Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]3[CH:18]=[C:17]([CH2:19][C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[C:16](=[O:26])[C:8]4[CH:9]=[C:10]([OH:15])[CH:11]=[C:12]([C:13]=2[CH:14]=1)[C:7]3=4.C(=O)([O-])[O-].[K+].[K+].[CH2:33](I)[CH3:34]>CS(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]3[CH:18]=[C:17]([CH2:19][C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[C:16](=[O:26])[C:8]4[CH:9]=[C:10]([O:15][CH2:33][CH3:34])[CH:11]=[C:12]([C:13]=2[CH:14]=1)[C:7]3=4
Reactant: O=c1c(Cc2cccnc2)cn2c3ccc(Br)cc3c3cc(O)cc1c32
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCOc1cc2c(=O)c(Cc3cccnc3)cn3c4ccc(Br)cc4c(c1)c23
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 45 %

Procedure:
10-bromo-2-hydroxy-5-(3-pyridylmethyl)-4H-pyrido[3,2,1-jk]carbazole-4-one (0.3 g) obtained in Example 2 was suspended in dimethyl sulfoxide (20 ml), and to the suspension was added potassium carbonate (0.2 g), and the mixture was stirred at room temperature for 30 minutes. Ethyl iodide (0.13 ml) was added and the mixture was stirred at 80° C. in a hot water bath for 6 hours. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, washed with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: ethyl acetate) to obtain the title compound (0.16 g, 45%).
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH:16]2[CH2:18][CH2:17]2)=[N:5][CH:4]=[C:3]1[C:19]([NH2:21])=O.N1C=CC=CC=1>P(Cl)(Cl)(Cl)=O>[O:1]=[C:2]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH:16]2[CH2:18][CH2:17]2)=[N:5][CH:4]=[C:3]1[C:19]#[N:21]
Reactant: NC(=O)c1cnc(-c2ccccc2OCC2CC2)[nH]c1=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: N#Cc1cnc(-c2ccccc2OCC2CC2)[nH]c1=O
Reaction time: 18 h
Yield: 59.7 %

Procedure:
1,6-Dihydro-6-oxo-2-(2-cyclopropylmethoxyphenyl)pyrimidine-5-carboxamide (13.6 g., 0.0476 mole) was added to a stirred, cold solution of pyridine (18.9 g., 0.24 mole) in phosphorus oxychloride (136 ml.), and the mixture heated under reflux for 15 minutes. The mixture was evaporated to dryness and the residue added to a mixture of ice and mthylene chloride. The mixture was neutralized with sodium bicarbonate. The methylene chloride layer was dried (sodium sulfate) and concentrated. To the residual oil was added 1N sodium hydroxide (15 ml.) and tetrahydrofuran (10 ml.). The mixture was allowed to stand at 25° for 18 hours. The mixture was washed with diethyl ether, filtered, and the filtrate acidified with acetic acid. The precipitate was recrystallized from toluene to give the title compound (7.6 g., 59.6%), m.p. 188°-190°. Two recrystallizations from ethyl acetate gave analytical material, m.p. 187°-189°.
Reaction SMILES: [C:1](Cl)(=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O1CCCC1.[NH2:17][C:18]1[C:25]([OH:26])=[C:24]([F:27])[C:23]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:22]([CH3:34])[C:19]=1[C:20]#[N:21].C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[C:20]([C:19]1[C:22]([CH3:34])=[C:23]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:24]([F:27])=[C:25]([OH:26])[C:18]=1[NH:17][C:1](=[O:10])/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)#[N:21]
Reactant: Cc1c(C#N)c(N)c(O)c(F)c1-c1ccccc1
Reactant: O=C(Cl)C=Cc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1c(C#N)c(NC(=O)/C=C/c2ccccc2)c(O)c(F)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
Under nitrogen atmosphere, cinnamoyl chloride (378 mg, 2.27 mmol) was dropwise added to a tetrahydrofuran solution (10 ml) of 2-amino-5-phenyl-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-41) (500 mg, 2.06 mmol) and sodium hydrogencarbonate (399 mg, 4.75 mmol) cooled with ice, followed by stirring at room temperature for 17 hours and stirring at 60° C. for 1 hour. After cooling, ethyl acetate was added to the reaction liquid, followed by washing with water and saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:7]([O:10]C)=[CH:6][C:4]=1[NH2:5].C[O:13][C:14]1[CH:22]=[CH:21][C:17](C(Cl)=O)=[CH:16][CH:15]=1>>[OH:13][C:14]1[CH:22]=[CH:21][C:17]([C:1]2[O:2][C:3]3[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:4]=3[N:5]=2)=[CH:16][CH:15]=1
Reactant: COc1ccc(OC)c(N)c1
Reactant: COc1ccc(C(=O)Cl)cc1
Product: Oc1ccc(-c2nc3cc(O)ccc3o2)cc1

