Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:21])[C@@H:10]([N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[CH:6][CH:7]=1.[F:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[N:35]=[C:34]([NH:36][CH2:37][CH2:38][CH3:39])[C:33]([CH:40]=O)=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(OCC)(=O)C.C(O)(=O)C>[F:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[N:35]=[C:34]([NH:36][CH2:37][CH2:38][CH3:39])[C:33]([CH2:40][NH:1][C:2]3[CH:3]=[C:4]([NH:8][C:9](=[O:21])[C@@H:10]([N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:17])([CH3:16])[CH3:18])[CH3:11])[CH:5]=[CH:6][CH:7]=3)=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1
Reactant: CCCNc1nc(Nc2cccc(F)c2)ncc1C=O
Reactant: C[C@@H](C(=O)Nc1cccc(N)c1)N(C)C(=O)OC(C)(C)C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCCNc1nc(Nc2cccc(F)c2)ncc1CNc1cccc(NC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C)c1
Reaction time: 5 h
Yield: 68.4 %

Procedure:
To a solution of (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (B9, 28 mg) and 2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidine-5-carbaldehyde (E14, 24 mg) in methylene chloride (2 mL), sodium triacetoxyborohydride (28 mg) and acetic acid (50 μL) were added at room temperature, and the mixture was stirred at the same temperature for 5 hours. To the reaction mixture, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 60 to 0% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((3-(((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)methyl)amino)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (E18, 33 mg).
Reaction SMILES: [I:1][C:2]1[C:3]([S:11][C:12]2[N:20]=[C:19]3[C:15]([N:16]=[CH:17][NH:18]3)=[C:14](N)[N:13]=2)=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.[C:22]([O:25][C:26]([CH3:35])([CH3:34])[C:27]([NH:29][CH2:30][CH2:31][CH2:32]Br)=[O:28])(=[O:24])[CH3:23].C([O-])([O-])=O.[Cs+].[Cs+].C[N:43](C=O)C>>[C:22]([O:25][C:26]([CH3:35])([CH3:34])[C:27]([NH:29][CH2:30][CH2:31][CH2:32][N:20]1[C:12]([S:11][C:3]2[C:2]([I:1])=[CH:10][C:6]3[O:7][CH2:8][O:9][C:5]=3[CH:4]=2)=[N:13][C:14]2[C:19]1=[N:18][CH:17]=[N:16][C:15]=2[NH2:43])=[O:28])(=[O:24])[CH3:23]
Reactant: CC(=O)OC(C)(C)C(=O)NCCCBr
Reactant: Nc1nc(Sc2cc3c(cc2I)OCO3)nc2[nH]cnc12
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CC(=O)OC(C)(C)C(=O)NCCCn1c(Sc2cc3c(cc2I)OCO3)nc2c(N)ncnc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 22 %

Procedure:
To a solution of 8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio-9H-purin-6-amine (59 mg, 0.14 mmol) in DMF (1.5 mL) was added 1-((3-bromopropyl)amino)-2-methyl-1-oxopropan-2-yl acetate (120 mg, 0.48 mmol) and Cs2CO3 (93 mg, 0.28 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was condensed under vacuum and the residue was purified by Prep TLC (CH2Cl2:NH3-MeOH (7N), 20:1) to yield WS57 as a white solid (19 mg, 22%). 1H NMR (600 MHz, CDCl3): δ 8.23 (s, 1H), 7.90 (t, J=6.0 Hz, 1H), 7.26 (s, 1H), 6.85 (s, 1H), 5.95 (s, 2H), 5.54 (br s, 2H), 4.21 (t, J=5.9 Hz, 2H), 2.93-2.99 (m, 2H), 2.08 (s, 3H), 1.83-1.90 (m, 2H), 1.59 (s, 6H); HRMS (ESI) m/z [M+H]+ calcd. for C21H24IN6O5S, 599.0574. found 599.0579.
Reaction SMILES: I[C:2]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:18][C:19]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:20]=1[NH2:21].CN1CCOCC1.Cl>[Cu].C(OCC)(=O)C.CN(C)C=O>[F:18][C:19]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:20]=1[NH:21][C:2]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: Nc1ccc(F)cc1F
Reactant: O=C(O)c1ccc(Oc2ccccc2)cc1I
Agent: [Cu]
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: O=C(O)c1ccc(Oc2ccccc2)cc1Nc1ccc(F)cc1F
Temperature: 100 °C
Reaction time: 5 h

