Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.C([N:6]([N:16]1[CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[N+:25]([O-:27])=[O:26])[C:17]1=[O:28])[C@H:7]([C:13]([OH:15])=[O:14])[CH2:8][CH2:9][C:10](=[O:12])[NH2:11])(C)(C)C.CCOCC>C(Cl)Cl>[O:28]=[C:17]1[C:18]2[C:23](=[C:22]([N+:25]([O-:27])=[O:26])[CH:21]=[CH:20][CH:19]=2)[CH2:24][N:16]1[NH:6][C@H:7]([C:13]([OH:15])=[O:14])[CH2:8][CH2:9][C:10](=[O:12])[NH2:11]
Reactant: CC(C)(C)N([C@@H](CCC(N)=O)C(=O)O)N1Cc2c(cccc2[N+](=O)[O-])C1=O
Agent: Cl
Solvent: CCOCC
Solvent: ClCCl
Product: NC(=O)CC[C@H](NN1Cc2c(cccc2[N+](=O)[O-])C1=O)C(=O)O
Temperature: 25 °C
Yield: 103.4 %

Procedure:
Hydrogen chloride gas as bubbled into a stirred 5° C. solution of t-butyl N-(1-oxo-4-nitro-isoindolin-2-yl)-L-glutamine (3.6 g, 9.9 mmol) in methylene chloride (60 mL) for 1 hour. The mixture was then stirred at room temperature for another hour. Ether (40 mL) was added and the resulting mixture was stirred for 30 minutes. The slurry was filtered, washed with ether and dried to afford 3.3 g of the product: 1H NMR (DMSO-d6) δ 8.45(d, J=8.1 Hz, 1H), 8.15(d, J=7.5 Hz, 1H), 7.83(t, J=7.9 H 1H), 7.24(s, 1H), 6.76(s, 1H), 4.93(s, 2H), 4.84–4.78(dd, J=4.8amd 10.4 Hz 2.34–2.10(m, 4H); 13C NMR (DMSO-d6) δ 173.03, 171.88, 165.96, 143.35, 137.49, 134.77, 130.10, 129.61, 126.95, 53.65, 48.13. 31.50, 24.69; Anal. Calcd for C13H13N3O6: C, 50.82; H, 4.26; N, 13.68. Found: C, 50.53; H, 4.37; N, 13.22,
Reaction SMILES: [C:1]([O:8]C)(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[Li+:10].[OH-]>CO.O>[C:3]([O:5][CH3:6])(=[O:4])[CH2:2][C:1]([O-:8])=[O:7].[Li+:10]
Reactant: COC(=O)CC(=O)OC
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COC(=O)CC(=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 77.7 %

Procedure:
A solution of 15.02 g of dimethyl malonate in 50 ml of MeOH was cooled to 15° C. and treated dropwise over a 2 h period with a solution of 2.4 g of LiOH in 20 ml of water. The mixture was stirred for 30 min after the addition was completed and then stripped of solvent under reduced pressure. The residue was taken up in 100 ml of hot MeOH, the solution cooled to room temperature and filtered. The filtrate was stripped of solvent to dryness. The residue was suspended in 100 ml of toluene and stripped further to remove the remaining water. The solution was cooled to room temperature and the precipitate collected by filtration to give 9.66 g (68%) of lithium mono methyl malonate. IR cm-1): 1730, 1605, 1580.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:18][N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)([CH2:14][CH2:15][CH2:16][CH3:17])C(N)=O)=[CH:6][CH:5]=1.[CH3:24][N:25]([CH3:28])[CH:26]=[O:27]>>[CH3:24][N:25]([CH3:28])[C:26](=[O:27])[C:10]([C:7]1[CH:8]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=1)([CH2:18][N:19]1[CH:23]=[N:22][CH:21]=[N:20]1)[CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CN(C)C=O
Reactant: CCCCC(Cn1cncn1)(C(N)=O)c1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Product: CCCCC(Cn1cncn1)(C(=O)N(C)C)c1ccc(Cl)cc1
Reaction time: 3 h
Yield: 45.1 %

