Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([O:20]CC)=[O:19])=[C:12]([CH3:23])[CH:11]=2)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[F:30][C:31]([F:42])([F:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:23][C:12]1[CH:11]=[C:10]([CH:9]=[CH:8][C:4]2[CH:3]=[C:2]([C:35]3[CH:36]=[CH:37][C:32]([C:31]([F:42])([F:41])[F:30])=[CH:33][CH:34]=3)[CH:7]=[CH:6][CH:5]=2)[CH:15]=[CH:14][C:13]=1[O:16][CH2:17][C:18]([OH:20])=[O:19]
Reactant: CCOC(=O)COc1ccc(C=Cc2cccc(Br)c2)cc1C
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: Cc1cc(C=Cc2cccc(-c3ccc(C(F)(F)F)cc3)c2)ccc1OCC(=O)O
Temperature: 25 °C
Yield: 57 %

Procedure:
Ethyl ({4-[2-(3-bromophenyl)ethenyl]-2-methylphenyl}oxy)acetate (150 mg, 0.40 mmol), Na2CO3 (106 mg, 1.00 mmol), 4-(triflouromethyl)benzeneboronic acid (83.5 mg, 0.44 mmol) and Pd(PPh3)4 (23 mg, 0.02 mmol) was dissolved in DME and water (2:1, 6 mL) and the mixture heated at reflux for 4 hours. The mixture was allowed to cool to rt, was concentrated under reduced pressure and the residue partitioned between EtOAc (15 mL) and water (15 mL). The aqueous layer was then acidified with aqueous HCl (1N) and extracted with EtOAc and the combined organic layers dried (MgSO4), filtered and reduced to give the title compound (94 mg).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][CH2:12][CH2:13][OH:14])[CH:4]=[CH:3][CH:2]=1.[S:15]([Cl:19])(=[O:18])(=[O:17])[NH2:16].Cl>C(#N)C.C(O)(C)C>[ClH:19].[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][CH2:12][CH2:13][O:14][S:15](=[O:18])(=[O:17])[NH2:16])[CH:4]=[CH:3][CH:2]=1
Reactant: NS(=O)(=O)Cl
Reactant: OCCOc1cccc2cccnc12
Agent: Cl
Solvent: CC#N
Solvent: CC(C)O
Product: NS(=O)(=O)OCCOc1cccc2cccnc12

Procedure:
Using the procedure of Example 4, 5.4 g (0.029 mole) of 2-(8-quinolinyloxy)ethanol was reacted with sulfamoyl chloride. During work-up of the reaction, a light-yellow material deposited out from the organic-aqueous system. 1H NMR of this material suggested that it might be a quaternary salt. The oily product obtained at the end of the work-up procedure weighed 2.7 g. This oil was dissolved in acetonitrile-isopropyl alcohol and acidified with 37% hydrochloric acid. The mixture was evaporated to almost dryness and then redissolved in methanol. To the solution was added ethyl acetate and most of the methanol was evaporated carefully. The light-yellow solid was collected and dried at 40° C. in vacuum overnight to give 2.4 g solid, mp 138°-140° C.
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([Cl:4])=[O:3].N1C=CC=CC=1.[OH:13][C:14]1[CH:15]=[CH:16][C:17]2[O:21][C:20](=[O:22])[CH:19]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:18]=2[CH:29]=1>ClCCl>[O:22]=[C:20]1[CH:19]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:18]2[CH:29]=[C:14]([O:13][C:1](=[O:5])[C:2]([Cl:4])=[O:3])[CH:15]=[CH:16][C:17]=2[O:21]1
Reactant: O=C1Oc2ccc(O)cc2C1c1ccccc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Cl)C(=O)Oc1ccc2c(c1)C(c1ccccc1)C(=O)O2

