Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[C:4]([C:14]2[CH:27]=[CH:26][C:25]3[N:24]([S:28]([C:31]4[CH:36]=[CH:35][C:34]([O:37]C)=[CH:33][CH:32]=4)(=[O:30])=[O:29])[CH:23]([CH2:39][CH3:40])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16]=3[CH:15]=2)=[CH:3][CH:2]=1.C1CCCCC=1.B(Br)(Br)Br>ClCCl>[CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[C:4]([C:14]2[CH:27]=[CH:26][C:25]3[N:24]([S:28]([C:31]4[CH:32]=[CH:33][C:34]([OH:37])=[CH:35][CH:36]=4)(=[O:29])=[O:30])[CH:23]([CH2:39][CH3:40])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16]=3[CH:15]=2)=[CH:3][CH:2]=1
Reactant: CCC1c2ccccc2-c2cc(-c3cccc4c3oc3ccccc34)ccc2N1S(=O)(=O)c1ccc(OC)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: C1=CCCCC1
Product: CCC1c2ccccc2-c2cc(-c3cccc4c3oc3ccccc34)ccc2N1S(=O)(=O)c1ccc(O)cc1
Temperature: 25 °C
Yield: 91 %

Procedure:
A stirred and cooled solution of 2-(dibenzo[b,d]furan-4-yl)-6-ethyl-5-[(4-methoxyphenyl)sulfonyl]-5,6-dihydrophenanthridine (0.855 g, 1.56 mmol) and cyclohexene (1.26 mL, 12.5 mmol) in dichloromethane (5 mL) was treated drop-wise under nitrogen at −30° C. with boron tribromide (1.18 mL, 12.5 mmol). After the addition was completed, the reaction mixture was allowed to warm to room temperature and stirred for four hours. The reaction was cooled to −30° C. and quenched with methanol (1 mL). The solvent was removed in vacuo, and the residue was purified by flash column chromatography on silica gel to yield the title compound (0.756 g, 1.42 mmol, 91%), which was characterized by LCMS (ES+, FA, CV=20 or 5), m.p. 218-220° C.;
Reaction SMILES: [N:1]1([C:6]2[N:11]=[C:10]3[CH2:12][CH2:13][CH:14]([C:15]([O:17]C)=[O:16])[C:9]3=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1.[OH-].[Li+].Cl>C1COCC1.O>[N:1]1([C:6]2[N:11]=[C:10]3[CH2:12][CH2:13][CH:14]([C:15]([OH:17])=[O:16])[C:9]3=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1
Reactant: COC(=O)C1CCc2nc(-n3cnnn3)ccc21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C1CCc2nc(-n3cnnn3)ccc21
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of methyl 2-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxylate (460 mg, 1.9 mmol) in THF (6 mL) was added lithium hydroxide (1.0 N aq. 3.8 mL, 3.8 mmol). The mixture was allowed to stir at 0° C. for 2 hours. The reaction was diluted with water (10 mL). The pH was carefully adjusted to about 5 with 1N HCl. The solution was then extracted with EtOAc (30 mL×3). The extractions were combined, dried over sodium sulfate, and concentrated to furnish the title compound: LC-MS (IE, m/z): 231 [M+1]+; 1H-NMR (500 MHz, CD3OD) δ ppm 9.87 (s, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 4.20 (t, J=8.0 Hz, 1H), 3.15 (m, 1H), 3.08 (m, 1H), 2.51 (m, 2H).
Reaction SMILES: C([O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[N:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:29]5[CH:30]=[CH:31][N:32]=[CH:33][C:28]=5[N:27]([CH:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)[C:25]=4[N:26]=3)=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])(=O)C.[Li+].[OH-]>C1COCC1.CO.O>[CH:34]1([N:27]2[C:25]3[N:26]=[C:21]([NH:20][C:17]4[N:16]=[CH:15][C:14]([N:11]5[CH2:12][CH2:13][N:8]([C:6](=[O:7])[CH2:5][OH:4])[CH2:9][CH2:10]5)=[CH:19][CH:18]=4)[N:22]=[CH:23][C:24]=3[C:29]3[CH:30]=[CH:31][N:32]=[CH:33][C:28]2=3)[CH2:35][CH2:36][CH2:37][CH2:38]1
Reactant: CC(=O)OCC(=O)N1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nc2)CC1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(CO)N1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nc2)CC1
Temperature: 60 °C
Reaction time: 8 h
Yield: 63.5 %

