Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:16][CH:15]([OH:17])[CH2:14][CH:13]2[CH2:12][O:11][N:10]3[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[CH:5]=[CH:6][C:7]=1[F:8].I[CH:28]([CH3:30])[CH3:29]>ClCCl.FC(F)(F)S([O-])(=O)=O.[Ag+]>[Br:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:16][CH:15]([O:17][CH:28]([CH3:30])[CH3:29])[CH2:14][CH:13]2[CH2:12][O:11][N:10]3[CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CC(C)I
Reactant: COc1ccc(CN2OCC3CC(O)CC32c2ccc(F)c(Br)c2)cc1
Agent: [Ag+]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Product: COc1ccc(CN2OCC3CC(OC(C)C)CC32c2ccc(F)c(Br)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 24.7 %

Procedure:
To a mixture of racemic (3aRS,5RS,6aSR)-6a-(3-bromo-4-fluorophenyl)-1-(4-methoxybenzyl)hexahydro-1H-cyclopenta[c]isoxazol-5-ol (1.72 g, 4.07 mmol) in dichloromethane (2.5 mL) is added silver trifluoromethanesulfonate (2.62 g, 10.2 mmol) and powdered dried 4A sieves (1.50 g). A solution of 2-iodopropane (1.73 g, 10.2 mmol) in dichloromethane (0.5 mL) is added to the mixture over 15 minutes. The thick mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane and is filtered through diatomaceous earth. The solvent is removed under reduced pressure and the residue is purified by silica gel chromatography with a linear gradient of 0% to 10% ethyl acetate in dichloromethane over 15 minutes to give the title compound (0.466 g, 25%). ES/MS m/e (79Br/81Br) 464, 466 (M+1).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][CH3:20])C(=O)C)[CH3:2].[OH-].[K+].O>CCO>[CH2:19]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[NH:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:1][CH3:2])[CH3:20]
Reactant: CCc1ccccc1N(C(C)=O)c1ccccc1CC
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCc1ccccc1Nc1ccccc1CC
Reaction time: 6 h
Yield: 85 %

Procedure:
The N,N-bis(2-ethylphenyl)acetamide (8.1 g, 30.30 mmol) and KOH (5 g), in EtOH (50 mL), was stirred and heated to reflux overnight. 20 hrs later additional KOH (10 g) was added, wth stirring to reflux continued for an additional 6 hrs. It was cooled, poured into H2O (125 mL) and extracted with ethyl acetate (2×350 mL). The combined organics were washed with brine, dried (MgSO4), filtered and concentrated to dryness, affording a dark red oil (5.8 g, 85%).
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][N:26]1[C:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[C:29]([C:37]([OH:39])=O)[C:28](=[O:40])[N:27]1[CH3:41].[F:42][C:43]1[CH:44]=[C:45]([NH2:62])[CH:46]=[CH:47][C:48]=1[O:49][C:50]1[C:59]2[C:54](=[CH:55][C:56]([O:60][CH3:61])=[CH:57][CH:58]=2)[N:53]=[CH:52][CH:51]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[F:42][C:43]1[CH:44]=[C:45]([NH:62][C:37]([C:29]2[C:28](=[O:40])[N:27]([CH3:41])[N:26]([CH3:25])[C:30]=2[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[O:39])[CH:46]=[CH:47][C:48]=1[O:49][C:50]1[C:59]2[C:54](=[CH:55][C:56]([O:60][CH3:61])=[CH:57][CH:58]=2)[N:53]=[CH:52][CH:51]=1
Reactant: COc1ccc2c(Oc3ccc(N)cc3F)ccnc2c1
Reactant: Cn1c(-c2ccccc2)c(C(=O)O)c(=O)n1C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc2c(Oc3ccc(NC(=O)c4c(-c5ccccc5)n(C)n(C)c4=O)cc3F)ccnc2c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 35.3 %

