Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:6][CH:5]=[C:4]([C:7]2[N:8]=[C:9]([C:14]3[N:22]=[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][N:16]4[N:15]=3)[C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH2:30]([S:32](Cl)(=[O:34])=[O:33])[CH3:31]>C(Cl)Cl>[N:22]1[C:14]([C:9]2[C:10]([NH2:13])=[N:11][CH:12]=[C:7]([C:4]3[CH2:3][CH2:2][N:1]([S:32]([CH2:30][CH3:31])(=[O:34])=[O:33])[CH2:6][CH:5]=3)[N:8]=2)=[N:15][N:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=12
Reactant: CCS(=O)(=O)Cl
Reactant: Nc1ncc(C2=CCNCC2)nc1-c1nc2ccccn2n1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCS(=O)(=O)N1CC=C(c2cnc(N)c(-c3nc4ccccn4n3)n2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
5-(1,2,3,6-tetrahydropyridin-4-yl)-3-([1,2,4]triazolo[1,5-a]pyridin-2-yl)pyrazin-2-amine (82 mg, 0.1291 mmol) was dissolved in DCM (4 mL) and treated with triethylamine (78.38 mg, 108.0 μL, 0.7746 mmol) followed by ethanesulfonyl chloride (18.26 mg, 13.46 μL, 0.1420 mmol). The reaction mixture was allowed to stir at ambient temperature for 1 hour when analysis showed SM remaining. The mixture was treated with further ethanesulfonyl chloride (16.60 mg, 12.23 μL, 0.1291 mmol) and stirred for a further hour. The reaction was diluted with DCM, washed with water and the aqueous layer extracted further with dichloromethane (2×). The combined organics were washed with saturated aqueous NaHCO3, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by column chromatography (ISCO Companion™, 12 g column, 0-2.5% MeOH/DCM) to afford the title compound which was freeze-dried to give a yellow solid (9 mg, 17% Yield). 1H NMR (400.0 MHz, DMSO) d 1.24 (t, J=7.4 Hz, 3H), 2.71 (br s, 2H), 3.14 (q, J=7.3 Hz, 2H), 3.48 (t, J=5.7 Hz, 2H), 3.98 (d, J=2.9 Hz, 2H), 6.62 (br s, 1H), 7.30-7.33 (m, 1H), 7.72 (br s, 2H), 7.75-7.79 (m, 1H), 7.98 (d, J=8.8 Hz, 1H), 8.40 (s, 1H) and 9.11 (d, J=6.7 Hz, 1H) ppm; MS (ES+) 386.0
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22](B(O)O)[CH:21]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:2]2[CH:10]=[CH:9][C:8]3[NH:7][C:6]4[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C:5]=4[C:4]=3[CH:3]=2)[CH:21]=1
Reactant: OB(O)c1cccnc1
Reactant: CCOC(=O)N1CCc2[nH]c3ccc(Br)cc3c2C1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)N1CCc2[nH]c3ccc(-c4cccnc4)cc3c2C1
Temperature: 100 °C
Yield: 64.3 %

Procedure:
Preparation of the title compound was carried out according to General Method 7. A mixture of ethyl 8-bromo-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (See Example 7) (100 mg, 0.3 mmol), pyridine-3-boronic acid (76 mg, 0.62 mmol) and K3PO4 (120 mg, 0.57 mmol) in DMF:H2O (2:1, 3 ml) was purged with nitrogen for 30 minutes. PdCl2(PPh3)2 (25 mg, 0.04 mmol) was added and the reaction was heated at 100° C. for 4 h. The contents were concentrated in vacuo and the crude product was purified by silica gel chromatography (230-400 mesh) using ethyl acetate-hexane gradient to obtain 62 mg of ethyl 3,4-dihydro-8-(pyridin-3-yl)-1H-pyrido[4,3-b]indole-2(5H)-carboxylate. This intermediate (25 mg, 0.078 mmol), 2-methyl-5-vinylpyridine (0.120 ml, 1 mmol) and NaH (10 mg, 60% dispersion in oil, 0.02 mmol) were heated in DMSO (0.3 ml) at 100° C. for 48 h, after which methanol was added and the contents were concentrated to dryness. The resulting crude product was purified by silica gel chromatography (100-200 mesh or 230-400 mesh) using methanol-dichloromethane gradient to obtain 7 mg of 3,4-dihydro-5-(2-(6-methylpyridin-3-yl)ethyl)-8-(pyridin-3-yl)-1H-pyrido[4,3-b]indole-2(5H)-carboxylate.
Reaction SMILES: O[C:2]1[C:7](C)=[C:6](O)[CH:5]=[C:4]([CH3:10])[N:3]=1.O=P(Cl)(Cl)[Cl:13].CN(C)C1C=CC=CC=1.[CH:25]([Cl:28])(Cl)Cl>>[Cl:13][C:2]1[C:7]([CH3:6])=[C:25]([Cl:28])[CH:5]=[C:4]([CH3:10])[N:3]=1
Reactant: Cc1cc(O)c(C)c(O)n1
Reactant: O=P(Cl)(Cl)Cl
Reactant: ClC(Cl)Cl
Solvent: CN(C)c1ccccc1
Product: Cc1cc(Cl)c(C)c(Cl)n1
Temperature: 0 °C