Procedure:
Oxalyl chloride (17.5 parts) and pyridine (0.5 parts) were added to a suspension of 5-hydroxy-2-oxo-3-phenyl-2,3-dihydrobenzfuran (22.6 parts) in dichloromethane (200 parts). After six hours reflux, chloro-oxo-acetic acid 2-oxo-3-phenyl-2,3-dihydro-benzofuran-5-yl ester was isolated and phenol (9.9 parts) added and the mixture refluxed for eighteen hours. Removal of the solvent gave the crude product oxalic acid (2-oxo-3-phenyl-2,3-dihydro-benzofuran-5-yl)ester phenyl ester (33.3 parts; 89%). Trituration in methanol and recrystallisation from ethyl acetate gave a pure product. Analysis C,70.4; H,3.7; C22H13O6 requires C,70.8; H,3.5%. M.pt.134° C., 1H and 13Cnmr gave spectra consistent with structure.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[O:6][C:7]3[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=3[CH:9]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[CH2:10][C:4]=2[CH:3]=1.Cl[CH2:24][CH2:25][CH2:26][OH:27]>>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[O:6][C:7]3[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=3[CH:9]([N:11]3[CH2:12][CH2:13][N:14]([CH2:24][CH2:25][CH2:26][OH:27])[CH2:15][CH2:16]3)[CH2:10][C:4]=2[CH:3]=1
Reactant: OCCCCl
Reactant: Clc1ccc2c(c1)CC(N1CCNCC1)c1ccccc1O2
Product: OCCCN1CCN(C2Cc3cc(Cl)ccc3Oc3ccccc32)CC1

Procedure:
In an analogous manner to that described in Example 5, from 1-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-piperazine and 3-chloro-1-propanol, there is obtained 3-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-1-propanol as an oil. The dihydrochloride, prepared in ethanol, melts at 206°-207° C (with decomposition).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([O:15][CH3:16])=[O:14])=[CH:8][CH:7]=[CH:6]2.OO.[Br:19]Br>C(O)(=O)C>[Br:19][C:4]1[C:3]([O:2][CH3:1])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]([O:15][CH3:16])=[O:14]
Reactant: BrBr
Reactant: COC(=O)c1cccc2cc(OC)ccc12
Agent: OO
Solvent: CC(=O)O
Product: COC(=O)c1cccc2c(Br)c(OC)ccc12
Temperature: 90 °C
Yield: 177.4 %

Procedure:
108 g (0.50 mol) of methyl 6-methoxy-1-naphthoate are dissolved in 500 ml of acetic acid, and 30 g of 35% aqueous hydrogen peroxide solution are added. 42 g (0.26 mol) of bromine are then added dropwise at 35° C. in the course of 45 minutes. The mixture is subsequently heated at 90° C. When the reaction has ended, the mixture is allowed to cool to 20° C. and is subjected to filtration with suction, and the filter cake is washed with water. Drying in vacuo at 60° C. gives 136.1 g of methyl 5-bromo-6-methoxy-1-naphthoate in the form of fine white needles.
Reaction SMILES: [CH2:1]([N:8]=[C:9]=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:11][C:12]1[N:17]=[N:16][C:15]([N:18]2[CH2:23][CH2:22][N:21]([C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:34])[F:33])=[O:25])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1>>[CH2:1]([NH:8][C:9]([NH:11][C:12]1[N:17]=[N:16][C:15]([N:18]2[CH2:19][CH2:20][N:21]([C:24](=[O:25])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:34])[F:33])[CH2:22][CH2:23]2)=[CH:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C=NCc1ccccc1
Reactant: Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1
Product: O=C(NCc1ccccc1)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 5, making variations only as required to use benzylisocyanate in place of (2-isocyanatocyclopropyl)benzene to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white solid (45.6% yield). 1H NMR (500 MHz, CDCl3) δ 12.0, 8.28, 7.80, 7.67, 7.62, 7.32, 7.23, 7.02-7.14, 4.54, 3.85-3.91, 3.69-3.76, 3.28-3.40, 2.94-3.10.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)=[CH:4][CH:3]=1.[CH3:32][N:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)N>>[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:33]([CH3:32])[C:35]3[C:40]([C:9]=2[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=4)[CH2:15][CH2:14]2)=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:4][CH:3]=1
Reactant: CN(N)c1ccccc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccc(I)cc3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4ccc(I)cc4)n(C)c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(4-iodophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 1-methyl-1-phenylhydrazine: ESMS m/e: 620.1 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[C:9](=[O:21])[CH2:8][CH2:7]2)([O-])=O.O.NN>CO.[Ni]>[NH2:1][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][CH2:15][N:16]1[CH2:17][CH2:18][CH2:19][CH2:20]1)[C:9](=[O:21])[CH2:8][CH2:7]2
Reactant: O=C1CCc2cc([N+](=O)[O-])ccc2N1CCN1CCCC1
Agent: [Ni]
Agent: NN
Solvent: CO
Solvent: O
Product: Nc1ccc2c(c1)CCC(=O)N2CCN1CCCC1