Procedure:
To a 100 mL 3 neck flask stirring under nitrogen was charged 1.5 g (0.9375 mole) 60% sodium hydride (prewashed with hexanes) in 50 mL of dimethyl formamide. To the slurry was charged 3.83 g (0.0125 mole) of 2-(4-chlorophenyl)-2-[(1,2,4-triazol-1-yl)methyl]hexanamide in 50 mL of dimethyl formamide. The mixture was sitrred at room temperature for 3 hours then quenched by adding 20 mL of water and 75 mL of ether. The ether was washed with 50 mL water and the aqueous phase was extracted with 50 ml ethyl acetate. The ether was dried and concentrated and gave 1.88 g (45.1% yield) of product as an oil, Example 160 of Table 1.
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13](O)=[O:14])=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl.[NH2:32][C@@H:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:32][C@@H:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[O:14])=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:23])[CH3:21])[C:7]3=[N:8][CH:9]=2)[CH2:2][CH2:3]1
Reactant: C[Si](C)(C)CCOCn1cc(C(=O)O)c2nc(C3CC3)cnc21
Reactant: C[C@H](N)C(=O)OC(C)(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: C[C@H](NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(C3CC3)nc12)C(=O)OC(C)(C)C
Reaction time: 8 h
Yield: 82.5 %

Procedure:
To a solution of 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (250 mg, 0.75 mmol) in DMF (6 mL) at room temperature was added triethylamine (0.52 mL, 3.75 mmol), (S)-tert-butyl 2-aminopropanoate hydrochloride (136 mg, 0.75 mmol) and PyBOP (429 mg, 0.83 mmol). The reaction mixture was stirred overnight then poured into EtOAc (50 mL) and washed with water (4×30 mL). The organic extracts were combined, dried (Na2SO4) and evaporated under reduced pressure. The crude residue was purified by SiO2 column chromatography (12 g, hexanes/EtOAc, 7:3 to 1:1) to give 285 mg (85%) of (S)-tert-butyl 2-(2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)propanoate as a viscous oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([CH:9]=O)=O.C(=O)(O)O.[NH2:15][NH:16][C:17]([NH2:19])=[NH:18]>CCO>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:18]=[C:17]([NH2:19])[N:16]=[N:15][CH:9]=1
Reactant: O=CC(=O)c1ccccn1
Reactant: N=C(N)NN
Agent: O=C(O)O
Solvent: CCO
Product: Nc1nncc(-c2ccccn2)n1
Yield: 19.7 %

Procedure:
5-(Pyridin-2-yl)-1,2,4-triazin-3-amine (1.5 g, 8% over 2 steps) was prepared from a crude sample of 2-pyridylglyoxal (8.0 g) and aminoguanidine hydrogen carbonate (6.0 g, 44 mmol). The reagents were refluxed in EtOH (100 mL) for 4 hours. The reaction mixture was then cooled, concentrated under reduced pressure and purified by gradient flash chromatography (eluting with 0-30% ethyl acetate/hexane). The sample contained a mixture of isomers at this stage and was used without further purification.
Reaction SMILES: [CH3:1][N:2]1[C:14]2[C:13](=[O:15])[C:12]3[CH:11]=[C:10]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-])=O)[CH:18]=4)[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH:4]=[N:3]1.[Cl-].[NH4+]>C(O)C.O.[Fe]>[NH2:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][C:10]1[CH:9]=[CH:8][C:7]2[NH:6][C:5]3[CH:4]=[N:3][N:2]([CH3:1])[C:14]=3[C:13](=[O:15])[C:12]=2[CH:11]=1
Reactant: Cn1ncc2[nH]c3ccc(Cc4cccc([N+](=O)[O-])c4)cc3c(=O)c21
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Cn1ncc2[nH]c3ccc(Cc4cccc(N)c4)cc3c(=O)c21
Temperature: 25 °C
Yield: 85.7 %