Procedure:
To N,N-dimethylformamide 15 mL solution of 2-iodo-4-phenoxybenzoic acid 1.5 g, were added 2,4-difluoroaniline 0.67 mL, copper powder 0.084 g and N-methylmorpholine 1.2 mL, and it was stirred at 100° C. for 5 hours. After the reaction mixture was cooled to room temperature,1.0 mol/L hydrochloric acid and ethyl acetate were added to it. The organic layer was separated and collected,dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [eluent; hexane:ethyl acetate=2:1] to give 2-(2,4-difluoroanilino)-4-phenoxybenzoic acid 0.60 g of white solid.
Reaction SMILES: [F:1][C:2]([F:30])([CH:8](OC(C(C1NC=CN=1)=O)=S)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[F:1][C:2]([F:30])([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCCCCCCCCCCC(OC(=S)C(=O)c1ncc[nH]1)C(F)(F)C(=O)OCC
Agent: CCCC[SnH](CCCC)CCCC
Solvent: Cc1ccccc1
Product: CCCCCCCCCCCCC(F)(F)C(=O)OCC
Yield: 77.5 %

Procedure:
Ethyl bromodifluoroacetate (6.0 g) and dodecyl aldehyde (1.84 g) were mixed with anhydrous tetrahydrofuran (40 ml) under argon atmosphere, and the solution was added dropwise to a suspension of zinc powder (2.2 g) and copper bromide (I) (0.22 g) in anhydrous tetrahydrofuran (40 ml) which was heated to a refluxing temperature. The mixture, after heating under reflux for 5 hours, was cooled and concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 20:1 to 10:1) to give ethyl 2,2-difluoro-3-hydroxytetradecanoate (0.92 g). After the mixture of ethyl 2,2-difluoro-3-hydroxytetradecanoate (0.92 g) and 1,1'-thiocarbonyl imidazole (1.26 g) in 1,2-dichloroethane was heated under reflux for 1 hour, it was cooled and concentrated. The residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 30:1 to 10:1) to give ethyl 2,2-difluoro-3-imidazoylthiocarbonyloxytetradecanoate (1.32 g). To a solution of ethyl 2,2-difluoro-3-imidazoylthiocarbonyloxytetradecanoate (1.32 g) dissolved in toluene (40 ml) under argon atmosphere, which was heated under reflux, was added dropwise a solution of tri-n-butyltin hydride (2.93 ml) in toluene (70 ml). The mixture, after heating under reflux for 2 hours, was concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 300:1 to 50:1) to give ethyl 2,2-difluorotetradecanoate (0.67 g). To a solution of ethyl 2,2-difluorotetradecanoate (489 mg) in N,N-dimethylformamide (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (300 mg) and triethylamine (1.5 ml). The mixture was stirred for 12 hours. After the solvent was evaporated, the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol-water (from 8.5:1:0.05 to 7:1:0.05) to give SPK182 in the yield of 95 mg.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[Cl:26])[C:5]([NH:7][C:8]1[CH:9]=[N:10][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21]Cl)=[CH:17][CH:16]=2)=[CH:12][CH:13]=1)=[O:6].C(N(CC)CC)C.[NH:34]1[CH2:39][CH2:38][S:37][CH2:36][CH2:35]1.Cl>CN(C=O)C.C(OCC)(=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[Cl:26])[C:5]([NH:7][C:8]1[CH:9]=[N:10][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][N:34]3[CH2:39][CH2:38][S:37][CH2:36][CH2:35]3)=[CH:17][CH:16]=2)=[CH:12][CH:13]=1)=[O:6]
Reactant: O=C(Nc1ccc(Oc2ccc(CCl)cc2)nc1)c1ccc(Cl)c(Cl)c1
Reactant: C1CSCCN1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(Nc1ccc(Oc2ccc(CN3CCSCC3)cc2)nc1)c1ccc(Cl)c(Cl)c1
Temperature: 40 °C
Reaction time: 8 h

