Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:26][CH2:27][NH2:28])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2.[C:29](OCC)(=[O:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31]>C1(C)C=CC=CC=1.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH2:26][CH2:27][NH:28][C:29](=[O:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:18][CH2:19]1)[N:11]=2
Reactant: NCCc1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)c(F)c1
Reactant: CCOC(=O)C(=O)OCC
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=O)NCCc1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)c(F)c1
Temperature: 110 °C
Reaction time: 16 h

Procedure:
2-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)-ethanamine (112 mg, 0.29 mmol) was dissolved in toluene (2.9 mL) before diethyl oxalate (0.39 mL, 2.88 mmol) was added and stirred at 110° C. for 16 h. The reaction mixture was diluted with 75 mL of DCM, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed with sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, and concentrated via rotovap to give ethyl 2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)ethylamino)-2-oxoacetate after flash chromatography. MS (ESI) m/z: Calculated: 489.2; Observed: 490.4 (M++H).
Reaction SMILES: [CH3:1][SiH:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C([O:18][CH2:19][CH:20]=[CH2:21])(=O)C>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[OH:18][CH2:19][CH2:20][CH2:21][Si:2]([CH3:1])([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=CCOC(C)=O
Reactant: C[SiH](c1ccccc1)c1ccccc1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: C[Si](CCCO)(c1ccccc1)c1ccccc1
Reaction time: 2 h
Yield: 51.7 %

Procedure:
Methyldiphenylsilane (100 g, 0.49 mol) was added at 90° over a period of 4 hrs, with stirring, to a mixture of 100 g (1.0 mol) of allyl acetate and 0.10 ml of a 0.1 M chloroplatinic acid solution in isopropanol. When half of the methyldiphenylsilane was added an additional 0.10 ml of the chloroplatinic acid solution was added. Excess allyl acetate was distilled 15 min. after the addition was completed. The residue was dissolved in 150 ml of methanol and a solution of 20 g of sodium hydroxide in 40 ml of water was added dropwise. After the mixture was stirred for 2 hrs, 200 ml of water was added, and the mixture was neutralized with hydrochloric acid. The product was extracted with methylene chloride, dried over magnesium sulfate and distilled to give 65 g (50%) of (3-hydroxypropyl) methyldiphenylsilane, bp 130°-140° (0.03 to 0.07 mm). p-Toluenesulfonyl chloride 3.5 g, 0.184 mol) was added to a solution of 29 g (0.118 mol) of (3-hydroxypropyl)methyldiphenylsilane and 14.6 g (0.184 mol) of pyridine in 60 ml of methylene chloride at 0°. The mixture was kept at 0°-5° for 18 hrs and 40 ml of ice water was added. The water layer was extracted with 40 ml of methylene chloride, and the combined organic layers were washed with 2-30 ml portions of water. Solvent was removed and the product was crystallized from ether to give 46 g (95%) (3-propyl)methyldiphenyl p-toluenesulfonate, mp 68°-69°.
Reaction SMILES: [CH3:1][CH:2]1[C:7](=O)[CH:6]2[CH2:9][CH2:10][N:3]1[CH2:4][CH2:5]2.[C:11]1([C:17]2[N:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][CH:2]1[N:3]2[CH2:10][CH2:9][CH:6](/[C:7]/1=[N:23]/[C:20]1[CH:21]=[N:22][C:17]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:18][CH:19]=1)[CH2:5][CH2:4]2
Reactant: CC1C(=O)C2CCN1CC2
Reactant: Nc1ccc(-c2ccccc2)nc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC1/C(=N\c2ccc(-c3ccccc3)nc2)C2CCN1CC2

Procedure:
A solution of 2-methyl-1-aza-bicyclo[2.2.2]octan-3-one (1.33 g, 9.5 mmol), 6-phenyl-pyridin-3-ylamine (1.25 g, 7.3 mmol) and p-toluene sulfonic acid monohydrate (139 mg, 0.73 mmol) in toluene (40 ml) is heated under reflux for 18 hours using a Dean-Stark apparatus. The toluene is evaporated and the residue is dissolved in ethyl acetate and washed with brine. The organic layer is dried over anhydrous magnesium sulfate, filtered and evaporated to dryness, and the residual oil purified by silica gel column chromatography (eluent: EtOAc: CH3OH:NH4OH; 9:1:0.1) to afford [2-Methyl-1-aza-bicyclo[2.2.2]oct-(3Z)-ylidene]-(6-phenyl-pyridin-3-yl)-amine. A solution of LiAlH4 (1.03 ml, 1 M) in THF is added to a solution of [2-Methyl-1-aza-bicyclo[2.2.2]oct-(3Z)-ylidene]-(6-phenyl-pyridin-3-yl)-amine (300 mg, 1.02 mmol) in THF (10 ml). The resulting mixture is stirred at room temperature for 18 hours and then quenched with a saturated aqueous solution of sodium sulfate (1 ml). The solvents are removed by evaporation and the residue is redissolved in ethyl acetate and filtered. The filtrate is evaporated and purified by silica gel column chromatography (eluent: EtOAc: CH3OH: NH4OH; 8.5:1.5:0.1) to afford Rac.-trans-2-Methyl-1-aza-bicyclo[2.2.2]oct-3-yl)-(6-phenyl-pyridin-3-yl)-amine. MS (ES+): m/e=294.4 (MH+); preparative enantiomer separation (column: Chiralpak AD-H 10 um; (4.6×250 mm), eluent: n-hexane : EtOH 50:50, flow: 1.0 ml/min, detector: UV 210 nm): peak 1: 6.29 min; peak 2: 20.16 min.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([I:9])[C:5]([NH2:8])=[N:6][CH:7]=1.Br[CH2:11][CH:12](OC)OC.Br>C(O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([I:9])[C:5]2[N:6]([CH:11]=[CH:12][N:8]=2)[CH:7]=1
Reactant: COC(CBr)OC
Reactant: Nc1ncc(Br)cc1I
Agent: Br
Solvent: O
Solvent: CCO
Product: Brc1cc(I)c2nccn2c1
Temperature: 25 °C

