Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[N:5]([CH2:7][CH2:8]OS(C)(=O)=O)[CH:6]=1.[NH:27]1[CH2:30][CH2:29][CH2:28]1.CN(C=O)C>CC(=O)OCC>[N:27]1([CH2:8][CH2:7][N:5]2[CH:6]=[C:2]([Br:1])[N:3]=[C:4]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:30][CH2:29][CH2:28]1
Reactant: C1CNC1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc(Br)cn2CCOS(C)(=O)=O)CC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(c2nc(Br)cn2CCN2CCC2)CC1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
A reaction mixture of tert-butyl 4-(4-bromo-1-(2-((methylsulfonyl)oxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (28.0 g) and azetidine (11 ml) in to DMF (200 ml) was stirred at 50° C. overnight. The reaction was diluted with EA, washed with water followed by saturated aqueous sodium chloride, dried and concentrated. The residue was purified by column chromatography to give tert-butyl 4-(1-(2-(azetidin-1-yl)ethyl)-4-bromo-1H-imidazol-2-yl)piperidine-1-carboxylate as off-white solid. (17.2 g).
Reaction SMILES: [H-].[Na+].[CH2:3]([N:5]([CH2:21][CH3:22])[C:6](=[O:20])[O:7][C:8]1[C:17]([Cl:18])=[C:16]2[C:11]([CH2:12][CH2:13][NH:14][C:15]2=[O:19])=[CH:10][CH:9]=1)[CH3:4].[CH2:23]([O:30][C:31]1[C:36]([CH2:37]Cl)=[C:35]([CH3:39])[CH:34]=[C:33]([CH3:40])[N:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O>CN(C=O)C>[CH2:21]([N:5]([CH2:3][CH3:4])[C:6](=[O:20])[O:7][C:8]1[C:17]([Cl:18])=[C:16]2[C:11]([CH2:12][CH2:13][N:14]([CH2:37][C:36]3[C:31]([O:30][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[N:32][C:33]([CH3:40])=[CH:34][C:35]=3[CH3:39])[C:15]2=[O:19])=[CH:10][CH:9]=1)[CH3:22]
Reactant: Cc1cc(C)c(CCl)c(OCc2ccccc2)n1
Reactant: CCN(CC)C(=O)Oc1ccc2c(c1Cl)C(=O)NCC2
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(CC)C(=O)Oc1ccc2c(c1Cl)C(=O)N(Cc1c(C)cc(C)nc1OCc1ccccc1)CC2
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 99.3 %

Procedure:
To a suspension of NaH (2.2 g, 54 mmol, 60% in oil) in dry DMF (20 mL) was added dropwise a solution of 8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1f, 8.0 g, 27 mmol) in dry DMF (40 mL) at 0° C. under N2. The mixture was stirred at 0° C. for 15 minutes. 2-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 8.5 g, 32.4 mmol) was added. The mixture was stirred at room temperature overnight. To the reaction mixture was added dropwise H2O (200 mL) carefully. The mixture was extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine (4×200 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 3:1) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1g, 14 g, 99%) as yellow oil.
Reaction SMILES: [CH3:1][N:2]([SiH:4]([N:8]([CH3:10])[CH3:9])[N:5]([CH3:7])[CH3:6])[CH3:3].[CH:11]#[CH:12].[SiH4]>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH2:11]([Si:4]([N:8]([CH3:10])[CH3:9])([N:5]([CH3:7])[CH3:6])[N:2]([CH3:3])[CH3:1])[CH3:12]
Reactant: CN(C)[SiH](N(C)C)N(C)C
Reactant: C#C
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Agent: [SiH4]
Product: CC[Si](N(C)C)(N(C)C)N(C)C
Temperature: 250 °C

Procedure:
A two liter stirred batch reactor was purged with nitrogen gas and thereafter charged with 840 g (5.22 moles) of tris(dimethylamino)silane and 5 ppm hexachloroplatinic acid. The reactor was then pressurized to approximately 5 psig with nitrogen gas and heated to approximately 250° C. The acetylene inlet feed was started and maintained at 100 psig. The reaction temperature was maintained at 250° C. After four hours the acetylene flow was stopped, the reaction mix cooled and the reaction products analyzed. Vinyltris(dimethyl)amino)silane was the single major product at 90% of theoretical. Ethyltris(dimethylamino)silane and 1,2-bis(trisdimethylamino)silylethane by-products were formed in amounts less than 0.5% each. Vinyltris(dimethylamino)silane polymer was also formed in an amount of 7-8%.
Reaction SMILES: [OH-].[K+].[Br:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([CH3:16])([CH3:15])[CH2:9][C:10](=[O:14])[NH:11]2)=[CH:6][C:5]=1[CH3:17].I[CH2:19][CH2:20][CH3:21].O>CS(C)=O>[Br:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([CH3:15])([CH3:16])[CH2:9][C:10](=[O:14])[N:11]2[CH2:19][CH2:20][CH3:21])=[CH:6][C:5]=1[CH3:17]
Reactant: Cc1cc2c(cc1Br)NC(=O)CC2(C)C
Reactant: CCCI
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CCCN1C(=O)CC(C)(C)c2cc(C)c(Br)cc21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 115.2 %

