Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[C:3]([CH:18]=[N:19][C@H:20]([CH:25]([CH3:27])[CH3:26])[C:21]([CH3:24])([OH:23])[CH3:22])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.[H][H]>CO.[Ni]>[F:1][C:2]1[C:3]([CH2:18][NH:19][C@H:20]([CH:25]([CH3:27])[CH3:26])[C:21]([CH3:22])([OH:23])[CH3:24])=[N:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:17])([F:15])[F:16])=[CH:12][CH:13]=2)=[CH:6][CH:7]=1
Reactant: CC(C)[C@@H](N=Cc1nc(-c2ccc(C(F)(F)F)cc2)ccc1F)C(C)(C)O
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: CC(C)[C@@H](NCc1nc(-c2ccc(C(F)(F)F)cc2)ccc1F)C(C)(C)O
Temperature: 25 °C
Reaction time: 48 h
Yield: 54.5 %

Procedure:
Example 17A (800 mg, 2.97 mmol) and Example 105C (498 mg, 2.97 mmol) were dissolved in methanol (20 mL) and triethylamine (0.453 mL, 3.27 mmol). The yellow solution was stirred at ambient temperature for 90 minutes, followed by the addition of sodium borohydride (247 mg, 6.54 mmol). The reaction mixture was stirred over the weekend at ambient temperature, quenched with 100 mL 1.0 N NaOH, and extracted twice with 100 mL dichloromethane, dried over Na2SO4, filtered, and concentrated to obtain (R)-3-[({3-fluoro-6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}methylene)amino]-2,4-dimethylpentan-2-ol (1.147 g, 3.00 mmol) as an orange oil. The imine (1.147 g, 3.00 mmol) in methanol (20 mL) was added to Raney Nickel (1.147 g) in a 50 mL pressure bottle. The mixture was pressurized with hydrogen (30 psi), and stirred for 48 hours at ambient temperature. The mixture was filtered through a nylon membrane, concentrated, and chromatographed on a Grace Reveleris 40 g column, eluted with 0-20% EtOAc in dichloromethane (30 mL/min) to provide the title compound (0.629 g, 1.636 mmol, 54.6% yield) as a colorless oil. MS (ESI+) m/z 385.0 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 8.29 (d, J=8.2, 2H), 8.06 (dd, J=8.7, 3.7, 1H), 7.92-7.78 (m, 3H), 4.25 (s, 1H), 4.16-3.99 (m, 2H), 2.36 (q, J=6.2, 1H), 2.26 (dd, J=5.9, 2.4, 1H), 2.03-1.89 (m, 1H), 1.11 (d, J=9.2, 6H), 0.93 (dd, J=6.8, 5.8, 6H).
Reaction SMILES: [CH2:1]([CH:5]([C:12]1[C:13](=[O:23])[O:14][C:15]2[C:20]([C:21]=1[OH:22])=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:2]([CH3:4])=[O:3].[C:24](Cl)(=[O:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]/[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>O1CCOCC1.N1C=CC=CC=1>[CH2:1]([CH:5]([C:12]1[C:13](=[O:23])[O:14][C:15]2[C:20]([C:21]=1[O:22][C:24](=[O:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]/[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[C:2]([CH3:4])=[O:3]
Reactant: CC(=O)CC(c1ccccc1)c1c(O)c2ccccc2oc1=O
Reactant: CCCCCCCC/C=C/CCCCCCCC(=O)Cl
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: CCCCCCCC/C=C/CCCCCCCC(=O)Oc1c(C(CC(C)=O)c2ccccc2)c(=O)oc2ccccc12
Temperature: 25 °C
Reaction time: 4 h
Yield: 74.2 %