Procedure:
A mixture of 1-methyl-7-(3-nitrobenzyl)-1,4-dihydro-9H-pyrazolo[4,3-b]quinolin-9-one (EXAMPLE 23, step 2, 76 mg, 0.23 mmol), iron powder (63 mg, 1.1 mmol), and ammonium chloride (12 mg, 0.023 mmol) in ethanol (15 ml) and water (5 ml) was refluxed for 2 h. After cooling to room temperature, the mixture was filtered through a pad of Celite and the filtrate was concentrated in vacuo. The residue was collected by filtration and washed with ethanol and diisopropyl ether to give 60 mg (88%) of 7-(3-aminobenzyl)-1-methyl-1,4-dihydro-9H-pyrazolo[4,3-b]quinolin-9-one. 24 mg of this solid was treated with methanolic hydrochloric acid and the mixture was evaporated. The residue was washed with diisopropyl ether to give 29 mg of the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH2:18][C:17]2[C:12](=[N:13][C:14](S(C)(=O)=O)=[N:15][CH:16]=2)[NH:11][C:10]1=[O:23].[CH2:24]([N:26]([CH2:37][CH3:38])[CH2:27][CH2:28][O:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)[CH3:25]>ClCCl.CO.C(O)(=O)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH2:18][C:17]2[C:12](=[N:13][C:14]([NH:34][C:33]3[CH:32]=[CH:31][C:30]([O:29][CH2:28][CH2:27][N:26]([CH2:37][CH3:38])[CH2:24][CH3:25])=[CH:36][CH:35]=3)=[N:15][CH:16]=2)[NH:11][C:10]1=[O:23]
Reactant: CS(=O)(=O)c1ncc2c(n1)NC(=O)N(c1c(Cl)cccc1Cl)C2
Reactant: CCN(CC)CCOc1ccc(N)cc1
Solvent: CO
Solvent: CC(=O)O
Solvent: O
Product: CCN(CC)CCOc1ccc(Nc2ncc3c(n2)NC(=O)N(c2c(Cl)cccc2Cl)C3)cc1
Temperature: 180 °C
Yield: 20.8 %

Procedure:
A mixture of 250 mg (0.67 mmol) of 3-(2,6-dichlorophenyl)-7-methanesulfonyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one and 600 mg (2.9 mmol) of 4-[2-(diethylamino)ethoxy]aniline was heated at 180° C. for 35 minutes and then cooled. The residue was subjected to column chromatography on silica gel using dichloromethane/methanol/acetic acid/water 240:24:3:2 for the elution. Product-containing fractions were combined and evaporated and the residue was evaporated with toluene. The residue was dissolved in 30 ml of dichloromethane, washed twice with 20 ml of saturated aqueous sodium bicarbonate solution each time, dried over magnesium sulfate, filtered and evaporated. The residue was triturated in hexane, filtered off and dried to give 70 mg (21%) of 3-(2,6-dichlorophenyl)-7-[4-[2-(diethylamino)ethoxy]anilino]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one as an off-white solid of melting point 248° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([O:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.[CH3:27][O:28][CH2:29][CH:30](O)[CH3:31].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH3:27][O:28][CH2:29][CH:30]([CH3:31])[O:1][C:2]1[CH:3]=[C:4]([O:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2
Reactant: CCOC(=O)c1cc2cc(Oc3ccc(S(C)(=O)=O)cc3)cc(O)c2[nH]1
Reactant: COCC(C)O
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2cc(Oc3ccc(S(C)(=O)=O)cc3)cc(OC(C)COC)c2[nH]1
Temperature: 50 °C
Reaction time: 1 h
Yield: 87 %

Procedure:
To a solution of ethyl 7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylate (2.0 g) in tetrahydrofuran (80 mL) were added 1-methoxypropan-2-ol (1.04 mL), tributylphosphine (2.46 mL) and 1,1′-(azodicarbonyl)dipiperidine (2.69 g) at room temperature. The mixture was stirred at 50° C. for 1 h. Then 1-methoxypropan-2-ol (0.5 mL), tributylphosphine (1.2 mL) and 1,1′-(azodicarbonyl)dipiperidine (1.34 g) were added to the mixture and the mixture was stirred at 50° C. overnight. The mixture was concentrated in vacuo. Ethyl acetate was added to the residue and insoluble materials were filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:hexane=1:9 to 6:4, volume ratio) to give the title compound (2.08 g, 87%) as a brown oil. MS 448 (MH+).
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.[NH2:21][CH:22]([CH2:35][OH:36])[CH2:23][O:24][C:25]1[C:29]2[CH:30]=[C:31]([Cl:34])[CH:32]=[CH:33][C:28]=2[O:27][N:26]=1.C(N(CC)CC)C.Cl>CN(C)C=O.C(OCC)(=O)C>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]2[O:27][N:26]=[C:25]([O:24][CH2:23][CH:22]([NH:21][C:1]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:35][OH:36])[C:29]=2[CH:30]=1
Reactant: NC(CO)COc1noc2ccc(Cl)cc12
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: OCC(COc1noc2ccc(Cl)cc12)NC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C