Procedure:
To solution of 6-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one (205 mg, 0.709 mmol) in 5 mL methanol was added to Raney Nickel (slurry in H2O, 50 mg) in a reaction vial. The suspension was treated with hydrazine hydrate (220 μL, 7.09 mmol) and heated at reflux for 2 hours and then filtered through a pad of celite. The celite pad was rinsed with 10 mL methanol. The filtrate was concentrated and the resulting product was subjected to flash silica gel chromatography using 2.5% 2M NH3 in MeOH/CH2Cl2 to afford a yellow oil. Yield: 180 mg (98%). 1H NMR (CDCl3) δ: 6.89 (d, J=8.4 Hz, 1H), 6.56 (dd, J=2.7, 8.4 Hz, 1H), 6.52 (d, J=2.1 Hz, 1H), 4.04 (t, J=7.5 Hz, 2H), 2.81-2.76 (m, 2H), 2.71-2.66 (m, 2H), 2.63-2.56 (m, 6H), 1.81-1.77 (m, 4H). MS (ESI): 260.2 (M+1, 100%).
Reaction SMILES: [CH3:1][C:2]1[CH:15]=[C:5]2[NH:6][C:7](=[O:14])[C:8]3[CH:13]=[N:12][CH:11]=[CH:10][C:9]=3[N:4]2[N:3]=1.CI.[CH3:18]N(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:1][C:2]1[CH:15]=[C:5]2[N:6]([CH3:18])[C:7](=[O:14])[C:8]3[CH:13]=[N:12][CH:11]=[CH:10][C:9]=3[N:4]2[N:3]=1
Reactant: Cc1cc2[nH]c(=O)c3cnccc3n2n1
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Product: Cc1cc2n(C)c(=O)c3cnccc3n2n1
Temperature: 25 °C

Procedure:
2 g. of 2-methylpyrazolo[1,5-a]pyrido[3,4-e]pyrimidin5(4H)-one are treated with 2 g. of methyl iodide in 20 ml. of dimethylformamide in the presence of 2 g. of potassium carbonate at 70° with stirring for 12 hours. The mixture is cooled to room temperature, 20 ml. of water are added and the precipitated 2,4-dimethylpyrazolo[1,5-a]pyrido[3,4-e]pyrimidin-5(4H)-one is filtered off, yield: 1.5 g. (70%); m.p. > 300° (DMF).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[O:13]1[CH2:17][CH2:16][CH2:15][CH:14]1[C:18]([O:20][CH3:21])=[O:19].[CH:22](=[O:26])[CH:23]([CH3:25])[CH3:24]>C1COCC1>[OH:26][CH:22]([C:14]1([C:18]([O:20][CH3:21])=[O:19])[CH2:15][CH2:16][CH2:17][O:13]1)[CH:23]([CH3:25])[CH3:24]
Reactant: COC(=O)C1CCCO1
Reactant: CC(C)C=O
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COC(=O)C1(C(O)C(C)C)CCCO1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 44.2 %

Procedure:
This procedure was adapted from J. Chem. Soc. Perkin Trans. I. 1997, p 771. To a solution of N,N-diisopropylamine (1 mL, 7.69 mmol) in THBF (13 mL) at 0° C. as added n-butyllithium (4.2 mL, 8.46 mmol, 2 M in hexanes). After stirring the mixture for 30 min, it was cooled to −78° C. and 2-tetrahydrofuroic acid, methyl ester (1 g, 7.69 mmol) in THF (13 mL) was added. The reaction mixture was stirred at the same temperature for 15 min and then warmed to −40° C. Isobutyraldehyde (1 mL, 11.5 mmol) was added and stirring was continued for 1 hr and −40° C. The reaction mixture was then warmed to 0° C. and stirred for 1 hr before it was quenched HCl (30 mL, 1M). Extracted with 2×50 mL of ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate. Filtration and evaporation gave the crude product 2.63 g as an oil. Flash column chromatography on silica gel eluted with 15:85 ethyl acetate/hexane gave the desired product (688 mg, 44% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=2)[NH2:10])=[CH:4][C:3]=1[CH2:16][CH3:17].[F:18][C:19]([F:24])([F:23])[CH:20]1[O:22][CH2:21]1>>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([N:10]([CH2:16][CH:3]3[CH2:4][CH2:5][CH2:14][CH2:15][CH2:2]3)[CH2:21][CH:20]([OH:22])[C:19]([F:24])([F:23])[F:18])[CH:11]=[CH:12][CH:13]=2)=[CH:4][C:3]=1[CH2:16][CH3:17]
Reactant: FC(F)(F)C1CO1
Reactant: CCc1cc(Oc2cccc(N)c2)ccc1Cl
Product: CCc1cc(Oc2cccc(N(CC3CCCCC3)CC(O)C(F)(F)F)c2)ccc1Cl
Temperature: 90 °C
Yield: 55.7 %

