Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11].C(N(CC)CC)C.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].O>ClCCl>[Si:19]([O:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1CCc2c(O)cccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.2 %

Procedure:
To a solution of 4-hydroxy-1-indanone (594 mg) and triethylamine (0.7 ml) in dry dichloromethane (10 ml) was added tert-butyldimethylsilyl chloride (724 mg) in several portions at 0° C. The mixture was stirred overnight at ambient temperature and then poured into a mixture of water (30 ml) and dichloromethane (20 ml). The separated organic layer was washed with 1N-hydrochloric acid, brine and aqueous saturated sodium bicarbonate solution, succeedingly. The solution was dried and evaporated in vacuo. The residue was purified by columnchromatography on silica gel eluted by dichloromethane to give 4-(tert-butyldimethylsilyl)oxy-1-indanone (1.002 g) as an oil.
Reaction SMILES: [C:1]([C:3]1[CH:17]=[C:16](I)[C:6]2[N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1)#[N:2].C1(C)C=CC=CC=1.[CH3:26][N:27]([CH3:37])[C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>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.C(O)C>[C:1]([C:3]1[CH:17]=[C:16]([C:32]2[CH:31]=[CH:30][CH:29]=[C:28]([N:27]([CH3:37])[CH3:26])[CH:33]=2)[C:6]2[N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1)#[N:2]
Reactant: CN(C)c1cccc(B(O)O)c1
Reactant: N#Cc1cc(I)c2c(c1)ncn2-c1ccccc1
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: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CN(C)c1cccc(-c2cc(C#N)cc3ncn(-c4ccccc4)c23)c1
Yield: 37.8 %

Procedure:
5-Cyano-7-iodo-1-phenylbenzimidazole (173 mg, 0.5 mmol), toluene (3.0 ml), tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol), 3-dimethylaminophenylboronic acid (82 mg, 0.5 mmol), ethanol (3.0 ml) and potassium carbonate (138 mg, 1.0 mmol) were combined and the mixture was stirred at reflux overnight. The solvent was removed under reduced pressure and crude product was purified on a 2 g silica Isolute® SPE column, eluting with dichloromethane/methanol (95:5). The eluent was concentrated under reduced pressure and the crude product was suspended in acetonitrile then treated with diethyl ether to precipitate the product Recrystallisation from diethyl ether afforded the title compound (64 mg, 38%) m/z, 339.0 (M+H)+.
Reaction SMILES: [CH3:1][C:2](/[CH:4]=[N:5]/O)=O.[CH3:7][C:8]1([CH3:16])[CH2:13][C:12](=O)[CH2:11][C:10](=[O:15])[CH2:9]1>OC(C)=O.O.[Zn]>[CH3:1][C:2]1[C:11]2[C:10](=[O:15])[CH2:9][C:8]([CH3:7])([CH3:16])[CH2:13][C:12]=2[NH:5][CH:4]=1
Reactant: CC(=O)/C=N/O
Reactant: CC1(C)CC(=O)CC(=O)C1
Agent: [Zn]
Solvent: O
Solvent: CC(=O)O
Product: Cc1c[nH]c2c1C(=O)CC(C)(C)C2
Temperature: 25 °C
Yield: 44.2 %

Procedure:
To a solution of anti-pyruvic aldehyde-1-oxime (10 g, 1 eq) and 5,5-dimethyl-1,3-cyclohexanedione (16.1 g, 1 eq) in HOAc-H2O (7:3, 200 mL) was added zinc powder (14.95 g, 2 eq) slowly with cooling by a water bath at room temperature. The mixture then was refluxed overnight, concentrated to dryness, partitioned between brine (300 mL) and dichloromethane (300 mL). The pH was adjusted to ca. 6 with saturated aqueous NaHCO3, then the mixture was extracted with dichloromethane (3×200 mL). The organic layers were combined, dried over Na2SO4, filtered, concentrated. The crude product was purified by flash chromatography eluting with 5% ethyl acetate in dichloromethane. The combined organic fractions were concentrated, triturated in ether-hexane (2:1) for 1 hour, then filtered, washed with hexane to give the pure title compound (9 g, 45% yield) as a solid. LCMS m/z: (M+H)=178.1.
Reaction SMILES: CN(C=O)C.[C:6]([Cl:11])(=O)[C:7](Cl)=O.[N:12]1[C:17]2[CH:18]=[CH:19][S:20][C:16]=2C(=O)N[CH:13]=1.O>C(Cl)Cl>[Cl:11][C:6]1[CH:7]=[CH:13][N:12]=[C:17]2[CH:18]=[CH:19][S:20][C:16]=12
Reactant: O=c1[nH]cnc2ccsc12
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O
Product: Clc1ccnc2ccsc12
Yield: 100 %