Procedure:
A mixture of 2,4-dihydroxy-3,6-dimethylpyridine (2.86 g, 20.58 mmol), POCl3 (15 ml) and N,N-dimethylaniline (3.6 ml, 22.64 mmol) was heated at reflux for 3 hours. The mixture was cooled, poured into ice water and extracted with diethyl ether. The organic layer was dried and concentrated to give 3.02 g of the crude material. After silica gel column chromatography using chloroform as eluent, 1.3102 g of the title compound was obtained as a yellow oil. 1H NMR (CDCl3) δ 7.07 (s, 1H), 2.43 (s, 3H), 2.39 (s, 3H) ppm.
Reaction SMILES: [CH:1]([C:3]12[CH2:9][N:6]3[CH2:7][CH:8]1[CH:4]2[CH2:5]3)=O.[C-:10]#[N:11].[K+].[NH3:13].[Cl-].[NH4+]>O>[NH2:13][CH:1]([C:3]12[CH2:9][N:6]3[CH2:7][CH:8]1[CH:4]2[CH2:5]3)[C:10]#[N:11]
Reactant: O=CC12CN3CC1C2C3
Reactant: [C-]#N
Reactant: N
Agent: [Cl-]
Agent: [K+]
Agent: [NH4+]
Solvent: O
Product: N#CC(N)C12CN3CC1C2C3
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.8 %

Procedure:
To an icecooled solution of 1-formyl-4-azatricyclo[2.2.1.02,6 ]heptane (3.56 g, 29 mmol) in water (5 ml) was added a solution of potassium cyanide (2.08 g, 31.9 mmol) in water (5 ml) over 30 min. After an additional 1 h, cooling was removed and the reaction stirred at room temperature for 16 h. The cyanohydrin product was then added 25% aqueous ammonia (4.0 ml, 52 mmol) and ammonium chloride (7.76 g, 145 mmol). The reaction mixture was stirred at room temperature for 18 h and then extracted with isopropanole/dichloromethane (1:10) (10×75 ml). The organic phases were dried and evaporated to give the title compound as an oil (2.5 g, 58%).
Reaction SMILES: [C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:13](Cl)(=[O:17])/[CH:14]=[CH:15]/[CH3:16].Cl>O.C(=S)=S>[CH:14]([C:13]([C:4]1[CH:5]=[CH:6][C:1]([O:7][CH3:8])=[CH:2][CH:3]=1)=[O:17])=[CH:15][CH3:16]
Reactant: C/C=C/C(=O)Cl
Reactant: COc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Solvent: O
Product: CC=CC(=O)c1ccc(OC)cc1

Procedure:
Into a round bottom three-necked flask equipped with a stirrer, a reflux condenser, and a dropping funnel were placed 583 g. of anisole, 720 g. of aluminum chloride, and 2.37 liters of carbon disulfide. The reaction solution was stirred and 565 g. of crotonyl chloride were added by dropwise addition at such a rate as to maintain a continuous reflux. As the reaction mixture thickened, an additional 2.37 liters of carbon disulfide were added. The resulting reaction mixture which had the consistency of a slurry was refluxed for 4 hours and thereafter was poured into a mixture of 9 kg. of ice, 2 liters of water and 900 ml. of concentrated hydrochloric acid. The carbon disulfide was removed from the dilute acidified reaction mixture under vacuum. The aqueous residue was then extensively extracted with dichloromethane. The extract was washed with water and dried and was then evaporated in vacuo to yield the condensation product, p-methoxyphenyl propenyl ketone as an oil having a boiling point of about 135° C. (0.5 mm).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[N:14]=[CH:15][NH:16][CH:17]=3)=[C:11]([CH2:18][O:19][CH3:20])[O:10][N:9]=2)=[CH:4][CH:3]=1.F[C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[N:14]=[CH:15][N:16]([C:22]4[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][CH:23]=4)[CH:17]=3)=[C:11]([CH2:18][O:19][CH3:20])[O:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: COCc1onc(-c2ccc(F)cc2)c1-c1c[nH]cn1
Reactant: CC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COCc1onc(-c2ccc(F)cc2)c1-c1cn(-c2ccc(C(C)=O)cc2)cn1
Temperature: 120 °C
Reaction time: 16 h
Yield: 84.3 %

