Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:20])[C@@H:5]([O:18][CH3:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([OH:17])=O)=[CH:9][CH:8]=1)C.[C:21]1([CH:27]([NH2:29])[CH3:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(O[C@@H](CC1C=CC(O[C@@H](C(=O)NCCC2C=CC(OC3C=CC=CC=3)=CC=2)C)=CC=1)C(O)=O)C>>[CH3:19][O:18][C@@H:5]([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][C:15](=[O:17])[NH:29][CH:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH3:28])=[CH:11][CH:12]=1)[C:4]([OH:3])=[O:20]
Reactant: CCOC(=O)[C@H](Cc1ccc(OCC(=O)O)cc1)OC
Reactant: CC(N)c1ccccc1
Agent: CCO[C@@H](Cc1ccc(O[C@H](C)C(=O)NCCc2ccc(Oc3ccccc3)cc2)cc1)C(=O)O
Product: CO[C@@H](Cc1ccc(OCC(=O)NC(C)c2ccccc2)cc1)C(=O)O

Procedure:
The title compound was prepared from (2S)-3-(4-carboxymethoxy-phenyl)-2-methoxy-propionic acid ethyl ester (PREPARATION 3, step 2) and 1-phenyl-ethylamine via the same procedure used for the preparation of (2S,1R)-2-ethoxy-3-(4-{1-[2-(4-phenoxy-phenyl)-ethylcarbamoyl]-ethoxy}-phenyl)-propionic acid (Example 1, step 3) to produce a yellow oil. MS (ES) For C20H23NO5 [M+H]+: 358.
Reaction SMILES: CO[C:3](=O)[CH:4]([N:22]1[C:30](=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:32])[CH2:5][N:6]([CH2:12][CH2:13][NH:14]C(OC(C)(C)C)=O)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[OH2:34].[OH2:35].[OH-:36].[Li+]>O1CCCC1>[NH2:14][CH2:13][CH2:12][N:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:5][CH:4]([NH:22][C:23](=[O:32])[C:24]1[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:30]([OH:31])=[O:36])[C:3]([OH:35])=[O:34]
Reactant: O
Reactant: CCOC(=O)N(CCNC(=O)OC(C)(C)C)CC(C(=O)OC)N1C(=O)c2ccccc2C1=O
Reactant: [OH-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)N(CCN)CC(NC(=O)c1ccccc1C(=O)O)C(=O)O
Temperature: 65 °C
Reaction time: 1 h

Procedure:
To a solution of 218.80 g (470.35 mmol) of 3-[(2-tert-butoxycarbonylamino-ethyl)-ethoxycarbonyl-amino]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester dissolved in 600 mL of tetrahydrofuran was added 100 mL of water and 39.47 g (940.70 mmol) of lithium hydroxide monohydrate. The resulting mixture was heated at 65° C. for 2 h. 19.73 g (470.35 mmol) of lithium hydroxide monohydrate was added. The resulting mixture was stirred at 65° C. for 1 h. The mixture was evaporated to dryness. Toluene was added to the residue and evaporated to dryness to give 225.00 g of the desired compound as a lithium salt. To the resulting lithium salt (225.00 g) suspension in 1 L of dichloromethane was added slowly 500 mL of trifluoroacetic acid. The resulting mixture was stirred at room temperature for 2 h30 and evaporated to dryness. The residue was triturated with a mixture of diethyl ether/dichloromethane and filtered to afford 300.00 g (89%) of a powder. The compound was used as such in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[N:13][C:5]2[NH:6][C:7]3[CH2:12][CH2:11][NH:10][CH2:9][C:8]=3[C:4]=2[CH:3]=1.CCN(C(C)C)C(C)C.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]=[C:33]=[O:34])=[CH:28][CH:27]=1.Cl.CCOCC>C(Cl)Cl.CCOCC>[ClH:1].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([N:10]2[CH2:11][CH2:12][C:7]3[NH:6][C:5]4[N:13]=[CH:14][C:2]([Cl:1])=[CH:3][C:4]=4[C:8]=3[CH2:9]2)=[O:34])=[CH:28][CH:27]=1
Reactant: COc1ccc(N=C=O)cc1
Reactant: Clc1cnc2[nH]c3c(c2c1)CNCC3
Agent: Cl
Solvent: CCOCC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(NC(=O)N2CCc3[nH]c4ncc(Cl)cc4c3C2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 31.8 %