Procedure:
To a solution of DMF (13.2 mL, 170 mmol) in DCM (100 mL) at 0° C. was added oxalyl chloride (22 mL, 252 mmol) in DCM (100 mL) very slowly over 1 hour. To the resulting white gel solution was added the 3H-thieno[3,2-d]pyrimidin-4-one (12 g, 79 mmol). The mixture was refluxed for 4 hours. After cooling, the mixture was purred into water (500 mL) and extracted with DCM (3×250 mL). Then the organic phase was dried over magnesium sulfate, filtered and concentrated to afford 7-chloro-thieno[3,2-b]pyridine as white solid (13.4 g, 99%). 1H NMR (CDCl3, 400 Hz) δ 9.00 (s, 1H), 8.06 (d, J=5.6 Hz, 1H), 7.61 (d, J=5.6 Hz, 1H). MS (ESI+) [M+H]+ 170
Reaction SMILES: Br[C:2]1[S:19][C:5]2[CH2:6][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C@H:9]([CH3:11])[O:10][C:4]=2[C:3]=1[CH:20]([CH3:22])[CH3:21].[CH3:23]B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].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.O>[CH3:11][C@H:9]1[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][C:5]2[S:19][C:2]([CH3:23])=[C:3]([CH:20]([CH3:22])[CH3:21])[C:4]=2[O:10]1
Reactant: CB(O)O
Reactant: CC(C)c1c(Br)sc2c1O[C@@H](C)CN(C(=O)OC(C)(C)C)C2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: Cc1sc2c(c1C(C)C)O[C@@H](C)CN(C(=O)OC(C)(C)C)C2
Yield: 92.9 %

Procedure:
A solution of tert-butyl (2S)-7-bromo-2-methyl-8-(1-methylethyl)-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate (400 mg), methylboronic acid (245 mg), potassium phosphate (870 mg), tetrakis(triphenylphosphine)palladium (118 mg) and DME (6 mL) was stirred at 80° C. for 16 hr, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 3→7% ethyl acetate/hexane) to give the title compound (310 mg, 93%) as a solid.
Reaction SMILES: [CH2:1]([S:5](Cl)(=[O:7])=[O:6])[CH2:2][CH2:3][CH3:4].[C:9]1([O:19][CH3:20])[C:10](=[CH:12][CH:13]=[C:14]([CH:18]=1)[CH2:15][CH:16]=[CH2:17])[OH:11].C(N(CC)CC)C.O>ClCCl>[CH2:1]([S:5]([O:11][C:10]1[CH:12]=[CH:13][C:14]([CH2:15][CH:16]=[CH2:17])=[CH:18][C:9]=1[O:19][CH3:20])(=[O:7])=[O:6])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCS(=O)(=O)Cl
Reactant: C=CCc1ccc(O)c(OC)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: C=CCc1ccc(OS(=O)(=O)CCCC)c(OC)c1
Temperature: -20 °C
Reaction time: 4 h
Yield: 94.9 %

Procedure:
13 ml (0.1 mol) of butanesulfonyl chloride are added dropwise to a solution of 15 g (0.09 mol) of eugenol and 16 ml (0.11 mol) of triethylamine in 150 ml of dichloromethane cooled beforehand to −20° C. The reaction mixture is stirred for 4 hours at room temperature. The reaction is treated by adding 50 ml of water and extracting with dichloromethane. The organic phase is dried over sodium sulfate, filtered and evaporated. The residue is purified by chromatography on a column of silica eluted with a 90/10 heptane/ethyl acetate mixture. 24.3 g (74%) of 4-allyl-2-methoxyphenyl 1-butane-1-sulfonate are obtained in the form of a yellow oil.
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][C:11]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(Cl)(Cl)Cl>[OH:8][CH2:9][CH2:10][C:11]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[CH2:12]1
Reactant: CC(C)(C)OC(=O)N1CCOC(CCO[Si](C)(C)C(C)(C)C)(c2ccccc2)C1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)N1CCOC(CCO)(c2ccccc2)C1
Yield: 83 %

