Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH:37]=2)O1.ClCCl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[CH3:14][Si:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][O:10][CH2:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]1[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=[C:2]([C:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH:37]=2)[CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(Cl)nc2ccnn12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N1CC=C(c2cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3nccc3n2)CC1
Temperature: 100 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
To a pressure tube was charged 5-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (Int-9d, 5.36 g, 12.5 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (4.26 g, 13.8 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (510 mg, 0.62 mmol), 2M Na2CO3 (30 ml) and DME (60 ml). The tube was degassed with Ar briefly, capped and heated at 100° C. with stirring overnight. After cooling, the reaction mixture was diluted with EtOAc and water, the organic layer was isolated, washed with brine and dried (MgSO4). After the solvent was removed under reduced pressure, the residue was purified on silica. Elution with EtOAc in hexanes (0-25%) gave tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Int-9e) (5.76 g, 80%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:18][NH:19][O:20][CH3:21]>C(Cl)Cl>[CH3:21][O:20][N:19]([CH3:18])[C:14]([CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:16]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Reactant: CNOC
Agent: Cl
Solvent: ClCCl
Product: CON(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 27.5 °C
Reaction time: 1 h

Procedure:
To a solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (50 g, 218 mmol) in DCM (500 mL), 1,1-carbonyldiimidazole (46 g, 284 mmol) was added and the reaction mixture was stirred for 1 h at 25-30° C. N,O-Dimethyl-hydroxylamine hydrochloride (30 g, 306 mmol) was then added and the resulting mixture was stirred for 15 h at 25-30° C. After completion of the reaction, the reaction mixture was diluted with DCM and washed with water, saturated NaHCO3 solution, and 10% NaOH solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to afford pure tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate product.
Reaction SMILES: Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:39]([N:46]1[CH2:51][CH2:50][CH:49]([C:52](O)=[O:53])[CH2:48][CH2:47]1)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>CN(C=O)C>[CH3:2][N:3]([O:4][CH3:5])[C:52]([CH:49]1[CH2:50][CH2:51][N:46]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:47][CH2:48]1)=[O:53]
Reactant: CNOC
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CON(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 176.5 %

Procedure:
N,O-Dimethylhydroxylamine hydrochloride (4.26 g, 43.7 mmols), di-isopropylethylamine (33.88 g, 45.66 mL, 262.2 mmols) and HATU (19.94 g, 52.4 mmols) were added to a solution of N-Boc-piperidine-4-carboxylic acid (11.03 g, 48.1 mmols) in dry DMF (250 mL). The reaction mixture was stirred at room temperature for 72 hrs. The DMF was removed in vacuo and the residue was partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (200 mL). The organic phase was separated, washed with saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL), and dried over MgSO4. Evaporation of the solvent afforded a dark oil (21.0 g) that was purified by flash chromatography (Silica, gradient elution with pentane/ethyl acetate 9:1 v/v to 3:2 v/v) to give the title compound 12.5 g (95%) as a gum.
Reaction SMILES: C([N:4]1[CH2:9][CH2:8][CH:7]([C:10](=[O:19])[C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[CH2:6][CH2:5]1)(=O)C>Cl>[F:18][C:12]1[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=1[C:10]([CH:7]1[CH2:6][CH2:5][NH:4][CH2:9][CH2:8]1)=[O:19]
Reactant: CC(=O)N1CCC(C(=O)c2ccc(F)cc2F)CC1
Agent: Cl
Product: O=C(c1ccc(F)cc1F)C1CCNCC1
Yield: 83 %

Procedure:
30 g of 1-acetyl-4-(2,4-difluorobenzoyl)piperidine are brought to reflux in 113 ml of 6N hydrochloric acid for 6 hours. The reaction medium is then concentrated and the residue obtained is crystallized in isopropanol. The expected compound is isolated after filtration.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[C:11]([N:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[CH2:14]1)=O.B.C1COCC1>>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:26])[F:28])[CH:20]=2)[CH2:14]1
Reactant: O=C([C@H]1COc2ccccc2O1)N1CCC[C@H](c2cccc(C(F)(F)F)c2)C1
Agent: B
Solvent: C1CCOC1
Product: FC(F)(F)c1cccc([C@H]2CCCN(C[C@H]3COc4ccccc4O3)C2)c1
Yield: 55.1 %

