Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[C:5]([C:7]([O:9]CC)=O)[CH:4]=[N:3][CH:2]=1.[OH-].[NH4+:13]>CO>[N:1]1[CH:6]=[C:5]([C:7]([NH2:13])=[O:9])[CH:4]=[N:3][CH:2]=1
Reactant: CCOC(=O)c1cncnc1
Reactant: [NH4+]
Agent: [OH-]
Solvent: CO
Product: NC(=O)c1cncnc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of ethyl pyrimidine-5-carboxylate (6.10 g, 40.0 mmol) in methanol (40 mL) was stirred with ammonium hydroxide (4.30 mL, 110 mmol) in a sealed tube at 50° C. for 10 hours. The reaction mixture was then concentrated and the residue was stirred in ethanol/ethyl acetate (v/v 1/4, 50 mL) at ambient temperature for 2 hours. The white precipitate was collected by filtration and dried to give the titled compound. 1H NMR (300 MHz, DMSO-d6) δ 7.85 [s (broad), 1 H], 8.33 [s (broad), 1 H], 9.18 (s, 2 H), 9.32 (s, 1 H) ppm; MS (DCI/NH3) m/z 124 (M+H)+, 141 (M+NH4)+.
Reaction SMILES: C(OC([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:16]2[CH:25]=[CH:24][CH:23]=[C:22]3[C:17]=2[C:18]([O:26][CH3:27])=[CH:19][N:20]=[CH:21]3)[CH2:11][CH2:10]1)=O)(C)(C)C.[ClH:28].CO>>[ClH:28].[CH3:27][O:26][C:18]1[C:17]2[C:22](=[CH:23][CH:24]=[CH:25][C:16]=2[NH:15][CH:12]2[CH2:13][CH2:14][CH:9]([NH2:8])[CH2:10][CH2:11]2)[CH:21]=[N:20][CH:19]=1
Reactant: COc1cncc2cccc(NC3CCC(NC(=O)OC(C)(C)C)CC3)c12
Agent: Cl
Solvent: CO
Product: COc1cncc2cccc(NC3CCC(N)CC3)c12
Temperature: 25 °C

Procedure:
According to the method of Example 1, Step C, deprotection was performed (50° C., 2 hours) by using Intermediate 97 (372 mg) and 10% hydrogen chloride/methanol solution (10 ml). The reaction mixture was cooled to room temperature, and then the solvent was evaporated under reduced pressure. The residue was added with methanol (2 ml) and diethyl ether (6 ml). The deposited precipitates were collected by filtration and washed with diethyl ether to obtain the title compound (348 mg) as light yellow powdery solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].Br[CH:27]([CH3:42])[CH2:28][CH2:29][CH2:30][N:31]1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41]>CCN(CC)CC>[CH3:25][O:24][C:4]1[C:5]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:6]2[C:11](=[C:2]([NH:1][CH:27]([CH3:42])[CH2:28][CH2:29][CH2:30][N:31]3[C:35](=[O:36])[C:34]4=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]4[C:32]3=[O:41])[CH:3]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12]
Reactant: COc1cc(N)c2nccc(C)c2c1OCCCCc1ccccc1
Reactant: CC(Br)CCCN1C(=O)c2ccccc2C1=O
Solvent: CCN(CC)CC
Product: COc1cc(NC(C)CCCN2C(=O)c3ccccc3C2=O)c2nccc(C)c2c1OCCCCc1ccccc1
Reaction time: 1.5 h
Yield: 109.7 %