Procedure:
To a solution of 3-(α-acetonylbenzyl)-4-hydroxycoumarin (warfarin) (3.70 g, 12 mmol) in 120 ml anhydrous dioxane and 25 ml pyridine was added elaidic acid chloride (3.60 g, 12 mmol) and the reaction mixture was stirred at ambient temperature for 4 hours. The solvents were evaporated at high vacuum. The residue was partitioned between ether and water. The organic phase was washed with tartaric acid (aq), NaHCO3 (aq) and water. The dried organic phase was concentrated and the product purified on a column of slica gel with heptane/ethylacetate (6:1) as the eluent system. Impure fractions were repurified and homogenous fractions were evaporated to give 5.1 g (70%) of the title compound as a pale yellow oil.
Reaction SMILES: [CH3:1][NH2:2].[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[N:7]=[C:6](S(C)(=O)=O)[N:5]=1>CCOC(C)=O>[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[N:7]=[C:6]([NH:2][CH3:1])[N:5]=1
Reactant: CN
Reactant: CS(=O)(=O)c1nc(Cl)cc(Cl)n1
Solvent: CCOC(C)=O
Product: CNc1nc(Cl)cc(Cl)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.5 %

Procedure:
Methylamine (2M solution, 113 mL, 217 mmol, 2.05 equiv) was charged to a 1 L 3-neck flask fitted with a magnetic stirrer and a thermometer. The mixture was chilled in an ice bath. To this stirred solution was added via addition funnel a solution of 4,6-dichloro-2-(methylsulfonyl)pyrimidine (25 g, 110 mmol) in EtOAc (250 mL) portionwise over a 25 minutes period. The temp was between 5-10° C. After completion of addition, the ice bath was removed, and the mixture was stirred for 1 hour at ambient temperature. LCMS showed conversion complete. The suspension was filtered, and washed with EtOAc. The filtrate was concentrated in vacuo. The residue was partitioned between water (100 mL) and EtOAc (450 mL). The organic was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give white solids, which were triturated in 150 mL of CH2Cl2. These solids were collected by filtration and washing with cold CH2Cl2 (50 mL). Drying under house vacuum at room temperature for 20 hours, and then high vacuum at room temperature for 3 hours gave 9.31 g of the title compound as a solid. LC-MS (ES) m/z=179 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=O)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:13]([O:15][C:16](=[O:25])[CH:17]([NH:21][C:22](=[O:24])[CH3:23])C(O)=O)[CH3:14].C(OC(=O)C)(=O)C>N1C=CC=CC=1>[CH2:13]([O:15][C:16](=[O:25])[C:17]([NH:21][C:22](=[O:24])[CH3:23])=[CH:11][C:6]1[C:5]2[C:9](=[CH:10][C:2]([CH3:1])=[CH:3][CH:4]=2)[NH:8][CH:7]=1)[CH3:14]
Reactant: CCOC(=O)C(NC(C)=O)C(=O)O
Reactant: Cc1ccc2c(C=O)c[nH]c2c1
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CCOC(=O)C(=Cc1c[nH]c2cc(C)ccc12)NC(C)=O
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 88.4 %

Procedure:
A 3-l. three-necked flask, equipped with a mechanical stirrer, a thermometer and a dropping funnel with pressure-equalizing arm was charged with 100 g (0.63 mol) of 6-methylindole-3-carboxaldehyde, 119 g (0.63 mol) of acetamidomalonic acid monoethylester and 500 ml of pyridine. The mixture was stirred and kept at 15° with a cold water bath while 175 ml of acetic anhydride was added over 15 minutes. The yellow solution was stirred at room temperature for 3 hours. Then an additional portion of 36 g (0.19 mol) of acetamidomalonic acid monoethyl ester was added and stirring at room temperature was continued for 22 hours before 1 kg of ice was added. The temperature fell to -10° and the product began to precipitate. The suspension was stirred at room temperature for 5 hours and poured into 2 l of water. After 20 minutes, the precipitate was collected by suction filtration, washed with water and dried at 50° in an air oven overnight to afford 159.5 g (89%) of crude product as yellow crystals, m.p. 159-162° (sinters at 75°).
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([C:10]3[S:11][C:12]4[C:18](=[O:19])[CH2:17][C:16]([CH3:21])([CH3:20])[CH2:15][C:13]=4[N:14]=3)[CH2:7][CH2:8][O:9][C:4]=2[CH:3]=1.[C:24]1([S:30](Cl)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:21][C:16]1([CH3:20])[CH2:15][C:13]2[N:14]=[C:10]([N:6]3[C:5]4[CH:22]=[CH:23][C:2]([NH:1][S:30]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)(=[O:32])=[O:31])=[CH:3][C:4]=4[O:9][CH2:8][CH2:7]3)[S:11][C:12]=2[C:18](=[O:19])[CH2:17]1
Reactant: CC1(C)CC(=O)c2sc(N3CCOc4cc(N)ccc43)nc2C1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC1(C)CC(=O)c2sc(N3CCOc4cc(NS(=O)(=O)c5ccccc5)ccc43)nc2C1
Yield: 35 %