Procedure:
(R)-2,3-Dihydrobenzo[1,4]dioxin-2-yl-[(R*)-3-(3-trifluoromethylphenyl)piperidin-1-yl]methanone (30 mg, 0.077 mmol) was treated with BH3THF according to the above general procedure. Flash chromatography gave 16 mg of the title compound.
Reaction SMILES: [CH2:1]([C:3]([CH2:8][OH:9])([CH2:6][OH:7])[CH2:4][CH3:5])[OH:2].[CH3:10][C:11]([CH3:13])=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCCCCC>[OH:2][CH2:1][C:3]1([CH2:4][CH3:5])[CH2:8][O:9][C:11]([CH3:13])([CH3:10])[O:7][CH2:6]1
Reactant: CCC(CO)(CO)CO
Reactant: CC(C)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCCCCC
Solvent: O
Product: CCC1(CO)COC(C)(C)OC1

Procedure:
In a 3-liter reaction vessel, 292.1 g (2.18 mol) of trimethylolpropane, 474.0 g (8.17 mol) of acetone, 6.0 g (0.0315 mol) of p-toluene sulfonic acid monohydrate, and 900 ml of hexane were placed and refluxed for 24 hours with removing the formed water off the reaction system. The reaction product was neutralized with aqueous solution of sodium hydroxide, and distilled under a reduced pressure to give 5-hydroxymethyl-5-ethyl-2,2-dimethyl-1,3-dioxane.
Reaction SMILES: [CH3:1][C:2]1([C:7]2([CH2:10][OH:11])[CH2:9][CH2:8]2)[O:6][CH2:5][CH2:4][O:3]1.C([O-])(=O)C.[Na+].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl.C(OCC)C>[CH3:1][C:2]1([C:7]2([CH:10]=[O:11])[CH2:9][CH2:8]2)[O:3][CH2:4][CH2:5][O:6]1
Reactant: CC1(C2(CO)CC2)OCCO1
Agent: O=[Cr](=O)([O-])Cl
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOCC
Product: CC1(C2(C=O)CC2)OCCO1
Reaction time: 2 h
Yield: 82 %

Procedure:
10 g of 96 in 500 ml of methylene chloride is dissolved, and 3.7 g of sodium acetate (anhydrous) and 19.3 g of pyridinium chlorochromate are added. It is now stirred for 2 hours under argon. It is diluted with 1 l of diethyl ether and then filtered on Celite. Concentration by evaporation of the solvent followed by chromatographic purification on silica gel with ethyl acetate/hexane yields 8.1 g of 1-(2-methyl-1,3-dioxolan-2-yl)cyclopropanecarbaldehyde 97 as a colorless oil.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH:7]=O)[C:3]([O:5][CH3:6])=[O:4].[C:10]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH3:6][O:5][C:3](=[O:4])[C:2]([CH3:1])([CH3:9])[CH2:7][N:20]1[CH2:19][CH2:18][N:17]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:22][CH2:21]1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: COC(=O)C(C)(C)C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: COC(=O)C(C)(C)CN1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 664.9 %

Procedure:
A solution of 567 (0.57 mmol, crude in 25 ml of DCM) and 1-Boc-piperazine (1.175 g, 6.31 mmol) in DCM (50 ml) was stirred for 1 h at rt under nitrogen, then cooled down to 0° C. To the cold solution NaBH(OAc)3 (4.22 g, 18.93 mmol) was added in one portion. The reaction mixture was stirred at 0° C. for 1 h, then at rt overnight, quenched by addition of water, stirred for 1 h and slowly neutralyzed with a saturated aqueous solution of sodium bicarbonate (pH=7-8). The alkaline solution was extracted with DCM. The organic extract was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by Biotage (Snap 25 g cartridge, MeOH/DCM: 0/100 to 10/90 over 30 CV), to afford the desired product 568 (1.137 g, 3.79 mmol, 60% yield) as colorless oily liquid. MS (m/z): 301.3 (M+H).
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:8](Cl)(=[O:12])[C:9](Cl)=[O:10].[Al+3].[Cl-].[Cl-].[Cl-].Cl>CCOCC.C(Cl)Cl>[S:7]1[C:9](=[O:10])[C:8](=[O:12])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]1=2
Reactant: O=C(Cl)C(=O)Cl
Reactant: Sc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCOCC
Product: O=C1Sc2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 75.4 %