Procedure:
The title compound was prepared in substantially the same manner as described in Example 1, from 2,5-dimethoxyaniline, and 4-methoxybenzoyl chloride and was obtained as a light yellow solid, m.p. 264-267° C.; MS m/e 228 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]3[CH2:11][CH2:12][C:13]4([CH2:18][C:9]=3[S:8][C:4]=2[N:5]=[CH:6][N:7]=1)[O:17][CH2:16][CH2:15][O:14]4.[F:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][C:21]=1[Cl:27].Cl>C(O)C>[Cl:27][C:21]1[CH:22]=[C:23]([NH:24][C:2]2[C:3]3[C:10]4[CH2:11][CH2:12][C:13]5([CH2:18][C:9]=4[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[O:17][CH2:16][CH2:15][O:14]5)[CH:25]=[CH:26][C:20]=1[F:19]
Reactant: Clc1ncnc2sc3c(c12)CCC1(C3)OCCO1
Reactant: Nc1ccc(F)c(Cl)c1
Agent: Cl
Solvent: CCO
Product: Fc1ccc(Nc2ncnc3sc4c(c23)CCC2(C4)OCCO2)cc1Cl
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 56.6 %

Procedure:
To a stirring solution of 4-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2′-[1,3]dioxolane] (7.0 g, 24.8 mmol) in ethanol (100 mL) was added 4-fluoro-3-chloroaniline (3.6 g, 24.8 mmol) and HCl (4N in dioxane, 0.05 mL). The contents were heated to reflux for 5 h, after which time the contents were removed from heating and allowed to cool to rt. The solvent was removed under reduced pressure, the crude residue suspended in aq NaHCO3 (100 mL), and stirred for 15 min. The contents were again filtered, and the solid filter cake washed with water. The collected yellow solid was triturated with diethyl ether (50 mL) to afford the final product (5.5 g, 57%) as a light yellow solid. 1H-NMR (DMSO-d6) δ 8.41 (s, 1H), 8.28 (s, 1H), 7.78 (dd, 1H), 7.58 (m, 1H), 7.35 (t, 1H), 3.97 (s, 4H), 3.22 (t, 2H), 3.00 (s, 2H), 1.93 (t, 2H); LCMS RT=3.26 min; [M+H]+=392.3.
Reaction SMILES: [CH3:1][C:2]([CH3:22])([CH3:21])[C@H:3]([NH:8][C:9]([O:11]C1C=CC([N+]([O-])=O)=CC=1)=O)[C:4]([O:6][CH3:7])=[O:5].C([CH2:30][NH2:31])C1C=CC=CC=1.[C:32]1([CH3:38])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[CH2:38]([N:31]([CH3:30])[C:9]([NH:8][C@@H:3]([C:2]([CH3:1])([CH3:21])[CH3:22])[C:4]([O:6][CH3:7])=[O:5])=[O:11])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: NCCc1ccccc1
Reactant: COC(=O)[C@@H](NC(=O)Oc1ccc([N+](=O)[O-])cc1)C(C)(C)C
Reactant: Cc1ccccc1
Product: COC(=O)[C@@H](NC(=O)N(C)Cc1ccccc1)C(C)(C)C
Temperature: 80 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
A solution containing the product from Example 63A (0.075 g, 0.242 mmol) in toluene (0.5 mL) was treated with N-benzylmethylamine (0.035 mL, 2.71 mmol), and the mixture was stirred at 80° C. for 1 hour. The reaction was partitioned between ethyl acetate and 10% Na2CO3, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-20% ethyl acetate in dichloromethane to give the title compound (0.046 g, 65% yield).
