Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:12]([O:13][C:14]3[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24]C(C)(C)C)=[O:23])=[CH:16][CH:15]=3)=[C:11]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH:35]([CH3:37])[CH3:36])[S:10][C:9]=2[CH:38]=1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:12]([O:13][C:14]3[CH:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([OH:24])=[O:23])=[CH:18][CH:19]=3)=[C:11]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH:35]([CH3:36])[CH3:37])[S:10][C:9]=2[CH:38]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1ccc2c(Oc3ccc(/C=C/C(=O)OC(C)(C)C)cc3)c(-c3ccccc3C(C)C)sc2c1
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Solvent: ClCCl
Product: CC(=O)Oc1ccc2c(Oc3ccc(/C=C/C(=O)O)cc3)c(-c3ccccc3C(C)C)sc2c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 67.5 %

Procedure:
To a solution of (E)-tert-butyl 3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (65 mg, 0.123 mmol) in DCM (3.0 mL) at 0° C. was added TFA dropwise over 5 min. The reaction was stirred at 0° C. for 1 h after which time it was warmed to room temperature for an additional 55 min. The mixture was then diluted with DCM and concentrated in vacuo to remove both DCM and TFA. The crude material was then further azeotroped with DCM (3×) to make sure all of the TFA was removed and gave a pale yellow solid. The resulting crude material was dissolved in MeOH (3 mL) and purified by reverse phase HPLC (acidic conditions, 0.1% TFA in 45-70% CH3CN/H2O) to afford (E)-3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (39.1 mg, 0.083 mmol, 67% yield). 1H NMR (400 MHz, CD3OD) δ ppm=7.69 (d, J=2.0 Hz, 11), 7.57 (d, J=15.9 Hz, 1H), 7.45 (dd, J=8.7, 6.4 Hz, 3H), 7.40-7.26 (m, 3H), 7.18-7.10 (m, 2H), 6.86 (d, J=8.8 Hz, 2H), 6.32 (d, J=16.0 Hz, 1H), 3.20 (p, J=6.9 Hz, 1H), 2.32 (s, 3H), 1.17 (d, J=6.9 Hz, 6H). HRMS (m/z, MH+): 473.1399.
Reaction SMILES: [C:1]([O:5][C:6](=[O:8])[NH2:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)[O:22][C:20](=O)[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15]C1=2)=O>C(Cl)Cl>[O:22]=[CH:20][CH2:19][CH:18]1[CH2:15][CH:16]([NH:7][C:6](=[O:8])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:17]1
Reactant: CC(C)(C)OC(N)=O
Reactant: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1CC(CC=O)C1
Temperature: 25 °C
Reaction time: 5 h
Yield: 52.5 %

Procedure:
To a solution of 3-(2-hydroxy-ethyl)-cyclobutyl]-carbamic acid tert-butyl ester (5.2 g, 24.1 mmol) in anhydrous DCM (100 mL) was added Dess-Martin periodinane (20.5 g, 48.3 mmol) and stirred at room temperature for 5 hrs. The mixture was quenched with Na2S2O3 solution, extracted with DCM. The organic phase was concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (eluted with PE:EA=5:1) to give the title compound (2.7 g, yield 52%) as an oily liquid.
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:10][C:9](=[O:11])[CH2:8]2)[CH:6]=1.[BH4-].[Na+].C(O)C>>[I:1][C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:8][CH:9]([OH:11])[CH2:10]2)[CH:6]=1
Reactant: O=C1CC(n2cc(I)cn2)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OC1CC(n2cc(I)cn2)C1
Temperature: 0 °C
Reaction time: 3 h
Yield: 94.9 %