Procedure:
A mixture of 3-(4-fluoro-phenyl)-4-(1H-imidazol-4-yl)-5-methoxymethyl-isoxazole (273 mg, 1.0 mmol), 1-(4-fluorophenyl)-ethanone (212 mg, 1.5 mmol), and potassium carbonate (276 mg, 2.0 mmol) in DMF (4 mL) was stirred at 120° C. for 16 h. After cooling to room temperature, the resulting solution was poured into cold water and stirred for 15 min. The precipitate was collected by filtration, washed with water, hexane, and dried to afford the title compound (330 mg, 79%) which was obtained as light brown solid. MS: m/e=392.5[M+H]+.
Reaction SMILES: N1C=CC=CC=1.ClC(Cl)(O[C:11](=[O:17])OC(Cl)(Cl)Cl)Cl.[CH3:19][C@H:20]1[CH2:25][CH2:24][CH2:23][C@@H:22]([CH3:26])[NH:21]1.C[C@H]1CCC[C@@H](C)N1.C(Cl)(=O)N.CCN(C(C)C)C(C)C.[F:48][C:49]1[CH:50]=[CH:51][C:52]([NH:55][NH2:56])=[N:53][CH:54]=1>C(Cl)Cl>[F:48][C:49]1[CH:50]=[CH:51][C:52]([NH:55][NH:56][C:11]([N:21]2[C@H:22]([CH3:26])[CH2:23][CH2:24][CH2:25][C@@H:20]2[CH3:19])=[O:17])=[N:53][CH:54]=1
Reactant: C[C@@H]1CCC[C@H](C)N1
Reactant: NNc1ccc(F)cn1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: NC(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: c1ccncc1
Solvent: ClCCl
Product: C[C@@H]1CCC[C@H](C)N1C(=O)NNc1ccc(F)cn1
Temperature: 45 °C
Reaction time: 3 h
Yield: 56 %

Procedure:
Pyridine (2.40 mL, 29.7 mmol) was added dropwise to an ice cold suspension of triphosgene (4.42 g, 14.9 mmol) in DCM (30.0 mL). cis-2,6-Dimethylpiperidine (2.00 mL, 14.9 mmol) was added and the reaction stirred for 3 hours, then quenched by dropwise addition of HCl (1M aqueous, 30 mL). The mixture was extracted into DCM (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The product was used in the next reaction without purification. cis-2,6-Dimethylpiperidine-carbamoylchloride (1.79 g, 10.2 mmol) was dissolved in DCM (90.0 mL) and DIPEA (2.42 mL, 13.9 mmol) was added followed by (5-fluoro-pyridin-2-yl)-hydrazine (WO 2010 022076, which is incorporated herein by reference in its entirety, 1.18 g, 9.30 mmol) and the reaction heated to 45° C. overnight. The reaction was cooled and quenched into water. The mixture was extracted into DCM (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC using 0-6% [2M NH3 in MeOH] in DCM to give the title compound (1.38 g, 56%). 1H NMR (300 MHz, CDCl3): 1.29 (6H, d, J=7.1 Hz), 1.48-1.90 (6H m), 4.26 (2H, qn, J=6.9 Hz), 6.39 (1H, d, J=2.3 Hz), 6.50 (1H, d, J=2.3 Hz), 6.74 (1H, dd, J 9.0, 3.6 Hz), 7.27 (1H, ddd, J 8.9, 8.0, 2.9 Hz), 8.03 (1H, d, J=2.9 Hz).
Reaction SMILES: ClCCl.Br[C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][N:11]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[C:8]2=[N:9][CH:10]=1.[C:24](O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:24][C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][N:11]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[C:8]2=[N:9][CH:10]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2cc(Br)cnc21
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: Cc1cnc2c(ccn2[Si](C(C)C)(C(C)C)C(C)C)c1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
In a round bottom flask, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (0.04 g, 0.05 mmol) is combined with 10 mL of toluene under an atmosphere of nitrogen, and 5-bromo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (5, 0.3 g, 0.8 mmol) in 1 mL of toluene is added dropwise. The reaction is stirred at 60° C. for 1 hour, then at 90° C. for 30 minutes. The reaction is cooled to room temperature, an ice/water solution of 0.1 N citric acid at pH 4 is added, and the mixture extracted with ethyl acetate. The organic layer is washed with brine, de-colored with charcoal, filtered through celite and the filtrate dried over sodium sulfate. The sodium sulfate is removed by filtration and the filtrate concentrated under vacuum to provide the desired compound (6, 218 mg).