Reaction SMILES: [C:1]([O:24][CH:25]1[CH2:30][C:29]([CH3:32])([CH3:31])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]1)(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12][CH:13]1[CH2:18][C:17]([CH3:20])([CH3:19])[NH:16][C:15]([CH3:22])([CH3:21])[CH2:14]1)=[O:11].[C:35]([O:39]O)([CH3:38])(C)C>[O-2].[Cr+6].[O-2].[O-2].CCCCCCCC>[C:1]([O:24][CH:25]1[CH2:30][C:29]([CH3:32])([CH3:31])[N:28]([O:39][CH2:35][CH2:38][CH2:21][CH2:15][CH2:14][CH2:13][CH2:18][CH3:17])[C:27]([CH3:34])([CH3:33])[CH2:26]1)(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12][CH:13]1[CH2:18][C:17]([CH3:19])([CH3:20])[N:16]([O:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH3:3])[C:15]([CH3:21])([CH3:22])[CH2:14]1)=[O:11]
Reactant: CC1(C)CC(OC(=O)CCCCCCCCC(=O)OC2CC(C)(C)NC(C)(C)C2)CC(C)(C)N1
Reactant: CC(C)(C)OO
Agent: [Cr+6]
Agent: [O-2]
Solvent: CCCCCCCC
Product: CCCCCCCCON1C(C)(C)CC(OC(=O)CCCCCCCCC(=O)OC2CC(C)(C)N(OCCCCCCCC)C(C)(C)C2)CC1(C)C
Temperature: 115 °C
Yield: 133 %

Procedure:
A mixture of 15.0 g (31.2 mmol) of di-(2,2,6,6-tetramethylpiperidin-4-yl) sebacate, 0.2 g of chromium (VI) oxide, and 120 ml of n-octane is heated to 115° C. To the above mixture is added 28.5 g (221 mmol) of 70% aqueous tert-butyl hydroperoxide over a 90-minute interval while the reaction mixture is heated at reflux. Water is collected in a Dean-Stark trap. The red mixture is heated at reflux for 3.25 hours after the addition is complete in order to discharge the color. The reaction mixture is passed through 150 g of silica gel with 2:1 heptane:ethyl acetate as the eluent. The organic solution is evaporated to obtain a yellow liquid which is purified (Waters 500A HPLC; silica gel; 20:1 hexane:ethyl acetate) to afford 15.3 g (67% yield) of the title compound. The product has the same LC retention time as the compound prepared in Example 31.
Reaction SMILES: [N+](=C)=[N-].N(CN[C:8](N)=[O:9])=O.[OH-].[Na+].[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[C:21]([C:23]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1[Cl:32])=O)=[O:22]>CCOCC.O1CCOCC1>[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[C:21]([C:23]1([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=2[Cl:32])[CH2:8][O:9]1)=[O:22]
Reactant: O=C(C(=O)c1ccc(Cl)cc1Cl)c1ccc(Cl)cc1Cl
Reactant: NC(=O)NCN=O
Agent: C=[N+]=[N-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: C1COCCO1
Product: O=C(c1ccc(Cl)cc1Cl)C1(c2ccc(Cl)cc2Cl)CO1
Reaction time: 16 h