Procedure:
To a solution of compound 189 (˜0.5 mmol) in THF/methanol/H2O (3:1:1, 10 mL) was added 12 mg of LiOH and the mixture was stirred at 60° C. overnight. The reaction mixture was concentrated and the residue was dissolved in dichloromethane then washed with water and brine then dried. The solvent was evaporated and the residue was purified by chromatography on silica gel eluting with CH2Cl2:methanol:NH4OH (400:10:1) to give compound 188 as a yellow solid (150 mg, 63% in two steps). 1H NMR (500 MHz, DMSO-d6) δ 9.82 (1H, s), 9.27 (1H, s), 9.01 (1H, s), 8.44 (1H, d, J=5 Hz), 8.21 (1H, d, J=10 Hz), 8.07 (1H, d, J=2 Hz), 8.04 (1H, d, J=5 Hz), 7.52 (1H, dd, J=10 Hz, J=2 Hz), 5.37 (1H, p, J=10 Hz), 4.65 (1H, t, J=5 Hz), 4.15 (2H, d, J=5 Hz), 3.65 (2H, m), 3.53 (2H, m), 3.15 (4H, m), 2.40 (2H, m), 2.08 (4H, m), 1.78 (2H, m) ppm; LCMS-ESI (POS), M/Z, M+1: Found 472.2, Calculated 472.3.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:11][NH:12]C(OC(C)(C)C)=O)[CH:9]=2)[NH:4][CH:3]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:11][NH2:12])[CH:9]=2)[NH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NCc1ccc2[nH]cc(Cl)c2c1
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCc1ccc2[nH]cc(Cl)c2c1

Procedure:
To a solution of 3-chloro-5-(t-butoxycarbonylaminomethyl)-indole (2.62 g, 9.33 mmol) in CH2Cl2 (25 mL), cooled to 0° C. was added trifluoroacetic acid (10 mL). After 1 h the reaction was basified with aqueous NaOH (1 N) to pH=10, extracted with CH2Cl2 (3×) and then with CH2Cl2:MeOH (3:1). The combined organics were dried over MgSO4, filtered, and concentrated in vacuo. Purification of the resulting orange residue by flash chromatography (30×150 mm column; gradient elution with MeOH:CH2Cl2:CH2Cl2 saturated with NH3, 4:66:30 to 10:60:30 500 mL each) afforded the title compound as a yellow oil:
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]([C:22](=[O:24])[CH3:23])[CH:13]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.O1CCC[CH2:26]1.C[Mg]Br.CCOCC>>[O:4]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[N:15]=[C:14]([C:22]([OH:24])([CH3:26])[CH3:23])[CH:13]=3)[CH2:7][CH2:6]2)[O:1][CH2:2][CH2:3]1
Reactant: C1CCOC1
Reactant: CC(=O)c1cc(OC2CCC3(CC2)OCCO3)nc(C(F)(F)F)n1
Agent: C[Mg]Br
Solvent: CCOCC
Product: CC(C)(O)c1cc(OC2CCC3(CC2)OCCO3)nc(C(F)(F)F)n1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
1-[6-(1,4-Dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidin-4-yl]ethanone (0.21 g, 0.60 mmol) was dissolved in tetrahydrofuran (6.00 mL, 74.0 mmol) and was cooled to −78° C., then 3.0 M methylmagnesium bromide in ether (0.30 mL, 0.90 mmol) was added. The reaction was stirred at −78° C. for 1 hour at which time LCMS analysis showed that it was mostly done. The reaction was quenched with sat. NH4Cl and was transferred to a separatory funnel and partitioned between water and EtOAc, the phases were separated and the aqueous phase was washed with additional EtOAc. The combined organic phase was washed with water, then sat. NaCl, dried over MgSO4 and filtered and the solvent removed in vacuo to leave the crude product. MS: 363 (M+H). 1H NMR (500 MHz, CDCl3): δ 6.90 (s, 1H); 5.30 (m, 1H, OCH); 3.96 (s, 4H, OCH2); 1.98 (m, 4H); 1.82 (m, 2H); 1.63 (m, 2H); 1.50 (s, 311, CH3). 13C NMR (125 MHz, CDCl3): δ 176 (s, NC); 171 (s, OC); 156 (q, N2C); 119 (q, CF3); 108 (s, O2C); 105 (s, CH); 74 (s, OCH); 73 (s, HOC); 65 (s, OCH2); 32 (s, CH2); 30 (s, CH3); 28 (s, CH2).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:27])[CH2:20][C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)=[CH:15][CH:14]=1.CO[CH:30](OC)[N:31]([CH3:33])[CH3:32]>CCOC(C)=O.CO>[N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([C:19](=[O:27])[C:20]([C:21]2[CH:22]=[CH:23][N:24]=[CH:25][CH:26]=2)=[CH:30][N:31]([CH3:33])[CH3:32])=[CH:17][CH:18]=1
Reactant: O=C(Cc1ccncc1)c1ccc(OCc2ccc3ncccc3n2)cc1
Reactant: COC(OC)N(C)C
Solvent: CCOC(C)=O
Solvent: CO
Product: CN(C)C=C(C(=O)c1ccc(OCc2ccc3ncccc3n2)cc1)c1ccncc1
Yield: 99.7 %