Procedure:
A mixture of HATU (458 mg, 1206 μmol), 1,2-dimethyl-3-oxo-5-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (140 mg, 603 μmol), 3-fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine (258 mg, 908 μmol), and Triethylamine (254 μL, 1809 μmol) in DMF (2 mL) was stirred at 60° C. overnight. The mixture was diluted with EtOAc (10 mL). The mixture was transferred to a separatory funnel with EtOAc (20 mL) and was washed with NaOH (1N, 10 mL), H2O (2×10 mL), NaHCO3 (sat), NaCl (sat), and dried over Na2SO4. The residue after concentration was purified on silica gel and the product was triturated with EtOAc-hexane (1:2) to afford a pink solid (106 mg, 35%). Calc'd for C28H23FN4O4: 498; MS (ESI pos. ion) m/z: 499 (MH+). 1HNMR (CDCl3, 400 MHz): 11.04 (1H, s), 8.56 (1H, d, J 5.3), 7.88 (1H, d, J 14.7), 7.55-7.40 (5H, m), 7.47 (1H, s), 7.35 (1H, d), 7.22 (1H, d, J 9.1), 7.13 (1H, t, J 8.8), 6.36 (1H, d, J 5.3), 3.96 (3H, s), 3.62 (3H, s), 3.41 (3H, s).
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH2:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[N+:20]([C:23]1[CH:24]=[C:25]2[C:30](=O)[O:29][C:27](=[O:28])[C:26]2=[CH:32][CH:33]=1)([O-:22])=[O:21]>ClCCl>[F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[C:30](=[O:29])[C:25]5=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:33][CH:32]=[C:26]5[C:27]4=[O:28])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: NCCN1CCC(c2noc3cc(F)ccc23)CC1
Reactant: O=C1OC(=O)c2cc([N+](=O)[O-])ccc21
Solvent: ClCCl
Product: O=C1c2ccc([N+](=O)[O-])cc2C(=O)N1CCN1CCC(c2noc3cc(F)ccc23)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A stirred mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethylamine (2.63 g, 0.01 mole) and 4-nitrophthalic anhydride (1.93 g, 0.01 mole) in dichloromethane (200 ml) is stirred at room temperature for 3 hours. The solvent is then removed under reduced pressure and the residual material is purified by flash chromatography. The product is purified further by recrystallization to give N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-4-nitrophthalimide.
Reaction SMILES: [CH2:1]([C:5]1[CH:15]=[CH:14][C:8]2[CH:9]=[C:10]([CH2:12][OH:13])[O:11][C:7]=2[CH:6]=1)[CH2:2][CH2:3][CH3:4].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:1]([C:5]1[CH:15]=[CH:14][C:8]2[CH:9]=[C:10]([CH:12]=[O:13])[O:11][C:7]=2[CH:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc2cc(CO)oc2c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCCCc1ccc2cc(C=O)oc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.4 %

Procedure:
To a solution of (6-butylbenzofuran-2-yl)methanol (85 mg, 0.42 mmol) in 1.5 mL dichloromethane at room temperature was added Dess-Martin periodinane (247 mg, 0.58 mmol). The resulting suspension was stirred vigorously for 2 h at room temperature, poured into 20 mL saturated sodium bicarbonate and extracted with dichloromethane (3×15 mL). The combined dichloromethane extracts were dried over magnesium sulfate, filtered and concentrated. The crude mixture was subjected to chromatography on silica gel (5% ethyl acetate in hexanes) to give 6-butylbenzofuran-2-carbaldehyde (81 mg, 96%) as an oil. Used without further characterization.
Reaction SMILES: F[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[C:4]([F:11])[N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][CH2:20][O:21][CH2:22][C:23]([NH2:25])=[NH:24]>>[F:11][C:4]1[CH:5]=[CH:6][C:7]2[C:8](=[O:10])[NH:25][C:23]([CH2:22][O:21][CH2:20][CH2:19][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[F:12])=[N:24][C:2]=2[N:3]=1
Reactant: N=C(N)COCCc1ccccc1F
Reactant: O=C(O)c1ccc(F)nc1F
Product: O=c1[nH]c(COCCc2ccccc2F)nc2nc(F)ccc12
Yield: 80 %

