Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(O)(=O)[CH2:14][C:15]([OH:17])=[O:16]>CCO.N1C=CC=CC=1>[CH3:1][S:2]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[CH:14][C:15]([OH:17])=[O:16])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: O=C(O)CC(=O)O
Reactant: CS(=O)(=O)c1ccc(C=O)cc1
Solvent: CCO
Solvent: c1ccncc1
Product: CS(=O)(=O)c1ccc(C=CC(=O)O)cc1
Temperature: 0 °C
Yield: 47.2 %

Procedure:
A solution of aldehyde 4-methylsulfonylbenzaldehyde 4 (1.0 g, 5.9 mmol) and malonic acid (0.63 g, 6.0 mmol) in 10:1 EtOH/pyridine (12.1 mL) was heated at a gentle reflux for 24 h. After cooling to 0° C., the resulting precipitate was collected and rinsed with cold Et2O. The solid was resuspended in EtOH (13 mL) and heated at reflux for an additional 2 h. After cooling to 0° C., the resulting precipitate was collected and dried in vacuo to afford 0.63 g (51%) of 3-(4-methanesulfonyl-phenyl)-acrylic acid 5 as a white solid; 1H NMR (DMSO) δ 3.18 (s, 3H), 6.65 (d, 1H, J=16.1), 7.60 (d, 1H, J=16.1), 7.89 (m, 4H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]=[C:9]=[O:10].[F:11][C:12]([F:26])([F:25])[C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH2:23][CH2:22][C@@H:21]([NH2:24])[CH2:20]2)=[N:17][CH:18]=1>C(OCC)C>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([NH:24][C@@H:21]1[CH2:22][CH2:23][N:19]([C:16]2[CH:15]=[CH:14][C:13]([C:12]([F:26])([F:25])[F:11])=[CH:18][N:17]=2)[CH2:20]1)=[O:10]
Reactant: N[C@@H]1CCN(c2ccc(C(F)(F)F)cn2)C1
Reactant: O=C=Nc1ccccc1Br
Solvent: CCOCC
Product: O=C(Nc1ccccc1Br)N[C@@H]1CCN(c2ccc(C(F)(F)F)cn2)C1
Reaction time: 18 h

Procedure:
A solution of 2-bromophenyl isocyanate (Aldrich Chemical Company) (27.4 ml, 0.222 mol) in dry diethyl ether (65 ml) was added dropwise over 0.5 h to an efficiently stirred solution of D2 (51.4 g, 0.222 mol) in dry diethyl ether (0.8 L) under argon at ambient temperature. After stirring for 18 h, a white precipitate was filtered off and washed with dry diethyl ether (2×150 ml). The solid was crushed to a fine powder and then re-stirred with diethyl ether (470 ml) for 4 h at ambient temperature. The insoluble product was filtered off, washed with diethyl ether (100 ml) and dried at 50° C./vacuum/24 h to afford title compound as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].[H-].[Na+].CN(C)C=O.[CH3:18][O:19][CH2:20]Cl>O1CCCC1>[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH2:18][O:19][CH3:20])[CH:5]=[O:6]
Reactant: O=Cc1ccc(O)c(O)c1
Reactant: COCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: COCOc1ccc(C=O)cc1O
Temperature: 25 °C
Reaction time: 1 h
Yield: 45 %