Procedure:
3-(4-Iodo-pyrazol-1-yl)cyclobutanone (Compound 100D, 1.000 g, 3.816 mmol), sodium borohydride (145.8 mg, 3.854 mmol) and ethanol (22.28 mL, 381.6 mmol) were added to a round bottom flask and the reaction mixture was stirred at 0° C. for 3 h. Reaction mixture was concentrated in vacuo and washed with water extracting with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to afford 956 mg of the final compound as colorless oil. Compound was taken on to the next step without further purification. MS (ES+): m/z 264.86 (100) [MH+]; HPLC: tR=2.50 min (Polar—5 min, ZQ3).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:8]([F:11])([F:10])[F:9])=[N:4][NH:5][C:6]=1[CH3:7].CO.[C:14]([O:18]CC)(=[O:17])[C:15]#[CH:16]>C(O)(=O)C>[Cl:1][C:2]1[C:3]([C:8]([F:9])([F:11])[F:10])=[N:4][N:5](/[CH:16]=[CH:15]/[C:14]([OH:18])=[O:17])[C:6]=1[CH3:7]
Reactant: Cc1[nH]nc(C(F)(F)F)c1Cl
Reactant: C#CC(=O)OCC
Solvent: CO
Solvent: CC(=O)O
Product: Cc1c(Cl)c(C(F)(F)F)nn1/C=C/C(=O)O
Temperature: 80 °C
Reaction time: 2 h
Yield: 56.7 %

Procedure:
To a vial containing 4-Chloro-5-methyl-3-trifluoromethyl-1H-pyrazole (2.83 g, 15.3 mmol) was added MeOH (5 mL) and ethyl propiolate (1.94 g, 19.7 mmol) and acetic acid (100 μL). The vial was capped and the reaction mixture was heated to 80° C. for 20 h. After cooling to room temperature, the volatiles were removed in vacuo to afford the crude products, which were purified by flash chromatography on silica gel (120 g) using gradient elution (0%-75% EtOAc in hexanes over 15 column volumes). The fractions containing the E and Z esters were collected separately and concentrated in vacuo. Each product was then transferred to a separate vial using THF (10 mL). Both vials were treated with a 1.0 N solution of LiOH (10 mL). The vials were heated to 40° C. After 2 h, the solutions were cooled, and each was diluted with water (50 mL). The pH was adjusted to 1 with 4 N HCl. Each aqueous phase was extracted with EtOAc (2×25 mL). The organic phases were dried over MgSO4 and concentrated in vacuo to afford (E)-3-(4-Chloro-5-methyl-3-trifluoromethylpyrazol-1-yl)-acrylic acid (2.21 g, 57% yield) HPLC retention time=2.18 minutes. MS (ES) [M−H]− expected 253.0, found 252.9; and (Z)-3-(4-Chloro-5-methyl-3-trifluoromethylpyrazol-1-yl)acrylic acid (749 mg, 19% yield). MS (ES) [M−H]− expected 253.0, found 252.9.
Reaction SMILES: [Br:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([C@@H:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]2[C:14]([OH:16])=[O:15])=[O:7])=[CH:4][CH:3]=1.[CH3:19][Si:20]([CH3:25])([CH3:24])[CH2:21][CH2:22]O.CCN=C=NCCCN(C)C.O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C@@H:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]2[C:14]([O:16][CH2:22][CH2:21][Si:20]([CH3:25])([CH3:24])[CH3:19])=[O:15])=[O:7])=[CH:17][CH:18]=1
Reactant: O=C(O)[C@@H]1CCCC[C@H]1C(=O)c1ccc(Br)cc1
Reactant: C[Si](C)(C)CCO
Agent: CCN=C=NCCCN(C)C
Solvent: ClCCl
Solvent: O
Product: C[Si](C)(C)CCOC(=O)[C@@H]1CCCC[C@H]1C(=O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 36.9 %