Procedure:
In a 5 mL round bottom flask equipped with a magnetic stirbar and a condenser with a calcium sulfate drying tube was stirred at reflux for 18 hours a mixture of Intermediate 4D, 1-(4-((1,5-naphthyridin-2-yl)methoxy)phenyl)-2-(pyridin-4-yl)ethanone (104 mg, 0.293 mmol) and N,N-dimethylformamide dimethyl acetal (1.0 mL, 7.53 mmol). The reaction mixture was checked by TLC (95:5 EtOAc/MeOH). The spot for starting material had been replaced by a lower Rf spot. Volatiles were removed under reduced pressure to give a brown oil, 1-(4-((1,5-naphthyridin-2-yl)methoxy)phenyl)-3-(dimethylamino)-2-(pyridin-4-yl)prop-2-en-1-one (120 mg, 0.292 mmol) that was dissolved in methanol (2.5 mL) and stirred at ambient temperature. Hydrazine monohydrate (0.02127 mL, 0.438 mmol) was added via syringe and the reaction mixture was stirred at reflux for 2 hours. Another 1.5 equivalents of hydrazine monohydrate was added and stirring at reflux was continued an additional 2 hours. Volatiles were removed under reduced pressure to give a tan solid that was rinsed with water 3 times then stirred with Et2O overnight. The Et2O was decanted away and the remaining solid was partitioned between CHCl3 and brine. The aqueous layer was extracted once more with CHCl3 and the combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give a crude, bright yellow solid. This solid was purified by column chromatography on an Analogix IF-280 (Agilent SF15-24 g, 100% DCM to 98:2 DCM/2M NH3 in MeOH). Fractions #5-20 were combined and concentrated under reduced pressure to give a pale yellow solid. The solid was dissolved in warm CHCl3 and the resulting solution was filtered and concentrated under reduced pressure. The solid residue was rinsed with Et2O, then dissolved in a minimum of hot MeOH. The solution was placed in a 0° C. freezer to induce crystallization. Intermediate 4, 2-((4-(4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-1,5-naphthyridine was obtained by filtration as white crystals (16.5 mg, 14.9%). 1H NMR (300 MHz, methanol-d4) δ 8.98 (dd, J=4.2, 1.6 Hz, 1H), 8.48 (dd, J=8.6, 1.8 Hz, 2H), 8.36 (dd, J=4.7, 1.6 Hz, 2H), 8.02 (d, J=8.8 Hz, 1H), 7.97 (br s, 1H), 7.82 (dd, J=8.5, 4.3 Hz, 1H), 7.42-7.36 (m, 2H), 7.33 (d, J=5.9 Hz, 2H), 7.16 (d, J=7.3 Hz, 2H), 5.47 (s, 2H). MS (ESI) m/z=380 (M+H)+.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])[CH3:2].[NH2-:11].[Na+]>>[NH2:11][C:4]1[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][CH3:10])[CH:7]=[CH:6][N:5]=1
Reactant: CCc1ccncc1CC
Reactant: [NH2-]
Agent: [Na+]
Product: CCc1ccnc(N)c1CC