Procedure:
3-Chloro-6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3′,4′-d]pyrrole (50 mg, 0.24 mmol), and DIEA (0.04 mL, 0.24 mmol) were dissolved in DCM (2 mL). 4-Methoxyphenyl isocyanate (0.03 mL, 0.26 mmol) was added dropwise, and the reaction solution was stirred overnight at room temperature. The crude reaction mixture was concentrated, and converted to the HCl salt by dissolving the crude material in MeOH (2 ml) and adding 1 M HCl/ether (2 equiv). The resulting solution was refrigerated overnight. Additional ether was added to drive precipitate formation. The resulting precipitate was filtered and dried under vacuum to provide 27 (15 mg, 16% yield) as a yellow solid. LC-MS (M+H=359, obsd.=359).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1.[O:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[CH:17]=O.C[O-].[Na+].Cl>CO>[O:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[CH:17]=[CH:10][C:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:11]
Reactant: COc1ccc(C(C)=O)cc1
Reactant: O=Cc1ccco1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COc1ccc(C(=O)C=Cc2ccco2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 92.3 %

Procedure:
To a solution of 1-(4-methoxyphenyl)ethanone (17.0 g, 113.0 mmol) in methanol (240 mL) was added a solution of 2-furaldehyde (12.0 g, 125.0 mmol) in methanol (240 mL) followed by the addition of sodium methoxide (6.10 g, 113.0 mmol). The reaction mixture was stirred at room temperature for 24 h, and then was neutralized with HCl aq. (6.0 M, 18.8 mL). The volatile was removed in vacuum. The residue was dissolved in ethyl acetate (500 mL), washed with water (250 mL) and brine (250 mL), dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (PE:EA=5:1˜3:1) to afford 3-(furan-2-yl)-1-(4-methoxyphenyl)prop-2-en-1-one (25B) as a yellow solid (23.80 g, 92%).
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=4)[CH2:15][CH2:14]3)[CH:10]=[N:11][C:5]=2[N:4]2[CH2:28][CH2:29][CH2:30][C@@H:3]12.[CH3:31][CH2:32][N:33](C(C)C)C(C)C.C(N)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:32]([NH:33][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][C:19]([N:16]2[CH2:15][CH2:14][N:13]([CH2:12][C:9]3[CH:10]=[N:11][C:5]4[N:4]5[CH2:28][CH2:29][CH2:30][C@H:3]5[C:2](=[O:1])[NH:7][C:6]=4[CH:8]=3)[CH2:18][CH2:17]2)=[CH:20][CH:21]=1)[CH3:31]
Reactant: O=C(O)c1ccc(N2CCN(Cc3cnc4c(c3)NC(=O)[C@@H]3CCCN43)CC2)cc1
Reactant: CCN(C(C)C)C(C)C
Agent: CCN
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: CCNC(=O)c1ccc(N2CCN(Cc3cnc4c(c3)NC(=O)[C@@H]3CCCN43)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 30 %

Procedure:
(S)-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzoic acid (75.0 mg, 0.184 mmol) was suspended in DMF (1.0 mL) and DIPEA (0.15 mL) was added followed by ethylamine (30 mg, 0.665 mmol) and HATU (85.0 mg, 0.224 mmol). The reaction mixture was stirred at ambient temperature for 2 h and another portion of HATU (60.0 mg, 0.158 mmol) was added. The reaction mixture was stirred overnight and purified using HPCL (10-75% acetonitrile in water, NH4HCO3 buffered). The fractions were concentrated in vacuo and the resulting residue was crystallized with MeOH-water (1:10, 5 mL) to afford the title compound as a light green solid (24.0 mg, 30%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.09 (t, J=7.20 Hz, 3H) 1.85-2.01 (m, 3H) 2.18 (dt, J=5.37, 2.75 Hz, 1H) 2.43-2.48 (m, 4H) 3.18-3.28 (m, 6H) 3.35 (s, 2H) 3.37-3.45 (m, 1H) 3.54-3.67 (m, 1H) 3.94-4.05 (m, 1H) 6.92 (d, J=9.09 Hz, 2H) 6.99 (d, J=2.02 Hz, 1H) 7.62 (d, J=2.02 Hz, 1H) 7.71 (d, J=9.09 Hz, 2H) 8.17 (t, J=5.56 Hz, 1H) 10.44 (s, 1H); [M+H] calc'd for C24H30N6O2, 435; found, 435.
Reaction SMILES: Cl.[C:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH2:10])=[CH:7][CH:6]=1)(=[O:4])[CH3:3].C(N(CC)CC)C.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>ClCCl>[C:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:10][S:27]([C:24]2[CH:25]=[CH:26][C:21]([CH3:20])=[CH:22][CH:23]=2)(=[O:29])=[O:28])=[CH:7][CH:6]=1)(=[O:4])[CH3:3]
Reactant: CC(=O)c1ccc(CN)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)c1ccc(CNS(=O)(=O)c2ccc(C)cc2)cc1
Temperature: 4 °C
Reaction time: 0.25 h