Procedure:
To a solution of trans-2-(4-bromobenzoyl)cyclohexanecarboxylic acid (5.0 g, 16.07 mmol) in DCM (80 mL) was added 2-(trimethylsilyl)ethanol (2.1 g, 17.68 mmol), N,N′-dimethylamino-pyridine (98 mg, 0.80 mmol), and EDCI (4.0 g, 20.89 mmol). The resulting reaction mixture was stirred at rt for 2 days. Water was added, and the mixture was diluted with DCM. The aqueous layer was separated and extracted with DCM. The combined organic phases were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Silica gel chromatography (Biotage cartridge), eluting with 10% EtOAc in hexane gave trans-(trimethylsilyl)ethyl 2-(4-bromobenzoyl)cyclohexanecarboxylate (2.44 g, 37%). 1H NMR (400 MHz, CD2Cl2) δ −0.01 (s, 9H), 0.85 (m, 2H), 1.45 (m, 3H), 1.73 (m, 2H), 1.90 (m, 2H), 2.18 (m, 1H), 2.71 (m, 1H), 3.80 (m, 1H), 4.05 (m, 2H), 7.58 (d, 2H), 7.70 (d, 2H).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([OH:12])=[CH:9]2)=[CH:4][CH:3]=1.[C:13]([OH:17])(=[O:16])[CH2:14]S.[OH-].[Na+].C(O)CO>O>[OH:12][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][C:2]([CH3:1])=[CH:3][CH:4]=2)[C:9]=1[CH2:14][C:13]([OH:17])=[O:16]
Reactant: Cc1ccc2ccc(O)cc2c1
Reactant: O=C(O)CS
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: Cc1ccc2ccc(O)c(CC(=O)O)c2c1
Reaction time: 20 h

Procedure:
A mixture of 7-methylnaphth-2-ol (5 g), thioglycolic acid (3 g), sodium hydroxide (2 g) and ethylene glycol (10 ml) was stirred at 145° under an atmosphere of argon for 20 h. The mixture was cooled, water (100 ml) was added, and the mixture was heated at 90° for 2 h. The mixture was then washed with ethyl acetate and the aqueous phase was separated, acidified with concentrated hydrochloric acid, and extracted twice with ethyl acetate. The ethyl acetate extracts were combined, dried and evaporated to dryness under reduced pressure, and the residue was triturated with toluene. The insoluble solid thus produced was filtered off, washed with toluene and dried to give 2-hydroxy-7-methyl-1-naphthylacetic acid, m.p. 138°-140°.
Reaction SMILES: [N+:1]([C:4]1[CH:23]=[CH:22][C:7]([O:8][C:9]2[CH:21]=[CH:20][C:12]3[C:13]([CH3:19])([CH3:18])[CH:14]=[C:15]([CH3:17])[O:16][C:11]=3[CH:10]=2)=[CH:6][CH:5]=1)([O-])=O.[H][H].C(OCC)(=[O:28])C>[C].[Pd]>[NH2:1][C:4]1[CH:23]=[CH:22][C:7]([O:8][C:9]2[CH:21]=[CH:20][C:12]3[C:13]([CH3:19])([CH3:18])[CH2:14][C:15]([OH:28])([CH3:17])[O:16][C:11]=3[CH:10]=2)=[CH:6][CH:5]=1
Reactant: CC1=CC(C)(C)c2ccc(Oc3ccc([N+](=O)[O-])cc3)cc2O1
Reactant: [H][H]
Reactant: CCOC(C)=O
Agent: [Pd]
Product: CC1(O)CC(C)(C)c2ccc(Oc3ccc(N)cc3)cc2O1
Yield: 93 %

Procedure:
A mixture of 5.0 g of 7-(4-nitrophenoxy)-2,4,4-trimethyl-4H-1-benzopyran, 0.5 g of 5% palladium-carbon and 50 ml of ethyl acetate was stirred at room temperature for 5.5 hours in an atmosphere of hydrogen. The palladium-carbon was separated by filtration, and the filtrate was concentrated. The residue was recrystallized from ethyl acetate-hexane to give 4.3 g (yield 93%) of the desired product as a white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:15](=[C:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:23]=1.[N:24]#CBr>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:15](=[C:16]3[CH2:17][CH2:18][N:19]([C:22]#[N:24])[CH2:20][CH2:21]3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:23]=1
Reactant: CN1CCC(=C2c3ccc(Cl)cc3CCc3cccnc32)CC1
Reactant: N#CBr
Solvent: c1ccccc1
Product: N#CN1CCC(=C2c3ccc(Cl)cc3CCc3cccnc32)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Dissolve 16.2 grams (0.05 mole) of 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (prepared by the methods described in U.S. Pat. No. 3,326,924) in 300 mL of dry benzene. To this solution, add slowly under nitrogen a solution of cyanogen bromide (6.4 g) dissolved in 75 mL of benzene. Allow this mixture to stir at room temperature overnight (approximately 20 hours).
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[O:8][C@H:7](Br)[C@@H:6]1[NH:21][C:22](=[C:24]1[C:29](=[O:30])[CH2:28][C:27]([CH3:32])([CH3:31])[CH2:26][C:25]1=[O:33])[CH3:23])(=[O:3])[CH3:2].C[Si]([N:38]=[N+:39]=[N-:40])(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(#N)C>[N:38]([C@H:7]1[O:8][C@H:9]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:5]([O:4][C:1](=[O:3])[CH3:2])[C@H:6]1[NH:21][C:22](=[C:24]1[C:29](=[O:30])[CH2:28][C:27]([CH3:32])([CH3:31])[CH2:26][C:25]1=[O:33])[CH3:23])=[N+:39]=[N-:40]
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: CC(=O)OC[C@H]1O[C@H](Br)[C@H](NC(C)=C2C(=O)CC(C)(C)CC2=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CC#N
Product: CC(=O)OC[C@H]1O[C@H](N=[N+]=[N-])[C@H](NC(C)=C2C(=O)CC(C)(C)CC2=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reaction time: 16 h