Procedure:
A mixture of Example 13 (46 mg, 0.14 mmol), benzenesulfonyl chloride (0.023 mL, 0.182 mmol) and pyridine (0.022 mL, 0.28 mmol) in DCM (4 mL) was stirred at r.t. for 5 h. The reaction mixture was concentrated in vacuo. Purification by prep HPLC gave the title compound as an off-white solid (23 mg, 35%). δH (CDCl3) 1.14 (6H, s), 2.43 (2H, s), 2.74 (2H, s), 4.08-4.16 (2H, m), 4.26-4.33 (2H, m), 6.64 (1H, dd, J 8.9, 2.4 Hz), 6.80 (1H, d, J 2.4 Hz), 7.02 (1H, s), 7.42-7.61 (3H, m), 7.77-7.87 (3H, m). LCMS (ES+) 470.1 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C@H:3]1[CH2:4][CH2:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C@@H:10]2[O:22][CH2:23][C:24]([OH:26])=[O:25].[C:27]1([C:33]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[N+]=[N-])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[CH3:1][N:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C@H:3]1[CH2:4][CH2:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C@@H:10]2[O:22][CH2:23][C:24]([O:26][CH:33]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:25]
Reactant: CN1C(=O)CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](OCC(=O)O)CC[C@H]4[C@@H]3CC[C@@H]12
Reactant: [N-]=[N+]=C(c1ccccc1)c1ccccc1
Solvent: ClCCl
Product: CN1C(=O)CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](OCC(=O)OC(c5ccccc5)c5ccccc5)CC[C@H]4[C@@H]3CC[C@@H]12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 4-methyl-5α-4-azaandrostan-3-on-17β-yloxyacetic acid (3.5 mg) in CH2Cl2 (0.2 ml) under N2 was added diphenyldiazomethane (ca. 20 mg) in portions during 15 minutes. The reaction stirred at room temperature for 2 hours, then additional diphenyldiazomethane (ca. 5 mg) was added and the reaction was allowed to stir overnight. The mixture was purified via preparative TLC on a silica gel plate (1000μ) developed with EtOAc to yield diphenylmethyl 4-methyl-5α-4-azaandrostan-3-on-17β-yloxyacetate, (Rf =0.4/EtOAc).
Reaction SMILES: CO[C:3](=[O:30])[CH2:4][CH2:5][C:6]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([O:17][CH2:18][C@@H:19]3[CH2:22][CH2:21][N:20]3[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:16]=2)[O:8][N:7]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][C@H:19]1[CH2:18][O:17][C:15]1[CH:16]=[C:11]([C:9]2[O:8][N:7]=[C:6]([CH2:5][CH2:4][C:3]([N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])[CH:10]=2)[CH:12]=[N:13][CH:14]=1)=[O:24])([CH3:27])([CH3:29])[CH3:28]
Reactant: C1CCNC1
Reactant: COC(=O)CCc1cc(-c2cncc(OC[C@@H]3CCN3C(=O)OC(C)(C)C)c2)on1
Product: CC(C)(C)OC(=O)N1CC[C@H]1COc1cncc(-c2cc(CCC(=O)N3CCCC3)no2)c1
Temperature: 100 °C
Yield: 100.8 %