Procedure:
A stirred mixture of 8-amino-6-methoxy-4-methyl-5-(4-phenylbutoxy)quinoline (12.8 g, 0.038 mol) and 4-bromo-1-phthalimidopentane (BPP) (22.6 g, 0.076 mol) was heated at 135°-140° C. while Et3N (7 ml) was added in small portions during 1 hr. After 1.5 h at 135°-140° C., second portions of BPP (11.3 g) and Et3N (3.5 ml) were added and heating was continued for 2 h. Third portions of BPP (11.3 g) and Et3N (3.5 ml) were introduced and heating was continued for another 2 h. The mixture was allowed to cool and thoroughly extracted with Et2O (total, ca. 600 ml). The extract was treated with charcoal and then with saturated ethereal hydrogen chloride (250 ml). The resulting dark red semi-solid mass was separated by decantation and basified with ethereal Et3N. Concentration of the ethereal solution left a brown oil which was dissolved in CHCl3, placed on a silica gel column (200 g) and eluted with CHCl3. The first fractions were combined on the basis of TLC and concentrated to give 23 g of 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(4-phenylbutoxy) quinoline as an oil which was used without further purification.
Reaction SMILES: Cl[C:2](=[O:7])[C:3]([O:5][CH3:6])=[O:4].[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[CH2:20][CH2:19][C@H:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)=[CH:11][CH:10]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:6][O:5][C:3](=[O:4])[C:2]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([C@H:15]2[CH2:16][CH2:17][C@H:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]2)=[CH:13][CH:14]=1)=[O:7]
Reactant: CC(C)(C)OC(=O)[C@H]1CC[C@H](c2ccc(N)cc2)CC1
Reactant: COC(=O)C(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)C(=O)Nc1ccc([C@H]2CC[C@H](C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Methyl chlorooxoacetate (2.5 g, 20.7 mmol) was added dropwise to a mixture of tert-butyl trans-4-(4-aminophenyl)cyclohexanecarboxylate (3.8 g, 13.8 mmol) and pyridine (2.2 mL, 27.6 mmol) in DCM (40 mL) at 10° C. The reaction mixture was warmed to room temperature and stirred for 16 h and then quenched with water. The layers were separated and the organic layer was washed with brine. The organic layer was dried and concentrated in vacuo and the residue was purified by chromatography, eluting with 10-50% ethyl acetate in isohexane, to give the title compound (4.0 g, 80%) as an oil; 1H NMR δ 1.4 (9H, s), 1.4-1.55 (4H, m), 1.8-1.9 (2H, m), 1.9-2.05 (2H, m), 2.2-2.3 (1H, m), 2.4-2.6 (1H, m), 3.75 (3H, s), 7.2 (2H, d), 7.65 (2H, d); MS m/e (M−H)− 360.
Reaction SMILES: C1(S([CH:10]2[CH:20]([C:21]3[C:26]([CH3:27])=[C:25]([Br:28])[CH:24]=[CH:23][N:22]=3)[NH:19][C:12]3([CH2:16][CH2:15][N:14]([CH3:17])[C:13]3=[O:18])[CH2:11]2)(=O)=O)C=CC=CC=1.CC(C)([O-])C.[K+].C(O)(=O)C>C1COCC1>[Br:28][C:25]1[CH:24]=[CH:23][N:22]=[C:21]([C:20]2[CH2:10][CH2:11][C:12]3([CH2:16][CH2:15][N:14]([CH3:17])[C:13]3=[O:18])[N:19]=2)[C:26]=1[CH3:27]
Reactant: Cc1c(Br)ccnc1C1NC2(CCN(C)C2=O)CC1S(=O)(=O)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: Cc1c(Br)ccnc1C1=NC2(CC1)CCN(C)C2=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 58 %

Procedure:
To an ice cooled solution of 7-(benzenesulfonyl)-8-(4-bromo-3-methyl-2-pyridyl)-3-methyl-3,9-diazaspiro[4.4]nonan-4-one (which may be prepared as described in Description 8) (3500 mg, 7.54 mmol) in THF (5 mL) was added potassium tert-butoxide (1691 mg, 15.07 mmol) and the reaction was stirred for 1 hour. Additional KOtBu (1.7 g, 15.1 mmol) was added and the reaction was stirred at 00° C. for 1 hour, and allowed to warm to room temperature overnight. The reaction was quenched by addition of acetic acid (3.45 mL, 60.3 mmol), concentrated in vacuo and loaded onto a silica column (100 g SNAP). Elution using EtOAc gave 2-(4-bromo-3-methyl-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one (1410 mg, 4.3762 mmol, 58.063% yield) as a pale yellow crystalline solid;
Reaction SMILES: Cl.[CH:2]1([C:5](=[NH:7])[NH2:6])[CH2:4][CH2:3]1.Br[C:9]1[C:10](=O)[CH2:11][CH2:12][C:13]=1[O:14]C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:2]1([C:5]2[NH:6][C:10]3[CH2:11][CH2:12][C:13](=[O:14])[C:9]=3[N:7]=2)[CH2:4][CH2:3]1
Reactant: N=C(N)C1CC1
Reactant: COC1=C(Br)C(=O)CC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1CCc2[nH]c(C3CC3)nc21
Temperature: 100 °C
Yield: 32 %