Procedure:
To a stirred suspension under argon of 4-acetylbenzylamine hydrochloride (700 mg) in dichloromethane (20 ml) was added triethylamine (1.15 ml) and stirring continued for 15 minutes. The mixture was cooled to 4° C., then 4-methylphenylsulphonyl chloride (790 mg) in dichloromethanie (5 ml) added dropwise over 30 minutes. The reaction mixture was stirred for 18 hours at ambient temperature, then diluted with further dichloromethane (50 ml), washed with water, dried (MgSO4) and evaporated. Trituration of the residue gave N-([4-acetylphenyl]methyl)-4-methylphenysulphonamide (A), 1.02 g., as an off-white solid: m.p. 125°-128° C.; NMR (d6DMSO) δ 8.13(1H,t), 7.86(2H,d), 7.68(2H,d), 7.37(4H,dd), 4.03(2H,d), 2.55(3H,s), 2.39(3H,s); m/e 304(M+H)+.
Reaction SMILES: CNC([C@@H:5]1[C@@H:9]([O:10][Si](C(C)(C)C)(C)C)[C@@H:8]([O:18][Si](C(C)(C)C)(C)C)[C@H:7]([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][C:29]([Cl:37])=[N:30][C:31]=3[NH:35][CH3:36])[S:6]1)=O.[F-].[CH2:39]([N+:43]([CH2:52]CCC)(CCCC)CCCC)CCC.[O:56]1CCCC1>>[CH3:39][NH:43][C:52]([C:7]1([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][C:29]([Cl:37])=[N:30][C:31]=3[NH:35][CH3:36])[CH:8]([OH:18])[CH:9]([OH:10])[CH2:5][S:6]1)=[O:56]
Reactant: CNC(=O)[C@H]1S[C@@H](n2cnc3c(NC)nc(Cl)nc32)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Reactant: C1CCOC1
Agent: [F-]
Product: CNC(=O)C1(n2cnc3c(NC)nc(Cl)nc32)SCC(O)C1O
Temperature: 25 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
48 mg (0.08 mmol) of (2S,3S,4R,5R)-3,4-bis(tert-butyldimethylsilanyloxy)-5-(2-chloro-6-methylaminopurin-9-yl)-tetrahydrothiophene-2-carboxylic acid methyl amide were dissolved in anhydrous tetrahydrofuran to which 0.22 mL (0.22 mmol, 1M tetrahydrofuran solution) of tetrabutylammonium fluoride was added. The reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was distilled under reduced pressure and the concentrate was purified by silica gel column chromatography using the eluant (dichloromethane:methanol=6:1) to obtain 19 mg (yield: 65%) of (2S,3S,4R,5R)-5-(2-chloro-6-methylaminopurin-9-yl-3,4-dihydroxytetrahydrothiophene-2-carboxylic acid methyl amide as white solids (see Table 3).
Reaction SMILES: [CH2:1]([N:3]1[C:7]([CH:8]([CH3:10])[CH3:9])=[C:6]([CH2:11][CH2:12][N:13]([CH2:15][CH:16]([OH:25])[CH2:17][C:18]([O:20]C(C)(C)C)=[O:19])[OH:14])[C:5]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[C:4]1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:2].C(Cl)(Cl)[Cl:40].CO>>[ClH:40].[CH2:1]([N:3]1[C:7]([CH:8]([CH3:9])[CH3:10])=[C:6]([CH2:11][CH2:12][N:13]([CH2:15][CH:16]([OH:25])[CH2:17][C:18]([OH:20])=[O:19])[OH:14])[C:5]([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)=[C:4]1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:2]
Reactant: CCn1c(-c2ccccc2)c(-c2ccc(F)cc2)c(CCN(O)CC(O)CC(=O)OC(C)(C)C)c1C(C)C
Reactant: ClC(Cl)Cl
Solvent: CO
Product: CCn1c(-c2ccccc2)c(-c2ccc(F)cc2)c(CCN(O)CC(O)CC(=O)O)c1C(C)C
Product: Cl

