Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na:1].[CH2:2]([NH:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([OH:17])(=[O:16])=[O:15])=[CH:10][CH:9]=1)=[O:6])[CH3:3].[C:18](O)(=[O:23])[CH2:19][C:20](O)=[O:21].C(OC(=O)C)(=O)C>C(O)(=O)C>[CH2:2]([N:4]1[C:18](=[O:23])[CH2:19][C:20](=[O:21])[N:7]([C:8]2[CH:9]=[CH:10][C:11]([S:14]([OH:17])(=[O:15])=[O:16])=[CH:12][CH:13]=2)[C:5]1=[O:6])[CH3:3].[Na:1]
Reactant: O=C(O)CC(=O)O
Reactant: CCNC(=O)Nc1ccc(S(=O)(=O)O)cc1
Agent: [Na]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: CCN1C(=O)CC(=O)N(c2ccc(S(=O)(=O)O)cc2)C1=O
Temperature: 95 °C
Yield: 93.5 %

Procedure:
A mixture of 26.6 g of N-ethyl-N'-(4-sulfophenyl)urea sodium salt, 13.5 g of malonic acid and 150 ml of glacial acetic acid was heated and dissolved at 60° to 70° C. Acetic anhydride (200 ml) was added dropwise to the solution with stirring. After addition of the acetic anhydride, the temperature of the reaction solution increased to 95° C. The reaction solution was stirred for 6 hours and then condensed under reduced pressure so as to precipitate crystals. 700 ml of ethanol was added to the condensed solution and the crystals were completely precipitated. The precipitated crystals were collected by filtration, washed thoroughly with ethanol and dried by heating under reduced pressure to obtain 31.2 g of crystals. The crystals obtained were recrystallized using a 90% methanol aqueous solution and, thereby, 23.5 g of white crystals was obtained. Melting point: 290° C.
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)([CH3:15])[CH3:14])=[CH:9][CH:8]=2)=[CH:5][NH:4][N:3]=1.C([O:24][CH:25]=[C:26]([C:32](OCC)=O)[C:27]([O:29][CH2:30][CH3:31])=[O:28])C.C[O-].[Na+]>C(O)C>[CH2:30]([O:29][C:27]([C:26]1[CH:32]=[N:1][C:2]2[N:3]([N:4]=[CH:5][C:6]=2[C:7]2[CH:8]=[CH:9][C:10]([C:13]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)([CH3:15])[CH3:14])=[CH:11][CH:12]=2)[C:25]=1[OH:24])=[O:28])[CH3:31]
Reactant: CC(C)(c1ccccc1)c1ccc(-c2c[nH]nc2N)cc1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cnc2c(-c3ccc(C(C)(C)c4ccccc4)cc3)cnn2c1O
Reaction time: 24 h
Yield: 94.6 %

Procedure:
To a suspention of 3-amino-4-[4-(2-phenylpropan-2-yl)phenyl]pyrazole (920 mg) in ethanol (10 ml) was added diethyl ethoxymethylenemalonate (1.34 ml), and the mixture was heated and refluxed for 3 days. To the mixture was added sodium methoxide (540 mg) under ice-cooling, and the mixture was stirred for 1 day. Ethanol was distilled away under reduced pressure, and thereto was added water (50 ml) under ice-cooling. The mixture was adjusted to acid with 10% hydrochloric acid, and the precipitate was separated by filtration, washed with water to give the title compound (1.26 g, 94.6%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:11](Cl)(=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1>C1COCC1>[C:12]1([C:11]2[O:5][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=3[N:1]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Nc1ccccc1C(=O)O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: O=c1oc(-c2ccccc2)nc2ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2-amino benzoic acid (10 mmol) in THF was added benzoyl chloride (2.8 g, 20 mmol) followed by pyridine (1.58 g, 20 mmol). The mixture was stirred for 1 h at room temperature. The 2-phenyl-benzo[d][1,3]oxazin-4-one formed was filtered and the residue was washed with water and dried in vacuum desiccator.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:17])[NH:4][C:5](=[S:16])[N:6]([CH2:9][C:10]2[C:14]([CH3:15])=[N:13][O:12][N:11]=2)[C:7]=1[NH2:8].[C:18](O)(=O)C.C(N)=N>O>[CH3:15][C:14]1[C:10]([CH2:9][N:6]2[C:7]3[N:8]=[CH:18][NH:1][C:2]=3[C:3](=[O:17])[NH:4][C:5]2=[S:16])=[N:11][O:12][N:13]=1
Reactant: CC(=O)O
Reactant: Cc1nonc1Cn1c(N)c(N)c(=O)[nH]c1=S
Agent: N=CN
Solvent: O
Product: Cc1nonc1Cn1c(=S)[nH]c(=O)c2[nH]cnc21
Temperature: 25 °C
Yield: 14166.7 %