Procedure:
A mixture of cyclopropanecarboximidamide hydrochloride (0.757 g), 2-bromo-3-(methyloxy)-2-cyclopenten-1-one (1 g) and potassium carbonate (2.171 g) in N,N-dimethylformamide (15 mL) were heated at 100° C. for 3 h. Potassium carbonate (1 g) was added and the mixture heated at 110° C. for further 16 h. The reaction mixture was cooled down to room temperature and partitioned between dichloromethane (60 mL) and sat. aq. NH4Cl (60 mL). The 2 phases were separated, the aqueous was extracted with DCM (2×40 mL), the organic extracts were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified on silica using a cyclohexane:ethyl acetate 0-100% gradient with a 0->20% Ethyl Acetate-MeOH wash at the end. The desired fractions (in the MeOH wash) were combined and concentrated under vacuum to give the title compound (272 mg), used crude in the next reaction. LC/MS MH+ 163, Rt 1.45 min (5 minute run).
Reaction SMILES: [Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]([NH2:28])=[N:15][CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=1)[CH3:11].Br[C:30]1[CH:31]=[N:32][N:33]([CH:35]2[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]2)[CH:34]=1>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]([NH2:28])=[N:15][CH:16]=[C:17]([C:30]2[CH:31]=[N:32][N:33]([CH:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)[CH:34]=2)[CH:18]=1)[CH3:11]
Reactant: CN1CCC(n2cc(Br)cn2)CC1
Reactant: C[C@@H](Oc1cc(B2OC(C)(C)C(C)(C)O2)cnc1N)c1c(Cl)ccc(F)c1Cl
Product: C[C@@H](Oc1cc(-c2cnn(C3CCN(C)CC3)c2)cnc1N)c1c(Cl)ccc(F)c1Cl

Procedure:
The title compound was prepared according to procedure 62 using 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine and 4-(4-bromo-pyrazol-1-yl)-1-methy-piperidine (prepared according to general procedure 11. 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.55 (s, 1H), 7.50 (s, 1H), 7.31 (m, 1H), 7.06 (m, 1H), 6.87 (s, 1H), 6.08 (m, 1H), 5.50 (bs, 2H), 4.18 (m, 1H), 3.11 (m, 2H), 2.40 (s, 3H), 2.30 (m, 2H), 2.20 (m, 4H), 2.07 (s, 3H), 1.86 (d, J=8 Hz, 3H); LCMS: 464 [M+1]; c-Met Ki: 0.01 μM.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11]([CH2:13]Br)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C-:15]#[N:16].[K+].O>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11]([CH2:13][C:15]#[N:16])[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [C-]#N
Reactant: CC(C)(C)OC(=O)n1cc(CBr)cn1
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CC(C)(C)OC(=O)n1cc(CC#N)cn1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To 4-bromomethyl-pyrazole-1-carboxylic acid tert-butyl ester (1.0 g, 3.5 mmol) in DMSO (25 mL) was added potassium cyanide (0.228 g, 3.5 mmol), and the reaction was stirred for 15 minutes at room temperature. The mixture was poured into H2O and extracted with EtOAc. The combined organic layers were dried and concentrated to give the title compound, along with some starting material and the unbrominated starting material from the previous step. The material was dissolved in DMSO (10 mL), and potassium cyanide (0.100 g, 1.5 mmol) was added. The reaction was stirred for 1 hour at room temperature, and then worked-up, dried, and concentrated to give the title compound, contaminated with a small amount of 4-methyl-pyrazole-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]([CH3:25])=[CH2:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:26])[CH3:9])=[C:4]([CH3:27])[CH:3]=1.ClC1C=C(C=CC=1)C(OO)=[O:33]>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]3([CH3:25])[CH2:24][O:33]3)([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[O:12][C:11]2=[O:26])[CH3:9])=[C:4]([CH3:27])[CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C(C)C[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(Br)cc2C)C(=O)O1
Solvent: ClCCl
Product: Cc1cc(Br)ccc1[C@H](C)N1CC[C@](CC2(C)CO2)(c2ccccc2)OC1=O
Temperature: 5 °C
Reaction time: 8 h