Procedure:
3,4,6-tri-O-Acetyl-2-deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-ethylamino]-α-D-glucopyranosyl bromide (3) (60 g, 0.112 mol) is suspended in acetonitrile (280 mL) and trimethylsilylazide (TMS-N3) (29.9 mL, 0.224 mol) is added dropwise followed by the dropwise addition of tetrabutylammonium fluoride (1 M TBAF in tetrahydrofuran) (225 mL, 0.225 mol). The reaction is stirred for 16 hr protected from light. The solvents are removed under reduced pressure, and the residue is preabsorbed on silica (150 g) and the product eluted with ethyl acetate/petroleum ether (1:1) (2 L). The solvents are evaporated and the crude residue used directly in the next step.
Reaction SMILES: C(N(CC)CC)C.Cl.Cl.[NH2:10][C@H:11]1[CH:16]2[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]2)[CH2:12]1.[CH2:19]([C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=1)[CH2:20][CH2:21][CH3:22].[I-].ClC1C=CC=C[N+]=1C>O.C(#N)C>[CH2:19]([C:23]1[CH:24]=[CH:25][C:26]([C:27]([NH:10][C@H:11]2[CH:16]3[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]3)[CH2:12]2)=[O:28])=[CH:30][CH:31]=1)[CH2:20][CH2:21][CH3:22]
Reactant: CCCCc1ccc(C(=O)O)cc1
Reactant: N[C@@H]1CN2CCC1CC2
Agent: C[n+]1ccccc1Cl
Agent: Cl
Agent: [I-]
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: CCCCc1ccc(C(=O)N[C@@H]2CN3CCC2CC3)cc1
Reaction time: 8 h
Yield: 95 %

Procedure:
1.5 ml of Acetonitrile and Triethylamine (700 uL, 5.0 mmol) was added to a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (199 mg, 1.0 mmol) and 4-Butylbenzoic acid (196 mg, 1.1 mmol), followed by addition of 2-Chloro-1-methylpyridinium iodide (383 mg, 1.5 mmol) at room temperature. After stirring overnight, about 2 ml of water was added to reaction mixture to resolve a clear solution that was subsequently injected into a Preparative HPLC instrument for purification. Desired fractions were combined and concentrated under vacuum. (S)-4-butyl-N-(quinuclidin-3-yl)benzamide (272 mg, 95% yield) was isolated as an oil. 1H NMR (400 MHz, Methanol-D4) δ (ppm): 8.24 (d, J=8.2 Hz, 2H), 8.41 (d, J=8.4 Hz, 2H), 4.42 (m, 1H), 3.84 (ddd, J=11.7, 9.9, 2.6 Hz, 1H), 3.35 (m, 4H), 2.69 (t, J=7.7 Hz, 2H), 2.36 (q, J=3.1 Hz, 1H), 2.24 (m, 1H), 2.10 (m, 2H), 1.94 (m, 1H), 1.62 (q, J=7.6 Hz, 2H), 1.37 (q, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H). LCMS (ESI): m/z 287.1 (M+H [C18H26N2O]=287.20).
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C1COCC1.[CH3:17][C:18]1[CH:23]=[C:22]([CH3:24])[CH:21]=[C:20]([CH3:25])[C:19]=1[Mg]Br>CCCCCC>[CH2:2]([C:19]1[C:20]([CH3:25])=[CH:21][C:22]([CH3:24])=[CH:23][C:18]=1[CH3:17])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: Cc1cc(C)c([Mg]Br)c(C)c1
Reactant: CCCCCCCCCCI
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCCCCCCCc1c(C)cc(C)cc1C