Procedure:
The title compound was prepared in accordance with the general method described in Example 12(d) by using 5,6-diamino-1-[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (0.41 g, 1.6 mmol, obtained from Example 16(c)) and formamidine acetate (0.25 g, 2.4 mmol) with the exception that after the reaction mixture had cooled to r.t., water (20 mL) was added. The cloudy solution was maintained at 5° C. o.n. and the precipitate that formed was collected by filtration, washed with water and methanol and dried. The material was further purified by recrystallization from DMSO/water to give the title compound (59.9 g, 14% yield).
Reaction SMILES: C([O:3][P:4]([CH2:9][CH2:10][NH:11][C:12](=[O:39])[CH2:13][CH2:14][C:15]([CH3:38])=[CH:16][CH2:17][C:18]1[C:19]([O:31]CC[Si](C)(C)C)=[C:20]2[C:24](=[C:25]([CH3:29])[C:26]=1[O:27][CH3:28])[CH2:23][O:22][C:21]2=[O:30])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C>C(#N)C>[OH:31][C:19]1[C:18]([CH2:17][CH:16]=[C:15]([CH3:38])[CH2:14][CH2:13][C:12]([NH:11][CH2:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[O:39])=[C:26]([O:27][CH3:28])[C:25]([CH3:29])=[C:24]2[C:20]=1[C:21](=[O:30])[O:22][CH2:23]2
Reactant: CCOP(=O)(CCNC(=O)CCC(C)=CCc1c(OC)c(C)c2c(c1OCC[Si](C)(C)C)C(=O)OC2)OCC
Agent: C[Si](C)(C)Br
Solvent: CC#N
Solvent: Cc1cccc(C)n1
Product: COc1c(C)c2c(c(O)c1CC=C(C)CCC(=O)NCCP(=O)(O)O)C(=O)OC2
Reaction time: 8 h
Yield: 21.5 %

Procedure:
To a solution of (2-{6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-ethyl)-phosphonic acid diethyl ester (36.6 mg, 0.063 mmol) in acetonitrile (1 mL) was added TMSBr (81 μL, 0.63 mmol) followed by 2,6-lutidine (73 μL, 0.63 mmol). The reaction was allowed to proceed overnight when it was completed as judged by LCMS. The reaction mixture was quenched with MeOH and concentrated to dryness. The residue was purified by preparative reverse-phase HPLC to afford 5.8 mg (29%) of desired product as a white solid. 1H NMR (300 MHz, CD3OD) δ 1.80 (s, 3H), 2.14 (m, 5H), 2.25 (m, 4H), 3.35 (m, 2H), 3.38-3.38 (m, 2H), 3.75 (s, 3H), 5.23 (s, 3H) ppm; 31p (121.4 MHz, CD3OD) δ 26.03 ppm; MS (m/z) 426 [M−H]−, 428 [M+H]+.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][C:16]=2[N+:25]([O-])=O)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H][H]>[Pd].CO>[Si:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:24])[F:23])=[CH:17][C:16]=2[NH2:25])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: [H][H]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1CCCN(c2ccc(C(F)(F)F)cc2[N+](=O)[O-])C1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)[Si](C)(C)O[C@@H]1CCCN(c2ccc(C(F)(F)F)cc2N)C1
Reaction time: 60 h