Procedure:
2-Amino-3,4-diethylpyridine is prepared by reacting 40.5 g. 3,4-diethylpyridine with 11.7 g sodium amide at a temperature of 250° in the presence of paraffin oil. The so-formed 2-amino-3,4-diethylpyridine is purified by distillation and is substituted for the 2-amino-3,4-dimethylpyridine in Example 7 to obtain the named compound.
Reaction SMILES: [CH3:1][C:2]1[C:3]([N+:13]([O-])=O)=[C:4]([C:8]2[NH:9][CH2:10][CH2:11][N:12]=2)[CH:5]=[CH:6][CH:7]=1>C(O)C.[OH-].[Pd+2].[OH-]>[NH:12]1[CH2:11][CH2:10][N:9]=[C:8]1[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[NH2:13]
Reactant: Cc1cccc(C2=NCCN2)c1[N+](=O)[O-]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: Cc1cccc(C2=NCCN2)c1N
Reaction time: 3 h
Yield: 88.9 %

Procedure:
To a solution of the title compound of Step A (0.5 g, 2.44 mmol) in ethanol (50 mL) was added palladium hydroxide (50 mg, 20 wt % on carbon). The flask was twice evacuated and flushed with nitrogen and then twice evacuated and flushed with hydrogen. The mixture was vigorously stirred under a balloon of hydrogen for 3 hours before being evacuated, exposed to air and filtered through a pad of Celite®. The solution was concentrated and filtered through a pad of silica gel, eluting with 5% then 10% methanol in dichloromethane, then 5% triethylamine, 10% methanol, 85% dichloromethane. The material eluting in triethylamine/methanol/dichloromethane was concentrated to give the title compound of Step B (0.38 g) as a light brown oil.
Reaction SMILES: [H][H].[CH3:3][CH:4]([OH:19])[CH:5]([OH:18])[C:6]1[N:11]=[C:10]2[C:12]([N:14]=[C:15]([NH2:17])[NH:16][C:9]2=[N:8][CH:7]=1)=[O:13].[ClH:20]>[Pt]=O>[ClH:20].[CH3:3][CH:4]([OH:19])[CH:5]([OH:18])[CH:6]1[NH:11][C:10]2[C:12]([N:14]=[C:15]([NH2:17])[NH:16][C:9]=2[NH:8][CH2:7]1)=[O:13]
Reactant: CC(O)C(O)c1cnc2[nH]c(N)nc(=O)c2n1
Reactant: [H][H]
Agent: O=[Pt]
Agent: Cl
Product: CC(O)C(O)C1CNc2[nH]c(N)nc(=O)c2N1