Procedure:
The above tert-butyl 2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-phenylmorpholine-4-carboxylate was stirred in 4 mL of a 1 M solution of tetrabutylammonium fluoride in THF for 1 h at room temperature. The reaction mixture was then diluted with CHCl3, washed with saturated aqueous NaHCO3, and purified (1:1 hex:EtOAc) to provide tert-butyl 2-(2-hydroxyethyl)-2-phenylmorpholine-4-carboxylate (449 mg, 83%) as an oil: 1H NMR (400 MHz, CDCl3), δ 7.47-7.41 (m, 2H), 7.40-7.35 (m, 2H), 7.28 (m, 1H), 4.34 (m, 1H), 3.77-3.63 (m, 2H), 3.63-3.48 (m, 3H), 3.35 (m, 1H), 3.17 (m, 1H), 2.08 (m, 1H), 1.89 (m, 1H), 1.50-1.37 (br., 9H); ESI-MS 330 (M+Na).
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2)([O-:5])=[O:4].C(OC([N:22]1[C:30]2[C:25](=[C:26]([CH2:31]Cl)[CH:27]=[CH:28][N:29]=2)[CH:24]=[CH:23]1)=O)(C)(C)C>C1COCC1>[N+:3]([C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][N:10]2[CH2:31][C:26]1[CH:27]=[CH:28][N:29]=[C:30]2[NH:22][CH:23]=[CH:24][C:25]=12)([O-:5])=[O:4]
Reactant: O=[N+]([O-])c1cccc2[nH]ccc12
Reactant: CC(C)(C)OC(=O)n1ccc2c(CCl)ccnc21
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cccc2c1ccn2Cc1ccnc2[nH]ccc12
Reaction time: 4 h
Yield: 15.8 %

Procedure:
The title compound was also prepared according to the following method. Specifically, sodium hydride (144 mg, 6 mmol) was added to a solution of 4-nitroindole (973 mg, 6 mmol) in THF and the resulting mixture was stirred for 4 h. 1-(t-butyloxycarbonyl)-4-chloromethyl-7-azaindole (Int-11, 1.5 g, 5.5 mmol) was then added. After the reaction was complete (by TLC), the mixture was quenched with saturated aqueous ammonium chloride. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by flash column chromatography to provide 4-[(4-nitro-1H-indol-1-yl)methyl]-1H-pyrrolo[2,3-b]pyridine (254 mg, 16%).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].FC(F)(F)C(O)=O.[Cl:15][C:16]1[CH:17]=[N:18][C:19]2[NH:20][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH:46]=3)[CH2:26][CH2:27][C:28]3[CH:36]=[C:32]([NH:33][C:34]=1[N:35]=2)[CH:31]=[CH:30][C:29]=3[NH:37][C:38]([CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)=[O:39].[C:47](Cl)(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:47]([N:43]1[CH2:44][CH2:45][CH:40]([C:38]([NH:37][C:29]2[CH:30]=[CH:31][C:32]3[NH:33][C:34]4[N:35]=[C:19]([NH:20][C:21]5[CH:22]=[CH:23][CH:24]=[C:25]([CH:46]=5)[CH2:26][CH2:27][C:28]=2[CH:36]=3)[N:18]=[CH:17][C:16]=4[Cl:15])=[O:39])[CH2:41][CH2:42]1)(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: O=C(Nc1ccc2cc1CCc1cccc(c1)Nc1ncc(Cl)c(n1)N2)C1CCNCC1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1ccc2cc1CCc1cccc(c1)Nc1ncc(Cl)c(n1)N2)C1CCN(C(=O)c2ccccc2)CC1
Yield: 18 %