Procedure:
To a solution of benzenthiol (1 ml, 9.7 mmol) in Et2O (30 ml) at 0° C. oxalyl chloride (0.94 ml, 10.7 mmol) was added dropwise. The mixture was stirred at room temperature for 1.5 hour, then, the solvent was evaporated under reduced pressure. The crude was dissolved in CH2Cl2 (40 ml) and a solution of AlCl3 (4.75 g, 35 mmol) in CH2Cl2 (32 ml) was added dropwise at 0° C. The mixture was stirred for 16 hours at room temperature, then, ice and 1M HCl were added until a clear mixture was obtained. After 1 hour, the phases were separated and the aqueous layer was extracted with CH2Cl2 (3×30 ml). The collected organic phases were dried over Na2SO4, filtered and evaporated, affording 18 (1.2 g, 78%) as orange solid that was used without further purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][N:12](CC3C=CC=CC=3)[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>C(O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]2[CH:14]([CH2:13][NH:12][CH2:11]2)[CH2:15]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CC2CN(Cc3ccccc3)CC2C1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CC2CNCC2C1
Temperature: 25 °C
Yield: 83.3 %

Procedure:
A mixture of compound 4 (130 mg), Pd/C (100 mg, 10%) and ammonium formate (160 mg) in ethanol (10 mL) was heated to reflux for 2 hours and then allowed to cool to room temperature. The solid was filtered off and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC to provide title compound 5 as a pale yellow oil (76 mg, 84%). LCMS: Rf: 0.371 min, M+H+: 213.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[Cl-].[Al+3].[Cl-].[Cl-].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21].Cl>ClC1C=CC=CC=1>[CH3:12][O:13][C:14]1[CH:19]=[C:18]([C:4](=[O:5])/[CH:3]=[CH:2]/[C:1]([OH:6])=[O:7])[CH:17]=[CH:16][C:15]=1[O:20][CH3:21]
Reactant: O=C1C=CC(=O)O1
Reactant: COc1ccccc1OC
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1
Product: COc1ccc(C(=O)/C=C/C(=O)O)cc1OC
Temperature: 10 °C
Reaction time: 24 h
Yield: 62.1 %

Procedure:
Into a 500 ml four-neck flask were charged 66.9 g (0.682 mol) of maleic anhydride and 150 ml of chlorobenzene under a nitrogen atmosphere. Then, the whole was cooled to 10° C. or lower and 67.6 g (0.507 mol) of aluminum chloride was added thereto. While temperature was maintained at 10 to 15° C., 25 ml (0.195 mol) of 1,2-dimethoxybenzene was added dropwise, followed by 48 hours of reaction at 20 to 30° C. After termination of the reaction was confirmed by HPLC analysis, the reaction solution was added dropwise to 200 ml of a 1N hydrochloric acid aqueous solution cooled to 0° C. to decompose excess aluminum chloride. The resulting mixture was extracted with 400 ml of ethyl acetate and washing was conducted twice with 200 ml of a 1N hydrochloric acid aqueous solution. The organic layer was washed three times with 200 ml of a saturated sodium hydrogen carbonate aqueous solution to extract (E)-4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoic acid into the aqueous layer, followed by adjusting the aqueous layer to pH 2.0. After 24 h of stirring at 5° C., filtration was carried out to obtain 28.6 g (yield 62.1%) of the aimed compound as light yellow crystals. As a result of HPLC analysis, the purity was found to be 96.5%.
Reaction SMILES: C(N1[C@H]2[C@@H](CC(=O)CC2)CCC1)CC.Br.BrBr.NC(N)=O.[NH2:22][C:23]1[O:24][C:25]2[CH2:34][C@H:33]3[C@@H:28]([CH2:29][CH2:30][CH2:31][N:32]3[CH2:35][CH2:36][CH3:37])[CH2:27][C:26]=2[N:38]=1.C(Cl)(Cl)[Cl:40]>C(O)(=O)C.CO>[ClH:40].[ClH:40].[NH2:22][C:23]1[O:24][C:25]2[CH2:34][C@H:33]3[C@@H:28]([CH2:29][CH2:30][CH2:31][N:32]3[CH2:35][CH2:36][CH3:37])[CH2:27][C:26]=2[N:38]=1
Reactant: ClC(Cl)Cl
Agent: Br
Agent: BrBr
Agent: CCCN1CCC[C@@H]2CC(=O)CC[C@H]21
Solvent: CO
Solvent: CC(=O)O
Product: Cl

