexanes/ethyl acetate, 4/1 to 3.5/1) as the eluent. The product was obtained as yellow syrup which upon trituration with hexanes became a white powder (2.40 g, 79%): 1H NMR d 3.52 (s, 3H), 3.74 (s, 3H), 4.65-4.80 (q, J=16.5 Hz, 2H), 6.32 (s, 1H), 7.10-7.30 (m, 4H), 7.36 (d, J=9 Hz, 2H), 8.27 (d, J=9 Hz, 2H).
Reaction SMILES: [CH3:1][C:2]1[C:3](=O)[CH:4]=[C:5]([CH3:10])[C:6](=[O:9])[C:7]=1[CH3:8].C(O)C.Cl.[NH2:16][OH:17].Cl>O>[CH3:1][C:2]1[C:3](=[N:16][OH:17])[CH:4]=[C:5]([CH3:10])[C:6](=[O:9])[C:7]=1[CH3:8]
Reactant: NO
Reactant: CC1=CC(=O)C(C)=C(C)C1=O
Agent: Cl
Solvent: CCO
Solvent: O
Product: CC1=CC(=NO)C(C)=C(C)C1=O
Temperature: 60 °C
Reaction time: 0.17 h

Procedure:
To a solution of 2,3,5-trimethyl-1,4-benzoquinone (70 g, 0.51 mol) of hot ethanol (200 mL) was added a warm solution of hydroxylamine hydrochloride (35 g, 0.50 mol) and conc. hydrochloric acid (5 mL) in water (100 mL). The resulting red solution was stirred for 10 min at 60° C., stoppered and allowed to cool overnight in a refrigerator. The bright yellow precipitate was collected by vacuum filtration and dried to yield 63.9 g (83% yield) of crude product. Recrystallization from 50% aq. ethanol afforded the product as a yellow solid, mp 175° C. (dec.) (lit.: Smith, L. I.; Schubert, W. M. J. Am. Chem. Soc. 1948, 70, 2656; mp 182° C.). Spectral data: 1H NMR (CD3SOCD3): δ 1.90 (s, 3H), 1.93 (s, 3H), 2.30 (s, 3H), 7.55 (s, 1H), 12.95 (s, 1H, exchangeable with D2O); 13C NMR (CD3COCD3): δ 11.49, 12.94, 16.09, 120.53, 132.77, 137.39, 140.72, 149.04, 186.13.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:14]2[O:18][C:17]([C@:19]([OH:25])([CH3:24])[C:20]([F:23])([F:22])[F:21])=[N:16][N:15]=2)=[N:4][C:5]([O:12][CH3:13])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Cl:26]N1C(=O)N(Cl)C(=O)N(Cl)C1=O>C(#N)C>[NH2:1][C:2]1[C:3]([C:14]2[O:18][C:17]([C@:19]([OH:25])([CH3:24])[C:20]([F:23])([F:22])[F:21])=[N:16][N:15]=2)=[N:4][C:5]([O:12][CH3:13])=[C:6]([C:8]([F:10])([F:9])[F:11])[C:7]=1[Cl:26]
Reactant: COc1nc(-c2nnc([C@@](C)(O)C(F)(F)F)o2)c(N)cc1C(F)(F)F
Reactant: O=c1n(Cl)c(=O)n(Cl)c(=O)n1Cl
Solvent: CC#N
Product: COc1nc(-c2nnc([C@@](C)(O)C(F)(F)F)o2)c(N)c(Cl)c1C(F)(F)F
Reaction time: 0.17 h