Procedure:
A 200 mL RBF was charged with (R)-3-(tert-butyldimethylsilyloxy)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine (4.10 g, 10.1 mmol) and palladium, 10 wt. % on activated carbon wet (0.179 ml, 2.03 mmol) under nitrogen. MeOH was added via syringe, and the atmosphere replaced with hydrogen via one or more balloons. The reaction was stirred rapidly for 60 h. The reaction was flushed with nitrogen, filtered through celite rinsing with 100 mL MeOH, and concentrated in vacuo. The crude material was treated with hexanes and passed through a Redi-Sep® pre-packed silica gel column (80 g) eluting with 0-40% EtOAc/hexane. The product-containing fractions were concentrated to afford (R)-2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)benzenamine as a brown oil. MS m/z=375 [M+H]+. Calc'd for C18H29F3N2OSi: 374.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23](C(OC(C)(C)C)=O)[CH:22]=[CH:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].O1CCOCC1.Cl.Cl.O1CCOCC1>CCOC(C)=O>[NH:23]1[C:24]2[C:20](=[CH:19][C:18]([C:15]3[N:14]=[C:13]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH:10]([CH3:12])[CH3:11])=[C:3]([CH:4]=4)[C:1]#[N:2])[O:17][N:16]=3)=[CH:26][CH:25]=2)[CH:21]=[CH:22]1
Reactant: CC(C)Oc1ccc(-c2nc(-c3ccc4c(ccn4C(=O)OC(C)(C)C)c3)no2)cc1C#N
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CC(C)Oc1ccc(-c2nc(-c3ccc4[nH]ccc4c3)no2)cc1C#N
Temperature: 25 °C
Reaction time: 8 h
Yield: 30 %

Procedure:
To a flask containing tert-butyl 5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1H-indole-1-carboxylate INT-67 (75 mg, 0.17 mmol) was added dioxane (2 mL) followed by 4N HCl in dioxane (0.5 mL, 2 mmol). The reaction mixture was stirred overnight at room temperature then heated at 50° C. overnight. Additional 4N HCl/dioxane (0.5 mL, 2 mmol) was added and the mixture was heated at 50° C. for an additional 2 h to complete the deprotection. The reaction mixture was diluted with EtOAc and washed with NaHCO3. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The material was purified by chromatography (EtOAc/hexanes) to provide 17 mg (30%) of 5-(3-(1H-indol-5-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 68 as a white solid. LCMS-ESI (m/z) calculated for C20H16N4O2: 344.5; found 345.1 [M+H]+, tR=2.34 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.51-8.47 (m, 1H), 8.45 (d, J=2.2 Hz, 1H), 8.38 (d, J=7.2 Hz, 1H), 8.35 (dd, J=8.9, 2.2 Hz, 1H), 7.99 (dd, J=8.5, 1.6 Hz, 1H), 7.51 (d, J=8.5 Hz, 1H), 7.33-7.28 (m, 1H), 7.11 (d, J=9.0 Hz, 1H), 6.72-6.64 (m, 1H), 4.79 (dt, J=12.2, 6.1 Hz, 1H), 1.47 (t, J=5.8 Hz, 6H).