Procedure:
With cooling and stirring, an ethereal diazomethane solution prepared from 3.1 g of nitrosomethylurea and aqueous sodium hydroxide solution in ether is added dropwise to a solution of 3.4 g of 2,2',4,4'-tetrachlorobenzil in 50 ml of dioxane. When the dropwise addition is complete, stirring is continued for 16 hours at room temperature, and the reaction mixture is then concentrated to dryness. The residual oil is crude 2-(2,4-dichlorobenzoyl)-2-(2,4-dichlorophenyl)oxirane which is purified by high vacuum distillation.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)#[CH:2].[S:9]1[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]1>>[S:9]1[CH2:10][CH:11]=[C:12]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:13][CH2:14]1
Reactant: O=C1CCSCC1
Reactant: C#Cc1ccccn1
Product: C(#Cc1ccccn1)C1=CCSCC1

Procedure:
Reactants: 2-ethynylpyridine (6.0 mmol, 618 mg), tetrahydrothiopyran-4-one (6.0 mmol, 696 mg); yields 2-(3,6-dihydro-2H-thiopyran-4-ylethynyl)pyridine as a transparent oil (150 mg, 12% overall yield). 1H NMR (CDCl3, 300 MHz) δ 8.57 (m, 1H), 7.61 (m, 1H), 7.40 (m, 1H), 7.21 (m, 1H), 6.46 (m, 1H), 3.27 (m, 2H), 2.78 (m, 2H), 2.57 (m, 2H). MS (EI ionization) 201 (M+).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([NH2:12])=[O:11])[C:2]1=2.C(O)(=O)C.C1C(=O)N([Br:24])C(=O)C1>ClCCl>[Br:24][C:4]1[C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([NH2:12])=[O:11])[C:2]=2[S:1][CH:5]=1
Reactant: NC(=O)c1cccc2ccsc12
Reactant: O=C1CCC(=O)N1Br
Solvent: CC(=O)O
Solvent: ClCCl
Product: NC(=O)c1cccc2c(Br)csc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 79 %

Procedure:
A solution of benzo[b]thiophene-7-carboxylic acid amide (500 mg, 2.82 mmol) in dichloromethane (5 mL) is stirred at rt and acetic acid (5 mL) is added followed by NBS (750 mg, 4.23 mmol, 1.5 equiv.). The reaction is stirred at room temperature for 1 hour at which point LC-MS analysis shows full conversion of the starting material to the desired compound (79%) and dibrominated material (21%). The reaction is diluted with water (50 mL), neutralized with aqueous potassium disulfite, followed by sodium bicarbonate. The aqueous layer is then extracted with dichloromethane and the resulting organic layers are combined, washed with brine, dried over Na2SO4 and evaporated. The crude material is purified by LC using DCM as the eluent to afford the title compound as a white solid (300 mg, 41%).
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][C:17]1([CH3:32])[CH:19]([CH:20]=[C:21]([O:26][CH2:27][CH3:28])[C:22]([F:25])([F:24])[F:23])[CH:18]1[C:29](Cl)=[O:30].N1C=CC=CC=1.Cl>C1(C)C=CC=CC=1.O>[O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH2:11][O:12][C:29]([CH:18]1[CH:19]([CH:20]=[C:21]([O:26][CH2:27][CH3:28])[C:22]([F:25])([F:23])[F:24])[C:17]1([CH3:16])[CH3:32])=[O:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=CC1C(C(=O)Cl)C1(C)C)C(F)(F)F
Reactant: OCc1cccc(Oc2ccccc2)c1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: O
Solvent: c1ccncc1
Product: CCOC(=CC1C(C(=O)OCc2cccc(Oc3ccccc3)c2)C1(C)C)C(F)(F)F
Reaction time: 3 h
Yield: 87.6 %