Procedure:
To (R)-2-(5-(3-amino-6-methoxy-5-(trifluoromethyl)pyridin-2-yl)-1,3,4-oxadiazol-2-yl)-1,1,1-trifluoropropan-2-ol (Example 2) (150 mg, 0.403 mmol) in acetonitrile (1 ml) was added trichloroisocyanuric acid (37.5 mg, 0.161 mmol) and the resulting mixture was heated using microwave radiation at 100° C. for 30 minutes followed by 125° C. for 10 minutes. The mixture was partitioned between EtOAc and water. The organic portion was separated and washed with sat.NaHCO3, brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-30% EtOAc in iso-hexane afforded the title compound;
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:10][CH2:11][CH2:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.[OH-].[Na+]>ClCCl.C(N(CC)CC)C.O1CCOCC1.O>[C:1]([N:16]1[CH2:17][CH2:18][CH:13]([CH2:12][CH2:11][OH:10])[CH2:14][CH2:15]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCCC1CCNCC1
Reactant: O=C(Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: C1COCCO1
Product: O=C(c1ccccc1)N1CCC(CCO)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Benzoyl chloride (25.8 ml) in dichloromethane (20 ml) was added dropwise over 30 minutes to a mixture of 4-(2-hydroxyethyl)piperidine (26 g) in dichloromethane (250 ml) and triethylamine (16.3 ml) at 0° C. The mixture was allowed to warm to ambient temperature and stirred at this temperature for 1 hour. The mixture was washed with sodium bicarbonate solution and then dried and evaporated to give a colourless oil. The oil was dissolved in 1,4-dioxane (250 ml) and then a solution of sodium hydroxide (5.0 g) in water (20 ml) was added and the mixture stirred at ambient temperature for 16 hours and then at 60° C. for 6 hours. The mixture was evaporated to near dryness, basified with 2M sodium hydroxide solution and the product extracted into dichloromethane to give 1-benzoyl-4-(2-hydroxyethyl)piperidine as an oil.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([CH3:24])[N:9]=2)[CH:5]=[CH:4][N:3]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][N:27]=1>>[CH3:24][C:10]1[N:9]=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:29]3[CH:30]=[CH:31][C:26]([NH2:25])=[N:27][CH:28]=3)[N:7]=2)[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:11]=1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2ccnc(Cl)n2)n1
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2ccnc(-c3ccc(N)nc3)n2)n1

Procedure:
The title compound was prepared from 2-chloro-4-[6-methyl-4-(4-trifluoromethylphenyl)-pyridin-2-yl]-pyrimidine (example E.83) (0.40 g, 1.14 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.302 g, 1.37 mmol) according to the general procedure VI. Obtained as an off-white solid (0.050 g, 10%). MS (ISP) 408.3 [(M+H)+]; mp 191° C.
Reaction SMILES: [CH:1]([O:3][C@@H:4]1[CH2:9][C@H:8]([CH3:10])[CH2:7][CH2:6][C@H:5]1[C:11](=[O:13])[CH3:12])=O.C([C@@H:19]1[CH2:24][CH2:23][C@@H:22](C)[CH2:21][C@H:20]1OCC1C=CC=CC=1)=CC(=C)C>>[C:11]([C@@H:5]1[CH2:6][CH2:7][C@@H:8]([CH3:10])[CH2:9][C@H:4]1[O:3][CH2:1][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:13])[CH3:12]
Reactant: CC(=O)[C@@H]1CC[C@@H](C)C[C@H]1OC=O
Reactant: C=C(C)C=C[C@@H]1CC[C@@H](C)C[C@H]1OCc1ccccc1
Product: CC(=O)[C@@H]1CC[C@@H](C)C[C@H]1OCc1ccccc1

Procedure:
As shown in Table 2,9-decene acetate (12) reacted smoothly to provide the carboxylic acid 9-acetoxy nonanoic acid (12a) in 93% yield. The alcohol functionality within the molecule appeared to be tolerated well in the case of isopulegol (13) which provided a combined yield of 78% of which (1R,2R,5R)-2-acetyl-5-methyl cyclohexanol (13a) was 44% and 34% was (1R,2R,5R)-2-acetyl-5-methyl cyclohexanol formate (13b). However, in contrast, the benzyl-protected version of this alcohol (14) provided 80% of the desired ketone, (1R,2R,5R)-(2-acetyl-5-methyl cyclohexyl)benzyl ether (14a). 13b and 14a are novel products. Substituted stilbenes 15 and 16 were cleanly converted into the corresponding acid products 15a and 16a, respectively, without difficulty in 91% and 95% yields, respectively.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:15][S:16]([C:19]3[CH:20]=[N:21][C:22]([Cl:26])=[C:23]([Br:25])[CH:24]=3)(=[O:18])=[O:17])[C:9]=2[CH:8]=[N:7]1)[CH3:2].CI.[C:30](=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([S:16]([C:19]3[CH:20]=[N:21][C:22]([Cl:26])=[C:23]([Br:25])[CH:24]=3)(=[O:18])=[O:17])[CH3:30])[C:9]=2[CH:8]=[N:7]1)[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)Cn1ncc2c1CCC[C@H]2NS(=O)(=O)c1cnc(Cl)c(Br)c1
Agent: [K+]
Solvent: CI
Solvent: CC#N
Product: CCOC(=O)Cn1ncc2c1CCC[C@H]2N(C)S(=O)(=O)c1cnc(Cl)c(Br)c1
Temperature: 65 °C
Reaction time: 5 h
Yield: 89.2 %