Procedure:
3 g of 3,4-dihydroxybenzaldehyde and 0.87 g of 60% oily sodium hydride were suspended in 13 ml of tetrahydrofuran, and a dimethylformamide solution (10 ml) of 3.3 ml of methoxymethyl chloride was added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was distributed between ethyl acetate and water, the organic layer was worked up in a customary manner, and then purified by silica gel column chromatography [Wakogel C-200, 150 g; eluting solvent: hexane/ethyl acetate=4/1] to give 1.78 g (yield 45%) of 3-hydroxy-4-methoxymethyloxybenzaldehyde.
Reaction SMILES: [N:1]1([C:7]([N:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[CH2:12][CH:11]([C:25]([OH:27])=O)[CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.O.S(O)(O)(=O)=O.O[NH:77][C:78]([NH2:80])=[NH:79].ONC(N)=N>CN(C=O)C>[NH2:80][C:78]1[N:79]=[C:25]([CH:11]2[CH2:12][CH:13]([C:15]3[CH:16]=[CH:17][C:18]([C:21]([F:22])([F:24])[F:23])=[CH:19][CH:20]=3)[CH2:14][N:9]([C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:8])[CH2:10]2)[O:27][N:77]=1
Reactant: N=C(N)NO
Reactant: O=C(O)C1CC(c2ccc(C(F)(F)F)cc2)CN(C(=O)N2CCOCC2)C1
Agent: F[P-](F)(F)(F)(F)F
Agent: O=S(=O)(O)O
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Nc1noc(C2CC(c3ccc(C(F)(F)F)cc3)CN(C(=O)N3CCOCC3)C2)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Under argon, a solution of 11.9 g (30.7 mmol) of carboxylic acid from Example 4A in 150 ml of DMF was admixed at RT with 19.2 g (36.8 mmol) of PYBOP and 10.7 ml (61.4 mmol) of N,N′-diisopropylethylamine. Subsequently, the mixture was stirred at RT for 30 min and then the solution was added dropwise within 1.5 h to a suspension of 24.5 g (92.1 mmol) of hydroxyguanidine hemisulphate hemihydrate, 16.1 ml (92.1 mmol) of N,N′-diisopropylethylamine and 4 Å molecular sieve. The reaction mixture was stirred at RT for 1 h and then filtered through a frit. The residue was washed with 200 ml of DMF and then the combined organic phases were stirred at 130° C. (preheated oil bath) for 1.5 h. Subsequently, the solvent was removed under reduced pressure and the residue was admixed with 300 ml of diethyl ether and 300 ml of 1 N aqueous sodium hydroxide solution, and stirred vigorously for 24 h. The solid formed was filtered off, washed with water and diethyl ether and then dried under high vacuum. Yield: 8.80 g (66% of theory)
Reaction SMILES: [CH3:1]OC(C1C(N)N(CC2C=CC=CC=2)CCC=1)=O.[OH-].[Na+].[CH3:21][O:22][C:23]([C:25]1[CH2:26][N:27]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:28][CH2:29][C:30]=1[NH2:31])=[O:24].C(O)(C(F)(F)F)=O.[BH4-].[Na+].[NH4+].[Cl-]>C(O)C.C1COCC1>[CH2:21]([O:22][C:23]([CH:25]1[CH:30]([NH2:31])[CH2:29][CH2:28][N:27]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:26]1)=[O:24])[CH3:1]
Reactant: COC(=O)C1=C(N)CCN(Cc2ccccc2)C1
Reactant: COC(=O)C1=CCCN(Cc2ccccc2)C1N
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O=C(O)C(F)(F)F
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)C1CN(Cc2ccccc2)CCC1N
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
Amino-1-benzyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester BH3 salt was heated in ethanol with NaOH 25%. After 72 h at 50° C. the mixture was cooled, washed with water/ice and extracted with AcOEt. The extract was washed with brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave an yellow oil. To a suspension of 4-amino-1-benzyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester (21 g) in 200 ml THF was added 50 ml TFA at 10° C. under an argon atmosphere. After stirring for 15 min at 0° C., NaBH4 (6.43 g) was added over a period of 75 min at 10° C. The mixture was stirred for additional 90 min at 0° C. After adding 100 ml NH4Cl saturated, the solution was extracted two times with CH2Cl2. The combined extracts were washed with water/ice and brine and dried over sodium sulfate. Evaporation of the solvent gave a yellow oil of the title compound which was taken for the next step without purification
Reaction SMILES: [CH2:1]1[C:3]([NH2:7])([C:4]([OH:6])=[O:5])[CH2:2]1.[C:8]([O:16][CH2:17][CH2:18][O:19][C:20](ON1C(=O)CCC1=O)=[O:21])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[C:9]1([C:8]([O:16][CH2:17][CH2:18][O:19][C:20]([NH:7][C:3]2([C:4]([OH:6])=[O:5])[CH2:2][CH2:1]2)=[O:21])=[O:15])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: O=C(OCCOC(=O)c1ccccc1)ON1C(=O)CCC1=O
Reactant: NC1(C(=O)O)CC1
Product: O=C(NC1(C(=O)O)CC1)OCCOC(=O)c1ccccc1
Yield: 38.5 %