Procedure:
A solution was prepared by dissolving 1.95 g. of trans-(±)-1-n-propyl-6-oxodecahydroquinoline in 25 ml. of glacial acetic acid. Two and three tenths milliliters of 37% (by weight) hydrogen bromide in glacial acetic acid were added followed by the dropwise addition of 0.6 ml. of bromine dissolved in 5 ml. of glacial acetic acid. The reaction mixture was stirred for one-half hour after all the reactants had been added. Volatile constituents were then removed in vacuo yielding, as a residue, trans-(±)-1-n-propyl-6-oxo-7-bromodecahydroquinoline hydrobromide. Ten millimoles of this salt were dissolved in 10 ml. of methanol. One and two-tenths grams of urea were added thereto. The resulting mixture was refluxed for about 24 hours under a nitrogen blanket. The reaction mixture was cooled to about room temperature, and the solvent removed in vacuo. The residue was dissolved in water, and the aqueous solution made basic by the addition of 14N aqueous ammonium hydroxide. The alkaline layer was extracted several times with an equal volume of methylene dichloride. The organic extracts were combined, and the combined extracts washed with saturated aqueous sodium chloride and ten dried. Removal of the solvent in vacuo yielded a brown viscous oil comprising trans-(±)-2-amino-5-n-propyl-4,4a,5,6,7,8,8a,9-octahydro-oxazolo[4,5-g]quinoline formed in the above reaction. The residue was dissolved in chloroform containing 5% methanol and a trace of ammonium hydroxide and chromatographed over silica gel (eluant was CHCl3 containing 5% methanol and a trace of ammonium hydroxide). Fractions containing the desired oxazoloquinoline were combined to yield, after evaporation of the solvent, a yellow viscous oil which slowly crystallized. The crystalline solid, trans-(±)-2-amino-5-n-propyl-4,4a,5,6,7,8,8a,9-octahydro-oxazolo[4,5-g]quinoline, was dissolved in methanol and the methanolic solution saturated with gaseous HCl. The solvent was removed and the residue recrystallized from ethanol. Two-tenths grams of trans-(±)-2-amino-5-n-propyl-4,4a,5,6,7,8,8a,9-octahydro-oxazolo[4,5-g]quinoline dihydrochloride were obtained melting above 225° C.; molecular ion at 235 by mass spectrum.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([C:8]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])=[O:9])[CH:7]=1.[C:19]([O:23][C:24](=[O:29])[NH:25][CH2:26][C:27]#[CH:28])([CH3:22])([CH3:21])[CH3:20]>C(Cl)Cl>[C:19]([O:23][C:24](=[O:29])[NH:25][CH2:26][C:27]#[C:28][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][C:6]=1[C:8](=[O:9])[C:10]1[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=1[F:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: O=C(c1cc(Cl)ccc1I)c1c(F)cccc1F
Reactant: C#CCNC(=O)OC(C)(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC#Cc1ccc(Cl)cc1C(=O)c1c(F)cccc1F
Temperature: 25 °C
Reaction time: 16 h

Procedure:
(5-Chloro-2-iodo-phenyl)-(2,6-difluoro-phenyl)-methanone (2aa) (5.5 g, 14.5 mmol), prop-2-ynyl-carbamic acid tert-butyl ester (2.5 g, 16 mmol), PdCl2 (PPh3)2 (0.6 g, 0.9 mmol) and Cu(I)I (0.2 g, 0.9 mmol) were suspended in anhydrous CH2Cl2 (50 mL) and the mixture was sparged with nitrogen for 30 min. Diethylamine (8 mL) was added and the solution was stirred at room temperature for 16 h. The solution was concentrated in vacuo and the resulting residue purified by column chromatography (silica gel, 0 to 15% EtOAc/hexanes) to afford 3aa (3.6 g, 61%) as a white solid, MS m/z=406 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([N+:12]([O-])=O)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Sn](Cl)Cl>CCO>[NH2:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([Cl:1])[CH:11]=1
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1Cl
Agent: Cl[Sn]Cl
Solvent: CCO
Product: COC(=O)c1ccc(N)cc1Cl
Temperature: 55 °C
Yield: 90.6 %