Procedure:
To a solution of [(R)-4-(5-bromo-6-chloro-pyridine-3-sulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester (prepared as described above in example 2-1, 1st step) (740 mg, 1.55 mmol) in acetonitrile (15 mL) was added methyl iodide (655 mg, 4.65 mmol) and potassium carbonate (641 mg, 4.65 mmol). The reaction mixture was stirred at 65° C. for 5 hours, then cooled to room temperature and filtered through a glass funnel. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (gradient elution, 0-10% methanol in dichloromethane) to afford {(R)-4-[(5-bromo-6-chloro-pyridine-3-sulfonyl)-methyl-amino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester (680 mg, 89%) as a yellow solid. Ms cald. for C17H20BrClN4O4S 490, obsd. (ESI+) [(M+H)+] 491.
Reaction SMILES: F[C:2](F)(F)[C:3]([OH:5])=O.[OH2:8]>C(O)C>[CH2:3]([OH:5])[C@H:2]([C@H:3]([C@@H:2]([C@@H:2]([CH2:3][OH:5])[OH:8])[OH:8])[OH:5])[OH:8]
Reactant: O=C(O)C(F)(F)F
Reactant: O
Solvent: CCO
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
In a second step the treatment of 0.5 g (0.4 mmol) of the intermediate product 40 dissolved in 4 ml of ethyl alcohol by a trifluoroacetic acid-water mixture (5/1 v/v) yields 0.32 g (70%) of 3,4-di-O-|3'-(F-octyl)-propanoyl|-D-mannitol, 41.
Reaction SMILES: Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:5]=2.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>COCCOC.CCO.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>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:7][CH:8]=3)[NH:3][C:2]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: CC(C)(C)OC(=O)c1ccc2c(C3CCCCC3)c(Br)[nH]c2c1
Reactant: OB(O)c1ccccc1
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: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: CC(C)(C)OC(=O)c1ccc2c(C3CCCCC3)c(-c3ccccc3)[nH]c2c1
Temperature: 80 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
To a solution of tert-butyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (from Step 2) in DME and EtOH (0.2 M, 3:1, v/v) was added phenyl-boronic acid (1.2 eq.) followed by 2 M aqueous Na2CO3 (8.5 eq.). The mixture was degassed with argon, then Pd(PPh3)4 (0.1 eq.) was added and the mixture stirred under argon at 80° C. for 1 h. After cooling to RT, EtOAc was added and the organic layer washed with HCl solution (1N, ×2) and brine. The organic layer was dried over Na2SO4 and evaporated and the residue purified by silica gel chromatography (Flashmaster Personal, PE:EtOAc, 20:1) to give the title compound (90%). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 1.21-1.48 (m, 3H), 1.56 (s, 9H), 1.65-1.80 (m, 5H), 1.90-2.05 (m, 2H), 2.79-2.95 (m, 1H), 7.50-7.57 (m, 6H), 7.40-7.50 (m, 1H), 7.79 (d, J 7.6, 1H), 7.94 (s, 1H); MS (ES+) m/z 376 (M+H)+.
Reaction SMILES: [CH2:1]([P:4]([C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=1)N)([CH2:6][CH2:7]C)=[O:5])[CH2:2]C.C(P(=O)CC)C.IC1C=CC([N+:29]([O-])=O)=CC=1>>[CH2:1]([P:4]([C:9]1[CH:10]=[CH:11][C:13]([NH2:29])=[CH:14][CH:15]=1)([CH2:6][CH3:7])=[O:5])[CH3:2]
Reactant: O=[N+]([O-])c1ccc(I)cc1
Reactant: CCCP(=O)(CCC)c1cccc(N)c1
Agent: CC[PH](=O)CC
Product: CCP(=O)(CC)c1ccc(N)cc1