Procedure:
The compound is obtained from the compound from Example 10 analogously to Example 8. Colorless foam Rf =0.2 (chloroform/methanol 5:1)
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:15]([NH:17][C:18]2[N:19]=[C:20]([C:24]([NH:26][C:27]3[CH:28]=[C:29]([C:33]([NH:35][C:36]4[CH:37]=C(C(O)=O)[N:39]([CH3:41])[CH:40]=4)=[O:34])[N:30]([CH3:32])[CH:31]=3)=[O:25])[N:21]([CH3:23])[CH:22]=2)=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.Cl.[C:50](=[O:58])([S:52][CH2:53][CH2:54]CNC)[CH3:51].[CH3:59][C:60]([N:62]([CH3:64])[CH3:63])=[O:61]>>[C:50](=[O:58])([S:52][CH2:53][CH2:54][CH2:63][N:62]([CH3:64])[C:60]([C:59]1[N:39]([CH3:41])[CH:40]=[C:36]([NH:35][C:33]([C:29]2[N:30]([CH3:32])[CH:31]=[C:27]([NH:26][C:24]([C:20]3[N:21]([CH3:23])[CH:22]=[C:18]([NH:17][C:15]([C:11]4[N:12]([CH3:14])[CH:13]=[C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:10]=4)=[O:16])[N:19]=3)=[O:25])[CH:28]=2)=[O:34])[CH:37]=1)=[O:61])[CH3:51]
Reactant: CNCCCSC(C)=O
Reactant: CC(=O)N(C)C
Reactant: Cn1cc(NC(=O)c2cc(NC(=O)c3nc(NC(=O)c4cc(NC(=O)OC(C)(C)C)cn4C)cn3C)cn2C)cc1C(=O)O
Agent: Cl
Solvent: ClCCCl
Product: CC(=O)SCCCN(C)C(=O)c1cc(NC(=O)c2cc(NC(=O)c3nc(NC(=O)c4cc(NC(=O)OC(C)(C)C)cn4C)cn3C)cn2C)cn1C
Reaction time: 24 h
Yield: 64 %

Procedure:
4-(4-(4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylic acid (256 mg, 0.42 mmol), NHS (60 mg, 0.52 mmol) and EDC (500 mg, 2.60 mmol) in 4 ml of DMA were stirred under Ar for 2 h, then S-3-(methylamino)propyl ethanethioate hydrogen chloride salt (76.5 mg, 0.42 mmol) was added and the mixture was kept stirring for 24 h, evaporated and purified on SiO2 chromatography eluted with THF/DCM (1:5 to 1:4) to afford 198 mg (64%) of the title compound. 1H NMR (DMSO) 10.21 (s, 1H), 10.09 (s, 1H), 10.06 (s, 1H), 9.08 (s, 1H), 7.76 (d, 1H, J=1.7 Hz), 7.52 (s, 1H), 7.28 (s, 1H), 7.21 (d, 1H, J=1.7 Hz), 6.97 (s, 1H), 6.87 (s, 1H), 3.98 (s, 1H), 3.86 (s, 3H), 3.75 (s, 3H), 3.73 (s, 3H), 3.66 (m, 2H), 2.85 (s, 3H), 2.60 (m, 2H), 2.01 (s, 3H), 1.45 (s, 9H); 13C NMR 173.31, 162.16, 160.05, 159.90, 157.20, 154.31, 137.88, 135.35, 124.56, 124.39, 123.51, 123.09, 121.76, 120.09, 119.83, 118.96, 115.32, 109.53, 105.58, 102.27, 79.32, 43.67, 38.13, 36.02, 35.81, 34.88, 31.84, 28.79, 28.26, 28.21, 27.01; MS m/z+759.2 (M+Na).
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:5]=1[C:6](=[O:19])[CH:7]1[CH:12]([C:13]2=[O:18])[CH2:11][CH:10]=[CH:9][CH2:8]1)([O-])=O.N1C=CC=CC=1.S>O>[NH2:1][C:4]1[C:5]2[C:6](=[O:19])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13](=[O:18])[C:14]=2[CH:15]=[CH:16][CH:17]=1
Reactant: O=C1c2cccc([N+](=O)[O-])c2C(=O)C2CC=CCC12
Agent: S
Solvent: c1ccncc1
Solvent: O
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Temperature: 90 °C
Reaction time: 2 h