Procedure:
A solution of 5.58 g of trityl chloride in 6 ml of N,N-dimethylformamide is added to a solution of 4.85 g of 3-(2-amino-3-hydroxypropoxy)-5-chloro-1,2-benzoisoxazole and 2.02 g of triethylamine in 12 ml of N,N-dimethylformamide at -40° to -30° C., and they are subjected to reaction at the same temperature for 30 minutes. Subsequently, ice water and ethyl acetate are added to the reaction mixture and the pH is adjusted to 2 with 2N hydrochloric acid. The organic layer is separated, and the separated organic layer is washed with a saturated saline solution and dried over anhydrous magnesium sulfate, after which the solvent is removed by distillation under reduced pressure. The residue obtained is crystallized from n-hexane and the crystals are collected by filtration, to obtain 7.28 g of colorless, crystalline 5-chloro-3-(2-tritylamino-3-hydroxypropoxy)-1,2-benzoisoxazole having a melting point of 142°-144° C.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:22]2[N:27]=[C:26]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:25]=[C:24]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:23]=2)[CH:5]=[C:6]([C:8]2[C:9]3[C:14]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[CH:21]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:7]=1.[C:40]1(B(O)O)[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][CH:41]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:40]1([C:2]2[CH:3]=[C:4]([C:22]3[N:23]=[C:24]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[N:25]=[C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[N:27]=3)[CH:5]=[C:6]([C:8]3[C:9]4[C:14]([C:15]5[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=5[CH:21]=3)=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH:7]=2)[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][CH:41]=1
Reactant: Clc1cc(-c2nc(-c3ccccc3)nc(-c3ccccc3)n2)cc(-c2cc3ccccc3c3ccccc23)c1
Reactant: OB(O)c1cccc2ccccc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Product: c1ccc(-c2nc(-c3ccccc3)nc(-c3cc(-c4cccc5ccccc45)cc(-c4cc5ccccc5c5ccccc45)c3)n2)cc1
Temperature: 25 °C
Yield: 95 %

Procedure:
Then in a stream of argon, 0.5 g (0.96 mmol) of the obtained 2-[3-chloro-5-(9-phenanthryl)phenyl]-4,6-diphenyl-1,3,5-triazine, 038 g (1.73 mmol) of 1-naphthaleneboronic acid, 12.9 mg (0.058 mmol) of palladium acetate and 1.13 g (3.46 mmol) of cesium carbonate were suspended in 50 mL of tetrahydrofuran, and the temperature of the obtained suspension was elevated to 70° C. and distilled under reflux for 40 hours. The resultant reaction mixture was cooled to room temperature, and then distilled under a reduced pressure to remove all volatile materials. Methanol was added to the concentrate, and the thus-deposited solid was collected by filtration. The thus-obtained crude product was purified by column chromatography to give 0.56 g of the target 2-[3-(1-naphthyl)-5-(9-phenanthryl)phenyl]-4,6-diphenyl-1,3,5-triazine as grayish white solid (yield: 95%).
Reaction SMILES: [OH-].[K+].[CH3:3][C@@H:4]1[CH2:8][CH2:7][C:6](=O)[CH:5]1[C:10]([O:12]CC)=O.[NH2:15][C:16]([NH2:18])=[S:17]>O.C(O)C>[SH:17][C:16]1[N:15]=[C:10]([OH:12])[C:5]2[C@H:4]([CH3:3])[CH2:8][CH2:7][C:6]=2[N:18]=1
Reactant: NC(N)=S
Reactant: CCOC(=O)C1C(=O)CC[C@H]1C
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C[C@@H]1CCc2nc(S)nc(O)c21
Yield: 56 %