Procedure:
3-[(S)-1-(4-Bromo-2-methyl-phenyl)-ethyl]-(R)-6-(2-methyl-allyl)-6-phenyl -[1,3]oxazin-an-2-one (1.34 g) dissolved in dichloromethane (15 mL) was added to a solution of 3-chloroperoxybenzoic acid (77%, 0.81 g) in dichloromethane (15 mL) cooled to 5° C. The cooling bath was removed and the solution was stirred at room temperature overnight. Aqueous 10% Na2S2O3 solution (10 mL) and aqueous saturated NaHCO3 solution (25 mL) were added and the resulting mixture was stirred for further 30 min. The organic phase was separated and washed with aqueous Na2S2O3 solution combined with aqueous saturated NaHCO3 solution, water, and brine. The organic phase was dried (MgSO4) and concentrated to furnish the title compound. Yield: 1.55 g (ca. 85-90% pure); LC-MS (Method 4): tR=4.28 min; Mass spectrum (ESI+): m/z=444/446 (Br) [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([CH2:9][O:10][C:11]3[CH:19]=[CH:18][CH:17]=[C:16]4[C:12]=3[CH:13]=[C:14]([C:20](O)=[O:21])[NH:15]4)=[CH:7][O:8][C:4]=2[CH:3]=1.[ClH:25].Cl.Cl.[C@H:28]1([CH2:38][N:39]2[CH2:44][CH2:43][CH:42]([NH2:45])[CH2:41][CH2:40]2)[C@@H:37]2[N:32]([CH2:33][CH2:34][CH2:35][CH2:36]2)[CH2:31][CH2:30][CH2:29]1>>[ClH:1].[ClH:25].[C@H:28]1([CH2:38][N:39]2[CH2:44][CH2:43][CH:42]([NH:45][C:20]([C:14]3[NH:15][C:16]4[C:12]([CH:13]=3)=[C:11]([O:10][CH2:9][C:6]3[C:5]5[CH:23]=[CH:24][C:2]([Cl:1])=[CH:3][C:4]=5[O:8][CH:7]=3)[CH:19]=[CH:18][CH:17]=4)=[O:21])[CH2:41][CH2:40]2)[C@@H:37]2[N:32]([CH2:33][CH2:34][CH2:35][CH2:36]2)[CH2:31][CH2:30][CH2:29]1
Reactant: O=C(O)c1cc2c(OCc3coc4cc(Cl)ccc34)cccc2[nH]1
Reactant: NC1CCN(C[C@@H]2CCCN3CCCC[C@H]23)CC1
Agent: Cl
Product: O=C(NC1CCN(C[C@@H]2CCCN3CCCC[C@H]23)CC1)c1cc2c(OCc3coc4cc(Cl)ccc34)cccc2[nH]1

Procedure:
This compound is synthesized from 4-(6-chloro-benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid (117) (preparation see below) and amine 61 analogously to the method described in example 1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:12][C:13]([CH3:15])=[CH2:14]>C1COCC1.CCOCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:14][C:13]([CH3:15])=[CH2:12])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: C=C(C)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: C=C(C)COc1ccc(Cl)cc1
Reaction time: 24 h