Procedure:
There was dispersed 100 mg of platinum oxide into 100 ml of a 1N hydrochloric acid, and then the catalyst was activated with hydrogen gas. Then, 100 ml of 1N hydrochloric acid solution containing 1 g of biopterin was added to the above dispersion. After the catalytic reduction was conducted for 5 hours under normal temperature and normal pressure in a hydrogen atmosphere, the catalyst was filtered off from the reaction mixture to give a hydrochloric acid solution of tetrahydrobiopterin having a (6R)/(6S) ratio of 60/40 as measured by HPLC. Light yellow powder was produced by repeating the cycle of concentration of the solution and addition of ethanol. The powder was filtered off from the above solution to give 1.08 g of powder. The (6R)/(6S) ratio of the powder thus obtained was 57/43 as measured by HPLC.
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[C:12]([C:13](=[O:15])[N:14]=1)=[CH:11][C:10]([C:16]1[N:17]=[N:18][N:19]([CH2:21][CH2:22][CH2:23][CH:24]=[CH2:25])[N:20]=1)=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH3:4].Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=2)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([C:5]1[N:14]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([C:34]3[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=3)=[CH:32][CH:33]=2)[C:13](=[O:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:16]3[N:17]=[N:18][N:19]([CH2:21][CH2:22][CH2:23][CH:24]=[CH2:25])[N:20]=3)[CH:11]=2)[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: N#Cc1ccccc1-c1ccc(CBr)cc1
Reactant: C=CCCCn1nnc(-c2ccc3[nH]c(CCCC)nc(=O)c3c2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCCCn1nnc(-c2ccc3nc(CCCC)n(Cc4ccc(-c5ccccc5C#N)cc4)c(=O)c3c2)n1
Yield: 94.9 %

Procedure:
A mixture of 1.01 g of 2-butyl-6-[2-(4-pentenyl)-2H-tetrazol-5-yl]-4(1H)-quinazolinone, 1.09 g of 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile and 2.0 g of potassium carbonate in 100 ml of acetone is refluxed for 24 hours. The reaction mixture is filtered and the filtrate evaporated in vacuo to a residue which is purified by chromatography on silica gel by elution with 30% ethyl acetate-hexanes to give 1.5 g of the desired product as a yellow foam.
Reaction SMILES: CS([C:5]1[N:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=2)[C:8]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[C:7]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=2[Cl:34])[N:6]=1)(=O)=O.[CH3:35][NH:36][CH3:37]>C1COCC1>[CH3:35][N:36]([CH3:37])[C:5]1[N:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=2)[C:8]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[C:7]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=2[Cl:34])[N:6]=1
Reactant: CS(=O)(=O)c1nc(Oc2ccc(F)c(F)c2)c(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1
Reactant: CNC
Solvent: C1CCOC1
Product: CN(C)c1nc(Oc2ccc(F)c(F)c2)c(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1

Procedure:
2-Methylsulfonyl-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine (from Example 20) (100 mg, 0.19 mmol) was reacted with excess dimethylamine (0.14 mL, 0.28 mmol) in THF in a sealed tube at 60° C. overnight by general procedure described in Example 103 to afford the title compound: HPLC/MS: m/e=506 (M++1); Rt=4.99 min. 1H-NMR 400 MHz (CDCl3); δ 3.00-3.20 (s, 6H), 6.89-6.94 (m, 1H), 7.08-7.21 (m, 8H), 7.35 (d, J=2 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:21][CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)=[C:6]2[C:11]=1[C:10](=[O:12])[C:9]([CH2:17][CH2:18][CH2:19][CH3:20])([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:8][CH2:7]2.O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[NH4+]>C(OCC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:21][CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)=[C:6]2[C:11]=1[CH:10]([OH:12])[C:9]([CH2:17][CH2:18][CH2:19][CH3:20])([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:8][CH2:7]2
Reactant: CCCCC1(CCCC)CCc2c(OCc3ccc4ccccc4n3)ccc(Cl)c2C1=O
Agent: [Al+3]
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCCCC1(CCCC)CCc2c(OCc3ccc4ccccc4n3)ccc(Cl)c2C1O
Yield: 78.5 %