Procedure:
The title compound was prepared according to the procedures leading to 3-(dipropylphosphoryl) aniline (Compound 168C) starting with the commercially available diethyl phosphine oxide and 4-iodonitrobenzene. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.47 (dd, J=8.46, 10.48 Hz, 2H), 6.74 (dd, J=2.27, 8.59 Hz, 2H), 3.97 (br. s., 2H), 1.76-2.02 (m, 4H), 1.11 (td, J=7.71, 16.67 Hz, 6H); MS (ES+): m/z: 198.0939 [MH+]. HPLC: tR=0.83 min (UPLC TOF MS: polar—3 min).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([N+:13]([O-])=O)[C:3]=1[O:16][CH3:17]>C(O)(=O)C.[Fe]>[NH2:13][C:4]1[C:3]([O:16][CH3:17])=[C:2]([Cl:1])[CH:11]=[C:10]([Cl:12])[C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1c(Cl)cc(Cl)c(OC)c1[N+](=O)[O-]
Agent: [Fe]
Solvent: CC(=O)O
Product: COC(=O)c1c(Cl)cc(Cl)c(OC)c1N
Temperature: 55 °C
Reaction time: 1.5 h
Yield: 9.7 %

Procedure:
Iron powder (18.2 g, 330 mmol) was added to a solution of methyl ester 2-2 (13.3 g, 480 mmol) in glacial acetic acid (120 mL). The mixture was stirred at 55° C. for 1.5 h and then filtered hot through celite, washing with ethyl acetate. The filtrate was concentrated then ethyl acetate and sat. aq. NaCO3 were added. The organic layer was isolated, washed with H2O, dried over K2CO3 and concentrated to give 2-3 as an off-white solid (11.6 g, 97% yield). 1H NMR (CDCl3, 400 MHz) δ 3.79 (s, 3H), 3.89 (s, 3H), 6.71 (s, 1H).
Reaction SMILES: C(N(CC)CC)C.Cl.[Cl:9][C:10]1[CH:11]=[C:12]([NH2:24])[CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][N:19]([CH2:22][CH3:23])[CH2:20][CH3:21].[Cl:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1/[CH:36]=[CH:37]/[C:38](O)=[O:39].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C1COCC1>[Cl:9][C:10]1[CH:11]=[C:12]([NH:24][C:38](=[O:39])/[CH:37]=[CH:36]/[C:27]2[CH:28]=[CH:29][C:30]([C:32]([F:34])([F:33])[F:35])=[CH:31][C:26]=2[Cl:25])[CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][N:19]([CH2:22][CH3:23])[CH2:20][CH3:21]
Reactant: CCN(CC)CCOc1ccc(N)cc1Cl
Reactant: O=C(O)/C=C/c1ccc(C(F)(F)F)cc1Cl
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCN(CC)CCOc1ccc(NC(=O)/C=C/c2ccc(C(F)(F)F)cc2Cl)cc1Cl

Procedure:
0.29 mL (2.10 mmol) of triethylamine was added to a solution of 0.28 g (1.00 mmol) of 3-chloro-4-(2-diethylamino-ethoxy)-phenylamine-hydrochloride (intermediate product Z1b), 0.25 g (1.00 mmol) of (E)-3-(2-chloro-4-trifluoromethyl-phenyl)-acrylic acid (Z37b) and 0.34 g (1.05 mmol) of TBTU in 10 mL abs. THF and the mixture was stirred for 1 hour at RT. The reaction mixture was evaporated down i. vac. and the residue was combined with dichloromethane and water. The org. phase was separated off, washed with sat. aqueous sodium bicarbonate solution and water and evaporated down i. vac. The residue was purified by column chromatography (silica gel, gradient dichloromethane/10% conc. aqueous ammonia in MeOH 100:0→5:95).