Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[C:13]([OH:21])(=O)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[N+:22]([C:25]1[CH:33]=[CH:32][C:28]([CH2:29][CH2:30][NH2:31])=[CH:27][CH:26]=1)([O-:24])=[O:23].C(N(CC)CC)C>C(OCC)(=O)C.C(Cl)Cl>[N+:22]([C:25]1[CH:26]=[CH:27][C:28]([CH2:29][CH2:30][NH:31][C:13](=[O:21])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:32][CH:33]=1)([O-:24])=[O:23]
Reactant: CCCCCCC(=O)O
Reactant: NCCc1ccc([N+](=O)[O-])cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCCCCCC(=O)NCCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 81.3 %

Procedure:
1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.86 g, 20.1 mmol) and heptanoic acid (2.38 mL, 16.8 mmol) were added sequentially to a solution of 4-nitrophenethylamine (3.40 g, 16.8 mmol), triethylamine (2.81 mL, 20.1 mmol) and methylene chloride (25 mL). After stirring 18 h at ambient temperature, the reaction mixture was diluted with ethyl acetate; washed sequentially with water, 1N aqueous hydrochloric acid, water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride; dried over anhydrous sodium sulfate; filtered and concentrated under reduced pressure to provide 3.80 g (81%) of heptanoic acid [2-(4-nitro-phenyl)-ethyl]-amide as an off-white solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:17](=[O:25])[NH:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1.[CH3:26][O:27][CH2:28][CH2:29][NH2:30]>>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12](=[O:13])[NH:30][CH2:29][CH2:28][O:27][CH3:26])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:17]([NH:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1)=[O:25]
Reactant: COCCN
Reactant: Nc1ncc(-c2ccc(C(=O)O)cc2)cc1C(=O)Nc1ccncc1
Product: COCCNC(=O)c1ccc(-c2cnc(N)c(C(=O)Nc3ccncc3)c2)cc1

Procedure:
Reaction of 4-[6-amino-5-(pyridin-4-ylcarbamoyl)-pyridin-3-yl]-benzoic acid with 2-methoxy-ethylamine gives “A92”; method 1: HPLC/MS: 1.25 min, [M+H]=392;
Reaction SMILES: C(O)(=O)CO.FC(F)(F)S([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])(=O)=O.[C:21](Cl)(=O)[C:22]([Cl:24])=[O:23]>N1C=CC=CC=1.ClCCl.CN(C=O)C>[Si:12]([O:11][CH2:21][C:22]([Cl:24])=[O:23])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: O=C(Cl)C(=O)Cl
Agent: O=C(O)CO
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)[Si](C)(C)OCC(=O)Cl
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 31.4 %

Procedure:
Glycolic acid (5.0 g, 66 mmol) in pyridine (65 ml) was purged with argon and then treated with tert-butyldimethylsilyl trifluoromethanesulfonate (42 g, 36 ml, 158 mmol) at 0° C., and the mixture was stirred for 2.5 hours. The 2-phase mixture was separated and the upper phase diluted with diethyl ether. This solution was cooled to 0° C., washed briefly with 10% hydrochloric acid, dried (MgSO4) and evaporated to the disilyl material (18 g, 97%). The disilyl material (3.48 g, 12.4 mmol) in dichloromethane (30 ml) at 0° C. was treated with DMF (6 drops) followed by oxalyl chloride (1.84 g, 1.30 ml, 14.50 mmol). After stirring for 3.5 hours, the solution was evaporated and the crude material purified by bulb-to-bulb distillation to afford the title product (60 mbar, 120° C.<T<150° C.) (0.95 g, 37%) contaminated with tert-butyldimethylsiloxane.
Reaction SMILES: [C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].C[O-].[Na+].[Cl:10][C:11]1[CH:29]=[CH:28][C:14]([C:15]([C:17]2[CH:26]=[CH:25][C:20]([CH2:21][N:22]=[N+:23]=[N-:24])=[CH:19][C:18]=2[Cl:27])=[O:16])=[CH:13][CH:12]=1>C(O)C>[NH2:2][C:1]1[N:22]([CH2:21][C:20]2[CH:25]=[CH:26][C:17]([C:15](=[O:16])[C:14]3[CH:28]=[CH:29][C:11]([Cl:10])=[CH:12][CH:13]=3)=[C:18]([Cl:27])[CH:19]=2)[N:23]=[N:24][C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: [N-]=[N+]=NCc1ccc(C(=O)c2ccc(Cl)cc2)c(Cl)c1
Reactant: N#CCC(N)=O
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: NC(=O)c1nnn(Cc2ccc(C(=O)c3ccc(Cl)cc3)c(Cl)c2)c1N
Temperature: 25 °C
Yield: 30.7 %