Procedure:
To a solution of 8-chloro-2,2-dibutyl-3,4-dihydro-5-(2-quinolylmethoxy)-1(2H)-naphthalenone (180 mg) in freshly distilled tetrahydrofuran (5 ml) was added lithium aluminum hydride (15 mg) with stirring in an ice bath under nitrogen and the mixture was stirred for minutes in an ice bath. To the mixture was carefully added aqueous saturated ammonium chloride solution (5 ml) in an ice bath, and then diethylether (10 ml) was added thereto. The separated aqueous layer was extracted two times with diethyl ether and the combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate and concentrated in vacuo to give the oily residue which was crystallized from diisopropyl ether to yield 8-chloro-2,2-dibutyl-5-(2-quinolylmethoxy)-1,2,3,4-tetrahydro-1-naphthol (142 mg). mp: 142.5°-143.5° C. IR (CHCl3) 3600, 3330, 2930, 2860, 1620, 1600, 1580, 1505, 1460, 1290, 1250, 1205, 1090, 820 cm-1. NMR (CDCl3, δ): 0.88 (3H, t, J=6 Hz) J=6 Hz), 1.05-2.05 (15H, m), 2.40-2.70 (1H, m), 2.98 (1H, dd, J=18, 6 Hz), 4.61 (1H, s), 5.37 (2H, s), 6.79 (1H, d, J=8 Hz), 7.18 (1H, d, J=8 Hz), 7.57 (1H, t, J=8 Hz), 7.66 (1H, d, J= 8 Hz), 7.75 (1H, t, J=8 Hz), 7.85 (1H, d, J=8 Hz), 8.08 (1H, d, J=8 Hz), 8.21 (1H, d, J=8 Hz).
Reaction SMILES: [C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:14][C:15]1[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][C:16]=1[C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)=[O:18]>>[C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:14][C:15]2[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][C:16]=2[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[O:18])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(NC(=O)c2cccc(C)c2N)cc1
Reactant: CC(C)(C)c1ccc(C(=O)Cl)cc1
Product: COc1ccc(NC(=O)c2cccc(C)c2NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Yield: 45 %

Procedure:
Using the procedure described in Example 93, Part A, 4-tert-butylbenzoyl chloride (1.76 mmol) and 2-amino-N-(4-methoxyphenyl)-3-methylbenzamide (1.6 mmol) yielded 0.30 g (45%) of the title compound.
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[NH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>>[N:16]1([CH2:15][CH2:14][NH:13][CH2:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: NCCN1CCNCC1
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CNCCN1CCNCC1

Procedure:
The product was made from D-glucose and N-(β-aminoethyl)-piperazine comparable as in Example A. A resin-like, pale pink product was obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][C:11]#[N:12])=[CH:4][C:3]=1[N+:13]([O-])=O.CO>[Fe].O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][C:11]#[N:12])=[CH:4][C:3]=1[NH2:13]
Reactant: N#CCCSc1ccc(N)c([N+](=O)[O-])c1
Agent: [Fe]
Solvent: O
Solvent: CO
Product: N#CCCSc1ccc(N)c(N)c1
Reaction time: 2 h

Procedure:
2.3 G. of 1-amino-2-nitro-4-(2-cyanoethylthio)benzene in 30 ml. of methanol and 6 ml. of water is treated with 2.5 g. of ferrous sulfate and 3.3 g. of iron powder at reflux. After 2 hours, 1.25 g. of ferrous sulfate and 3.3 g. of iron powder are added and heating is continued for four hours. The mixture is poured into 600 ml. of hot tetrahydrofuran and filtered. 1,2-Diamino-4-(2-cyanoethylthio)benzene is obtained from the filtrate by evaporation.
Reaction SMILES: [C:1]1([C:15](OC)=[O:16])[CH:6]=[C:5]([C:7](OC)=[O:8])[CH:4]=[C:3]([C:11](OC)=[O:12])[CH:2]=1.CO>C1COCC1>[OH:8][CH2:7][C:5]1[CH:4]=[C:3]([CH2:11][OH:12])[CH:2]=[C:1]([CH2:15][OH:16])[CH:6]=1
Reactant: COC(=O)c1cc(C(=O)OC)cc(C(=O)OC)c1
Solvent: C1CCOC1
Solvent: CO
Product: OCc1cc(CO)cc(CO)c1
Temperature: 70 °C
Yield: 100 %