Procedure:
5-bromo-3-iodopyridin-2-amine (1.0 g, 3.34 mmol) and 2-bromo-1,1-dimethoxyethane were dissolved in ethanol (20 ml). To this solution was added a 50% mixture of HBr in water (4 ml). The mixture was stirred at reflux temperature overnight. After the completion of the reaction, the mixture was cooled to room temperature and filtered. The residue was suspended in DCM (10 ml) and stirred with the saturated aqueous solution of Na2CO3. The organic layer was separated and washed with saturated brine, dried over sodium sulfate and concentrated. The desired product was obtained as a yellow solid (950 mg, yield 88%). LC-MS: 323 [M+1]+, tR=1.299 min.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C:10]2[CH:28]=[CH:27][CH:26]=[CH:25][C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)=[O:13])[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[C:36](Cl)(=[O:42])[CH2:37][CH2:38][C:39](Cl)=[O:40]>ClCCl>[O:40]=[C:39]1[CH2:38][CH2:37][C:36](=[O:42])[N:1]1[C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C:10]2[CH:28]=[CH:27][CH:26]=[CH:25][C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:24])[F:23])[CH:16]=2)=[O:13])[CH:5]=[CH:4][N:3]=1
Reactant: Nc1cc(CNc2ccccc2C(=O)Nc2cccc(C(F)(F)F)c2)ccn1
Reactant: O=C(Cl)CCC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1ccccc1NCc1ccnc(N2C(=O)CCC2=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.2 %

Procedure:
193 mg (0.5 mmol) of 2-[(2-amino-pyridin-4-ylmethyl)-amino]-N-(3-trifluoromethyl-phenyl)-benzamide is mixed in 20 ml of dichloromethane with 0.21 ml (1.5 mmol) of triethylamine, and it is mixed at room temperature drop by drop with a solution of 93 mg (0.6 mmol) of succinic acid dichloride in 3 ml of methylene chloride. After stirring overnight at room temperature, it is diluted with methylene chloride and washed in succession with water, saturated sodium bicarbonate solution and saturated common salt solution. Then, the organic phase is dried, filtered and concentrated by evaporation. The residue is chromatographed on Isolute (Separtis Company) with a gradient of methylene chloride:ethanol=100:0 to 95:5. 120 mg (51% of theory) of 2-{[2-(2,5-dioxo-pyrrolidin-1-yl)-pyridin-4-ylmethyl]-amino}-N-(3-trifluoromethyl-phenyl)-benzamide is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2=O)=[CH:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Mg]Br.Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)[CH2:6][CH:7]=1
Reactant: COc1ccccc1[Mg]Br
Reactant: O=C1CCc2ccc(Cl)cc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: COc1ccccc1C1=CCc2ccc(Cl)cc21
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Under an argon atmosphere, a solution of 12.80 g of 6-chloroindan-1-one (73.45 mol) from Example 16A in 60 ml of THF is added drop wise to 88 ml of a 1 M solution of 2-methoxyphenylmagnesium bromide in THF (88.0 mol) at 0° C. The reaction mixture is stirred at room temperature for 1.5 h and 200 ml of 1 N hydrochloric acid are added for working up. The mixture is extracted three times with ethyl acetate, the combined organic phases are dried over sodium sulphate, and the solvent is removed in a rotary evaporator. The residue is dissolved in 400 ml of dichloromethane, mixed with 0.10 g of 4-toluenesulphonic acid monohydrate (0.53 mol) and stirred at room temperature for 16 h. The reaction mixture is washed with saturated sodium bicarbonate solution and saturated sodium chloride solution and dried over sodium sulphate. The solvent is removed in a rotary evaporator, and the residue is purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 150:1). 12.02 g (61% of theory) of the title compound are obtained.