Procedure:
EX-18C) The 3-(4-chloro-3-ethylphenoxy)aniline (0.545 g, 0.002 mol) product from EX-18B was mixed with neat 3,3,3-trifluoro-1,2-epoxypropane (0.220 g, 0.002 mol) in a pressurized vial. The resulting mixture was heated at 90° C. for 18 h, cooled, and the excess 3,3,3-trifluoro-1,2-epoxypropane was removed in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane to give 0.254 g (35%) of the desired 3-[[3-(4-chloro-3-ethyl-phenoxy)phenyl]amino]-1,1,1-trifluoro-2-propanol product as a pure orange oil. Anal calcd. for C17H17NOF3Cl: C, 56.75; H, 4.76; N, 3.89. Found: C, 56.72; H, 4.70; N, 3.85. HRMS calcd.: 360.0978 [M+H]+, found: 360.0969. 1H NMR (CDCl3) δ 1.50 (t, 3H), 2.72 (m, 2H), 3.36 (m, 1H), 3.54 (m, 1H), 4.20 (m, 1H), 6.42 (m, 2H), 6.81 (dd, 1H), 6.94 (d, 1H), 7.18 (d, 1H), 7.25 (m, 2H).
Reaction SMILES: C[O:2][C:3]1[C:8]2[O:9][CH:10]([CH3:14])[C:11](=[O:13])[NH:12][C:7]=2[CH:6]=[C:5]([CH:15]=[O:16])[CH:4]=1.B(Br)(Br)Br>C(Cl)Cl>[OH:2][C:3]1[C:8]2[O:9][CH:10]([CH3:14])[C:11](=[O:13])[NH:12][C:7]=2[CH:6]=[C:5]([CH:15]=[O:16])[CH:4]=1
Reactant: COc1cc(C=O)cc2c1OC(C)C(=O)N2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC1Oc2c(O)cc(C=O)cc2NC1=O
Temperature: -10 °C
Reaction time: 1 h
Yield: 96.2 %

Procedure:
In a 20 mL scintillation vial was added 8-methoxy-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde 17 (111 mg, 0.502 mmol) and boron tribromide (2.0 mL, 2.000 mmol) in DCM (2.5 mL) and stirred at −10° C. for 1 h then slowly warmed to 23° C. and stirred overnight. The reaction was quenched with MeOH, taken up in EtOAc, washed with water and brine, dried over MgSO4, and concentrated in vacuo to give the title compound as a tan solid (100 mg, 0.483 mmol, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (d, J=6.82 Hz, 3H) 4.75 (q, J=6.82 Hz, 1H) 6.92 (d, J=2.02 Hz, 1H) 7.03 (d, J=1.77 Hz, 1H) 9.74 (s, 1H) 9.98 (br. s., 1H) 10.85 (s, 1H). ESI-MS: m/z 208.0 (M+H)+.
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][O:8][C:9]1[CH:18]=[CH:17][C:12]([C:13](OC)=[O:14])=[C:11]([O:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH:10]=1>C1(C)C=CC=CC=1>[CH3:24][O:23][C:21]([C:20]1[O:19][C:11]2[CH:10]=[C:9]([O:8][CH3:7])[CH:18]=[CH:17][C:12]=2[C:13]=1[OH:14])=[O:22]
Reactant: COC(=O)COc1cc(OC)ccc1C(=O)OC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: COC(=O)c1oc2cc(OC)ccc2c1O
Temperature: 0 °C
Yield: 54 %