Procedure:
To 3-[5-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]-3-isoxazolyl]propionic acid methyl ester (210 mg, 0.5 mmol) was added pyrrolidine (1.2 mL, 15 mmol). The mixture was heated at 100° C. for 12 h, cooled, and concentrated. The residue was dissolved in water and extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by CC on SiO2 with EtOAc/hexane 1:1 to give 3-[5-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]-3-isoxazolyl]-1-(1-pyrrolidinyl)-1-propanone (230 mg, 99%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[O:12]1[CH:16]=[CH:15][C:14]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:29])[CH2:25][C:26](O)=[O:27])[CH:20]=[CH:21][CH:22]=2)=[CH:13]1>>[Cl:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][C:26](=[O:27])[CH2:25][C:24]([NH:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:14]3[CH:15]=[CH:16][O:12][CH:13]=3)[CH:18]=2)=[O:29])=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]
Reactant: O=C(O)CC(=O)Nc1cccc(-c2ccoc2)c1
Reactant: Nc1ccc(Cl)cc1C(=O)O
Product: O=C(CC(=O)Nc1ccc(Cl)cc1C(=O)O)Nc1cccc(-c2ccoc2)c1

Procedure:
Using the same method as in Example 15-(i), 2-amino-5-chlorobenzoic acid.benzylester was reacted with the 3-([3-(furan-3-yl)phenyl]amino)-3-oxopropanoic acid to give 5-chloro-2-[(3-([3-(furan-3-yl)phenyl]amino)-3-oxopropanoyl)amino]benzoic acid.benzylester (yield: 48%).
Reaction SMILES: [C:1]([OH:5])(=[O:4])[C:2]#[CH:3].[CH3:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12]O.C1(C)C=CC=CC=1>O>[C:1]([O:5][CH2:12][CH2:11][O:10][CH2:9][CH2:8][O:7][CH3:6])(=[O:4])[C:2]#[CH:3]
Reactant: COCCOCCO
Reactant: C#CC(=O)O
Solvent: O
Solvent: Cc1ccccc1
Product: C#CC(=O)OCCOCCOC

Procedure:
12.3 ml (0.2 mol) of propiolic acid were boiled at reflux for 20 hours together with 23.6 ml (0.2 mol) of diethylene glycol monomethyl ether, 1.5 g (8 mmol) of P-toluenesulphonic acid monohydrate and 80 ml of toluene, with the resulting reaction water being distilled off azeotropically and being collected in a water separator. After completion of the water separation the reaction mixture was washed in succession with saturated sodium bicarbonate solution and with water. The toluene phase was dried over sodium sulphate and concentrated. The crude product was purified by flash chromatography on 500 g of silica gel (elution agent methylene chloride/ethyl acetate 9:1). There was obtained 2-(2-methoxyethoxy)ethyl propiolate as a colorless oil.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[S:11][C:12]([CH3:17])=[CH:13][C:14]=2[C:15]#[N:16])=[C:5]([N+:18]([O-])=O)[CH:4]=1)#[N:2].[Sn](Cl)(Cl)(Cl)[Cl:22]>C(O)C.Cl>[ClH:22].[NH2:16][C:15]1[C:14]2[CH:13]=[C:12]([CH3:17])[S:11][C:10]=2[NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:18]=1
Reactant: Cc1cc(C#N)c(Nc2ccc(C#N)cc2[N+](=O)[O-])s1
Reactant: Cl[Sn](Cl)(Cl)Cl
Agent: Cl
Solvent: CCO
Product: Cc1cc2c(s1)Nc1ccc(C#N)cc1N=C2N
Temperature: 85 °C