Procedure:
A mixture of 4chlorophenol (10 g, 0.78 mol) and sodium hydride (1.9 g, 0.08 mol) is heated to reflux for 30 min in 30 ml of THF and then cooled. 3-Chloro-2-methyl-1-propene (7.3 g, 0.08 mol) in 10 ml THF is added and the mixture is heated to reflux. After 24 hr, an additional equivalent of 3-chloro-2-methyl-1-propene is added and the mixture heated under reflux for another 24 hr. The reaction mixture is cooled and diluted with ether to 150 ml, washed with 20% NaOH (2X) and with water until neutral, then dried and solvent is removed to yield 3-(4-chloro-phenoxy)-2-methyl-1-propene.
Reaction SMILES: [CH2:1]([NH:3][C:4]([NH:6][C:7]([NH2:9])=[O:8])=[O:5])[CH3:2].[CH2:10](O)C>C1C=CC=CC=1>[CH2:1]([N:3]1[CH:10]=[N:9][C:7](=[O:8])[NH:6][C:4]1=[O:5])[CH3:2]
Reactant: CCNC(=O)NC(N)=O
Reactant: CCO
Solvent: c1ccccc1
Product: CCn1cnc(=O)[nH]c1=O
Temperature: 60 °C
Yield: 58.7 %

Procedure:
The ethylbiuret prepared in Part A, above, [592 gm. 4.7 mole] is dispersed in 24 liter absolute ethanol and 1.6 liter benzene. This reaction mixture is heated to the reflux temperature and 3.5 liter of solvent medium is removed by distillation. The solution is cooled to 60° C. and 2090 gm. of a 25 percent solution of sodium methoxide in methanol is slowly added over an interval of five minutes. That addition is followed by the addition of 820 gm. of ethylformate. This reaction mixture is heated at the reflux temperature for three (3) hours, whereupon the solution is cooled to 38° C. and concentrated hydrochloric acid is added slowly until the pH of the solution is 2. To the acidified solution is added more (3.4 liter) benzene. Then 2 liter of the solvent medium is removed by distillation under reduced pressure and 50° C. The mixture is then heated to 75° C. and filtered in order to remove the sodium chloride produced by the reaction. The filter cake of salt is washed with hot absolute ethanol which washings are added to the filtrate. The volume of the combined filtrate and absolute ethanol washings is reduced to 5 liter by evaporation under reduced pressure at 50° C. The resulting concentrate is cooled at 5° C. for 18 hours while crystals form. The crystals are collected on a filter and washed with cold (5°) ethanol. The washed crystals are dried in an oven under reduced pressure at 50° C. for 18 hours. There is thus obtained 408 gm. of crude product having a melting point at 137° to 139° C. A further purification is achieved by dissolving the 408 gm. in 4 liter methanol at reflux temperature. This solution is concentrated by allowing the methanol to evaporate to a volume of 2 l. while being heated on a steam bath. The concentrated solution is allowed to cool slowly to 25° C. It is then chilled to 5° C. for two hours. The crystals that form are collected on a filter and the filter cake is washed with ice-cold methanol. After drying there is obtained 389 gm. (58.7 percent yield) of 1-ethyl-5-azauracil having a melting point of 141° to 142° C. A second crop of crystals is recovered from the mother liquor after further concentration and cooling.
Reaction SMILES: [CH2:1]([N:8]1[N:12]=[C:11]([CH:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22](/[N:25]=[CH:26]/[C:27]4[O:28][C:29]([N+:32]([O-:34])=[O:33])=[CH:30][CH:31]=4)=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)[O:10][C:9]1=[O:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CC(O)=O.CO>[CH2:1]([N:8]1[N:12]=[C:11]([CH:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][CH2:26][C:27]4[O:28][C:29]([N+:32]([O-:34])=[O:33])=[CH:30][CH:31]=4)=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)[O:10][C:9]1=[O:35])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=c1oc(C2CCN(c3ccc(/N=C/c4ccc([N+](=O)[O-])o4)cc3)CC2)nn1Cc1ccccc1
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: O=c1oc(C2CCN(c3ccc(NCc4ccc([N+](=O)[O-])o4)cc3)CC2)nn1Cc1ccccc1
Yield: 84.8 %