Procedure:
A mixture of 10.4 g (0.093 mole) of potassium tert-butoxide in 175 ml of toluene (under a nitrogen atmosphere) is stirred and cooled in a cold water bath. A solution of 18.1 g (0.071 mole) of 4-methoxy-2-(2-methoxy-2-oxoethoxy) benzoic acid, methyl ester is added over 80 minutes. The mixture is stirred and heated on the steam bath for three hours, then cooled and added to 600 g of ice/water. The organic layer is separated, washed with water (2×100 ml), and the aqueous washes are combined with the original aqueous layer. The combined aqueous layers are washed with dichloromethane (2×250 ml), then filtered. The filtrate is cooled in ice and acidified with glacial acetic acid to precipitate the crude product, which is filtered and washed with water. Recrystallizatin from aqueous methanol yields 8.5 g 54% yield) of the 3-hydroxy-6-methoxy-2-benzofurancarboxylic acid methyl ester product, mp 93°-95 ° C. (mp of 80°-85° C. is reported in the J. D. Brewer, et al reference cited above).
Reaction SMILES: [C:1](Cl)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:9]1([OH:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>N1C=CC=CC=1>[C:1]([O:15][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: Oc1ccccc1
Reactant: CCCCCC(=O)Cl
Solvent: c1ccncc1
Product: CCCCCC(=O)Oc1ccccc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 94.7 %

Procedure:
30 ml (0.22 mole) of hexanoyl chloride were added dropwise over 30 minutes with stirring and cooling on an ice bath to a solution of 18.8 g (0.2 mole) of phenol in 80 ml of anhydrous pyridine and then the reaction mixture stood at room temperature for 3 hours and was poured into ice water. The mixture was extracted with ether and the ether extracts were washed with water, dilute hydrochloric acid and with water, dried over magnesium sulfate and evaporated to dryness to obtain 36.4 g of phenyl hexanoate as a yellow oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[CH:17])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:21]=[C:22]([S:27]([NH:30][CH2:31][CH2:32][O:33][CH3:34])(=[O:29])=[O:28])[CH:23]=[CH:24][C:25]=1[CH3:26]>>[C:1]([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[C:17][C:20]1[CH:21]=[C:22]([S:27]([NH:30][CH2:31][CH2:32][O:33][CH3:34])(=[O:29])=[O:28])[CH:23]=[CH:24][C:25]=1[CH3:26])([CH3:4])([CH3:3])[CH3:2]
Reactant: COCCNS(=O)(=O)c1ccc(C)c(Br)c1
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Product: COCCNS(=O)(=O)c1ccc(C)c(C#Cc2cc(Cl)ccc2OCC(=O)OC(C)(C)C)c1

Procedure:
Following the general method as outlined in Intermediate 20, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 3-bromo-N-(2-methoxy-ethyl)-4-methyl-benzenesulfonamide (Intermediate 149), the title compound was obtained as a orange sticky solid after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]([C:16](=[O:18])[CH3:17])=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[C:7]([C:19](=[O:28])[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[CH3:27])[CH:8]=2)[CH3:2].[CH3:29][C:30](C)([O-:32])C.[K+].CCCCCC>C(OCC)(=O)C>[CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]([C:16](=[O:18])[CH2:17][C:30](=[O:32])[CH3:29])=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[C:7]([C:19](=[O:28])[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[CH3:27])[CH:8]=2)[CH3:2]
Reactant: CCn1c2ccc(C(C)=O)cc2c2cc(C(=O)c3ccc(F)cc3C)ccc21
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CCn1c2ccc(C(=O)CC(C)=O)cc2c2cc(C(=O)c3ccc(F)cc3C)ccc21
Temperature: 25 °C
Yield: 10.3 %