Procedure:
A stirred suspension of 2-cyanoacetamide (378 mg, 4.50 mmol) in ethanol (15 ml) was treated with sodium methoxide (236 mg, 4.37 mmol), refluxed 10 minutes, cooled slightly, and treated with 4-(4-chlorobenzoyl)-3-chlorobenzyl azide (1.03 g, 3.36 mmol) dissolved in ethanol (4 ml). The mixture was refluxed 2 hours, cooled to ambient temperature, and filtered. The solids were washed with ethanol, and the combined filtrate and wash were evaporated to dryness under vacuum. The residue was dissolved in 19:1 (v/v) dichloromethane-methanol (40 ml) and chromatographed on a column of silica gel (60 g) eluted in 20 ml fractions with 97:3 (v/v) dichloromethane-methanol. Fractions 15-42 were combined and evaporated under vacuum to provide 402 mg (32%) of 5-amino-1-(4-[4-chlorobenzoyl]-3-chlorobenzyl)-1,2,3-triazole-4-carboxamide, m.p. 203°-205° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N+:21]([O-:23])=[O:22])[C:5]2[N:9]=[C:8]([CH3:10])[N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:13]=3[Cl:19])[C:6]=2[CH:20]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:13]1[C:14]([Cl:18])=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][N:7]1[C:6]2[CH:20]=[C:2]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:3]=[C:4]([N+:21]([O-:23])=[O:22])[C:5]=2[N:9]=[C:8]1[CH3:10]
Reactant: C1COCCN1
Reactant: Cc1nc2c([N+](=O)[O-])cc(Br)cc2n1Cc1cccc(Cl)c1Cl
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1nc2c([N+](=O)[O-])cc(N3CCOCC3)cc2n1Cc1cccc(Cl)c1Cl
Temperature: 80 °C
Reaction time: 3 h
Yield: 48.4 %

Procedure:
A mixture of 6-bromo-1-(2,3-dichlorobenzyl)-2-methyl-4-nitro-1H-benzo[d]imidazole (1.69 g), morpholine (1.07 g), Pd2(dba)3 (376 mg), Cs2CO3 (2 g) and X-Phos (383 mg) in dioxane (80 mL) was degassed with nitrogen and then stirred at 80° C. for 3 h. When TLC showed complete consumption of starting material, the mixture was cooled to room temperature and the solvent was removed in-vacuo. The remaining residue was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in-vacuo. The residue was then purified by silica gel chromatography eluted with EtOAc:Petrolium ether=1:1 to afford the desired product as a yellow solid (831 mg, 48%). 1H NMR (300 MHz, CDCl3) δ ppm 2.62 (s, 3H), 3.18 (t, 4H, J=4.8 Hz), 3.87 (t, 4H, J=4.8 Hz), 5.41 (s, 2H), 6.28 (d, 1H, J=7.8 Hz), 6.86 (d, 1H, J=2.4 Hz), 7.08 (t, 1H, J=7.8 Hz), 7.46 (d, 1H, J=7.8 Hz), 7.79 (d, 1H, J=2.4 Hz); LC-MS: m/e=421 [M+1]+
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH3:28])[CH2:23][CH2:22]2)=[O:20])[CH:5]=[C:6]([F:18])[C:7]=1[NH:8]CC1C=CC(OC)=CC=1.C(O)(=O)C>CO.[Pd]>[NH2:8][C:7]1[C:6]([F:18])=[CH:5][C:4]([C:19]([N:21]2[CH2:22][CH2:23][N:24]([CH2:27][CH3:28])[CH2:25][CH2:26]2)=[O:20])=[CH:3][C:2]=1[F:1]
Reactant: CCN1CCN(C(=O)c2cc(F)c(NCc3ccc(OC)cc3)c(F)c2)CC1
Agent: [Pd]
Solvent: CO
Solvent: CC(=O)O
Product: CCN1CCN(C(=O)c2cc(F)c(N)c(F)c2)CC1
Reaction time: 24 h
Yield: 90.6 %