Procedure:
3-Benzyl-5-[1-(4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9d, 0.47 g, 1 mmol) on reduction with sodiumcyano borohydride (0.12 g, 2 mmol) in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0° C. for 12 h. After completion of the reaction as indicated by TLC, the reaction mixture is neutralized with sodium bi carbonate and extracted into chloroform. The crude product thus obtained was purified by column chromatography using ethyl acetate-hexane (8:2) as eluant to obtain product 3-benzyl-5-[1-(4-[(5-nitro-2-furyl) methyl]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (10d, 403 mg, 85%).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]2[CH:28]=[CH:27][C:21]([C:22]([O:24]CC)=[O:23])=[CH:20][CH:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].C(O)C.O.Cl>O>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]2[CH:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[CH:27][CH:28]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1ccc(NCCCCCCCCCCc2ccccc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1ccc(NCCCCCCCCCCc2ccccc2)cc1

Procedure:
A mixture of 7.0 g. of ethyl p-[(10-phenyldecyl)amino]benzoate (prepared as described in Example 28), 7 g. of potassium hydroxide and 100 ml. of ethanol-water (9:1) is refluxed for 3.5 hours. The mixture is acidified while hot with concentrated hydrochloric acid, diluted with water, cooled and filtered to give white crystals, m.p. 80°-87° C. Recrystallization from ethanol gives white crystals, m.p. 96°-98° C.
Reaction SMILES: N1C=CC=CC=1P([CH2:14][P:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)C1C=CC=CC=1.ClC[CH2:30][O:31][CH2:32][CH2:33][O:34][CH2:35][CH2:36]Cl>ClCCl>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[P:15]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:36][CH2:35][O:34][CH2:33][CH2:32][O:31][CH2:30][CH2:14][P:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: c1ccc(P(CP(c2ccccc2)c2ccccn2)c2ccccn2)cc1
Reactant: ClCCOCCOCCCl
Solvent: ClCCl
Product: c1ccc(P(CCOCCOCCP(c2ccccc2)c2ccccn2)c2ccccn2)cc1

Procedure:
Some 1,8-bis[(2-pyridyl)(phenyl)phosphino]-3,6-dioxaoctane was prepared substantially in the same way as the diphosphine of Example 2, except that instead of dichloromethane, 1,8-dichloro-3,6-dioxaoctane was employed.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:12][C:13]([OH:15])=[O:14])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.Cl[C:17]1[CH:24]=[CH:23][C:22]([S:25]([CH2:28][CH3:29])(=[O:27])=[O:26])=[CH:21][C:18]=1[C:19]#[N:20]>>[C:19]([C:18]1[CH:21]=[C:22]([S:25]([CH2:28][CH3:29])(=[O:27])=[O:26])[CH:23]=[CH:24][C:17]=1[O:1][C:2]1[CH:3]=[C:4]([CH2:12][C:13]([OH:15])=[O:14])[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1)#[N:20]
Reactant: O=C(O)Cc1cc(O)cc(C(F)(F)F)c1
Reactant: CCS(=O)(=O)c1ccc(Cl)c(C#N)c1
Product: CCS(=O)(=O)c1ccc(Oc2cc(CC(=O)O)cc(C(F)(F)F)c2)c(C#N)c1

Procedure:
The title compound was prepared as described in example 2 step (iii) but instead using the product from example 25 step (iv) and the product from example 12 step (i).
Reaction SMILES: [CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][O:4][C:5]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:6]=1/[CH:13]=[CH:14]/[C:15]1[N:16]=[C:17]2[N:21]([C:22]=1[C:23](O)=[O:24])[CH:20]=[CH:19][S:18]2.[F:28][C:29]([F:37])([F:36])[C:30]1[N:31]=[C:32]([NH2:35])[S:33][CH:34]=1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl.CN(C=O)C>[CH3:26][C:2]([CH3:1])([CH3:27])[CH2:3][O:4][C:5]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:6]=1/[CH:13]=[CH:14]/[C:15]1[N:16]=[C:17]2[N:21]([C:22]=1[C:23]([NH:35][C:32]1[S:33][CH:34]=[C:30]([C:29]([F:37])([F:36])[F:28])[N:31]=1)=[O:24])[CH:20]=[CH:19][S:18]2
Reactant: Nc1nc(C(F)(F)F)cs1
Reactant: COc1cccc(/C=C/c2nc3sccn3c2C(=O)O)c1OCC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1cccc(/C=C/c2nc3sccn3c2C(=O)Nc2nc(C(F)(F)F)cs2)c1OCC(C)(C)C