Procedure:
3,4-dichloro-N-[6-(4-chloromethylphenoxy)-pyridin-3-yl]benzamide (0.61 g, 1.5 mmol) was dissolved in DMF (5 mL). To the resulting solution were added triethylamine (0.84 mL, 6.0 mmol) and thiomorpholine (0.15 mL, 1.5 mmol), and this solution was stirred overnight at 40° C. The resulting reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate and washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate and evaporated. This residue was purified by silica gel column chromatography (chloroform:methanol=80:1). The obtained solid (0.56 g, 1.18 mmol) was dissolved in ethyl acetate (50 mL), and a solution of 4 N hydrogen chloride in ethyl acetate (0.295 mL, 1.18 mmol) was added, and this solution was stirred for 1 hour at room temperature. The precipitated crystals were collected by suction filtration, and recrystallized from methanol, to thereby yield 0.38 g of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH2:12][CH3:13])[N:8]=[C:7]2[C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(N(CC)C(C)C)(C)C.[C:30](Cl)(=[O:33])[CH2:31][CH3:32].O>C(Cl)Cl>[C:30]([O:20][C:17]1[CH:16]=[CH:15][C:14]([C:7]2[C:6]3[C:10](=[C:2]([Cl:1])[CH:3]=[CH:4][CH:5]=3)[N:9]([CH2:11][CH2:12][CH3:13])[N:8]=2)=[CH:19][CH:18]=1)(=[O:33])[CH2:31][CH3:32]
Reactant: CCC(=O)Cl
Reactant: CCCn1nc(-c2ccc(O)cc2)c2cccc(Cl)c21
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCn1nc(-c2ccc(OC(=O)CC)cc2)c2cccc(Cl)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 88.3 %

Procedure:
To a solution of 4-(7-chloro-1-propyl-1H-indazol-3-yl)phenol (0.100 g, 0.35 mmol) and N,N-diisopropylethyl amine (0.5 g, 0.38 mmol) in CH2Cl2 (5 mL) was added dropwise propionyl chloride (0.035 g, 0.38 mmol). The solution was allowed to stir overnight at room temperature. Water was added and the solution was extracted with CH2Cl2. The organic layer was washed with brine and dried (MgSO4). The product was purified by flash chromatography (5/1 hexane/ethyl acetate) to yield a white solid (0.106 g, 88%).
Reaction SMILES: C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[Cl:12][C:13]1[CH:27]=[CH:26][C:16]([C:17]([NH:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:18])=[C:15]([CH2:28][CH2:29]O)[CH:14]=1.C(N(CC)CC)C.CO>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:12][C:13]1[CH:14]=[C:15]2[C:16](=[CH:26][CH:27]=1)[C:17](=[O:18])[N:19]([CH:20]1[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1)[CH2:29][CH2:28]2
Reactant: O=C(NC1CCOCC1)c1ccc(Cl)cc1CCO
Agent: CN(C)c1ccncc1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1c2ccc(Cl)cc2CCN1C1CCOCC1
Reaction time: 8 h
Yield: 9.4 %

Procedure:
A round bottomed flask was charged with p-toluenesulfonyl chloride (1.85 g, 9.7 mmol, 2.2 equiv.) and 40 mL of DCM. The solution was cooled to an ice-water bath and evacuated and purged with nitrogen. To this solution was added a solution of 4-chloro-2-(2-hydroxy-ethyl)-N-(tetrahydro-pyran-4-yl)-benzamide (1.25 g, 4.4 mmol, 1 equiv.) in 40 mL of DCM, followed by triethylamine (1.5 ml, 11 mmol, 2.5 equiv.) and a few crystals of DMAP. The solution was stirred under nitrogen overnight from 0° C. to rt. TLC (5% MeOH in DCM for SM) showed the reaction was almost complete. LC/MS: 266 at 2.050 min; SM of 284 at 2.35 min. The reaction was quenched by addition of 1.6 g of polymer-supported ethyleneamine and stirred for 30 min. The reaction solution was filtered through a Celite pad, rinsed with DCM and concentrated to dryness. The residue was re-dissolved in 30 mL of DCM, washed with 10 mL of NaHCO3 aq. The aqueous layer was extracted with DCM (3×5 mL). The combined organic solutions were washed with brine (5 mL), dried (K2CO3), filtered and concentrated. The crude product was purified on a 50-g silica gel column, eluted with 2.5% 7N NH3 of MeOH in DCM to get 110 mg (10% yield) of the title compound as a light yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([OH:14])=O)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Br:15][C:16]1[CH:17]=[C:18]([CH2:24][CH2:25][NH2:26])[CH:19]=[CH:20][C:21]=1[O:22][CH3:23]>>[Br:15][C:16]1[CH:17]=[C:18]([CH2:24][CH2:25][NH:26][C:12]([C:8]2([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:9][CH2:10][CH2:11]2)=[O:14])[CH:19]=[CH:20][C:21]=1[O:22][CH3:23]
Reactant: O=C(O)C1(c2ccc(Cl)cc2)CCC1
Reactant: COc1ccc(CCN)cc1Br
Product: COc1ccc(CCNC(=O)C2(c3ccc(Cl)cc3)CCC2)cc1Br