Procedure:
The desired compound was prepared according to the procedure of Example A20, using N-[6-chloro-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20), 3(22),4,6,9(21),10,12,16,18-nonaen-12-yl]piperidine-4-carboxamide bis(trifluoroacetate) and benzoyl chloride as starting materials in 18% yield. LCMS for C31H30ClN6O2 (M+H)+: m/z=553.2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:15]([NH:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)=[CH:14][NH:13][N:12]=2)=[O:10])=[CH:4][CH:3]=1.[C:23]1(=O)CCCCC1.C=O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[C:15]([N:16]([CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[CH3:23])=[CH:14][NH:13][N:12]=2)=[O:10])=[CH:6][CH:7]=1
Reactant: O=C(Nc1ccc(F)cc1)c1n[nH]cc1NC1CCCCC1
Reactant: O=C1CCCCC1
Agent: C=O
Product: CN(c1c[nH]nc1C(=O)Nc1ccc(F)cc1)C1CCCCC1

Procedure:
This compound was prepared in a manner analogous to the compound of Example 19 by succssive reductive alkylations using firstly cyclohexanone and then formaldehyde. (LC/MS: Rt 2.77 [MH]+ 316.71).
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH2:11][C:10]([F:22])([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:9]1)(C)(C)C.Cl>O1CCOCC1>[F:22][C:10]1([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:11][CH2:12][CH2:13][CH:8]([NH2:7])[CH2:9]1
Reactant: CC(C)(C)OC(=O)NC1CCCC(F)(Cc2ccccc2F)C1
Agent: Cl
Solvent: C1COCCO1
Product: NC1CCCC(F)(Cc2ccccc2F)C1
Reaction time: 8 h

Procedure:
tert-Butyl-3-fluoro-3-(2-fluorobenzyl)cyclohexylcarbamate was reacted with HCl in dioxane (4 M) at room temperature. After stirring for overnight, 3-fluoro-3-(2-fluorobenzyl)cyclohexanamine was obtained after the removal of solvent by rotary evaporation.
Reaction SMILES: [CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([O:16][CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH:23]([N:26]=[C:27]=[O:28])([CH3:25])[CH3:24]>ClCCl>[CH:23]([NH:26][C:27]([N:20]1[CH2:21][CH2:22][CH:17]([O:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][N:5]([CH:1]4[CH2:2][CH2:3][CH2:4]4)[CH2:11][CH2:10][C:9]=3[CH:12]=2)[CH2:18][CH2:19]1)=[O:28])([CH3:25])[CH3:24]
Reactant: CC(C)N=C=O
Reactant: c1cc2c(cc1OC1CCNCC1)CCN(C1CCC1)CC2
Solvent: ClCCl
Product: CC(C)NC(=O)N1CCC(Oc2ccc3c(c2)CCN(C2CCC2)CC3)CC1

Procedure:
A solution of 3-cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (E6) (150 mg, 0.5 mmol) and isopropyl isocyanate (60 μL, 0.6 mmol) in dichloromethane (5 ml) was stirred at room temperature for 16 hours. The solution was concentrated in vacuo and the residue was purified by column chromatography eluting with dichloromethane then a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90) to afford the title product (E66). MS (ES+) m/e 386 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([C:15]([O:17]CC)=[O:16])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.O[Li].O.Cl.CCOC(C)=O>C1COCC1.O>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([C:15]([OH:17])=[O:16])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1
Reactant: CCOC(=O)[C@@H]1CCC[C@H](Nc2nc(Cl)ncc2F)C1
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)[C@@H]1CCC[C@H](Nc2nc(Cl)ncc2F)C1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To a solution of (1R,3S)-ethyl 3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexane-carboxylate, 19, (20.0 g, 66.3 mmol) in THF (150 mL) was added added a solution of LiOH hydrate (8.3 g, 198.8 mmol) in 100 ml water. The reaction mixture was stirred at 50° C. overnight, To the reaction mixture was added HCl (16.6 mL of 12 M solution, 198.8 mmol) and EtOAc. The organic phase was washed with brine and dried over MgSO4 and the solvent was removed under reduced pressure to afford 17.5 g of product that was used without further purification: 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J=2.7 Hz, 2H), 5.24 (d, J=7.3 Hz, 2H), 4.19-4.03 (m, 3H), 3.84-3.68 (m, 3H), 2.59 (ddd, J=11.5, 8.2, 3.6 Hz, 2H), 2.38 (d, J=12.4 Hz, 2H), 2.08 (d, J=9.6 Hz, 6H), 1.99-1.76 (m, 5H), 1.63-1.34 (m, 6H), 1.32-1.15 (m, 4H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O[N:19]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.N>C(Cl)(Cl)Cl.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14](=[O:16])[NH2:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: On1nnc2ccccc21
Reactant: CC(C)(C)OC(=O)N1CC=C(C(=O)O)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: N
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(C)(C)OC(=O)N1CC=C(C(N)=O)CC1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 25.6 %