Procedure:
The title compound was prepared according to the general procedure (Method B) by coupling Intermediate 3 (200 mg, 0.517 mmol) with 4-(trifluoromethyl)-1,3-thiazol-2-amine (105 mg, 0.621 mmol) in the presence of EDCI hydrochloride (198 mg, 1.035 mmol) and DMAP (95 mg, 0.776 mmol) in a mixture of DCM and DMF (4:1, 5 mL) to give 114 mg of the product as a pale yellow solid; 1H NMR (300 MHz, DMSO-d6) δ 1.01 (s, 9H), 3.56 (s, 2H), 3.80 (s, 3H), 6.98-6.99 (m, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.34 (d, J=7.8 Hz, 1H), 7.43-7.48 (m, 2H), 7.85 (d, J=16.2 Hz, 1H), 8.05-8.09 (m, 2H), 12.97 (br s, 1H); ESI-MS (m/z) 535.20 (M−H)−.
Reaction SMILES: [N+:1]([C:4]1[CH:45]=[C:44]([CH3:46])[C:7]([O:8][C:9]2[CH:43]=[CH:42][C:12]([C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([CH3:41])([CH3:40])[C:23]4[CH:28]=[CH:27][C:26]([O:29][C:30]5[C:35]([CH3:36])=[CH:34][C:33]([N+:37]([O-])=O)=[CH:32][CH:31]=5)=[CH:25][CH:24]=4)[CH:17]=3)([CH3:15])[CH3:14])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-])=O.[H][H]>[Pd].C(O)(C)C>[NH2:37][C:33]1[CH:34]=[C:35]([CH3:36])[C:30]([O:29][C:26]2[CH:25]=[CH:24][C:23]([C:22]([C:18]3[CH:19]=[CH:20][CH:21]=[C:16]([C:13]([CH3:15])([CH3:14])[C:12]4[CH:42]=[CH:43][C:9]([O:8][C:7]5[C:44]([CH3:46])=[CH:45][C:4]([NH2:1])=[CH:5][CH:6]=5)=[CH:10][CH:11]=4)[CH:17]=3)([CH3:41])[CH3:40])=[CH:28][CH:27]=2)=[CH:31][CH:32]=1
Reactant: [H][H]
Reactant: Cc1cc([N+](=O)[O-])ccc1Oc1ccc(C(C)(C)c2cccc(C(C)(C)c3ccc(Oc4ccc([N+](=O)[O-])cc4C)cc3)c2)cc1
Agent: [Pd]
Solvent: CC(C)O
Product: Cc1cc(N)ccc1Oc1ccc(C(C)(C)c2cccc(C(C)(C)c3ccc(Oc4ccc(N)cc4C)cc3)c2)cc1
Yield: 82 %

Procedure:
Successively, to a reduction vessel equipped with a thermometer, reflux condenser and stirrer, 120 g (0.195 mol) of 1,3-bis[4-(4-nitro-6-methylphenoxy)-α, α-dimethylbenzyl]benzene, 400 g of isopropyl alcohol and 5 g of 5%-Pd/c having a moisture content of 50% were charged and reacted at 70°~80° C. for 4 hours in a hydrogen atmosphere. After finishing the reaction, the catalyst was filtered off and the filtrate was concentrated under reduced pressure to obtain 89.0 g (82% yield) of 1,3-bis[4-(4-amino-6-methylphenoxy)-α, α-dimethylbenzyl]benzene as a light yellow crystal having a melting point of 118.1~118.2.