Procedure:
To 5 g of methyl 2-chloro-4-nitrobenzoate in 100 mL of EtOH was added 20 g of Tin (II) Chloride in portions. The reaction was heated to 55° C. and monitored by TLC until complete. Solvent was concentrated and extraction was performed in Ethyl Acetate and water with TEA to reduce emulsions. The organic layer was dried over Magnesium Sulfate, filtered and concentrated to give 3.9 g of methyl 4-amino-2-chlorobenzoate. 1 g of methyl 4-amino-2-chlorobenzoate was cooled to 0° C. in DCM with 485 μL of Pyridine before Methanesulfonyl Chloride was added dropwise. The reaction was allowed to warm to room temperature and stir overnight. Solvent was concentrated and the crude material was dissolved in Ethyl Acetate and extracted with saturated bicarbonate solution and then brine. The crude material was dried over Magnesium Sulfate, filtered and concentrated to give 1.54 g of methyl 2-chloro-4-(methylsulfonamido)benzoate. 107 μL of 1-bromo-2-methoxyethane and 556 mg of Cesium Carbonate were added to 150 mg of methyl 2-chloro-4-(methylsulfonamido)benzoate in DMF and stirred at room temperature for 16 hours. The reaction mixture was extracted in Ethyl Acetate twice with saturated bicarbonate and once with brine, dried over Magnesium Sulfate, filtered and concentrated to give methyl 2-chloro-4-(N-(2-methoxyethyl)methylsulfonamido)benzoate. 182 mg of methyl 2-chloro-4-(N-(2-methoxyethyl)methylsulfonamido)benzoate was hydrolyzed via Procedure M to yield 169 mg of crude 2-chloro-4-(N-(2-methoxyethyl)methylsulfonamido)benzoic acid. 65 mg of 4-chloro-3-(pyridin-2-yl)aniline was coupled to 2-chloro-4-(N-(2-methoxyethyl)methylsulfonamido)benzoic acid via Procedure G. The crude product was purified by reverse phase HPLC to yield 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(N-(2-methoxyethyl)methylsulfonamido)benzamide. MS (Q1) 494 (M)+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[Cl:10][CH2:11][CH2:12][CH2:13]I.O>CN(C)C=O>[Cl:10][CH2:11][CH2:12][CH2:13][O:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1cccnc1
Reactant: ClCCCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: ClCCCOc1cccnc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.3 %

Procedure:
Under a nitrogen atmosphere, a solution of 3-hydroxypyridine (5.00 g, 52.58 mmol) in N,N-dimethylformamide (DMF) (55 mL) was slowly added to a cold (0-5° C.), stirring slurry of sodium hydride (2.52 g of an 80% dispersion in mineral oil, 84.0 mmol) in DMF (10 mL). The mixture was allowed to warm to ambient temperature and further stirred for 1 h. To this slurry was added 1-choro-3-iodopropane (12.90 g, 63.10 mmol), and the resulting dark-brown mixture was stirred at ambient temperature for 48 h. Cold water was added and the mixture was extracted with chloroform (4×100 mL). The combined chloroform extracts were washed with water (2×50 mL), dried (Na2SO4), filtered, and concentrated by rotary evaporation. Water (150 mL) was added, and the mixture was basified with 20% NaOH solution (5.0 mL). The alkaline solution was extracted with methyl t-butyl ether (MTBE) (5×100 mL). The combined MTBE extracts were washed with water (4×100 mL), dried (Na2SO4), filtered, and concentrated by rotary evaporation to give 4.90 g (54.3%) of an oil. 1H NMR (CDCl3, 300 MHz): δ8.34 (s, 1H), 8.24 (s, 1H), 7.22 (t, 2H, J=2.13 Hz), 4.18 (t, 2H, J=5.85 Hz), 3.77 (t, 2H, J=6.19 Hz), 2.27 (p, 2H, J=6.03 Hz). 13C NMR (CDCl3, 75 MHz): δ154.99, 142.38, 138.07, 123.93, 121.09, 64.60, 41.22, 32.11. EI-MS: m/z (relative intensity) 171 (M+, 27.25%), 136 (4.66%), 95 (100.00%), 78 (17.98%), 41 (37.74%), 39 (34.23%).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]([CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[O:14].C(N(C(C)C)CC)(C)C>C1COCC1>[CH3:11][O:12][C:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:17][CH2:16]1)=[O:14]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: COC(=O)C1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COC(=O)C1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Temperature: 150 °C
Yield: 37.4 %

Procedure:
To a solution of 4-fluoronitrobenzene (0.70 g, 4.96 mmol) in THF (8 mL) was added piperadine-4-carboxylic acid methyl ester (0.71 g, 4.96 mmol) and diisopropylethylamine (0.66 g, 5.11 mmol). The mixture was heated in a microwave oven at 150° C. for 1.5 hr. The resulting mixture was extracted with ethyl acetate and hydrochloric acid (0.2 N). The organic layer was washed with brine and concentrated sodium bicarbonate solution. After the evaporation of solvents, the residue was purified through a Biotage flash column chromatography using ethyl acetate and hexanes (1:1 ratio) to give a yellow solid as 1-(4-nitrophenyl)-piperidine-4-carboxylic acid methyl ester (490 mg). 1H-NMR is consistent with the structure.