Reaction SMILES: [C:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=S)#[N:2].C(N=C(NC1C=CC=CC=1)N[C@@H]1C2C=C(C#N)C=CC=2OC(C)(C)[C@H]1O)#N.[C:40]([C:43]1[CH:44]=[CH:45][C:46]2[O:51][C:50]([CH3:53])([CH3:52])[CH:49]([OH:54])[CH:48]([NH2:55])[C:47]=2[CH:56]=1)(=[O:42])[CH3:41].Cl.CN(C)CCCCCN=C=N>CN(C)C=O>[C:40]([C:43]1[CH:44]=[CH:45][C:46]2[O:51][C:50]([CH3:53])([CH3:52])[C@@H:49]([OH:54])[C@H:48]([NH:55][C:4]([NH:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:3][C:1]#[N:2])[C:47]=2[CH:56]=1)(=[O:42])[CH3:41]
Reactant: N#CNC(=S)Nc1ccccc1
Reactant: CC(=O)c1ccc2c(c1)C(N)C(O)C(C)(C)O2
Agent: CC1(C)Oc2ccc(C#N)cc2[C@@H](NC(=NC#N)Nc2ccccc2)[C@@H]1O
Agent: CN(C)CCCCCN=C=N
Agent: Cl
Solvent: CN(C)C=O
Product: CC(=O)c1ccc2c(c1)[C@@H](NC(=NC#N)Nc1ccccc1)[C@H](O)C(C)(C)O2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The solution of N-cyano-N'-phenylthiourea (0.98 g, 5.5 mmol, compound of Example 3, part A) and 6-acetyl-3,4-dihydro-2,2-dimethyl-3-hydroxy-4-amino-2H-1-benzopyran (1.0 g, 4.25 mmol, prepared according to Evans et al., J. Med. Chem., 1983, 26, 1582 and J. Med. Chem., 1986, 29, 2194) in dimethylformamide (6 ml) under argon was treated with 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride (1.1 g, 5.5 mmol). The reaction was stirred at room temperature for 2 hours and then partitioned between 10% citric acid and ethyl acetate. The aqueous phase was reextracted with ethyl acetate and the combined extracts were washed with water, sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the residue was crystallized from ethyl acetate to yield the title compound (0.43 g), m.p. 182°-184° C.: 1H NMR (DMSO-d6) δ 9.45 (s, 1H), 7.82 (m, 3H), 7.44 (s, 3H), 7.25 (s, 1H), 6.96 (d, J=9.0 Hz, 1H), 6.0 (s, 1H), 5.1 (m, 1H), 4.15 (m, 1H), 3.8 (s, 1H), 2.61 (s, 3H), 1.52 (s, 3H), 1.29 (s, 3H); 13C NMR (CDCl3) δ 196.2, 159.3, 156.6, 137.6, 129.7, 129.1, 128.4, 124.7, 123.5, 123.3, 117.2, 116.6, 80.0, 71.2, 52.3, 26.7, 26.3, 18.6; IR (KBr) 3412.3, 2978.3, 2935.8, 2179.7, 1670.5, 1602.9, 1577.9, 1493.0, 1359.9, 1271.2, 1126.5 cm-1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([CH3:15])[O:14][CH2:13][CH2:12][CH2:11][O:10]1.[H-].C([Al+]CC(C)C)C(C)C.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([O:10][CH2:11][CH2:12][CH2:13][OH:14])[CH3:15]
Reactant: COc1ccccc1C1(C)OCCCO1
Agent: CC(C)C[Al+]CC(C)C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccccc1C(C)OCCCO