Procedure:
A one liter four-necked flask equipped with a stirrer, a nitrogen inlet tube, a reflex condenser, and a thermometer was charged with 74.69 g of 1-[9-ethyl-6-(4-fluoro-2-methylbenzoyl)-9H-carbazol-3-yl]ethanone, 538.66 g of ethyl acetate, and 67.33 g of potassium t-butoxide, and the mixture was refluxed in a nitrogen atmosphere for 1 hour. The reaction mixture was cooled to room temperature, and the white solid thus precipitated was collected by filtration by suction and washed with 500 ml of ethyl acetate. The resulting solid was stirred in 500 ml of 2N hydrochloric acid and 1.5 liters of ethyl acetate. The organic phase was washed with water until neutral. The organic phase was separated, dried with 70 g of magnesium sulfate, and filtered by suction. The solvent was removed by evaporation to give a pale yellow solid. The solid was dissolved in 150 ml of ethyl acetate and refluxed, and 100 ml of n-hexane was added thereto, followed by cooling to room temperature for crystallization. The filtrate was dissolved in 50 ml of ethyl acetate, refluxed, and 100 ml of n-hexane was added, followed by cooling to room temperature for crystallization. The resulting crystals were combined, collected by filtration by suction, and dried under reduced pressure to give 8.52 g (21%) of white crystals, which had a melting point of 132° C. and was identified by various analyses to be β-diketone compound No. 2 having a carbazolyl group.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:32])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([NH2:31])=[CH:10][C:11]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:13]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:12]=2[CH:30]=1.[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>>[CH3:1][O:2][C:3](=[O:32])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([NH:31][S:40]([C:37]2[CH:38]=[CH:39][C:34]([Cl:33])=[CH:35][CH:36]=2)(=[O:42])=[O:41])=[CH:10][C:11]2[N:15]=[C:14]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:13]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[C:12]=2[CH:30]=1
Reactant: COC(=O)CCCOc1cc2c(cc1N)nc(-c1ccccc1)n2-c1ccc(OC)cc1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Product: COC(=O)CCCOc1cc2c(cc1NS(=O)(=O)c1ccc(Cl)cc1)nc(-c1ccccc1)n2-c1ccc(OC)cc1

Procedure:
4-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]butanoic acid methyl ester was reacted with 4-chlorobenzenesulfonic acid chloride according to general operating instructions 13.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9].OO.C(=O)(O)[O-].[Na+].[ClH:17]>>[NH2:1][C:2]1[C:3]([Cl:17])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: Cl
Reactant: COc1ccncc1N
Agent: O=C([O-])O
Agent: OO
Agent: [Na+]
Product: COc1ccnc(Cl)c1N

Procedure:
To a solution of 6.4 g (51 mmol) of 3-amino-4-methoxypyridine in 30 mL of 37 percent aqueous hydrochloric acid was slowly added 7.8 g of 30 percent aqueous hydrogen peroxide at room temperature with stirring. After 30 min this solution was slowly poured into 300 mL of saturated aqueous sodium bicarbonate and the resulting mixture was extracted with ether (3×200 mL). The ethereal extracts were combined, dried over magnesium sulfate, and filtered. The filtrate was concentrated by evaporation under reduced pressure to obtain a light brown solid. This solid was purified by column chromatography eluting with 17:83 acetone:hexane to obtain 6.54 g (81 percent of theory) of the title compound as colorless needles melting at 86°-87° C.
Reaction SMILES: Cl[C:2]([O:4][CH:5]([CH:19]1[C:31]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:3].C1COCC1.[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1C=CC=CC=1>[C:2](=[O:3])([O:4][CH:5]([CH:19]1[C:31]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: O=C(Cl)OC(C1c2ccccc2-c2ccccc21)C1c2ccccc2-c2ccccc21
Reactant: Nc1ccccc1
Solvent: c1ccccc1
Solvent: C1CCOC1
Product: O=C(Nc1ccccc1)OC(C1c2ccccc2-c2ccccc21)C1c2ccccc2-c2ccccc21
Temperature: 0 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
To a solution of 1.0 g (1.18 mmol) of bis(9-fluorenyl)-methyl chloroformate in 15 mL of freshly distilled THF and 15 mL of dry benzene was added 0.21 mL (2.3 mmol) of freshly distilled aniline in one portion at 0° C. The mixture was stirred at 0° C. for 3 hours and quenched with 10 mL of sat'd NH4Cl. The organic layer was washed with water (10mL) and the pooled aqueous layer was extracted with CHCl3 (2×10 mL). The combined organic extracts were dried over MgSO4 and the solvent was evaporated in vacuo to give 1.13 g (100%) of the crude urethane as a white solid. Recrystallization from chloroform gave 0.93 g (82.03%) of the pure α-F-Fmoc-aniline as white crystals, m.p. 225°-227° C. (dec.); IR (KBr): 3340 (NH), 1705 (C=O) cm-1 ; 1H NMR (DMSO-d6): δ 4.59 (d, 2H, ArCH), 5.70 (t, 1H, CHO), 6.80-7.95 (m, 21H, aryl), 9.38 (b, 1H, NH).