Procedure:
1-Iododecane (133.9 mg, 0.5 mmol) and a THF solution (0.66 mL, 1.14 M, 0.75 mmol) of 2,4,6-trimethylphenylmagnesium bromide were used as starting materials, and reacted as in Entry 1. Conditions: The THF solution of 2,4,6-trimethylphenylmagnesium bromide was added dropwise at 40° C. over 3 hours. After thin-layer chromatography (hexane), the title compound was obtained as a colorless liquid (0.121 g, yield 93%).
Reaction SMILES: [C:1]1([CH3:36])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[N:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][C:18]=2[CH2:27][NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[N:12]=1.CO.[BH3-]C#N.[Na+]>C(O)=O.O>[CH3:36][C:1]1[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[NH:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][C:18]=2[CH2:27][NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[N:12]=1
Reactant: Cc1cc(C)c(N=Cc2cccc(-c3c(CNc4ccccc4C)ccc4ccccc34)n2)c(C)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O=CO
Solvent: CO
Solvent: O
Product: Cc1cc(C)c(NCc2cccc(-c3c(CNc4ccccc4C)ccc4ccccc34)n2)c(C)c1

Procedure:
To a solution of 1.25 g (2.67 mmol) of mesityl{[6-(2-{[(2-methylphenyl)amino]methyl}-1-naphthyl)pyridin-2-yl]methylene}amine in 20 ml of methanol 0.27 g (4.30 mmol) of NaBH3CN was added in one portion followed by addition of three drops of 88% formic acid. The reaction mixture was refluxed for 1 h and then poured into 50 ml of water. The crude product was extracted with 2×20 ml of ether. The organic extract was washed by 2×30 ml of water, dried over K2CO3, and then evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 um; eluent: hexanes-ethyl acetate=5:1, vol.). Yield 1.00 g (80%) of yellow oil. Anal. calc. for C33H33N3: C, 84.04; H, 7.05; N, 8.91. Found: C, 84.19; H, 7.20; N, 8.76. 1H NMR (CDCl3): 7.90 (d, J=8.5 Hz, 1H, 4-H in naphthyl), 7.88 (m, 1H, 8-H in naphthyl), 7.74 (m, 1H, 4-H in Py), 7.66 (d, J=8.5 Hz, 1H, 3-H in naphthyl), 7.47 (m, 1H, 7-H in naphthyl), 7.38 (m, 2H, 5,6-H in naphthyl), 7.32 (m, 1H, 3-H in Py), 7.31 (m, 1H, 5-H in Py), 7.02 (m, 1H, 5-H in ortho-tolyl), 7.01 (m, 1H, 3-H in ortho-tolyl), 6.78 (s, 2H, 3,5-H in mesityl), 6.62 (m, 1H, 4-H in ortho-tolyl), 6.51 (m, 1H, 6-H in ortho-tolyl), 4.31 (m, 2H, PyCH2N), 4.22 (m, 2H, NaphCH2N), 3.94 (br. s, 2H, NH), 2.21 (s, 3H, Me in ortho-tolyl), 2.19 (s, 6H, 2,6-Me in mesityl), 2.10 (s, 3H, 4-Me in mesityl).
Reaction SMILES: [F:1][C@:2]12[C@@H:19]([OH:20])[CH2:18][C@@:16]3([CH3:17])[C@@H:12]([CH2:13][CH2:14][C:15]3=[O:21])[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:23])[CH2:4][CH2:5][C:6](=[O:22])[CH:7]=1.[CH2:24](OC(OCC)OCC)[CH3:25].S(=O)(=O)(O)O>O1CCOCC1>[CH2:24]([O:22][C:6]1[CH2:5][CH2:4][C@@:3]2([CH3:23])[C:8](=[CH:9][CH2:10][C@@H:11]3[C@:2]2([F:1])[C@@H:19]([OH:20])[CH2:18][C@@:16]2([CH3:17])[C@H:12]3[CH2:13][CH2:14][C:15]2=[O:21])[CH:7]=1)[CH3:25]
Reactant: C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3CCC(=O)[C@@]3(C)C[C@H](O)[C@@]12F
Reactant: CCOC(OCC)OCC
Agent: O=S(=O)(O)O
Solvent: C1COCCO1
Product: CCOC1=CC2=CC[C@H]3[C@@H]4CCC(=O)[C@@]4(C)C[C@H](O)[C@]3(F)[C@@]2(C)CC1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To 1 gm. of 9α-fluoro-11β-hydroxy-4-androstene-3,17 -dione in a solution of 1 ml. of triethylorthoformate in 7 ml. of dioxane add 0.6 ml. of 5% concentrated sulfuric acid in dioxane. Stir at room temperature for five minutes then add 1 ml. of pyridine and evaporate in vacuo to a residue. Add cold ethanol and filter off the resultant precipitate comprising 3-ethoxy-9α-fluoro-11β-hydroxy-3,5 -androstadiene- 3,17-dione (0.8 gm.).
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4][CH2:3]1.[CH2:15]([O:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]2[C:24]=1[CH:25]=[CH:26][N:27]2[CH2:33][CH3:34])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.FC(F)(F)C(O)=O>C(O)(=O)C>[CH2:15]([O:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]2[C:24]=1[C:25]([C:2]1[CH2:3][CH2:4][NH:5][CH2:6][CH:7]=1)=[CH:26][N:27]2[CH2:33][CH3:34])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CCn1ccc2c(OCc3ccccc3)cc(F)cc21
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Solvent: CC(=O)O
Solvent: O=C(O)C(F)(F)F
Product: CCn1cc(C2=CCNCC2)c2c(OCc3ccccc3)cc(F)cc21
Temperature: 80 °C
Yield: 32.4 %