Procedure:
KOH (8.3 g, 147.9 mmol) in water (60 mL) was added to a solution of a mixture of (2R)-ethyl 2-methyl-5-oxocyclopentanecarboxylate (20 g, 117.5 mmol) and thiourea (9.2 g, 120.9 mmol) in ethanol (100 mL). The mixture was refluxed for 10 hours. After cooling, the solvent was removed. The resulting residue was neutralized with concentrated HCl (12 mL) at 0° C. and then extracted with DCM (3×150 mL). The solvent was removed, and the resulting residue was purified by silica gel chromatography, eluting with hexane/ethyl acetate (2:1) to give (R)-2-mercapto-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (12 g, 56%). MS (APCI+) [M+H]+183.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]1([CH2:12][C:13]2[CH:18]=[C:17]([NH:19][C:20](=O)[CH3:21])[CH:16]=[C:15]([CH2:23][N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[C:14]=2[OH:29])[CH2:11][CH2:10][CH2:9][CH2:8]1.O.[OH-].[Na+]>O1CCCC1>[N:7]1([CH2:12][C:13]2[CH:18]=[C:17]([NH:19][CH2:20][CH3:21])[CH:16]=[C:15]([CH2:23][N:24]3[CH2:25][CH2:26][CH2:27][CH2:28]3)[C:14]=2[OH:29])[CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: CC(=O)Nc1cc(CN2CCCC2)c(O)c(CN2CCCC2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CCNc1cc(CN2CCCC2)c(O)c(CN2CCCC2)c1
Yield: 72.9 %

Procedure:
To a stirred solution of lithium aluminum hydride (2.7 g) in tetrahydrofuran (25 ml) was added dropwise a solution of 2,6-bis(1-pyrrolidinomethyl)-4-acetamidophenol (5.6 g) in tetrahydrofuran (5 ml). The mixture was heated to reflux for 5 hours and was added dropwise water and aqueous 20% NaOH solution with cooling in an ice bath then was filtered by suction. The filtered cake was washed with tetrahydrofuran. The combined filtrate and washings were evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (CH3COOEt:CH3OH: H4OH=5:1:0.1) to give 2,6-bis(1-pyrrolidinomethyl)-4-ethylaminophenol (3.9 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=2)[C:15](=[O:29])[CH2:14][NH:13][CH2:12]1.[CH3:30]I>C1COCC1.[Cl-].[Na+].O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:27])([F:28])[F:26])=[CH:20][CH:19]=2)[C:15](=[O:29])[CH2:14][N:13]([CH3:30])[CH2:12]1
Reactant: CI
Reactant: COc1cccc(OC)c1C1CNCC(=O)N1Cc1ccc(OC(F)(F)F)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COc1cccc(OC)c1C1CN(C)CC(=O)N1Cc1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
A cooled (0° C.) solution of 6-(2,6-dimethoxyphenyl)-1-(4-(trifluoromethoxy)benzyl)-piperazin-2-one (106 mg; 0.25 mmol) in anh. THF (1.5 ml) was treated with a solution of CH3I (33 mg; 0.23 mmol) in anh. THF (0.5 ml). The resulting mixture was allowed to warm-up slowly to rt, and stirring at rt was then continued for 15 h. Brine was added, and the mixture was extracted with AcOEt (3×20 ml). The mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions D): tR=0.87 min.; [M+H]+: 425.02 g/mol.
Reaction SMILES: [Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[CH3:22][C:23]([Si:26]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[O:27][CH2:28][CH2:29][C:30]1([CH2:37][CH3:38])[CH:35]([OH:36])[CH:34]=[CH:33][CH2:32][CH2:31]1)([CH3:25])[CH3:24]>CN(C)C=O.[Cl-].[Na+].O>[CH3:22][C:23]([Si:26]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[O:27][CH2:28][CH2:29][C:30]1([CH2:37][CH3:38])[C:35](=[O:36])[CH:34]=[CH:33][CH2:32][CH2:31]1)([CH3:24])[CH3:25]
Reactant: CCC1(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CCC=CC1O
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC1(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CCC=CC1=O
Reaction time: 1 h
Yield: 87.8 %