Procedure:
A mixture of 5.0 parts of 5-nitro-1,4,4a,9a-tetrahydroanthraquinone with 50 parts of pyridine was stirred at 90°C for 2 hours with introducing thereinto 0.8 parts/hour of gaseous hydrogen sulfide. The reaction mixture was then cooled to 25°C and added with 50 parts of water to precipitate crystals. The crystals were recovered by filtration, washed with water and dried under reduced pressure to obtain 3.9 parts of 1-aminoanthraquinone.
Reaction SMILES: [Cl:1][C:2]1[O:12][C:5]2=[C:6]([NH2:11])[N:7]=[CH:8][C:9](I)=[C:4]2[CH:3]=1.[Si:13]([O:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([N:27]2[CH:31]=[C:30](B(O)O)[CH:29]=[N:28]2)[CH2:23][CH2:22]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[Si:13]([O:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([N:27]2[CH:31]=[C:30]([C:9]3[CH:8]=[N:7][C:6]([NH2:11])=[C:5]4[O:12][C:2]([Cl:1])=[CH:3][C:4]=34)[CH:29]=[N:28]2)[CH2:23][CH2:22]1)([C:16]([CH3:19])([CH3:17])[CH3:18])([CH3:15])[CH3:14]
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](n2cc(B(O)O)cn2)CC1
Reactant: Nc1ncc(I)c2cc(Cl)oc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](n2cc(-c3cnc(N)c4oc(Cl)cc34)cn2)CC1
Temperature: 70 °C

Procedure:
A mixture of 2-chloro-4-iodo-furo[2,3-c]pyridin-7-ylamine (2 g, 7 mmol), [1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]boronic acid (2.75 g, 8.49 mmol), (1,1′bis-(diphenylphosphino)-ferrocene)palladium dichloride (248 mg, 0.340 mmol) and potassium carbonate (2.35 g, 17.0 mmol) in 1,4-dioxane (20 mL) and water (9.5 mL) was heated to 70° C. for 22 h. The mixture was partitioned between ethyl acetate and water and the aqueous phase extracted with DCM. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Purification by ISCO chromatography (10% to 50% ethyl acetate:heptane) followed by trituration with ether:heptane afforded 2.0 g (60%) of the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1 H), 7.76-7.69 (m, 1 H), 7.62 (s, 1 H), 6.73 (s, 1 H), 4.73 (s, 2 H), 4.17 (tt, J=3.9, 11.6 Hz, 1 H), 3.73 (tt, J=4.3, 10.5 Hz, 1 H), 2.23 (d, J=12.1 Hz, 2 H), 2.09-1.99 (m, 2 H), 1.91 (dq, J=3.5, 11.9 Hz, 2 H), 1.61-1.48 (m, 2 H), 0.92 (s, 9 H), 0.10 (s, 6 H); MS (ESI): 447.39, 449.35 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:5][C:4](=[O:13])[CH:3]=1.[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[CH2:33][CH2:34][NH:35][C:36](=[O:38])[CH3:37]>>[OH:1][C:2]1[CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:5][C:4](=[O:13])[C:3]=1[CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:28]1[NH:29][C:30]2[C:26]([C:27]=1[CH2:33][CH2:34][NH:35][C:36](=[O:38])[CH3:37])=[CH:25][C:24]([O:23][CH3:22])=[CH:32][CH:31]=2
Reactant: O=C1C=C(O)C(c2ccccc2)C1
Reactant: O=Cc1ccccc1
Reactant: COc1ccc2[nH]cc(CCNC(C)=O)c2c1
Product: COc1ccc2[nH]c(C(C3=C(O)C(c4ccccc4)CC3=O)c3ccccc3)c(CCNC(C)=O)c2c1