Procedure:
Following the general procedure for the synthesis of acyloxyalkyl carbamates, ACPC (121 mg, 1.1 mmol) and (2,5-dioxoazolidinyloxycarbonyloxy)ethyl benzoate (341 mg, 1.0 mmol) were reacted to provide 113 mg (35% yield) of the title compound (4) as a white powder after work-up and mass-guided preparative HPLC purification. M.p.: 173.8-175.8° C. 1H NMR (CD3CN, 400 MHz): δ=8.00 (d, 2H), 7.61 (t, 1H), 7.50 (t, 2H), 6.99 (q, 1H), 6.31 (s, 0.8H), 6.01 (br s, 0.2H), 1.60 (d, 3H), 1.42 (m, 2H), 1.09 (m, 2H). MS (ESI) m/z 294.10 (M+H)+; 311.12 (M+NH4)+; 316.11 (M+Na)+; 292.12 (M−H)−.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[C:9]([F:21])=[C:10]([OH:20])[C:11]([CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)=[CH:12][CH:13]=2)=[N:6][CH:7]=1.Cl[C:23]1[N:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C([O-])([O-])=O.[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CS(C)=O>[CH:14]1([C:11]2[CH:12]=[CH:13][C:8]([C:5]3[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=3)=[C:9]([F:21])[C:10]=2[O:20][C:23]2[N:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: Clc1ncccn1
Reactant: Nc1cnc(-c2ccc(C3CCCCC3)c(O)c2F)cn1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: Nc1cnc(-c2ccc(C3CCCCC3)c(Oc3ncccn3)c2F)cn1
Temperature: 120 °C
Yield: 57.5 %

Procedure:
A mixture consisting of 3-(5-aminopyrazin-2-yl)-6-cyclohexyl-2-fluorophenol (0.05 g, 0.2 mmol), 2-chloropyrimidine (0.025 g, 0.22 mmol), K2CO3 (0.05 g, 0.4 mmol), and 18-crown-6 (0.01 g, 0.04 mmol), and DMSO (2 mL) was heated via microwave irradiation for 1 hour at 120° Celsius. After cooling to room temperature, the reaction mixture was filtered and purified directly via HPLC to yield the title compound (42 mg, 65%). MS (ESI): mass calcd. for C20H20FN5O, 365.17; m/z found, 366.1 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.63-8.60 (m, 2H), 8.28-8.24 (m, 1H), 8.20-8.18 (m, 1H), 7.80-7.76 (m, 1H), 7.31-7.23 (m, 2H), 2.81-2.74 (m, 1H), 1.83-1.68 (m, 5H), 1.53-1.43 (m, 2H), 1.35-1.24 (m, 3H).
Reaction SMILES: [CH3:1][S-:2].[Na+].F[C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[CH3:13]>CN(C=O)C>[CH3:13][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:5]=1[S:2][CH3:1])[C:9]#[N:10]
Reactant: C[S-]
Reactant: Cc1cc(C#N)ccc1F
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1ccc(C#N)cc1C
Temperature: 80 °C

Procedure:
Sodium methanethiolate (1.60 g, 22.8 mmol) is added to a solution of 4-fluoro-3-methyl-benzonitrile (2.50 g, 18.5 mmol) in DMF, and the mixture is heated at 80° C. for 15 min. All volatiles are evaporated, and the residue is treated with water. The mixture is extracted with ethyl acetate twice, and the organic layer is dried over Na2SO4 and concentrated. Yield: 3.0 g (99% of theory); ESI mass spectrum: [M+H]+=164; r.t. HPLC: 0.61 min (X011_S03).
Reaction SMILES: [S:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]=[O:11].[BH4-].[Na+]>C(O)C>[OH:11][CH2:10][C:2]1[S:1][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1
Reactant: O=Cc1cc2cccnc2s1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OCc1cc2cccnc2s1
Yield: 84.8 %