Procedure:
The title compound was synthesized in analogy to example 85 using 2,6-difluoropyridine-3-carboxylic acid and 2-[2-(2-fluorophenyl)-ethoxy]-acetamidine to give 7-fluoro-2-[2-(2-fluorophenyl)-ethoxymethyl]-3H-pyrido[2,3-d]pyrimidin-4-one as the desired product (80%) as a white solid. MS: m/e=318.2 [M+H+].
Reaction SMILES: C([O:5][C:6]([C:8]1[S:12][C:11]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][C:23]=3[F:33])(=[O:21])=[O:20])[C@@H:15]([C:34](=[O:46])[NH:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([CH2:43][CH2:44][CH3:45])=[CH:39][CH:38]=3)[CH2:14]2)=[N:10][C:9]=1[CH3:47])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[F:33][C:23]1[CH:24]=[C:25]([O:28][C:29]([F:30])([F:31])[F:32])[CH:26]=[CH:27][C:22]=1[S:19]([N:16]1[CH2:17][CH2:18][N:13]([C:11]2[S:12][C:8]([C:6]([OH:7])=[O:5])=[C:9]([CH3:47])[N:10]=2)[CH2:14][C@@H:15]1[C:34](=[O:46])[NH:35][CH2:36][C:37]1[CH:38]=[CH:39][C:40]([CH2:43][CH2:44][CH3:45])=[CH:41][CH:42]=1)(=[O:20])=[O:21]
Reactant: CCCc1ccc(CNC(=O)[C@H]2CN(c3nc(C)c(C(=O)OC(C)(C)C)s3)CCN2S(=O)(=O)c2ccc(OC(F)(F)F)cc2F)cc1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: CCCc1ccc(CNC(=O)[C@H]2CN(c3nc(C)c(C(=O)O)s3)CCN2S(=O)(=O)c2ccc(OC(F)(F)F)cc2F)cc1
Temperature: 25 °C
Yield: 82.9 %

Procedure:
To a solution of the compound (59 mg) obtained in Step 7 in chloroform (0.3 ml) was added, with stirring at room temperature, trifluoroacetic acid (0.3 ml). After stirring at room temperature for 7 hr, the reaction mixture was concentrated under reduced pressure, toluene was added to the residue, and the mixture was concentrated again under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2-10% methanol/chloroform) to give the title compound (45 mg).
Reaction SMILES: CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:43][N:44](C)CCN(C)C.Br[C:52]1[CH:57]=[CH:56][C:55]([C:58]2[CH:59]=[N:60][C:61]3[N:62]([C:64]([CH2:67][C:68]4[CH:69]=[C:70]5[C:75](=[CH:76][CH:77]=4)[N:74]=[CH:73][CH:72]=[CH:71]5)=[CH:65][N:66]=3)[N:63]=2)=[CH:54][C:53]=1[F:78]>CN(C)C=O.[C-]#N.[Zn+2].[C-]#N.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]>[F:78][C:53]1[CH:54]=[C:55]([C:58]2[CH:59]=[N:60][C:61]3[N:62]([C:64]([CH2:67][C:68]4[CH:69]=[C:70]5[C:75](=[CH:76][CH:77]=4)[N:74]=[CH:73][CH:72]=[CH:71]5)=[CH:65][N:66]=3)[N:63]=2)[CH:56]=[CH:57][C:52]=1[C:43]#[N:44]
Reactant: CN(C)CCN(C)C
Reactant: Fc1cc(-c2cnc3ncc(Cc4ccc5ncccc5c4)n3n2)ccc1Br
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CN(C)C=O
Product: N#Cc1ccc(-c2cnc3ncc(Cc4ccc5ncccc5c4)n3n2)cc1F
Temperature: 160 °C