Procedure:
In pressure vessel, tert-butyl 4-oxopiperidine-1-carboxylate (370 mg, 1.86 mmol) was dissolved in acetic acid (3 mL) and then 4-(benzyloxy)-1-ethyl-6-fluoro-1H-indole (200 mg, 0.74 mmol) was added, followed by trifluoroacetic acid (1 mL). The reaction mixture was heated to 80° C. for 1 hour. Volatiles were evaporated and then water was added. The pH was adjusted to ˜12 with 15% aqueous NaOH and partitioned between EtOAc-water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give a crude product. The resulting residue was purified on alumina column chromatography eluting with DCM/methanol (0-6%) to afford 37-3 (84 mg, 32%). 1H NMR (300 MHz, DMSO-d6) δ (ppm) 8.78 (br. s, 2H), 7.51-7.41 (m, 5H), 7.27 (s, 1H), 6.99 (dd, J=9.9 Hz and 2.1 Hz, 1H), 6.63 (dd, J=11.8 Hz and 2.1 Hz, 1H), 5.84, (br. s, 1H), 5.16 (s, 2H), 4.11 (q, J=7.2 Hz, 2H), 3.46 (br. s, 2H), 2.93 (br.s, 2H), 2.61 (br. s, 2H), 1.31 (t, J=7.2 Hz, 3H). LCMS: calc 350.4 and found: 351.1 [MH]+.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:7]2[N:8]([CH2:24][CH3:25])[C:9]3[C:14]([CH2:15][NH:16][CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)=[CH:13][N:12]=[CH:11][C:10]=3[N:23]=2)=[N:4][O:5][N:6]=1.[C:26]([O:30][C:31](N1CCC(N)CC1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>>[C:26]([O:30][C:31]([N:20]1[CH2:21][CH2:22][CH:17]([NH:16][CH2:15][C:14]2[C:9]3[N:8]([CH2:24][CH3:25])[C:7]([C:3]4[C:2]([NH2:1])=[N:6][O:5][N:4]=4)=[N:23][C:10]=3[CH:11]=[N:12][CH:13]=2)[CH2:18][CH2:19]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]
Reactant: CCn1c(-c2nonc2N)nc2cncc(CNC3CCNCC3)c21
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Product: CCn1c(-c2nonc2N)nc2cncc(CNC3CCN(C(=O)OC(C)(C)C)CC3)c21