Procedure:
Thieno[2,3-b]pyridine-2-carboxaldehyde (1.63 g) prepared according to J. Het. Chem. 355 (1974) was dissolved in ethanol (20 ml) and to the solution was added sodium borohydride (0.19 g). After 30 minutes the solution was evaporated to dryness and the residue extracted with methylene chloride (50 ml). The organic extract was washed with water (2×25 ml), the extract dried and then evaporated to obtain 2-hydroxymethylthieno[2,3-b]pyridine (1.40 g) as an amber oil. 'HNMR (CDCl3,60 MHz): 4.9 (s, 1H), 6.3 (s, 1H), 6.9 s, 1H), 7.1 (m, 1H), 7.8 (m, 1H), 8.4 (m, 1H). This product was dissolved in a solution of pyridine (2 ml) in methylene chloride (20 ml) and to the resulting solution was added methane sulfonyl chloride (1.14 g). Upon stirring overnight at room temperature, the solution was poured onto ice water (25 ml). The methylene chloride layer was separated, washed with water (2×10 ml) and then dried and evaporated. The residue was purified by chromatography on silica gel with a mixture of methylene chloride-ethyl acetate (9:1) as eluant to obtain the title compound (0.76 g; m.p. 47°-49° C.).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.C(Cl)(=O)C(Cl)=O.[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:25]C)=[CH:21][CH:20]=1.[Al+3].[Cl-].[Cl-].[Cl-]>ClCCl.CN(C=O)C>[F:18][C:19]1[CH:20]=[CH:21][C:22]([OH:25])=[C:23]([C:9](=[O:11])[CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH:24]=1
Reactant: COc1ccc(F)cc1
Reactant: O=C(O)Cc1ccccc1F
Agent: O=C(Cl)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cc1ccccc1F)c1cc(F)ccc1O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 54 %

Procedure:
2-Fluorophenylacetic acid (2.0 g, 13.14 mmoles) was dissolved in 20 ml dichloromethane. To this mixture, oxalylchloride (1.66 g, 13.14 mmoles) and DMF (3 drops) were added at 0° C. and stirred for 30 min. The solvent was evaporated and dissolved in 20 ml dichloromethane. To this mixture, 4-fluoroanisole (1.10 g, 8.76 mmoles) was added and cooled to 0° C. At 0° C. AlCl3 (1.75 g, 13.14 mmoles) was added and the reaction mixture was warmed to RT and stirred for 12 h. The reaction mixture was quenched by the addition of 2N HCl, extracted with ethyl acetate, dried over sodium sulphate and concentrated. The crude product was purified by column chromatography with ethyl acetate:petroleum ether to afford the title compound as off-white solid (1.17 g, 54% yield. 1H-NMR (δ ppm, DMSO-D6, 400 MHz): δ 11.25 (s, 1H), 7.73 (dd, J=9.5, 3.2 Hz, 1H), 7.43 (dt, J=8.8, 3.1 Hz, 1H), 7.35 (d, J=6.2 Hz, 1H), 7.31 (d, J=7.2 Hz, 1H), 7.19 (d, J=8.2 Hz, 1H), 7.03 (dd, J=9.1, 4.6 Hz, 1H), 4.50 (s, 2H).
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11](=[O:38])[C@H:12]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[NH:13][C:14](=[O:30])[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][NH:22]C(OC(C)(C)C)=O)=[CH:17][CH:16]=1)[CH3:9]>C(Cl)Cl>[NH2:22][CH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:14]([NH:13][C@H:12]([C:11]([O:10][CH2:8][CH3:9])=[O:38])[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:30])=[CH:20][CH:19]=1
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(CNC(=O)OC(C)(C)C)cc1)C(=O)OCC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)CC[C@H](NC(=O)c1ccc(CN)cc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 88.2 %