Procedure:
Zinc cyanide (131 mg, 1.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (78.5 mg, 0.136 mmol), and N,N,N′,N′-Tetramethylethylenediamine (0.22 mL, 1.4 mmol) were added successively to a mixture of 6-[2-(4-bromo-3-fluorophenyl)imidazo[1,2-b][1,2,4]-triazin-7-yl]methylquinoline (480 mg, 1.10 mmol) in N,N-dimethylformamide (8.7 mL) in a microwave tube. The tube was sealed and degassed three times and heated to 160° C. under microwave irradiation for 500 s. Most of the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, water and brine, and dried over magnesium sulfate. Filtration and concentration afforded a residue which was purified on a silica gel column with methanol in dichloromethane (0-6%) to give the desired product. (90%) LCMS: (M+H)=381.0.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[C:7]([OH:9])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[CH:23]=[C:24]([CH:41]=[CH:42][CH:43]=1)[O:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]3[CH2:40][CH2:39]3)=[O:37])[N:34]=2)[N:31]=1>CN(C)C(=O)C.O1CCCC1>[CH:38]1([C:36]([NH:35][C:33]2[N:34]=[C:29]3[CH:28]=[CH:27][C:26]([O:25][C:24]4[CH:23]=[C:22]([NH:21][C:7]([C:3]5[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=5)=[O:9])[CH:43]=[CH:42][CH:41]=4)=[N:31][N:30]3[CH:32]=2)=[O:37])[CH2:39][CH2:40]1
Reactant: Nc1cccc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)c1
Reactant: Cn1ccnc1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CC(=O)N(C)C
Solvent: CN(C)C=O
Product: Cn1ccnc1C(=O)Nc1cccc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)c1
Yield: 47.9 %

Procedure:
Using 1-methyl-1H-imidazole-2-carboxylic acid (36.7 mg, 0.29 mol), tetrahydrofuran (1.5 mL), N,N-dimethylformamide (30 μL, 0.39 mmol), oxalyl chloride (51 μL, 0.58 mmol), N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropylcarboxamide (75 mg, 0.24 mmol) and N,N-dimethylacetamide (1.5 mL) as starting materials and in the same manner as in Example 119, the title compound (48 mg, 47%) was obtained as a white powder.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[N:14]=[CH:13][C:12]([C:15]([O-:17])=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].[K+].[NH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][OH:32].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[OH:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][NH:19][C:15]([C:12]1[CH:13]=[N:14][C:9]([N:6]2[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:8][CH2:7]2)=[CH:10][CH:11]=1)=[O:17]
Reactant: NCCCCCCCCCCCCO
Reactant: CCN1CCN(c2ccc(C(=O)[O-])cn2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: CCN1CCN(c2ccc(C(=O)NCCCCCCCCCCCCO)cn2)CC1
Temperature: 25 °C
Yield: 91 %

Procedure:
To 4.07 g of potassium 6-(4-ethyl-1-piperazinyl)-pyridine-3-carboxylate and 3.00 g of 12-aminododecanol was added 50 ml of methylene chloride and then 2.86 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCI) and 2.01 g of 1-hydroxybenzotriazole (HOBt) were added while stirring at room temperature. The mixture was stirred at room temperature for 15 hours. To the reaction solution were added water and diisopropyl ether and subsequent filtration and drying under reduced pressure afforded 5.67 g of the title compound as a crystal.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([NH2:6])=[O:5].[CH3:7][NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1.C(N(CC)CC)C>C(#N)C>[CH3:20][O:19][C:13]1[CH:12]=[C:11]([CH2:10][CH2:9][N:8]([CH3:7])[CH2:2][CH2:3][C:4]([NH2:6])=[O:5])[CH:16]=[CH:15][C:14]=1[O:17][CH3:18]
Reactant: NC(=O)CCCl
Reactant: CNCCc1ccc(OC)c(OC)c1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COc1ccc(CCN(C)CCC(N)=O)cc1OC
Yield: 64.1 %