Procedure:
To a suspension of 2-(4-Cyano-2-nitro-phenylamino)-5-methyl-thiophene-3-carbonitrile, prepared as described in the previous step, (0.52 g) in ethanol (5 mL), was added tine chloride (1.36 g, 7.2 mmol) in 6 N HCl. The mixture was heated in an 85° C. oil bath for 3 hours and then cooled in ice bath. The solid was filtered, washed with water, and dried to brown give the title compound as a brown solid containing inorganic salt, which was used in the next step without additional purification. LC-MS: m/z 255 (M+1 of free base). 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 11.18 (br, 1H), 10.09 (s, 1H), 9.35 (br, 1H), 8.94 (br, 1H), 7.54 (d, 1H), 7.27 (s, 1H), 6.95 (d, 1H), 2.26 (s, 3H).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[OH:13]>C(Cl)Cl>[CH3:5][O:6][C:7]1[C:12]([N+:1]([O-:4])=[O:2])=[CH:11][CH:10]=[CH:9][C:8]=1[OH:13]
Reactant: COc1ccccc1O
Reactant: O=[N+]([O-])O
Solvent: ClCCl
Product: COc1c(O)cccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 29562.2 %

Procedure:
Fuming HNO3 (0.34 mL, 0.008 mmol) was carefully added to a mixture of 2-methoxyphenol (0.886 mL, 0.008 mmol) in anhydrous DCM (10 mL) at −20° C. After stirring for 2 h at RT, the mixture was concentrated under vacuum. Chromatography (10-30% EtOAc/hexanes) provided 9A12 (400 mg, 29%) and 2-methoxy-3-nitrophenol (400 mg, 29%).
Reaction SMILES: [CH3:1][N:2]([CH3:34])[C:3]1[CH:30]=[CH:29][CH:28]=[C:27]([N+:31]([O-])=O)[C:4]=1[C:5]([NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:6]>[Ni].CCO>[NH2:31][C:27]1[CH:28]=[CH:29][CH:30]=[C:3]([N:2]([CH3:34])[CH3:1])[C:4]=1[C:5]([NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:10][CH2:9]1)=[O:6]
Reactant: CN(C)c1cccc([N+](=O)[O-])c1C(=O)NC1CCN(C(c2ccccc2)c2ccccc2)CC1
Agent: [Ni]
Solvent: CCO
Product: CN(C)c1cccc(N)c1C(=O)NC1CCN(C(c2ccccc2)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Step 4): A mixture of 2-dimethylamino-6-nitro-N-(1-diphenylmethylpiperidin-4-yl)benzamide (1.60 g, 3.5 mmol) and Raney Nickel in EtOH (75 ml) was stirred under H2 at room temperature for 4 hours. The mixture was filtered, and the filtrate was concentrated under vacuum to obtain 2-amino-6-dimethylamino-N-(1-diphenylmethylpiperidin-4-yl) benzamide. 1.42 g (95%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:23])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.[CH2:24]([O:26][NH2:27])[CH3:25]>>[CH2:24]([O:26][N:27]=[CH:19][C:18]1[CH:21]=[CH:22][C:15]([O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][N:8]([C:5]2[N:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH3:23])=[CH:16][CH:17]=1)[CH3:25]
Reactant: CCON
Reactant: CN(CCCCCOc1ccc(C=O)cc1)c1ccc(Cl)nn1
Product: CCON=Cc1ccc(OCCCCCN(C)c2ccc(Cl)nn2)cc1