Procedure:
To a solution of [3,5-difluoro-4-(4-methoxy-benzylamino)-phenyl]-(4-ethyl-piperazin-1-yl)-methanone (11.8 g, 30.4 mmol) obtained in Step C in methanol (150 ml), palladium black was added, followed by stirring for 24 hours under a hydrogen gas atmosphere. Acetic acid (15 ml) was added, followed by further stirring for 17 hours at room temperature. This was filtered through Celite, and the solvent was distilled off under reduced pressure. This was purified by silica gel column chromatography (dichloromethane/methanol=100/1 to 10/1), to obtain the desired compound as a brown solid (7.42 g, 91%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[C:23]([C:24]([OH:26])=O)=[CH:22][N:21]=[CH:20][CH:19]=3)[C:11]3[CH2:16][O:15][CH2:14][C:12]=3[N:13]=2)[CH:7]=1.C[N:29](C=O)C>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[C:23]([C:24]([NH2:29])=[O:26])=[CH:22][N:21]=[CH:20][CH:19]=3)[C:11]3[CH2:16][O:15][CH2:14][C:12]=3[N:13]=2)[CH:7]=1
Reactant: O=C(O)c1cnccc1Nc1nc(-c2cc(Cl)ccc2F)nc2c1COC2
Reactant: CN(C)C=O
Product: NC(=O)c1cnccc1Nc1nc(-c2cc(Cl)ccc2F)nc2c1COC2
Temperature: 70 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
To a suspension of 4-[2-(5-chloro-2-fluoro-phenyl)-5,7-dihydro-furo[3,4-d]pyrimidin-4-ylamino]-nicotinic acid (50 mg, 0.13 mmol, 1 eq) in DMF (2 ml) was added 1-1′-carbonyldiimidazole (50 mg, 0.31 mmol, 2.4 eq) and the reaction mixture was warmed to 70° C. for 2 h. The mixture was cooled to r.t. and NH3(g) was bubbled through for 10 min. The reaction mixture was stirred at rt for an additional 1 h. The reaction was concentrated in vacuo and the residue was triturated with water (2×5 ml). To the crude residue was added 1N NaOH (5 ml) and the suspension was heated to 100° C. for 2 h. The reaction mixture was cooled to room temperature and neutralized with 1N HC1 and the solid was filtered to give 4-[2-(5-Chloro-2-fluoro-phenyl)-5,7-dihydro-furo[3,4-d]pyrimidin-4-ylamino]-nicotinic amide, 34 (25 mg, 50%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([OH:24])=[CH:4][C:5]([CH2:8][NH:9][CH:10]=[C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([I:21])[CH:19]=3)[C:14](=[O:22])[NH:13][C:12]2=[O:23])=[N:6][CH:7]=1.[Cl-]>CC(N(C)C)=O>[OH:24][C:3]1[CH:4]=[C:5]([CH2:8][NH:9][CH:10]=[C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([I:21])[CH:19]=3)[C:14](=[O:22])[NH:13][C:12]2=[O:23])[N:6]=[CH:7][C:2]=1[NH:1][C:14](=[O:22])[CH:15]=[CH2:16]
Reactant: Nc1cnc(CNC=C2C(=O)NC(=O)c3ccc(I)cc32)cc1O
Agent: [Cl-]
Solvent: CC(=O)N(C)C
Product: C=CC(=O)Nc1cnc(CNC=C2C(=O)NC(=O)c3ccc(I)cc32)cc1O