Procedure:
6.42 g (60 mmol) 3-Chloropropanamide, 5.85 g (30 mmol) N-methyl-3,4-dimethoxybenzeneethanamine and 7.7 g (75 mmol) triethylamine in 100 ml acetonitrile were stirred under reflux for 18 hours. The reaction mixture was concentrated in vacuo and the residue purified by chromatography on silicagel using methylene chloride/methanol: 92/8 to yield 5.12 g (64.1%) of the desired compound as an orange oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[Br:24][CH2:25][CH2:26][CH2:27][CH2:28]Br>CC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:28][CH2:27][CH2:26][CH2:25][Br:24])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: BrCCCCBr
Reactant: CC(C)(C)OC(=O)n1ccc2cc(O)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)n1ccc2cc(OCCCCBr)ccc21
Temperature: 100 °C
Reaction time: 3 h
Yield: 75.2 %

Procedure:
6.07 g (26 mmol) 5-Hydroxy-indole-1-carboxylic acid tert-butyl ester in 10 ml acetone were treated with 13.8 g (100 mmol) powdered K2CO3 and 11.8 ml (100 mmol) 1,4-dibromobutane. The suspension was stirred at 100° C. for 3 h, cooled to RT, and acetone was added. The suspension was filtered and concentrated. The residue was redissolved in ether and 0.5 M HCl, the inorganic phase was extracted with ether and the combined organic phases were washed with water, and dried over Na2SO4. Column chromatography on silica gel with a gradient hexane to hexane/EtOAc 19:1 yielded 7.2 g (65%, 3 steps) 5-(4-Bromo-butoxy)-indole-1-carboxylic acid tert-butyl ester as colorless oil, MS: 367 (M, 1Br).
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C(C)=C(S(O)(=O)=O)C(C)=C(N)C=2C)=[CH:4][C:3]=1S(O)(=O)=O>N1C=CC=CC=1>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Cc1c(N)c(C)c(S(=O)(=O)O)c(C)c1Sc1cc(S(=O)(=O)O)c(N)c2c1C(=O)c1ccccc1C2=O
Solvent: c1ccncc1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 27 was repeated, provided that the compounds shown in 1st, 2nd and 3rd columns of the following table were used in place of the 1-amino-4-(3'-amino-2',4', 6'-trimethyl-5'-sulfophenylthio)anthraquinone-2-sulfonic acid, 1-aminobenzene-3-β-sulfatoethylsulfone and pyridine, respectively, thereby obtaining a corresponding anthraquinone compound. A color shade on cotton of the compound is as shown in a 4th column of the table.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([C:12]([OH:14])=O)[S:7][C:8]=1[CH:9]([CH3:11])[CH3:10])([CH3:3])[CH3:2].[OH:15][C:16]1[CH:25]=[C:24]([NH2:26])[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19]>>[OH:15][C:16]1[CH:25]=[C:24]([NH:26][C:12]([C:6]2[S:7][C:8]([CH:9]([CH3:10])[CH3:11])=[C:4]([CH:1]([CH3:2])[CH3:3])[CH:5]=2)=[O:14])[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19]
Reactant: COC(=O)c1ccc(N)cc1O
Reactant: CC(C)c1cc(C(=O)O)sc1C(C)C
Product: COC(=O)c1ccc(NC(=O)c2cc(C(C)C)c(C(C)C)s2)cc1O
Yield: 33 %