Procedure:
Prepared from 1-(4-chlorophenyl)cyclobutanecarboxylic acid and 2-(3-bromo-4-methoxyphenyl)ethanamine following the procedure described in example 85, step 1.
Reaction SMILES: [CH2:1]([O:5][C:6]([C:8]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:11]2[C:20]([CH3:23])=[N:21][S:22][C:10]=2[C:9]=1[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[O:7])[CH2:2][CH2:3][CH3:4].[Br:31]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:1]([O:5][C:6]([C:8]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:11]2[C:20]([CH2:23][Br:31])=[N:21][S:22][C:10]=2[C:9]=1[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)c1nc(-c2ccccc2)c2c(C)nsc2c1OC(=O)C(C)(C)C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCOC(=O)c1nc(-c2ccccc2)c2c(CBr)nsc2c1OC(=O)C(C)(C)C
Temperature: 25 °C
Yield: 85.7 %

Procedure:
To a solution of 7-(2,2-dimethyl-propionyloxy)-3-methyl-4-phenyl-isothiazolo[4,5-c]pyridine-6-carboxylic acid butyl ester (392 mg) in CCl4 (1.8 mL) was added N-bromosuccinimide (172 mg) and benzoyl peroxide (11.1 mg). The reaction mixture was refluxed for 18 h. After cooling to r.t. the mixture was filtered. The filtrate was concentrated in vacuo and purified by flash chromatography on silica gel. Eluting with 0-20% EtOAc/CH2Cl2 gave the title compound (398 mg) as a yellow oil: MS (m/z) 505.1 (M+1), 507.1 (M+1).
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:23]2[CH2:28][CH2:27][CH:26]([CH2:29][NH:30]C(=O)OC(C)(C)C)[CH2:25][CH2:24]2)[C:5]2[C:10]([C:11]#[N:12])=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:6]=2[N:7]=1.[NH2:38][C:39]1[CH:44]=[CH:43][C:42]([N:45]2[CH2:50][CH2:49][N:48]([C:51](=[O:53])[CH3:52])[CH2:47][CH2:46]2)=[CH:41][CH:40]=1.C[Si](Cl)(C)C>CCCCO>[C:51]([N:48]1[CH2:47][CH2:46][N:45]([C:42]2[CH:43]=[CH:44][C:39]([NH:38][C:2]3[N:3]=[C:4]([N:23]4[CH2:24][CH2:25][CH:26]([CH2:29][NH2:30])[CH2:27][CH2:28]4)[C:5]4[C:10]([C:11]#[N:12])=[CH:9][NH:8][C:6]=4[N:7]=3)=[CH:40][CH:41]=2)[CH2:50][CH2:49]1)(=[O:53])[CH3:52]
Reactant: CC(=O)N1CCN(c2ccc(N)cc2)CC1
Reactant: Cc1ccc(S(=O)(=O)n2cc(C#N)c3c(N4CCC(CNC(=O)OC(C)(C)C)CC4)nc(Cl)nc32)cc1
Agent: C[Si](C)(C)Cl
Solvent: CCCCO
Product: CC(=O)N1CCN(c2ccc(Nc3nc(N4CCC(CN)CC4)c4c(C#N)c[nH]c4n3)cc2)CC1
Yield: 16 %