Procedure:
In a mixed solution of 400 ml of chloroform and 100 ml of dimethylformamide, 20.0 g of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine-4-carboxylic acid was dissolved, and 14.2 g of 1-hydroxybenzotriazole hydrate and 17.7 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added thereto. The reaction mixture was stirred for 40 minutes at room temperature. The reaction solution was ice-cooled, and subsequently, 5.6 ml of 28% aqueous ammonia was added thereto, followed by stirring for 6 hours. The reaction mixture was warmed up to room temperature, and was concentrated under reduced pressure. A 5% aqueous solution of potassium hydrogensulfate was poured thereinto. The reaction mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, and was then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:2) to yield 5.1 g of 1-tert-butoxycarbonyl-4-carbamoyl-1,2,3,6-tetrahydropyridine as a crystal.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].Br[C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:12]([O:15][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[CH2:11][CH2:10][CH2:9][CH2:14][CH3:13]
Reactant: Oc1ccc(Br)cc1
Reactant: CCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCCOc1ccc(Br)cc1

Procedure:
A solution of 1-bromohexane (60 g) in acetone (150 ml) is added dropwise to a stirred mixture of 4-bromphenol (71 g) and K2CO3 (120 g) in acetone 600 ml) at room temperature. The stirred mixture is heated under reflux for 43 hrs (i.e. until glc revealed complete reaction). The product is extracted into ether twice, and the combined ethereal extracts are washed with water, 5% NaOH water and dried (MgSO4). The solvent is removed in vacuo and the residue was distilled (bp=100°-110° C. at 0.1 mm Hg) to yield a colourless liquid.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:11][CH2:12][CH2:13]OS(C3C=CC(C)=CC=3)(=O)=O)[CH:8]=2)[NH:3]1.[F:25][C:26]1[CH:38]=[CH:37][C:29]([CH2:30][CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:30][CH:31]2[CH2:32][CH2:33][N:34]([CH2:13][CH2:12][O:11][C:7]3[CH:8]=[C:9]4[C:4](=[CH:5][CH:6]=3)[NH:3][C:2](=[O:1])[CH2:10]4)[CH2:35][CH2:36]2)=[CH:37][CH:38]=1
Reactant: Cc1ccc(S(=O)(=O)OCCOc2ccc3c(c2)CC(=O)N3)cc1
Reactant: Fc1ccc(CC2CCNCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=C1Cc2cc(OCCN3CCC(Cc4ccc(F)cc4)CC3)ccc2N1
Temperature: 25 °C
Yield: 75.8 %

Procedure:
A suspension of toluene-4-sulfonic acid 2-(2-oxo-2,3-dihydro-1H-indol-5-yloxy)-ethyl ester (0.77 g, 2.22 mmol), 4-(4-fluorobenzyl)piperidine (1.1 g, 5.63 mmol), and potassium carbonate (2.2 g, 15.92 mmol) in acetonitrile (75 ml) was refluxed overnight under argon. The reaction mixture was cooled to room temperature and the solid was filtered off and washed with THF (3×20 ml). The filtrate was evaporated, and the solid chromatographed on silica gel eluting with 35% methanol/ethyl acetate to give the title compound (0.62 g, 76%) as a solid, mp 149-150° C. Analysis calculated for C22H25FN2O2 ·0.14H2O: C, 71.21; H, 6.87; N, 7.55; F, 5.12. Found: C, 71.21; H, 6.68; N, 7.49; F, 5.26.
Reaction SMILES: [C:1]1([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16](B(O)O)[CH:17]=3)[CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28](I)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([C:16]2[CH:15]=[CH:14][C:13]3[C:18](=[CH:19][CH:20]=[C:11]([C:1]4[C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[CH:4]=[CH:3][CH:2]=4)[CH:12]=3)[CH:17]=2)=[CH:27][CH:26]=1
Reactant: OB(O)c1ccc2cc(-c3cccc4ccccc34)ccc2c1
Reactant: Brc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1ccc(-c2ccc3cc(-c4cccc5ccccc45)ccc3c2)cc1
Yield: 88.9 %