Procedure:
The solution of 61.9 g of 2-(2-methoxyphenyl)-2-methyl-[1,3]dioxane in 450 ml of toluene is cooled to 0° C. with stirring and admixed at 0-10° C. with 487 ml of diisobutylaluminum hydride (1.5M in toluene) over 1 hour. The mixture is stirred over 2.5 hours and subsequently poured onto the stirred solution of 382 g of citric acid monohydrate in 2 l of water. The organic phase is removed and the water phase extracted with tert-butyl methyl ether (1 l). The organic phases are washed with brine (1 l), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.12 (1:2 EtOAc-heptane); Rt=3.56.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=1)=[O:5])[CH3:2].[I:16]N1C(=O)CCC1=O>ClCCl>[CH2:1]([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[I:16])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc(-c2cccs2)n[nH]1
Reactant: O=C1CCC(=O)N1I
Solvent: ClCCl
Product: CCOC(=O)c1[nH]nc(-c2cccs2)c1I
Temperature: 25 °C
Reaction time: 16 h

Procedure:
1.0 g (4.5 mmol) of 5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 15 ml of dichloromethane and 1.01 g (4.5 mmol) of N-iodosuccinimide was added. The resulting solution was stirred at room temperature for 16 h. The solution was washed with aqueous sodium thiosulfate solution. The organic phase was dried with sodium sulfate and filtered. The resulting solution was passed through a short silica gel column, washing with dichloromethane. The solvent was removed under reduced pressure.
Reaction SMILES: [C:1]([NH:4][C@@:5]1(O)[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][CH:6]1Cl)(=[O:3])[CH3:2].[CH3:26][CH2:27][O:28][C:29]1[CH:34]=[C:33]2[C:35]([CH3:41])=[CH:36][C:37]([CH3:40])([CH3:39])[NH:38][C:32]2=[CH:31][CH:30]=1>CC(C)=O>[C:1]([NH:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][CH:6]1[N:38]1[C:32]2[C:33](=[CH:34][C:29]([O:28][CH2:27][CH3:26])=[CH:30][CH:31]=2)[C:35]([CH3:41])=[CH:36][C:37]1([CH3:39])[CH3:40])(=[O:3])[CH3:2]
Reactant: CC(=O)N[C@]1(O)C(Cl)O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CCOc1ccc2c(c1)C(C)=CC(C)(C)N2
Solvent: CC(C)=O
Product: CCOc1ccc2c(c1)C(C)=CC(C)(C)N2C1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1NC(C)=O
Reaction time: 0.5 h
Yield: 63 %

Procedure:
2-Acetamido-3,4,6-tri-O-acetyl-D-glucopyranosyl chloride (18.3 g) and ethoxyquin (22.1 g) were vigourously stirred together at 80° for 3 hours. Acetone (50 ml) was added to the hot reaction mixture and stirring was continued for 0.5 hours. After cooling, the solid ethoxyquin-hydrochloride was filtered, washed with acetone and the combined filtrates were evaporated under reduced pressure. The crude product was purified by column chromatography on silica (ethylacetate-benzene 1:4). 16.5 g of 1-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranosyl)-6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline were obtained. Analytical grade sample was obtained by recrystallisation from ether or isopropanol. m.p. 186°-187°.
Reaction SMILES: [CH:1]([C:4]1[C:9]([C:10](OCC)=[O:11])=[C:8]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[C:7]([CH:22]=[CH:23][CH2:24][CH2:25][CH3:26])=[C:6]([CH:27]([CH3:29])[CH3:28])[N:5]=1)([CH3:3])[CH3:2]>C(OCC)(=O)C.CCCCCC>[CH:1]([C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)[C:7]([CH:22]=[CH:23][CH2:24][CH2:25][CH3:26])=[C:6]([CH:27]([CH3:28])[CH3:29])[N:5]=1)([CH3:3])[CH3:2]
Reactant: CCCC=Cc1c(C(C)C)nc(C(C)C)c(C(=O)OCC)c1-c1ccc(C)cc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCC=Cc1c(C(C)C)nc(C(C)C)c(CO)c1-c1ccc(C)cc1

Procedure:
The title compound was prepared from the intermediate obtained in Step A by the procedure described in Example 125, Step F. 1H NMR (300 MHz, CDCl3) (reported as a mixture of olefin isomers): δ 0.77 (t, J=7.0 Hz, 3 H), 1.1-1.3 (m, 15 H), 2.27 (m, 2 H), 2.42 (s, 3 H), 3.4 (m, 2 H), 4.34 (d, J=6.0 Hz, 2 H), 5.30-5.40 (m, 1 H), 5.90 (d, J=16.0 Hz, 1 H), 7.0 (d, J=8.0 Hz, 2 H), 7.18 (d, J=8.0 Hz, 2 H). FAB-MS: calculated for C24H33NO 352; found 352 (M+H, 100%). Rf=0.38 (10% ethyl acetate/n-hexane). mp 72-75° C.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([N:13]([CH2:21][C:22]([OH:24])=O)[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2].[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][NH:32][CH2:33][CH2:34][OH:35]>>[OH:35][CH2:34][CH2:33][N:32]([CH2:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=1)[C:22](=[O:24])[CH2:21][N:13]([S:10]([C:7]1[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][N:8]=1)(=[O:11])=[O:12])[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1
Reactant: OCCNCc1ccccn1
Reactant: Cc1ccc(N(CC(=O)O)S(=O)(=O)c2ccc(C(C)C)cn2)cc1
Product: Cc1ccc(N(CC(=O)N(CCO)Cc2ccccn2)S(=O)(=O)c2ccc(C(C)C)cn2)cc1