Procedure:
Reaction of 4-{N-(6-Chloro-3-pyridazinyl)-N-methyl-5-aminopentan-1-oxy}benzaldehyde with ethoxyamine following similar conditions to those in Example 1 gave 4-{N-(6-Chloro-3-pyridazinyl)-N-methyl-5-aminopentan-1-oxy}benzaldehyde O-ethyloxime (Compound 161) as a colourless oil. The nmr and mass spectral data are given below in Table 11.
Reaction SMILES: BrC1C=CC([C:8]2[CH:21]=[CH:20][C:19]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH:12]=[CH:11][C:10]=3[CH:9]=2)=CC=1.Br[C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([Br:33])[CH:29]=2)[CH:24]=1>>[Br:33][C:28]1[CH:29]=[C:30]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[C:23]([C:8]1[CH:21]=[CH:20][C:19]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH:12]=[CH:11][C:10]=3[CH:9]=1)[CH:32]=[CH:31]2
Reactant: Brc1ccc2cc(Br)ccc2c1
Reactant: Brc1ccc(-c2ccc3c(ccc4ccccc43)c2)cc1
Product: Brc1ccc2cc(-c3ccc4c(ccc5ccccc54)c3)ccc2c1

Procedure:
Synthesis was performed in the same manner as in the synthesis of 2-(4-bromophenyl)phenanthrene except that 2,6-dibromo naphthalene was used instead of 4-bromoiodobenzene.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[S:15][C:16]1[S:20][C:19]([NH2:21])=[CH:18][CH:17]=1.C1([O:28][C:29](=O)[NH:30][C:31]2[S:32][CH:33]=[CH:34][N:35]=2)C=CC=CC=1.C(OCC)(=O)C.O>CS(C)=O.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[S:15][C:16]1[S:20][C:19]([NH:21][C:29]([NH:30][C:31]2[S:32][CH:33]=[CH:34][N:35]=2)=[O:28])=[CH:18][CH:17]=1
Reactant: COc1cc2nccc(Sc3ccc(N)s3)c2cc1OC
Reactant: O=C(Nc1nccs1)Oc1ccccc1
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cc2nccc(Sc3ccc(NC(=O)Nc4nccs4)s3)c2cc1OC
Yield: 58 %

Procedure:
5-(6,7-Dimethoxyquinolin-4-ylsulfanyl)thiophen-2-ylamine (31.8 mg, 0.100 mmol) and thiazol-2-ylcarbamic acid phenyl ester (33.0 mg, 0.150 mmol) were stirred in dimethylsulfoxide (1 ml) at 85° C. for 2 hours. The reaction solution was distributed between ethyl acetate and water, the organic layer was washed with water and saturated saline and dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was distilled off under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (eluent-ethyl acetate:methanol=20:1), and the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, after which the crystals were filtered out, washed with hexane and then blow-dried to obtain the title compound (25.6 mg, 0.058 mmol, 58%) as colorless crystals.
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13]1([CH:19]2[CH2:23][CH2:22][CH2:21][NH:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[Cl:12][C:9]1[CH:10]=[N:11][C:2]([N:20]2[CH2:21][CH2:22][CH2:23][CH:19]2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cc(Cl)cnc1Cl
Reactant: c1ccc(C2CCCN2)cc1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cc(Cl)cnc1N1CCCC1c1ccccc1
Temperature: 25 °C
Yield: 90.9 %

Procedure:
To a solution of Methyl 2,5-dichloronicotinate (120 mg, 0.58 mmol,) in isopropanol (10 ml), 2-phenylpyrrolidine (86 mg, 0.58 mmol, available from Matrix Scientific #018619) and N,N-Diisopropylethylamine (90 mg, 0.70 mmol) were added. The mixture was heated under reflux overnight. After cooling to room temperature, the mixture was evaporated and the residue was dissolved in ethyl acetate (10 ml), washed with water (10 ml) and brine (10 ml), dried over Na2SO4 and evaporated in vacuo. The crude residue was purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate 20:1 to afford the title compound (D72) (167 mg) as colorless oil.
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].[C:9]([C:17]1[C:18](=[O:28])[N:19]([CH3:27])[C:20](=[O:26])[N:21]([CH3:25])[C:22]=1[CH2:23]Br)(=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CCO>[NH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[N:8]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:17]2[C:22]([N:21]([CH3:25])[C:20](=[O:26])[N:19]([CH3:27])[C:18]2=[O:28])=[CH:23]1
Reactant: Cn1c(CBr)c(C(=O)c2ccccc2)c(=O)n(C)c1=O
Reactant: Nc1ccccc1N
Solvent: CCO
Product: Cn1c(=O)c2c(-c3ccccc3)n(-c3ccccc3N)cc2n(C)c1=O
Yield: 96.3 %