Procedure:
A mixture of 4-{[(5-Amino-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione (334 mg, 0.766 mmole), 20 mL of dimethylacetamide is stirred, acryoyl chloride (651 uL, 7.66 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, stirred overnight with a saturated aqueous sodium bicarbonate solution, filtered, washed well with water, and dried to give a green solid, 98 mg, (27%); MS (ES−): m/z 489 (M−H).
Reaction SMILES: C(OC([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11]([C:21]#[N:22])([C:16]1[S:17][CH:18]=[CH:19][N:20]=1)[CH2:12]2)=O)(C)(C)C.[ClH:23]>O1CCOCC1>[ClH:23].[S:17]1[CH:18]=[CH:19][N:20]=[C:16]1[C:11]1([C:21]#[N:22])[CH2:12][CH:13]2[NH:8][CH:9]([CH2:15][CH2:14]2)[CH2:10]1
Reactant: CC(C)(C)OC(=O)N1C2CCC1CC(C#N)(c1nccs1)C2
Agent: Cl
Solvent: C1COCCO1
Product: N#CC1(c2nccs2)CC2CCC(C1)N2
Temperature: 40 °C
Reaction time: 1 h

Procedure:
3-Cyano-3-thiazol-2-yl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.2 g) was dissolved in a solution of hydrogen chloride in dioxane (4 N, 3 mL). The mixture was stirred for 1 hour at 40° C. The solvent was removed by evaporation under vacuum afford the title compound as a white solid. LCMS m/z 220.1 [M+H]+. R.T.=0.58 min (Analytical Method 3).
Reaction SMILES: [O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][C:8]([C:12]([O:14]C)=[O:13])=[CH:7][C:6]=2[N:5]=[C:4]2[CH:16]=[CH:17][C:18]([C:20]([O:22]CC)=[O:21])=[N:19][N:3]12>Cl>[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][C:8]([C:12]([OH:14])=[O:13])=[CH:7][C:6]=2[N:5]=[C:4]2[CH:16]=[CH:17][C:18]([C:20]([OH:22])=[O:21])=[N:19][N:3]12
Reactant: CCOC(=O)c1ccc2nc3cc(C(=O)OC)ccc3c(=O)n2n1
Agent: Cl
Product: O=C(O)c1ccc2c(=O)n3nc(C(=O)O)ccc3nc2c1

Procedure:
A suspension of 2-ethyl 7-methyl 10-oxo-10H-pyridazino[6,1-b]quinazoline-2,7-dicarboxylate (Example 3, Step A) in 10% hydrochloric acid was refluxed under nitrogen for 12 h. The mixture was cooled and filtered to give the titled compound as a yellow solid, mp>360° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[CH2:11][CH:10]([CH3:12])[CH:9]2[CH:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[NH:3]1.[CH:14](O)=O.C=O.[OH-].[Na+]>O.C(OCC)C>[CH3:14][N:3]1[CH:4]2[CH:9]([CH2:8][CH2:7][CH2:6][CH2:5]2)[CH:10]([CH3:12])[CH2:11][C:2]1([CH3:13])[CH3:1]
Reactant: CC1CC(C)(C)NC2CCCCC12
Reactant: O=CO
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: O
Product: CC1CC(C)(C)N(C)C2CCCCC12