Procedure:
prepared by reaction of [(5-isopropyl-pyridine-2-sulfonyl)-p-tolyl-amino]-acetic acid with 2-[(pyridin-2-ylmethyl)-amino]-ethanol
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:19]([O-])([O-])=O.[Cs+].[Cs+].CI>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([N:13]([CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH3:19])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)c1cc(Br)cc(NC2CCCC2)c1C
Agent: [Cs+]
Solvent: CI
Solvent: CC#N
Product: COC(=O)c1cc(Br)cc(N(C)C2CCCC2)c1C
Temperature: 80 °C
Reaction time: 4 h

Procedure:
To a stirred solution of methyl 5-bromo-3-(cyclopentylamino)-2-methylbenzoate (0.5 g, 1.75 mmol) in acetonitrile (10 mL), Cs2CO3 (1.02 g, 2.63 mmol) and methyl iodide (1.45 g, 3.5 mmol) were added to it. The resulting reaction mixture was stirred at 80° C. for 4 h. Upon completion, the solvent was removed under reduced pressure and residue dissolved in water and extracted with ethyl acetate. Crude material obtained was purified by column chromatography over silica gel affording the desired compound product without further purification (0.39 g).
Reaction SMILES: FC(F)(F)[C:3](O)=[O:4].[CH3:8][CH:9]([S:11]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:28]3[C:23](=[C:24]([C:40]([NH2:42])=[O:41])[CH:25]=[C:26]([C:29]4[CH:33]=[C:32]([CH2:34][N:35]([CH3:39])[CH2:36][CH2:37]C)[S:31][CH:30]=4)[CH:27]=3)[NH:22][CH:21]=2)[CH2:16][CH2:15]1)(=[O:13])=[O:12])[CH3:10].CNCCC>>[CH3:10][CH:9]([S:11]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:28]3[C:23](=[C:24]([C:40]([NH2:42])=[O:41])[CH:25]=[C:26]([C:29]4[CH:33]=[C:32]([CH2:34][N:35]([CH3:39])[CH2:36][CH2:37][O:4][CH3:3])[S:31][CH:30]=4)[CH:27]=3)[NH:22][CH:21]=2)[CH2:16][CH2:15]1)(=[O:13])=[O:12])[CH3:8]
Reactant: CCCN(C)Cc1cc(-c2cc(C(N)=O)c3[nH]cc(C4CCN(S(=O)(=O)C(C)C)CC4)c3c2)cs1
Reactant: O=C(O)C(F)(F)F
Agent: CCCNC
Product: COCCN(C)Cc1cc(-c2cc(C(N)=O)c3[nH]cc(C4CCN(S(=O)(=O)C(C)C)CC4)c3c2)cs1
Yield: 69.4 %

Procedure:
The title compound was prepared according to the general procedure of 3-{1-[(1-methylethyl)sulfonyl]-4-piperidinyl}-5-(5-{[methyl(propyl)amino]methyl}-3-thienyl)-1H-indole-7-carboxamide trifluoroacetate, substituting methyl[2-(methyloxy)ethyl]amine (89 mg, 1.0 mmol) for methyl(propyl)amine to afford 37.0 mg of the title compound (69.4%).
Reaction SMILES: [C:1](=[O:41])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH:3]1[CH2:7][CH2:6][CH:5]([N:8]2[C:12]3[N:13]=[CH:14][N:15]=[C:16]([NH2:17])[C:11]=3[C:10]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:20][CH:19]=3)=[CH:9]2)[CH2:4]1.[O:42]1[CH2:47][CH2:46][N:45]([CH2:48][CH2:49][NH2:50])[CH2:44][CH2:43]1>ClCCl.C(OCC)(=O)C>[O:42]1[CH2:47][CH2:46][N:45]([CH2:48][CH2:49][NH:50][C:1](=[O:41])[O:2][CH:3]2[CH2:7][CH2:6][CH:5]([N:8]3[C:12]4[N:13]=[CH:14][N:15]=[C:16]([NH2:17])[C:11]=4[C:10]([C:18]4[CH:19]=[CH:20][C:21]([O:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[CH:22][CH:23]=4)=[CH:9]3)[CH2:4]2)[CH2:44][CH2:43]1
Reactant: Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2C1CCC(OC(=O)Oc2ccc([N+](=O)[O-])cc2)C1
Reactant: NCCN1CCOCC1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2C1CCC(OC(=O)NCCN2CCOCC2)C1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
3-[4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl (4-nitrophenyl) carbonate (0.052 mmol) in dichloromethane (1 ml) was added to 2-morpholinoethylamine (0.2 ml). The resulting mixture was stirred under nitrogen at ambient temperature for 24 hours. The reaction mixture was diluted with ethyl acetate and washed, dried (MgSO4), filtered and evaporated. The solid was purified by preparative HPLC to give 3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl N-(2-morpholinoethyl)carbamate. The structure was confirmed by 1H NMR and LC/MS (MH+=543).
Reaction SMILES: [C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].CC1(C)OC(=O)[CH:10]([C:14]([CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[C:9](=O)[O:8]1>C1(C)C=CC=CC=1>[C:1]([O:5][C:9](=[O:8])[CH2:10][C:14](=[O:15])[CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)O
Reactant: CC1(C)OC(=O)C(C(=O)C2CCOCC2)C(=O)O1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)CC(=O)C1CCOCC1
Yield: 97.5 %