Procedure:
A mixture of tert-butyl (1-(2-chloro-5-cyano-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methylcarbamate (180 mg, 0.330 mmol), 1-(4-(4-aminophenyl)piperazin-1-yl)ethanone (137 mg, 0.625 mmol) and trimethylsilyl chloride (0.300 mL, 2.37 mmol) in n-BuOH (5 mL) was stirred at 135° C. for 40 h. n-BuOH was removed in vacuo. The residue was purified by HPLC to give the titled compound (25 mg). MS 474.5 (M+H); UV 200.8, 277.8 nm.
Reaction SMILES: S([C:11]1[C:24]2[C:23](=[O:25])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:26])[C:15]=2[C:14]([S:27]([C:30]2[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=2)(=[O:29])=[O:28])=[CH:13][CH:12]=1)(C1C=CC(C)=CC=1)(=O)=O.[CH:37]([NH2:40])([CH3:39])[CH3:38]>>[CH:37]([NH:40][C:11]1[C:24]2[C:23](=[O:25])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:26])[C:15]=2[C:14]([S:27]([C:30]2[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=2)(=[O:28])=[O:29])=[CH:13][CH:12]=1)([CH3:39])[CH3:38]
Reactant: Cc1ccc(S(=O)(=O)c2ccc(S(=O)(=O)c3ccc(C)cc3)c3c2C(=O)c2ccccc2C3=O)cc1
Reactant: CC(C)N
Product: Cc1ccc(S(=O)(=O)c2ccc(NC(C)C)c3c2C(=O)c2ccccc2C3=O)cc1
Yield: 76 %

Procedure:
1-(isopropylamino)-4-tosylanthraquinone was prepared by reaction of 1,4-ditosylanthraquinone with isopropyl amine. The isolated and purified reaction product has the structure illustrated below (where "Ts" is ##STR9## The yield was 76% and the m.p. 164°-165.5° C.; mass spec m/e 435 (M+), 420 (M-CH3), 280 (M-C7H7SO2), 238(280-C3H7 +H), 210 (238-CO), 182 (210-CO), 155 (C7H7SO2), 91 (C7H7); 1H-NMR (CD2Cl2)δ9.97 (br s, 1H), 8.19-8.10 (m, 2H), 7.85-7.67 (m, 4H), 7.27-6.97 (m, 4H), 4.02-3.68 (m, 1H), 2.30 (s, 3H), 1.38, 1.31 (d, 6H); IR (Nujol) 1180 cm-1 (symmetrical SO2 stretch), 890 cm-1, 860, 820, 780 (S--O--C stretch); UV/VIS max (Xylenes) 500 nm (ε6660).
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[CH2:6][N:7]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:9]3[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:10]=3[C:11]=2[N:12]=1.[CH3:25][NH2:26]>CN(C)C=O>[Cl:17][C:15]1[CH:14]=[CH:13][C:10]2[C:11]3[N:12]=[C:2]([NH:26][CH3:25])[N:3]=[CH:4][C:5]=3[CH2:6][N:7]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:9]=2[CH:16]=1
Reactant: CN
Reactant: Fc1ccccc1C1=NCc2cnc(Cl)nc2-c2ccc(Cl)cc21
Solvent: CN(C)C=O
Product: CNc1ncc2c(n1)-c1ccc(Cl)cc1C(c1ccccc1F)=NC2
Temperature: 0 °C
Reaction time: 64 h

Procedure:
A solution of 1 g(0.00279 mol) of 2,9-dichloro-7-(2-fluorophenyl)-5H-pyrimido[5,4-d][2]benzazepine in 4 ml of N,N-dimethylformamide was cooled in an ice bath and saturated with methylamine. After 64 hr at room temperature, 50 ml of ice water was added and the reaction was filtered. The precipitated was partitioned between 50 ml ofdichloromethane and 50 ml of water, and the organic layer was washed with 25 ml of brine solution, dried and evaporated to dryness. The oil was crystallized from ether and then recrystallized from dichloromethane/ether and then from methanol to give the end product as white prisms, mp 172°-179°.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([OH:12])=O)[CH:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:44]([C:48]1[CH:65]=[CH:64][C:51]([CH2:52][NH:53][CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([Cl:63])[CH:57]=2)=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C.O>[C:44]([C:48]1[CH:65]=[CH:64][C:51]([CH2:52][N:53]([CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([Cl:63])[CH:57]=2)[C:10]([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[NH:1][CH:2]=[CH:3]3)=[O:12])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
Reactant: CC(C)(C)c1ccc(CNCCc2ccc(Cl)c(Cl)c2)cc1
Reactant: O=C(O)c1cccc2cc[nH]c12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(CN(CCc2ccc(Cl)c(Cl)c2)C(=O)c2cccc3cc[nH]c23)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 95.2 %