Procedure:
About 1.8 ml trifluoroacetic acid was added dropwise to a stirred solution containing about 1.0 g of Compound 34 in about 20 ml CH2Cl2. The mixture was stirred at room temperature for 15 minutes, evaporated to dryness under reduced pressure, and co-evaporated twice with about 30 ml absolute ethanol. The residue was then subjected to column chromatography on silica gel (1.5×15 cm), eluting with a gradient of 5-10% methanol in CHCl3 to yield about 0.68 g of Compound 35.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C:21](=[O:31])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[F:30])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CN(C)[CH:34]=[O:35].Cl>O1CCCC1.O>[CH2:13]([O:20][C:21](=[O:31])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([CH:34]=[O:35])[C:24]=1[F:30])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CN(C)C=O
Reactant: O=C(Nc1ccc(F)cc1F)OCc1ccccc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Solvent: O
Product: O=Cc1c(F)ccc(NC(=O)OCc2ccccc2)c1F
Temperature: -78 °C
Reaction time: 1 h
Yield: 93.5 %

Procedure:
Into a round bottom flask under nitrogen, diisopropylamine (17.68 g, 174.7 mmol) and 100 mL of anhydrous tetrahydrofuran were added under nitrogen. The solution was cooled to −78° C. and n-butyllithium (1.60 M in hexane, 109.2 mL, 174.7 mmol) was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour. (2,4-difluoro-phenyl)-carbamic acid benzyl ester (24, 20.00 g, 76.0 mmol) in 100 mL of anhydrous tetrahydrofuran was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour. Anhydrous dimethylformamide (13.88 g, 190.0 mmol) was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 15 minutes. The reaction mixture was poured into 150 mL of water, acidified to pH 1 with 2 M aqueous hydrochloric acid, and extracted with 3×150 mL of ethyl acetate. The organic layers were combined and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was slurried in hexane, filtered and the solid collected and dried to provide the desired compound (25, 20.69 g, 93%).
Reaction SMILES: [C:1](Cl)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:21]1[CH:25]=[C:24]([CH2:26][OH:27])[N:23]=[CH:22]1.C(N(CC)CC)C>CN(C=O)C>[C:1]([N:21]1[CH:25]=[C:24]([CH2:26][OH:27])[N:23]=[CH:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1c[nH]cn1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: OCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1

Procedure:
Trityl chloride (45.57 g, 0.163 mol), (1H-imidazol-4-yl)-methanol (20.00 g, 0.148 mol) and triethylamine (37.46 g, 0.370 mol) in DMF (150 mL) are stirred at r.t. for 16 h, whereupon the mixture is poured into ice-cold water. The precipitate is filtered off and dried under high vacuum to give (1-trityl-1H-imidazol-4-yl)-methanol as a solid. Crude (1-trityl-1H-imidazol-4-yl)-methanol (26.4 g, 0.077 mol), imidazole (15.88 g, 0.233 mol), DMAP (0.950 g, 7.7 mmol) and TBSCl (12.89 g, 0.085 mol) in DMF (0.1 L) are stirred at r.t. for 2 h, whereupon water is added. The mixture is extracted three times with dichloromethane. The organic layer is dried over Na2SO4 and concentrated in vacuo. The residue is purified by silica gel flash chromatography (elution with hexanes-ethyl acetate, 7:3) to yield 4-(tert-butyl-dimethyl-silanyloxymethyl)-1-trityl-1H-imidazole as a white solid; MS (ESI) m/z 243, 455 (M+H).
Reaction SMILES: [C:1]([C:5]1[C:14](=O)[C:13]2[C:8](=[C:9]([O:16][CH3:17])[CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)(=[O:4])[CH2:2][CH3:3].P(Cl)(Cl)([Cl:20])=O>>[C:1]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([C:14]=1[Cl:20])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][CH3:17])(=[O:4])[CH2:2][CH3:3]
Reactant: CCC(=O)c1c[nH]c2c(OC)cccc2c1=O
Reactant: O=P(Cl)(Cl)Cl
Product: CCC(=O)c1cnc2c(OC)cccc2c1Cl