Procedure:
In the same manner as that of Example 24, 4,5-diisopropylthiophene-2-carboxylic acid (80 mg, 0.377 mmol) and methyl 2-hydroxy-4-aminobenzoate (113 mg, 0.676 mmol) were condensed, the reaction mixture was treated in a conventional manner, and then the residue was purified by silica gel chromatography [n-hexane-ethyl acetate (40:1)] and recrystallized to obtain methyl 2-hydroxy-4-[(4,5-diisopropylthiophene-2-carbonyl)amino]benzoate (45 mg, 33%) as colorless prisms.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]([C:19]3[CH:20]=[CH:21][C:22]([O:28]CC4C=CC=CC=4)=[C:23]([CH:27]=3)[C:24]([NH2:26])=[O:25])=[O:18])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+]>>[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]([C:19]3[CH:27]=[C:23]([C:24]([NH2:26])=[O:25])[C:22]([OH:28])=[CH:21][CH:20]=3)=[O:18])[CH2:9][CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NC(=O)c1cc(C(=O)CCCCN2CCN(c3ccccc3)CC2)ccc1OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: NC(=O)c1cc(C(=O)CCCCN2CCN(c3ccccc3)CC2)ccc1O

Procedure:
1.7 Gram of this benzamide was liberated in an aqueous potassium carbonate solution, extracted with chloroform, dried over anhydrous sodium sulfate and concentrated. The thus-produced residue was dissolved in 50 ml of ethanol and then the solution was subjected to hydrogenolysis on 500 mg of 5% Pd - C. After the reaction was finished, the precipitated crystals were dissolved in hot methanol and the catalyst was filtered off. Then the solvent was distilled away and the residue was crystallized from ethanol to obtain 1.0 g of the titled compound. The characteristics of this compound were shown in Table 1. And, IR spectrum of this compound was shown in FIG. 1 of the accompanying drawings.
Reaction SMILES: [CH3:1][C:2]1[CH:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][C:5](=[O:7])[CH:6]=1.O.O.O.O.O.O.O.[Cl-].[Ce+3].[Cl-].[Cl-].[BH4-].[Na+].[NH4+].[Cl-]>CCOCC.CO>[OH:7][C@@H:5]1[CH2:4][C@H:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:2]([CH3:1])=[CH:6]1
Reactant: CCOC(=O)C1CC(=O)C=C1C
Agent: [BH4-]
Agent: [Ce+3]
Agent: [Cl-]
Solvent: O
Solvent: CCOCC
Solvent: CO
Product: CCOC(=O)[C@H]1C[C@@H](O)C=C1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 46.6 %