Procedure:
The title compound was prepared from the product of Step 1 and 4-Amino-piperidine-1-carboxylic acid tert-butyl ester according to the general method of Example 149; MS (ES+) m/e 443 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([C:21]#[N:22])([CH3:20])[CH2:3][C:4]1[C:9]([CH3:10])=[C:8]([CH3:11])[C:7]([CH2:12][C:13]([C:16]#[N:17])([CH3:15])[CH3:14])=[C:6]([CH3:18])[C:5]=1[CH3:19].[H-].C([Al+]CC(C)C)C(C)C.O>C1(C)C=CC=CC=1.CO>[CH3:14][C:13]([CH3:15])([CH2:16][NH2:17])[CH2:12][C:7]1[C:8]([CH3:11])=[C:9]([CH3:10])[C:4]([CH2:3][C:2]([CH3:1])([CH3:20])[CH2:21][NH2:22])=[C:5]([CH3:19])[C:6]=1[CH3:18]
Reactant: Cc1c(C)c(CC(C)(C)C#N)c(C)c(C)c1CC(C)(C)C#N
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: O
Solvent: CO
Solvent: Cc1ccccc1
Product: Cc1c(C)c(CC(C)(C)CN)c(C)c(C)c1CC(C)(C)CN
Temperature: 25 °C
Reaction time: 72 h

Procedure:
In a 1-liter flask, equipped as described in Example 1(b), was put 6.17 g of 1,4-bis(2-methyl-2-cyanopropyl)tetramethylbenzene and 200 ml of reagent grade toluene which had been passed through acid alumina under nitrogen directly into the reaction vessel. With stirring at room temperature, 71.3 ml of a 24.1% solution of diisobutylaluminum hydride in toluene was added in 25 min. The mixture was refluxed for 22 hrs and allowed to stand at room temperature for 3 days. After the mixture had been cooled in an ice-water bath, a solution of 4 ml of water in 20 ml of methanol was added dropwise with stirring. This was followed by the dropwise addition of a solution of 20 ml of water in 40 ml of methanol. The mixture was then stirred at room temperature for several hours and allowed to stand at room temperature for 3 days. The mixture was filtered under nitrogen, the solid was washed thoroughly with toluene on the filter, and the combined filtrate and rinsings were distilled on the water pump. A solid residue resulted which, after further drying in a vacuum oven at room temperature, weighed 5.21 g and melted at 97° to 99°. Sublimation of this material at 125° to 145°/0.50 mm gave 1,4-bis(2,2-dimethyl-3-aminopropyl)tetramethylbenzene as a colorless crystalline solid melting at 97.5° to 98.5°.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([N:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[N:5]=[CH:4][N:3]=1.[C:14](O)(=O)[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1>P(Cl)(Cl)(Cl)=O>[CH2:10]([N:9]([CH2:12][CH3:13])[C:6]1[N:5]=[CH:4][N:3]=[C:2]2[C:7]=1[NH:8][C:14]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)=[N:1]2)[CH3:11]
Reactant: O=C(O)c1ccncc1
Reactant: CCN(CC)c1ncnc(N)c1N
Solvent: O=P(Cl)(Cl)Cl
Product: CCN(CC)c1ncnc2nc(-c3ccncc3)[nH]c12
Yield: 45.9 %

Procedure:
A mixture obtained by grinding homogeneously 5 g of 4,5-diamino-6-diethylaminopyrimidine and 3.4 g of isonicotinic acid in a mortar is added to 110 ml of phosphorus oxychloride under stirring, and refluxed with heating for 3 hours. The reaction solution is concentrated and 180 ml of water is added to the residual oil. The resulting solution is neutralized with an ammonia solution and the precipitated crystals are filtered and washed with water. Recrystallization from ethanol gives 3.4 g of 6-diethylamino-8-(4-pyridyl)purine, melting at 260°-262° C.