Procedure:
Pyridinium dichromate (64.45 g, 171.33 mmol) was added to a solution of 6-[2-[[(1,1-dimethylethyl)diphenylsilyl]oxy]ethyl]-6-ethyl-2-cyclohexenol (56.01 g, 137.06 mmol) in 274 mL of dry N,N-dimethylformamide at 0° C. under nitrogen. After 1 hour, the reaction was poured into 2 L of brine and extracted with 10×500 mL of ether. The ethereal solutions were concentrated in vacuo and flash chromatographed in two batches (95 mm column, 51/2 inches of silica gel, 8% ethyl acetate in petroleum ether eluent) to afford 48.94 g (88%) of product as a pale yellow oil.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][C:8]1[CH:9]=[C:10]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:13]([CH2:20][CH2:21][C:22](OC)=[O:23])[C:12](=O)[N:11]2[CH:27]=1.O.[OH-].[Na+]>CCOCC>[OH:23][CH2:22][CH2:21][CH2:20][N:13]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=2[C:10]2=[CH:9][C:8]([CH3:7])=[CH:27][N:11]2[CH2:12]1
Reactant: COC(=O)CCn1c(=O)n2cc(C)cc2c2ccccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: Cc1cc2n(c1)CN(CCCO)c1ccccc1-2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
LiAlH4 (2.88 g, 0.076 m) was slurried in ether (250 ml) and to this was added a solution of the product of Example XXXV (5.5 g, 0.019 m) in ether (100 ml). The reaction mixture was stirred at ambient temperature for 1/2 hr. To the reaction mixture was added dropwise and successively H2O (3.0 ml), NaOH (3.0 ml of 15% aqueous), and H2O (9.0 ml). The resulting precipitate was filtered and washed with ether. The solvent was removed in vacuo from the filtrate and the residue crystallized from pentane to yield the desired product as a pale yellow solid; m.p. 77°-78° C.
Reaction SMILES: [N+]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.CN(C)C=[O:23].C([O-])=O.[Na+].Cl>O>[OH:23][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1
Reactant: CN(C)C=O
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Agent: Cl
Agent: O=C[O-]
Agent: [Na+]
Solvent: O
Product: O=C1c2ccccc2C(=O)c2c(O)cccc21
Reaction time: 1 h

Procedure:
1-Nitroanthraquinone (96.4%, 3.4%-dinitroanthraquinones), (7.6 g; 0.03 mole), dimethylformamide (50 ml), and sodium formate (4.1 g; 0.06 mole) were stirred at 130° C. for 17 hours. There was a slow evolution of gas during the reaction period. The reaction mass was cooled, mixed with water (300 ml) and acidified with 32% hydrochloric acid. The resulting suspension was stirred for one hour and filtered. The cake obtained was washed with water, then dried to give 1-hydroxyanthraquinone (6.6 g; 0.03 mole) which by gas chromatographic analysis contained 96.4% 1-hydroxyanthraquinone; 1.8% 1-nitroanthraquinone and 1.8% anthraquinone.
Reaction SMILES: C(O[CH:4]=[N:5][C:6]1[N:10]([CH3:11])[N:9]=[CH:8][C:7]=1[C:12]([O:14]CC)=O)C.[NH3:17]>C(O)C>[CH3:11][N:10]1[C:6]2[N:5]=[CH:4][NH:17][C:12](=[O:14])[C:7]=2[CH:8]=[N:9]1
Reactant: CCOC=Nc1c(C(=O)OCC)cnn1C
Reactant: N
Solvent: CCO
Product: Cn1ncc2c(=O)[nH]cnc21
Reaction time: 40 h

Procedure:
57.2 g. of 5 -[(ethoxymethylene)amino]-1-methyl-1H- pyrazole-4-carboxylic acid, ethyl ester are dissolved in 200 ml. of ethanol, 4.4 g. of ammonia are added and the reaction mixture is autoclaved at 60° for 40 hours. After cooling, the mixture is filtered and the residual 1-methyl-1,5-dihydro-4H-pyrazolo- [3,4-d]pyrimidin-4-one is crystallized from dimethylformamide, m.p. 289°-290° (yield 31 g. - 80.7%).