Procedure:
A round-bottom flask was charged with ethyl 2-methyl-4-oxocyclopent-2-enecarboxylate (2.04 g, 12.1 mmol, Preparation #CC.1), MeOH (30 mL), and cerium(III) chloride heptahydrate (5.65 g, 15.2 mmol) followed by portion-wise addition of sodium borohydride (0.574 g, 15.2 mmol). The suspension was stirred at room temperature over about 16 h. Saturated aqueous NH4Cl solution (50 mL) was added. The mixture was stirred for about 10 min and Et2O (60 mL) was added. The layers were separated and the aqueous layer was extracted with Et2O (3×30 mL). The combined organic layers were washed with saturated aqueous NaHCO3, dried over anhydrous MgSO4, filtered, and concentrated to dryness under reduced pressure. The residue was purified via silica gel chromatography eluting with 20-60% EtOAc/pentane to yield cis-ethyl 4-hydroxy-2-methylcyclopent-2-enecarboxylate (0.96 g, 46%): 1H NMR (400 MHz, CDCl3) δ 5.77-5.71 (m, 1H), 4.63 (m, 1H), 4.28-4.11 (m, 2H), 3.27-3.20 (m, 1H), 2.59 (bs, 1H), 2.41-2.30 (m, 1H), 2.00 (d, J=14.2 Hz, 1H), 1.79 (d, =1.2 Hz, 3H), 1.30 (t, J=7.1 Hz, 3H) and trans-ethyl 4-hydroxy-2-methylcyclopent-2-enecarboxylate (0.69 g, 33%): 1H NMR (400 MHz, CDCl3) δ 5.63 (dd, J=1.8, 3.4 Hz, 1H), 4.98 (m, 1H), 4.20-4.11 (m, 2H), 3.60-3.53 (m, 1H), 2.57 (ddd, J=4.4, 7.1, 13.9 Hz, 1H), 1.98 (ddd, J=3.5, 8.4, 13.9 Hz, 1H), 1.80 (d, J=1.4, 3H), 1.46 (bs, 1H), 1.27 (t, J=7.1 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:16](=[O:23])[CH2:17][N:18]1[CH:22]=[N:21][CH:20]=[N:19]1.[CH:24]([Mg]Cl)([CH3:26])[CH3:25]>ClCCl.C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=2)[CH:5]=[CH:4][C:3]=1[C:16]([OH:23])([CH:24]([CH3:26])[CH3:25])[CH2:17][N:18]1[CH:22]=[N:21][CH:20]=[N:19]1
Reactant: O=C(Cn1cncn1)c1ccc(Oc2ccc(Cl)cc2)cc1Cl
Reactant: CC(C)[Mg]Cl
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C)C(O)(Cn1cncn1)c1ccc(Oc2ccc(Cl)cc2)cc1Cl
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
The above-mentioned ethanone (120.0 g, 0.34 mol) was added to a solution of MgBr diethyl etherate (195.8 g, 0.76 mol) in dichloromethane (DCM, 2.5 L) and the mixture stirred at room temperature for about 90 min. This mixture was then cooled to about 0° C. and isopropyl magnesium chloride (344.5 mL of a 2 M solution in THF, 0.69 mol) was added dropwise. The mixture was allowed to warm to room temperature and was then quenched by addition of a saturated ammonium chloride solution. The organic components were extracted three times with DCM, the organic phases combined, dried and the solvents evaporated. Addition of MTBE resulted in precipitation of the unreacted starting material, which was filtered off. The filtrate was then purified using reverse phase chromatography to give 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-3-methyl-1-(1,2,4-triazol-1-yl)butan-2-ol as a brown oil (31.1 g, 23%, HPLC Rt=1.305 min, masse=392).
Reaction SMILES: I[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]2[N:14]=[CH:13][N:12]([CH3:15])[C:11](=[O:16])[CH:10]=2)=[CH:4][C:3]=1[CH3:17].[F:18][C:19]1[CH:20]=[CH:21][C:22](B2OC(C)(C)C(C)(C)O2)=[C:23]2[C:27]=1[C@H:26]([O:28][C:29]1[CH:42]=[CH:41][C:32]3[C@H:33]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH2:34][O:35][C:31]=3[CH:30]=1)[CH2:25][CH2:24]2.BrC1C=CC(F)=C2C=1CC[C@H]2OC1C=CC2[C@H](CC(OC)=O)COC=2C=1>>[CH3:17][C:3]1[CH:4]=[C:5]([C:9]2[N:14]=[CH:13][N:12]([CH3:15])[C:11](=[O:16])[CH:10]=2)[CH:6]=[C:7]([CH3:8])[C:2]=1[C:22]1[CH:21]=[CH:20][C:19]([F:18])=[C:27]2[C:23]=1[CH2:24][CH2:25][C@H:26]2[O:28][C:29]1[CH:42]=[CH:41][C:32]2[C@H:33]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH2:34][O:35][C:31]=2[CH:30]=1
Reactant: Cc1cc(-c2cc(=O)n(C)cn2)cc(C)c1I
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(B5OC(C)(C)C(C)(C)O5)ccc(F)c43)ccc21
Agent: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(Br)ccc(F)c43)ccc21
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(-c5c(C)cc(-c6cc(=O)n(C)cn6)cc5C)ccc(F)c43)ccc21

Procedure:
The title compound is prepared from 6-(4-iodo-3,5-dimethylphenyl)-3-methylpyrimidin-4(3H)-one and methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate following a procedure analogous to that described in Step 5 of Intermediate 1. LC (method 11): tR=1.19 min; Mass spectrum (ESI+): m/z=555 [M+H]+.