Procedure:
1,2,2,4-tetramethyl decahydroquinoline was prepared. 36.3 grams (0.2 mole) of 2,2,4-trimethyl decahydroquinoline of about 58% cis structure was placed in a reactor vessel equipped for agitation. Formic acid, 20.2 grams (0.44 mole) was added dropwise to the reactor vessel followed by the slow addition of 17.4 grams of 38% by weight formaldehyde in water solution. After addition, the mix was refluxed at for 4 hours. A 5N sodium hydroxide solution was then added until the mix was basic. Diethyl ether was added and the mix separated out and the ether fraction obtained. The fraction was concentrated and then distilled using a 3 inch Vigreaux column to yield 5.4 grams of a product boiling at 70° C. at 0.6 mm Hg. The NMR spectra of the product was consistent with the desired product, 1,2,2,4-tetramethyl decahydroquinoline. The theoretical carbon, hydrogen, nitrogen analysis for the formula C13H25N is 79.92% carbon, 12.90% hydrogen, and 7.17% nitrogen while measured values were 77.23% carbon, 13.13% hydrogen, and 6.56% nitrogen.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[CH:18]=[CH:17][N:16]=[N:15]2)=[CH:9][C:4]=1[C:5]([O:7]C)=[O:6].C(OCC)(=O)C.CCCCCC.[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[CH:18]=[CH:17][N:16]=[N:15]2)=[CH:9][C:4]=1[C:5]([OH:7])=[O:6]
Reactant: COC(=O)c1cc(Cn2ccnn2)ccc1OC
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: O
Product: COc1ccc(Cn2ccnn2)cc1C(=O)O
Reaction time: 4 h

Procedure:
Combine methyl 2-methoxy-5-(1H-triazol-1-ylmethyl)benzoate (1.14 g, 4.61 mmol) and methanol/tetrahydrofuran (1/1, 30 mL). Add a 1 M aqueous solution of lithium hydroxide (15 mL, 15 mmol). After 4 hours, acidify the reaction mixture with a 10% aqueous citric acid solution, add water, and extract twice with ethyl acetate. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give 2-methoxy-5-(1H-triazol-1-ylmethyl)benzoic acid: Rf=0.09 (silica gel, ethyl acetate).
Reaction SMILES: C([O:5][C:6](=[O:20])[CH2:7][S:8][C:9]1[NH:10][CH:11]=[C:12]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[N:13]=1)(C)(C)C.[C:21]([OH:27])([C:23]([F:26])([F:25])[F:24])=[O:22]>>[F:24][C:23]([F:26])([F:25])[C:21]([OH:27])=[O:22].[N:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:12]2[N:13]=[C:9]([S:8][CH2:7][C:6]([OH:20])=[O:5])[NH:10][CH:11]=2)[CH:15]=1
Reactant: CC(C)(C)OC(=O)CSc1nc(-c2cccnc2)c[nH]1
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)CSc1nc(-c2cccnc2)c[nH]1

Procedure:
30 mg (0.1 mmol) of (4-(pyridin-3-yl)-1H-imidazol-2-ylsulfanyl)-acetic acid tert-butyl ester were allowed to stand in 1 ml of 90% aqueous TFA at room temperature for 1 h. The mixture was evaporated, and the product employed in the subsequent step without further purification. Yield: 33 mg.
Reaction SMILES: [N+:1]([C:4]1[CH:25]=[CH:24][C:7]([O:8][C:9]2[N:17]=[CH:16][N:15]=[C:14]3[C:10]=2[N:11]=[CH:12][N:13]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][CH:5]=1)([O-])=O.C([O-])=O.[NH4+]>C(O)C>[O:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH:18]1[N:13]1[CH:12]=[N:11][C:10]2[C:14]1=[N:15][CH:16]=[N:17][C:9]=2[O:8][C:7]1[CH:24]=[CH:25][C:4]([NH2:1])=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ncnc3c2ncn3C2CCCCO2)cc1
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: Nc1ccc(Oc2ncnc3c2ncn3C2CCCCO2)cc1