Procedure:
Under the atmosphere of argon, 3.2 g of 2-(naphthalen-1-yl)naphthalene-6-boronic acid and 2.8 g of 4-bromoiodobenzene were dissolved into 30 ml of toluene, and 0.23 g of tetrakis(triphenyl-phosphine)palladium was added to the obtained solution. After 28 ml of a 2 M aqueous solution of sodium carbonate was added, the resultant mixture was heated under the refluxing condition for 8.5 hours. After the obtained mixture was left standing for one night, the mixture was subjected to extraction with toluene. The extract was washed with a saturated aqueous solution of sodium chloride, and the solvent was removed using an evaporator. The residue was purified in accordance with the silica gel column chromatography (the developing solvent: toluene), and 3.6 g of 2-(4-bromophenyl)-6-(naphthalen-1-yl)naphthalene was obtained as a light yellow solid substance (the yield: 83%).
Reaction SMILES: [CH:1]1[C:18]2[CH:17]=[CH:16][C:15]3[C:6](=[CH:7][CH:8]=[C:9]4[C:14]=3[CH:13]=[CH:12][CH:11]=[CH:10]4)[C:5]=2[CH:4]=[C:3]([C:19](OCC)=[O:20])[CH:2]=1.[Li+].[BH4-].Cl>C1COCC1>[CH:1]1[C:18]2[CH:17]=[CH:16][C:15]3[C:6](=[CH:7][CH:8]=[C:9]4[C:14]=3[CH:13]=[CH:12][CH:11]=[CH:10]4)[C:5]=2[CH:4]=[C:3]([CH2:19][OH:20])[CH:2]=1
Reactant: CCOC(=O)c1ccc2ccc3c4ccccc4ccc3c2c1
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1ccc2ccc3c4ccccc4ccc3c2c1
Yield: 98.3 %

Procedure:
A solution of ethyl chrysene-3-carboxylate (19E 17.7 g, 0.059 mol) in 40 mL THF was treated with LiBH4 (Morton Thiokol, Inc.--Alfa Products, PO Box 299, 152 Andover St., Danvers, MA 01923, 2.7 g, 0.12 mol) in three portions then refluxed for 3 days. The reaction mixture was poured into ice and acidified carefully to pH 1 with 1N HCl. The precipitate was filtered and recrystallized from THF/hexane to afford 14.98 g (98%) of 3-chrysenemethanol mp 187°-189°, (C, H).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C@@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10](OC(C)(C)C)=O)[CH3:3].FC(F)(F)C(O)=O.C(N(CC)CC)C.[CH:31]1([C:34]2[O:35][C:36]3[C:37](=[C:39]([C:51]#[N:52])[C:40]([CH3:50])=[C:41]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)C=3F)[N:38]=2)[CH2:33][CH2:32]1>ClCCl>[CH:31]1([C:34]2[O:35][C:36]3[C:37](=[C:39]([C:51]#[N:52])[C:40]([CH3:50])=[C:41]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)[C:10]=3[N:6]3[CH2:7][CH2:8][CH2:9][C@H:5]3[CH2:4][N:2]([CH3:1])[CH3:3])[N:38]=2)[CH2:33][CH2:32]1
Reactant: CN(C)C[C@@H]1CCCN1C(=O)OC(C)(C)C
Reactant: Cc1c(-c2ccccc2)c(F)c2oc(C3CC3)nc2c1C#N
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1c(-c2ccccc2)c(N2CCC[C@H]2CN(C)C)c2oc(C3CC3)nc2c1C#N
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.8 %

Procedure:
tert-Butyl (2S)-2-[(dimethylamino)methyl]pyrrolidine-1-carboxylate (I-328) (92.0 mg, 0.403 mmol) was dissolved in dichloromethane (1 ml), and at room temperature, trifluoroacetic acid (1 ml) was added, followed by stirring at room temperature for 1 hour. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in dimethyl sulfoxide (2 ml), then triethylamine (84.2 μl, 0.604 mmol) and 2-cyclopropyl-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-173) (118 mg, 0.403 mmol) was added, followed by stirring in an oil bath at 100° C. for 5 hours. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, and washed with water and saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, the residue obtained by concentration was purified by preparative TLC (eluent, chloroform:methanol=10:1, v/v) to obtain the entitled compound (32.0 mg, 20%) as a colorless oily substance.