Procedure:
tert-Butanol (600 ul, 6 mmol) was added to a solution of 2,2-dimethyl-5-(tetrahydro-pyran-4-carbonyl)-[1,3]dioxane-4,6-dione (1.1 g, 4 mmol) in toluene (9.6 ml). The reaction mixture was heated under reflux conditions for 6 h and partitioned between ice water/brine 1/1 and iPrOAc. The layers were separated and the aqueous layer was extracted one more time with iPrOAc. The combined extracts were washed with ice water/brine 1/1, dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give the title compound (891 mg, 3.9 mmol; 91%) as brown oil which was sufficiently pure to be used in the next reaction step. MS (EI): m/z=228 [M]+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[CH3:16][O:10][C:9](=[O:11])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=1
Reactant: CO
Reactant: O=C(O)Cc1cccc(O)c1
Solvent: O=S(Cl)Cl
Product: COC(=O)Cc1cccc(O)c1

Procedure:
To 3-hydroxyphenylacetic acid (5.07 g, 33.32 mmol) in MeOH (50 mL) was added thionyl chloride (4.85 mL, 66.65 mmol) dropwise over 30 minutes by addition funnel. Once no starting material was seen by analytical LCMS, the mixture was concentrated, and the residue was partitioned between EtOAc and 1N aqueous NaOH. The aqueous layer was extracted twice with EtOAc, and the combined organic layers were dried and concentrated to give the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:9])[CH:8]=1)[NH2:5].[NH:10]([C:17]1[C:30]2[C:29](=[O:31])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22](=[O:32])[C:21]=2[C:20](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[NH:10]([C:17]1[C:30]2[C:29](=[O:31])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22](=[O:32])[C:21]=2[C:20]([NH:5][C:4]2[CH:6]=[C:7]([CH3:9])[CH:8]=[C:2]([CH3:1])[CH:3]=2)=[CH:19][CH:18]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: Cc1cc(C)cc(N)c1
Reactant: Cc1ccc(S(=O)(=O)Oc2ccc(Nc3ccccc3)c3c2C(=O)c2ccccc2C3=O)cc1
Product: Cc1cc(C)cc(Nc2ccc(Nc3ccccc3)c3c2C(=O)c2ccccc2C3=O)c1
Yield: 56 %

Procedure:
1-anilino-4-(3,5-dimethylanilino)anthraquinone was prepared by reaction of 3,5-dimethylaniline with 1-(anilino)-4-tosyloxyanthraquinone. The isolated and purified reaction product has the structure illustrated below. ##STR15## The yield was 56% and m.p. 219.5°-220.5° C. Mass spectrum, m/e 418 (M+); 1H-NMR (CD2Cl2)δ12.20 (br s, 2H), 8.41-8.30 (m, 2H) 7.80-7.69 (m, 2H), 7.52-7.34 (m, 7H), 6.90 (br s, 3H), 2.32 (s, 6H); UV/VIS max (Xylenes) 404 nm (ε6 600), 600 (13 400), 641 (14 400).