Procedure:
To a round bottom flask equipped with a magnetic stir bar was added 6-(4-nitro-phenoxy)-9-(tetrahydro-pyran-2-yl)-9H-purine (4 g, 12.86 mmol, 1.0 eq.), 5% PtS (20% by weight, 800 mg), ammonium formate (3.2 g, 51.44 eq), and ethanol (100 ml). The reaction was stirred at reflux for 30 min upon which the reaction was filtered hot through celite. Removal of the ethanol was followed by the addition of 1N HCl, which was further washed twice with DCM (50 ml). The aqueous layer was basified and extracted with DCM. The organic layer was then washed twice with brine (50 ml) and dried over sodium sulfate. After removal of the DCM in vacuo, 4-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-yloxy]-phenylamine was obtained (3 g, 83%) as a solid. 1H NMR (400 MHz, CDCl3): δ 8.4 (s, 1H), 8.2 (s, 1H), 7.0 (m, 2H), 6.75 (m, 2H), 5.8 (m, 1H), 4.20 (m, 1H), 4.0 (m, 2H), 3.8 (m, 1H), 2.20 (m, 3H), 1.80 (m, 3H). MS (ESI) for C16H17N5O2: 312 (MH+).
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH2:9][C:10](=O)[CH3:11])[CH:3]=1.C([BH3-])#[N:14].[Na+].C([O-])(=O)C.[NH4+].Cl>CO>[CH3:11][CH:10]([NH2:14])[CH2:9][CH2:8][C:4]1[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)CCc1cccnc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [NH4+]
Solvent: CO
Product: CC(N)CCc1cccnc1
Yield: 80.4 %

Procedure:
A solution of 12.0 g of 4-(3-pyridinyl)-2-butanone hydrochloride, 3.38 g of sodium cyanoborohydride, and 42.78 g of ammonium acetate in 200 ml of methanol was stirred at room temperature for 2.5 days, acidified with dilute hydrochloric acid, and concentrated. The residue was dissolved in aqueous potassium carbonate solution and was extracted with dichloromethane. The residue obtained after evaporation of the dichloromethane was distilled to give 6.5 g (80%) of α-methyl-3-pyridinepropanamine, bp 126°-148° C./0.3 mm. The picrate was crystallized from methanol-ether; mp 146°-148° C.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:17])[CH2:11][S:12][CH2:13][C:14]([OH:16])=O)=[CH:5][CH:4]=1)#[N:2].[CH2:18]([N:20]1[C:32]2[CH:31]=[CH:30][C:29]([NH2:33])=[CH:28][C:27]=2[C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH3:19].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>CN(C=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10](=[O:17])[CH2:11][S:12][CH2:13][C:14]([NH:33][C:29]2[CH:30]=[CH:31][C:32]3[N:20]([CH2:18][CH3:19])[C:21]4[C:26]([C:27]=3[CH:28]=2)=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:16])=[CH:7][CH:8]=1)#[N:2]
Reactant: CCn1c2ccccc2c2cc(N)ccc21
Reactant: N#Cc1ccc(NC(=O)CSCC(=O)O)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCn1c2ccccc2c2cc(NC(=O)CSCC(=O)Nc3ccc(C#N)cc3)ccc21
Yield: 58.4 %

Procedure:
A solution of the compound obtained in Step 1 (145 mg, 0.58 mmol), 9-ethyl-9H-carbazol-3-amine (122 mg, 0.58 mmol), HATU (330 mg, 0.87 mmol) and DIEA (225 mg, 1.74 mmol) in DMF (4 mL) was stirred at room temperature for 16 hr. To the reaction solution was added dilute hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound (150 mg, 0.339 mmol, 59%) as a white powder.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:10](=[O:17])[CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][NH:13]2)[CH:7]=[CH:8][CH:9]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>CC(CC)=O>[CH2:25]([N:13]1[CH2:14][CH2:15][CH2:16][CH:12]1[CH2:11][C:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH3:2])[CH:5]=1)=[O:17])[CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCBr
Reactant: COc1cccc(C(=O)CC2CCCN2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCCCCN1CCCC1CC(=O)c1cccc(OC)c1