Procedure:
To a solution of 48 mg (0.3 mmol) of 1H-indole-7-carboxylic acid and 96 mg of TBTU (0.3 mmol) in 4 ml DMF, were added 0.26 ml (1.5 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 95 mg (0.3 mmol) (4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amine in 1 ml DMF was added. After 1.5 h stirring at rt, the reaction mixture was diluted with 50 ml water and extracted with 2×50 ml EtOAc. The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The yellow solid foam was purified by column chromatography (8 g silica gel; heptane/EtOAc 9:1) to give 137 mg (94%) of a white solid. MS (ISP) 479.5 (M+H)+.
Reaction SMILES: [OH:1][CH:2](CO)[CH2:3][C@H:4]([NH:15][C:16]([C:18]1[C:19]2[CH:26]=[N:25][N:24]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:20]=2[CH:21]=[N:22][CH:23]=1)=[O:17])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:6]=1>CC(C)=O.O>[CH3:14][S:11]([C:7]1[CH:6]=[C:5]([C@@H:4]([NH:15][C:16]([C:18]2[C:19]3[CH:26]=[N:25][N:24]([C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)[C:20]=3[CH:21]=[N:22][CH:23]=2)=[O:17])[CH2:3][CH:2]=[O:1])[CH:10]=[CH:9][N:8]=1)(=[O:13])=[O:12]
Reactant: CS(=O)(=O)c1cc([C@H](CC(O)CO)NC(=O)c2cncc3c2cnn3-c2ccc(F)cc2)ccn1
Solvent: O
Solvent: CC(C)=O
Product: CS(=O)(=O)c1cc([C@H](CC=O)NC(=O)c2cncc3c2cnn3-c2ccc(F)cc2)ccn1
Reaction time: 18 h

Procedure:
To a room temperature solution of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[(S)-3,4-dihydroxy-1-(2-methanesulfonyl-pyridin-4-yl)-butyl]-amide (0.710 g, 1.42 mmol) in acetone (18 mL) and water (9 mL) was added NaIO4 (608 mg, 2.84 mmol). After 18 hours, the mixture was filtered through diatomaceous earth washing with acetone (3×20 mL). The acetone was removed in vacuo and the aqueous layer was diluted with brine (50 mL) and extracted with EtOAc (3×50 mL). The combined organics layers were dried over magnesium sulfate, filtered, and evaporated to afford 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[(S)-1-(2-methanesulfonyl-pyridin-4-yl)-3-oxo-propyl]-amide as white solid which was used without purification.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([CH:11]1[CH2:16][CH2:15][NH:14][CH:13]([C:17](=[O:19])[NH2:18])[CH2:12]1)[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH2:30]([O:37][C:38](Cl)=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[CH2:30]([O:37][C:38]([N:14]1[CH2:15][CH2:16][CH:11]([C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:20])[CH2:9][CH3:10])[CH2:12][CH:13]1[C:17](=[O:19])[NH2:18])=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC[C@H](NC(=O)OC(C)(C)C)C1CCNC(C(N)=O)C1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@H](NC(=O)OC(C)(C)C)C1CCN(C(=O)OCc2ccccc2)C(C(N)=O)C1
Reaction time: 1 h

Procedure:
To a chilled (0° C.) solution of [(S)-1-(2-carbamoyl-piperidin-4-yl)-propyl]-carbamic acid tert-butyl ester (780 mg, 2.73 mmol) in methylene chloride (25 mL) was added DIPEA (0.41 mL, 2.9 mmol) followed by benzylchloroformate (723 μL, 4.1 mmol). After 1 hour, the reaction was diluted with dichloromethane (200 mL), washed with saturated ammonium chloride, brine, dried over sodium sulfate, filtered and concentrated to afford 4-((S)-1-tert-butoxycarbonylamino-propyl)-2-carbamoyl-piperidine-1-carboxylic acid benzyl ester.
Reaction SMILES: [NH3:1].C1(=O)CCCCC1.[H][H].[CH3:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[C:13]=1O>[Pd].O>[CH3:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[C:13]=1[NH2:1]
Reactant: N
Reactant: [H][H]
Reactant: Cc1cccc(C)c1O
Agent: [Pd]
Solvent: O
Solvent: O=C1CCCCC1
Product: Cc1cccc(C)c1N

Procedure:
Hydroxy aromatics are aminated to form the corresponding aromatic amine by reaction at 200°-400°C with ammonia in the presence of a cyclohexanone and water in contact with a hydrogen transfer catalyst. For example, 2,6-dimethylphenol reacts with ammonia in the presence of cyclohexanone, water and a supported palladium catalyst to form 2,6-dimethylaniline.