Procedure:
Using general procedure C, 3-hydroxy-4-phenyl-cyclopent-2-enone (Lit. 17) was reacted with benzaldehyde and N-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-acetamide to give the title compound as a pale red solid. MS: 495.4 ([M+H]+).
Reaction SMILES: [Br:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([S:11](=[O:14])(=[O:13])[NH2:12])[C:8]([Cl:15])=[CH:7][C:6]=1[Cl:16])=[O:4].[CH:17]1([NH:20][C:21]([NH:23][CH:24]2[CH2:26][CH2:25]2)=[S:22])[CH2:19][CH2:18]1>>[BrH:1].[Cl:16][C:6]1[CH:7]=[C:8]([Cl:15])[C:9]([S:11](=[O:14])(=[O:13])[NH2:12])=[CH:10][C:5]=1[C:3]1([OH:4])[CH2:2][S:22][C:21](=[N:20][CH:17]2[CH2:19][CH2:18]2)[N:23]1[CH:24]1[CH2:26][CH2:25]1
Reactant: NS(=O)(=O)c1cc(C(=O)CBr)c(Cl)cc1Cl
Reactant: S=C(NC1CC1)NC1CC1
Product: Br
Product: NS(=O)(=O)c1cc(C2(O)CSC(=NC3CC3)N2C2CC2)c(Cl)cc1Cl

Procedure:
was obtained in a manner analogous to that described in Example 10 from 3.5 g of 2-bromo-2',4'-dichloro-5'-sulfamoylacetophenone and 1.6 g of 1,3-dicyclopropyl-thiourea. M.p. 226° C (decomposition).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:9])[CH:8]=1)[NH2:5].[Cl-].[Cl:11][C:12]1[S:13][S+:14]=[C:15](Cl)[C:16]=1[Cl:17]>>[Cl:17][C:16]1[C:15](=[N:5][C:4]2[CH:3]=[C:2]([Cl:1])[CH:8]=[C:7]([Cl:9])[CH:6]=2)[S:14][S:13][C:12]=1[Cl:11]
Reactant: Clc1s[s+]c(Cl)c1Cl
Reactant: Nc1cc(Cl)cc(Cl)c1
Agent: [Cl-]
Product: Clc1cc(Cl)cc(N=c2ssc(Cl)c2Cl)c1

Procedure:
If 3,5-dichloro-aniline is reacted with 3,4,5-trichloro-1,2-dithiolium chloride to give 4,5-dichloro-3-(3,5-dichlorophenylimino)-1,2-dithiolene, the course of the reaction can be represented by the following equation: ##STR6##
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([NH2:12])[CH2:4][CH2:3]1.C([NH:15][C:16](=O)[O-:17])C>C(O)C>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([NH:12][C:16]([NH2:15])=[O:17])[CH2:4][CH2:3]1
Reactant: NC1CCC(=O)c2ccccc21
Reactant: CCNC(=O)[O-]
Solvent: CCO
Product: NC(=O)NC1CCC(=O)c2ccccc21

Procedure:
Equimolar quantities of 1,2,3,4-tetrahydro-4-oxo-1-naphthylamine and ethylcarbamate are mixed and heated until ethanol is no longer released. The crude product, 1,2,3,4-tetrahydro-4-oxo-1-naphthylurea is washed with water then with cold ethanol and dried.
Reaction SMILES: I[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.O1CCCC1.[OH-].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:21]1([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[C:8]2[O:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=3[N:12]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: FC(F)(F)c1ccc2oc(-c3ccncc3I)nc2c1
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: FC(F)(F)c1ccc2oc(-c3ccncc3-c3ccccc3)nc2c1
Yield: 26.5 %