Procedure:
1,2-Phenylenediamine (1.320 g, 12.2 mmol) in absolute EtOH (25 mL) was stirred in a 50 mL round bottom flask. The mixture was warmed on an oil bath until homogenous, and then 4a (2.055 g, 6.1 mmol) was added with the aid of a powder funnel and EtOH (5 mL). The solution was stirred vigorously at refluxed for 1 h, during which a white precipitate formed. The reaction was then cooled in an ice bath, filtered, and the precipitate washed with cold ethanol to yield 5a (2.0357 g, 96.5%) as a white powder. 1H NMR (600 MHz, DMSO-d6) δ 7.37-7.31 (m, 2H), 7.25-7.19 (m, 3H), 7.08-7.02 (m, 1H), 6.92 (s, 1H), 6.83 (dd, J=1.3, 7.8, 1H), 6.75 (d, J=8.1, 1H), 6.48-6.43 (m, 1H), 5.08 (s, 2H), 3.33 (s, 3H), 3.19 (s, 3H). 13C NMR (151 MHz, DMSO-d6) δ 159.07, 150.89, 144.76, 133.51, 130.42, 129.49, 129.36, 129.05, 128.64, 127.89, 127.13, 123.10, 115.65, 115.46, 105.49, 102.23, 31.50, 27.40. MS (ES+) (m/z): [M+1]+ calculated for C20H19N4O2, 347.39. found 347.05.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[N:20]=[C:19]3[N:21]=[C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-])=O)[CH:25]=4)[O:23][C:18]3=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.[SH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[N:20]=[C:19]3[N:21]=[C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH2:30])[CH:25]=4)[O:23][C:18]3=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc3oc(-c4cccc([N+](=O)[O-])c4)nc3n2)CC1
Agent: [Na+]
Agent: [SH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCN(Cc2ccc3oc(-c4cccc(N)c4)nc3n2)CC1
Temperature: 25 °C

Procedure:
4-[2-(3-Nitro-phenyl)-oxazolo[4,5-b]pyridin-5-ylmethyl]-piperazine-1-carboxylic acid tert-butyl ester (330 mg, 0.75 mmol) was dissolved in 6 mL of MeOH and 2 mL of water along with 210 mg of sodium hydrosulfide hydrate (3.75 mmol). The reaction mixture was stirred under reflux for 4 hours. The reaction appeared to be complete based on LC/MS. The reaction mixture was cooled to room temperature and concentrated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4) and concentrated to afford essentially quantitative yield of 4-[2-(3-amino-phenyl)-oxazolo[4,5-b]pyridin-5-ylmethyl]-piperazine-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [C:1]([CH:3](C#N)[CH2:4][NH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH:16](C#N)[C:17]#[N:18])#[N:2].[ClH:23].[H][H]>O=[Pt]=O>[ClH:23].[ClH:23].[ClH:23].[ClH:23].[NH2:18][CH2:17][CH2:16][CH2:15][NH:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][NH:5][CH2:4][CH2:3][CH2:1][NH2:2]
Reactant: N#CC(C#N)CNCCCCCCCCNCC(C#N)C#N
Reactant: [H][H]
Agent: O=[Pt]=O
Agent: Cl
Product: NCCCNCCCCCCCCNCCCN

Procedure:
Combine 50.0 gm of the product of Example 1, 2.0 gm PtO2, 133 ml of conc. HCl at 45 lbs./sq.in. in a shaker flask until hydrogen is no longer taken up. Filter the resulting mixture, evaporate the solvent and triturate the product with 1 liter of EtOH. Filter and dry the product to obtain 51.6 gm of the title compound, Rf is 0.17 (silica gel plates eluted with 40% conc. NH3 /CH3OH).