Procedure:
A mixture of powdered potassium hydroxide (1.26 g, 22.38 mmol) in DMSO (40 mL) was stirred at 0° C. for 10 min. 7-bromo-4,4,6-trimethyl-3,4- dihydro-1H-quinoline-2-one (Example 1e) (3.0 g, 11.19 mmol) was added cautiously, followed immediately by the addition of 1-iodopropane (5.5 mL, 55.95 mmol). The reaction mixture was warmed up to room temperature and stirred overnight at room temperature. The reaction mixture was poured into water and extracted with dichloromethane washed with water and brine, dried (MgSO4), filtered and evaporated to give 4.0 g of 7-bromo-1-propyl-4,4,6-trimethyl-3,4-dihydro-1H-quinoline-2-one and used without further purification in the Suzuki coupling (step a). 1H NMR (300 MHz; CDCl3): 0.98 (t, J=7.5 Hz,1 H), 1.26 (s, 6 H), 1.65 (t, J=7.5 Hz, 1 H), 2.37 (s, 3 H), 2.46 (s, 2 H), 3.88 (t, J=7.8 Hz, 2 H), 7.13 (s, 1 H), 7.15 (s, 1 H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([CH3:15])[CH:10]=1.C([O-])(O)=O.[Na+].Br[C:25]1[CH:30]=[CH:29][N:28]([CH2:31][CH2:32][CH2:33][CH3:34])[C:27](=[O:35])[C:26]=1[C:36]#[N:37]>O1CCOCC1.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>[CH2:31]([N:28]1[CH:29]=[CH:30][C:25]([C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:14]=[CH:13][N:12]=[C:11]([CH3:15])[CH:10]=3)=[C:2]([F:1])[CH:3]=2)=[C:26]([C:36]#[N:37])[C:27]1=[O:35])[CH2:32][CH2:33][CH3:34]
Reactant: Cc1cc(Oc2ccc(B(O)O)cc2F)ccn1
Reactant: CCCCn1ccc(Br)c(C#N)c1=O
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: C1COCCO1
Product: CCCCn1ccc(-c2ccc(Oc3ccnc(C)c3)c(F)c2)c(C#N)c1=O
Yield: 67.4 %

Procedure:
To a solution of intermediate 16 (1.77 mmol) in 1,4-dioxane (6 ml) and a saturated solution of NaHCO3 (6 ml) was added intermediate 6 (0.451 g, 1.77 mmol). The resulting solution was degassed using a stream of nitrogen and to this was added Pd(PPh3)4 (0.204 mg, 0.177 mmol). The reaction was then microwaved in a sealed tube at 150° C. for 10 minutes. The resulting cooled reaction mixture was filtered through a pad of diatomaceous earth and concentrated in vacuo. The crude reaction mixture was then purified by column chromatography (silica gel; DCM to DCM/MeOH up to 3% as eluent). The desired fractions were collected and evaporated in vacuo to yield compound 5 (0.45 g, 68%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH:17][C:18]3[N:23]=[C:22]([C:24]([O:26]C)=O)[CH:21]=[CH:20][N:19]=3)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.CO.[CH3:30][NH2:31].Cl>CC(O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH:17][C:18]3[N:23]=[C:22]([C:24]([NH:31][CH3:30])=[O:26])[CH:21]=[CH:20][N:19]=3)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CN
Reactant: COC(=O)c1ccnc(NCCCN2CCN(c3cccc(Cl)c3)CC2)n1
Agent: Cl
Solvent: CO
Solvent: CC(C)O
Product: CNC(=O)c1ccnc(NCCCN2CCN(c3cccc(Cl)c3)CC2)n1
Temperature: 25 °C

Procedure:
4.5 g (11.5 mmols) of methyl 2-[[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]amino]pyrimidine-4-carboxylate and 200 ml of methanol are introduced into a 0.5 l, round bottomed flask and then the solution is saturated with gaseous methylamine. The reaction mixture is stirred at room temperature while saturating several times with gaseous methylamine. The solvent is evaporated under reduced pressure. 4.05 g (10.4 mmols) of base are obtained to which 104 ml of 0.1N hydrochloric acid in 2-propanol are added. The solvent is evaporated and the product is recrystallised from 2-butanone. 3.8 g of compound are obtained.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][C:3]=1[O:12][CH3:13].[F:14][C:15]1[C:20](O)=[C:19]([F:22])[C:18]([F:23])=[C:17]([F:24])[C:16]=1[F:25].Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl>[F:14][C:15]1[C:20]([O:10][C:9](=[O:11])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[C:3]([O:12][CH3:13])[CH:4]=2)=[C:19]([F:22])[C:18]([F:23])=[C:17]([F:24])[C:16]=1[F:25]
Reactant: COc1cc(CC(=O)O)ccc1O
Reactant: Oc1c(F)c(F)c(F)c(F)c1F
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COc1cc(CC(=O)Oc2c(F)c(F)c(F)c(F)c2F)ccc1O
Temperature: 25 °C
Reaction time: 18 h
Yield: 98.2 %