Procedure:
To a mixture of 0.78 g of 2-(3-iodopyridin-4-yl)-5-(trifluoromethyl)benzoxazole, 0.27 g of phenylboronic acid, 5 ml of tetrahydrofuran and 0.14 g of dichlorobis(triphenylphosphine)palladium (II), 3 ml of 10% aqueous solution of sodium hydroxide was added and heated to reflux for three hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate twice. The combined organic layers were washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.18 g of 2-(3-phenyl pyridin-4-yl)-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as “active compound 32”).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[C:14]3[CH:39]=[CH:38][N:37](S(C4C=CC(C)=CC=4)(=O)=O)[C:15]=3[N:16]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]4)=[CH:22][C:21]=3[O:35][CH3:36])[N:18]=2)[C:3]=1[C:4]([NH2:6])=[O:5].[OH-].[K+]>O1CCOCC1.CC(O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[N:18]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:27][CH2:28][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:30][CH2:31]4)=[CH:22][C:21]=3[O:35][CH3:36])[NH:16][C:15]3=[N:37][CH:38]=[CH:39][C:14]=23)[C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: COc1cc(N2CCN(C(C)C)CC2)ccc1Nc1nc(Nc2cc(F)cc(F)c2C(N)=O)c2ccn(S(=O)(=O)c3ccc(C)cc3)c2n1
Agent: [K+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: COc1cc(N2CCN(C(C)C)CC2)ccc1Nc1nc(Nc2cc(F)cc(F)c2C(N)=O)c2ccnc-2[nH]1
Yield: 85.9 %

Procedure:
To a solution of 2,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (1.5 g, 2.17 mmols) in 1,4-dioxane (100 ml) and 2-propanol (2 ml) was added 1.0M potassium hydroxide (21 ml, 21.7 mmol) and the reaction was heated at 80C overnight. The resulting solution was diluted with ethyl acetate, washed with water, adsorbed onto silica gel and purified by LC (DCM to 10% MeOH/DCM) to afford 2,4-difluoro-6-[(2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide (1.0 g, 86%). ESIMS (M+H)+=537. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00 (d, J=6.60 Hz, 6H) 2.54-2.60 (m, 4H) 2.64-2.72 (m, 1H) 3.05-3.11(m, 4H) 3.78 (s, 3H) 6.18 (dd, J=3.48, 2.02 Hz, 1H) 6.45 (dd, J=8.62, 2.38 Hz, 1H) 6.61 (d, J=2.57 Hz, 1H) 6.86-6.92 (m, 1H) 6.96 (dd, J=3.67, 2.20 Hz, 1H) 7.59 (s, 1H) 7.68 (d, J=8.80 Hz, 1H) 8.01 (br. s., 1H) 8.16 (s, 1H) 8.53-8.59 (m, 1H) 11.08 (s, 1H) 11.32 (s, 1H).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[C:12]2[N:13]([CH:25]=[N:26][N:27]=2)[C:14](SC)=[N:15][C:16]=1[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1.[C:28]1([CH2:34][C@H:35]([NH2:38])[CH2:36][NH2:37])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O>CN(C=O)C>[NH2:38][C@@H:35]([CH2:34][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:36][NH:37][C:14]1[N:13]2[CH:25]=[N:26][N:27]=[C:12]2[C:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)=[C:16]([C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[N:15]=1
Reactant: CSc1nc(-c2ccncc2)c(-c2ccc3ccccc3c2)c2nncn12
Reactant: NC[C@@H](N)Cc1ccccc1
Solvent: O
Solvent: CN(C)C=O
Product: N[C@H](CNc1nc(-c2ccncc2)c(-c2ccc3ccccc3c2)c2nncn12)Cc1ccccc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
8-(2-naphthyl)-5-methylthio-7-(4-pyridyl)-1,2,4-triazolo[4,3-c]pyrimidine (350 mg, 1 mmol), K3CO3 (100 mg) and (2S)-3-phenylpropane-1,2-diamine (150 mg, 1 mmol) were combined in dry DMF (ca. 5 mL) and the mixture was stirred at room temperature for 48 h. To the reaction solution was added water (ca. 10 mL) at RT and a precipitate formed. The suspension was stirred at RT for 1 h. The solid was filtered off and washed with water (3×10 ml) and dried under vacuum at 50° C. overnight; MS (m/z) 472.3 (M+H)+; C29H25N7 requir. 471.56.