Procedure:
3-Propanoyl-8-methoxy-4(1H)-quinolone (35.4 g, 0.15 mol) was dissolved in phosphoryl chloride (400 ml) and heated at reflux for 1 hour, then the excess phosphoryl chloride evaporated. The residue was mixed with ice, then diluted with water and extracted into dichloromethane. Drying and evaporation gave 3-propanoyl-4-chloro-8-methoxyquinoline (39.7 g) as a dark oil which was used without further purification.
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:6]=[CH:7][C:8]2[O:14][CH2:13][CH:12]3[CH2:15][CH2:16][CH2:17][CH2:18][N:11]3[CH2:10][C:9]=2[CH:19]=1)([O-])=O>CO.[Pd]>[ClH:1].[NH2:2][C:5]1[CH:6]=[CH:7][C:8]2[O:14][CH2:13][CH:12]3[CH2:15][CH2:16][CH2:17][CH2:18][N:11]3[CH2:10][C:9]=2[CH:19]=1
Reactant: O=[N+]([O-])c1ccc2c(c1)CN1CCCCC1CO2
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: Nc1ccc2c(c1)CN1CCCCC1CO2
Reaction time: 1 h
Yield: 103.6 %

Procedure:
2-Nitro-6,6a,7,8,9,10-hexahydro-12H-pyrido[2,1-c][1,4]benzoxazepine hydrochloride (2.46 g) dissolved in methanol (50 ml) was treated with 10% Pd-C (0.25 g), and hydrogenated on a Parr Hydrogenator for one hour, filtered and evaporated to yield a tacky solid (2.28 g).
Reaction SMILES: Br[C:2]1[CH:20]=[CH:19][C:5]([N:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH3:21][C:22]1([CH3:67])[C:26]([CH3:28])([CH3:27])[O:25][B:24]([C:29]2[CH:41]=[CH:40][C:39]3[C:38]4[C:33](=[CH:34][C:35](B5OC(C)(C)C(C)(C)O5)=[CH:36][CH:37]=4)[C:32]([CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH3:66])([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[C:31]=3[CH:30]=2)[O:23]1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].CC(C)=O.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.C1(C)C=CC=CC=1.CCCCCC.O>[CH2:59]([C:32]1([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[C:33]2[CH:34]=[C:35]([C:2]3[CH:20]=[CH:19][C:5]([N:6]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[CH:4][CH:3]=3)[CH:36]=[CH:37][C:38]=2[C:39]2[C:31]1=[CH:30][C:29]([B:24]1[O:23][C:22]([CH3:21])([CH3:67])[C:26]([CH3:27])([CH3:28])[O:25]1)=[CH:41][CH:40]=2)[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH3:66]
Reactant: CCCCCCCCC1(CCCCCCCC)c2cc(B3OC(C)(C)C(C)(C)O3)ccc2-c2ccc(B3OC(C)(C)C(C)(C)O3)cc21
Reactant: Brc1ccc(N(c2ccccc2)c2ccccc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCCCCC
Solvent: CC(C)=O
Product: CCCCCCCCC1(CCCCCCCC)c2cc(B3OC(C)(C)C(C)(C)O3)ccc2-c2ccc(-c3ccc(N(c4ccccc4)c4ccccc4)cc3)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-Bromo-N,N-diphenylaniline (11) (19.44 g, 60 mmole, 1 equiv), 2-[9,9-dioctyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluoren-2-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2) (76.9 g, 120 mmole, 2 equiv), Aliquat® 336 (6 g, 15 mmole, 0.25 equiv) and 2M sodium carbonate solution (75 mL, 150 mmole, 2.5 equiv) were added to 600 mL of toluene. This was purged with a stream of nitrogen for about 30 min. Under a nitrogen purge, tetrakis(triphenylphosphine)palladium (348 mg, 0.30 mmole, 0.005 equiv) was added. The reaction mixture was then refluxed for 16 hrs. The reaction was cooled to RT and water added. The organic layer was separated and washed with water followed by brine. Drying of the organic layer over Na2SO4 and evaporation of the solvent gave a light yellow solid. This was suspended in acetone and the mixture brought to reflux and then allowed to stand at RT overnight. Filtration of the solid and concentration of the filtrate gave a solid that was subjected to column chromatography (toluene/hexane 3:7) to give 4-[9,9-dioctyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluoren-2-yl]-N,N-diphenylaniline (12).