Procedure:
A mixture of 4-hydroxy-3-methoxyphenylacetic acid (4.65 g), pentafluorophenol (4.2 g), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (4.9 g) and methylene chloride (50 ml) was stirred at room temperature for 18 hours. The reaction solution was washed with water, and the organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate) to give 4-hydroxy-3-methoxyphenylacetic acid pentafluorophenyl ester (7.8 g). This product is dissolved in ethyl acetate (80 ml), and thereto is added 3-iodeaniline (7.4 g). The mixture is heated at 60° C. under stirring for 18 hours. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate) to give the desired compound (6.2 g).
Reaction SMILES: CN1C=C(C2C=CN=CC=2)C(C2C=CC(O)=CC=2)=N1.C([O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[C:38]([C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)=[CH:37][N:36]([CH2:45][C:46]([F:49])([F:48])[F:47])[N:35]=2)=[CH:30][CH:29]=1)C1C=CC=CC=1>>[N:42]1[CH:43]=[CH:44][C:39]([C:38]2[C:34]([C:31]3[CH:30]=[CH:29][C:28]([OH:27])=[CH:33][CH:32]=3)=[N:35][N:36]([CH2:45][C:46]([F:48])([F:49])[F:47])[CH:37]=2)=[CH:40][CH:41]=1
Reactant: FC(F)(F)Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccccc3)cc2)n1
Agent: Cn1cc(-c2ccncc2)c(-c2ccc(O)cc2)n1
Product: Oc1ccc(-c2nn(CC(F)(F)F)cc2-c2ccncc2)cc1

Procedure:
Following the procedure for the preparation of 4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenol but substituting 4-[3-(4-Benzyloxy-phenyl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-4-yl]-pyridine provided the title compound. MS: (M+H m/z=320.1)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1F.[C:12]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)(=[O:14])[CH3:13]>CCOC(C)=O.O>[C:12]([N:15]1[CH2:20][CH2:19][N:18]([C:3]2[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=2[Cl:1])[CH2:17][CH2:16]1)(=[O:14])[CH3:13]
Reactant: CC(=O)N1CCNCC1
Reactant: O=[N+]([O-])c1ccc(F)c(Cl)c1
Solvent: CCOC(C)=O
Solvent: O
Product: CC(=O)N1CCN(c2ccc([N+](=O)[O-])cc2Cl)CC1
Temperature: 25 °C

Procedure:
2-Chloro-1-fluoro-4-nitrobenzene (10 g, 57 mmol) and 1-acetylpiperazine (14.6 g, 114 mmol) were heated neat at 55° C. for 1 h. Then the reaction mixture was allowed to cool down to room temperature. The viscous orange solution was diluted with EtOAc and water. The organics were washed with water (3 times), brine, dried and evaporation of the solvent gave an orange oil which was triturated with isohexane. After evaporation of solvent the title compound was obtained as a yellow solid which was dried overnight in vac oven at 50° C. (15.68 g, 97%). It was used without further purification. NMR (400 MHz) 2.03 (d, 3H), 3.18 (dt, 4H), 3.62 (m, 4H), 7.30 (d, 1H), 8.17 (dd, 1H), 8.26 (d, 1H); m/z 284-286.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:22][C:23]([O:25]C(C)(C)C)=[O:24])[CH:5]=[CH:6][C:7]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:21])([F:20])[F:19])=[O:10].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:22][C:23]([OH:25])=[O:24])[CH:5]=[CH:6][C:7]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:20])([F:21])[F:19])=[O:10]
Reactant: Cc1cc(CC(=O)OC(C)(C)C)ccc1NC(=O)Nc1ccccc1C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 4 h
Yield: 76.6 %

Procedure:
To a stirred solution of tert-butyl 3-methyl-4-[N′-(2-trifluoromethylphenyl)ureido]phenylacetate (1.06 g, 2.60 mmol) in CH2Cl2 (10 ml) was added TFA (10 ml) and the reaction mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated to a small volume and poured into ice-H2O. The resulting precipitate was collected under a reduced pressure and the crude solid was recrystallized from MeOH—CHCl3-IPE to give 3-methyl-4-[N′-(2-trifluoromethylphenyl)ureido]phenylacetic acid (702 mg, 77%) as a white crystalline powder. mp 262–263° C.; 1H-NMR (DMSO-d6) δ 2.24 (s, 3 H), 3.48 (s, 2 H), 7.03 (d, J=8.3 Hz, 1 H), 7.08 (s, 1 H), 7.26–7.30 (m, 1 H), 7.61–7.69 (m, 3 H), 7.88 (d, J=8.3 Hz, 1 H), 8.39 (s, 1 H), 8.55(s, 1 H), 12.28 (br s, 1 H); Anal. Calcd for C17H15F3N2O3: C, 57.96; H, 4.29; N, 7.95; F, 16.18. Found: C, 57.73; H, 4.23; N, 7.92; F, 16.05.