Procedure:
To a stirring solution of trimethyl 1,3,5-benzenetricarboxylate (10.45 g, 41.4 mmol) in 70 ml of anhydrous THF is added at room temperature a 10M solution of borane-methyl sulfide complex (25 ml, 248 mmol) and the solution is heated to reflux for 3 h. The mixture is then added slowly to 50 ml of MeOH and the resulting mixture is heated at 70° C. for 10 min to remove the methyl sulfide. Evaporation of solvent, washing twice with 50 ml of MeOH and evaporation of MeOH gives 1,3,5-tris(hydroxymethyl)benzene (6.96 g, 100%). 1H NMR (D2O): δ 4.52 (6H, s), 7.15 (3H, s).
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][O:4][CH:3]=1.C([Li])CCC.CCCCCC.[N:18]12[CH2:25][CH2:24][CH:21]([CH2:22][CH2:23]1)[C:20](=[O:26])[CH2:19]2.C(=O)([O-])[O-].[K+].[K+]>CCOCC>[O:4]1[CH:5]=[CH:6][C:2]([C:20]2([OH:26])[CH:21]3[CH2:24][CH2:25][N:18]([CH2:23][CH2:22]3)[CH2:19]2)=[CH:3]1
Reactant: Brc1ccoc1
Reactant: O=C1CN2CCC1CC2
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: OC1(c2ccoc2)CN2CCC1CC2
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 26.8 %

Procedure:
A stirred solution of 3-bromofuran (5.0 g of technical grade, 0.034 mole) in dry ether (130 ml) at -60° C. under nitrogen was treated with 1.6M n-butyllithium in hexane (18.7 ml, 0.030 mole) and then stirred for 5 minutes. A solution of 1-azabicyclo[2.2.2]octan-3-one (3.37 g, 0.027 mole) in dry ether (10 ml) was added and the resulting mixture stirred for 40 minutes at -60° C., then allowed to warm to room temperature. The mixture was treated with potassium carbonate solution (100 ml) and extracted with ethyl acetate (2×100 ml). The combined extracts were dried (Na2SO4) and concentrated in vacuo to leave a yellow oil, which was chromatographed on basic alumina eluting with ethyl acetate. The pale yellow oil obtained crystallised on standing. This material was recrystallised from acetone to give the title compound (D20) as a white solid (1.40 g, 21%) m.p. 130°-133° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][C:5](=[O:7])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:20])([F:19])[CH:16]([F:18])[F:17])=[C:10]([CH3:21])[CH:9]=2)[C:3]1=[O:22].[BH4-].[Na+]>C(O)(C)C>[OH:7][CH:5]1[CH2:6][N:2]([CH3:1])[C:3](=[O:22])[N:4]1[C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:20])([F:19])[CH:16]([F:17])[F:18])=[C:10]([CH3:21])[CH:9]=1
Reactant: Cc1cc(N2C(=O)CN(C)C2=O)ccc1OC(F)(F)C(F)F
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Product: Cc1cc(N2C(=O)N(C)CC2O)ccc1OC(F)(F)C(F)F
Temperature: 40 °C
Reaction time: 0.5 h

Procedure:
16.0 g (0.05 mol) of 1-methyl-3-[3-methyl-4-(1,1,2,2-tetrafluoroethoxy)phenyl]imidazolidine-2,4-dione are dissolved in 100 ml of isopropanol, and 2.85 g (0.075 mol) of sodium borohydride are added at a rate such that the temperature increases to 40° C. After the addition is complete, the mixture is stirred for a further 30 minutes at 40° C., and poured into 300 ml of ice-water. The mixture is extracted twice with 100 ml of methylene chloride in each case, and the combined methylene chloride phases are washed with 100 ml of water and dried over sodium sulfate. After removing the solvent by distillation, 15.4 g (96% of theory) of 4-hydroxy-1-methyl-3-[3-methyl-4-(1,1,2,2-tetrafluoroethoxy)phenyl]imidazolidin-2-one are obtained in the form of a pale yellow viscous oil.