Procedure:
5.11 g of 1-(3-methoxyphenyl)-2-(2-pyrrolidinyl)-ethanone hydrochloride, 5.6 g of anhydrous potassium carbonate, 3.7 g of 1-bromohexane and 60 ml of ethyl methyl ketone are heated under reflux for 18 hours. The solvent is distilled off, the residue is taken up with 50 ml of water and extraction is effected twice with, in each case, 50 ml of diethyl ether. After drying over sodium sulfate, the united organic phases are concentrated to an oil, which is distilled under a high vacuum to obtain 5.0 g (82% of theory) of the title compound: b.p. 138° to 144° at 0.005 mm Hg.
Reaction SMILES: [F:1][C:2]1[C:7]([S:8](Cl)(=[O:10])=[O:9])=[C:6]([F:12])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[F:15].[OH-:16].[K+:17]>O>[F:1][C:2]1[C:7]([S:8]([O-:16])(=[O:10])=[O:9])=[C:6]([F:12])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[F:15].[K+:17]
Reactant: O=S(=O)(Cl)c1c(F)c(F)c(F)c(F)c1F
Reactant: [OH-]
Agent: [K+]
Solvent: O
Product: O=S(=O)([O-])c1c(F)c(F)c(F)c(F)c1F
Temperature: 25 °C
Reaction time: 18 h
Yield: 82.1 %

Procedure:
A mixture of pentafluorobenzenesulfonyl chloride (25.0 g, 94 mmoles) and potassium hydroxide (86% purity, 12.3 g, 188 mmoles) was dissolved in 230 ml water and stirred at room temperature for 18 hours. The produced precipitate was filtered off and recrystallized from water (about 6 ml/g product). Colorless needles formed were filtered, washed with cool water and ethanol and dried in a vacuum oven for 24 hours to yield 22.1 g of potassium pentafluorobenzene sulfonate (82% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:3]=1[CH2:4][CH2:5][NH:6][C:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([O:27]C)=[O:26])=[CH:20][C:19]=1[C:29]#[N:30])[CH:13]=[CH:12]2)=[O:8].[OH-].[Na+]>CO.O.C(Cl)Cl>[C:29]([C:19]1[CH:20]=[C:21]([CH2:24][C:25]([OH:27])=[O:26])[CH:22]=[CH:23][C:18]=1[N:14]1[C:15]2[C:11](=[CH:10][C:9]([C:7](=[O:8])[NH:6][CH2:5][CH2:4][C:3]3[CH:31]=[CH:32][C:33]([Cl:35])=[CH:34][C:2]=3[Cl:1])=[CH:17][CH:16]=2)[CH:12]=[CH:13]1)#[N:30]
Reactant: COC(=O)Cc1ccc(-n2ccc3cc(C(=O)NCCc4ccc(Cl)cc4Cl)ccc32)c(C#N)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: N#Cc1cc(CC(=O)O)ccc1-n1ccc2cc(C(=O)NCCc3ccc(Cl)cc3Cl)ccc21
Reaction time: 1 h

Procedure:
To a stirred solution of methyl 2-(4-(5-((2,4-dichlorophenethyl)carbamoyl)-1H-indol-1-yl)-3-cyanophenyl)acetate in methanol (1 mL) at ambient temperature was added aqueous sodium hydroxide (5.0 N, 0.036 mL) and 5 drops of water, and the reaction was stirred for 1 hour. The reaction mixture was taken up in DCM (5 mL) and washed with 2 M HCl (5 mL). The organic layer was dried over MgSO4 and concentrated to give the desired compound as a white solid 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.80 (s, 1H), 7.70 (dd, J=8.5, 2.1 Hz, 1H), 7.65 (d, J=8.6Hz, 1H), 7.57 (d, J=8.9 Hz, 1H), 7.44 (d, J=5.9 Hz, 1H), 7.32 (d, J=8.7 Hz, 1H), 7.17-7.25 (m, 3H), 6.82 (d, J=3.0 Hz, 1H), 6.24 (d, J=5.9 NH), 3.81 (s, 2H), 3.74 (q, J=6.6 Hz, 2H), 3.10 (t, J=7.0 Hz, 2H), MS(ESI)=492.3 (M+1).