Procedure:
5.2 g (0.026 mol) of 3-phenoxy-benzyl alcohol and 7 g (0.026 mol) of 2,2-dimethyl-3-(3,3,3-trifluoro-2-ethoxy-prop-1-enyl)-cyclopropanecarboxylic acid chloride were dissolved in 100 ml of anhydrous toluene, and 2.5 g of pyridine, dissolved in 20 ml of anhydrous toluene, were added dropwise at 20°-25° C., while stirring. Stirring was then continued at 25°-35° C. for 3 hours. The reaction mixture was poured into 150 ml of water, to which 10 ml of concentrated hydrochloric acid were added, and the organic phase was separated off and washed again with 100 ml of water. The toluene phase was then dried over sodium sulphate and the solvent was distilled off under a water-pump vacuum. Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 9.9 g (87.7% of theory) of 2,2-dimethyl-3-(3,3,3-trifluoro-2-ethoxy-prop-1-enyl)-cyclopropanecarboxylic acid 3-phenoxybenzyl ester were obtained as a yellow oil with the refractive index nD25 : 1.5130.
Reaction SMILES: [CH2:1]([OH:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][OH:7].[O:9]1[CH:14]=[CH:13][CH2:12][CH2:11][CH2:10]1.Cl>O>[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:8]
Reactant: OCCCCCCO
Reactant: C1=COCCC1
Agent: Cl
Solvent: O
Product: OCCCCCCOC1CCCCO1
Yield: 48.5 %

Procedure:
Hexane-1,6-diol (70.9 g) was melted in a water bath at ca. 60°, the melt cooled to 45° and dihydropyran (16.82 g) quickly added followed by 10 N hydrochloric acid (0.1 ml). The mixture was stirred and cold water added to maintain a reaction temperature of approximately 50°. When the exotherm had subsided, the mixture was stirred at room temperature for 0.5 h, then diluted with water (500 ml) and extracted with ER (2×250 ml). The ER solution was washed with water (3×500 ml), dried and concentrated to yield an oil which was purified by [FCS] elution with EA/hexane (1:1) affording the title compound (19.6 g). T.l.c. (EA/hexane 1:1) Rf 0.40.
Reaction SMILES: C([O-])(=O)C.[NH4+].[F:6][C:7]1[CH:8]=[C:9]([C:17]2[C:25]3[CH2:24][CH2:23][C:22](=O)[C:21]=3[CH:20]=[N:19][CH:18]=2)[CH:10]=[CH:11][C:12]=1[C:13]([F:16])([F:15])[F:14].C([BH3-])#[N:28].[Na+]>CO.C(O)C>[F:6][C:7]1[CH:8]=[C:9]([C:17]2[C:25]3[CH2:24][CH2:23][CH:22]([NH2:28])[C:21]=3[CH:20]=[N:19][CH:18]=2)[CH:10]=[CH:11][C:12]=1[C:13]([F:16])([F:15])[F:14]
Reactant: [BH3-]C#N
Reactant: O=C1CCc2c1cncc2-c1ccc(C(F)(F)F)c(F)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: CCO
Product: NC1CCc2c(-c3ccc(C(F)(F)F)c(F)c3)cncc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of ammonium acetate (117 mg, 1.52 mmol) in MeOH (1 mL) was treated with 4-(3-fluoro-4-trifluoromethyl-phenyl)-5,6-dihydro-[2]pyrindin-7-one (intermediate A-14 [C1]) (15 mg, 0.051 mmol) dissolved in ethanol (0.5 mL) and the reaction mixture stirred at room temperature for 1 h. Sodium cyanoborohydride (11.2 mg, 0.18 mmol) was added and stirring continued at room temperature. After 15 min, the reaction mixture was heated to reflux for 30 min. The solvent was removed under reduced pressure, a sat. aq. solution of ammonium chloride (2 mL) and a 1 M solution of HCl (1 mL) were added and the aq. phase washed with dichloromethane (3×5 mL). To the aq. phase was added a 1 M solution of NaOH (2 mL) and extracted with dichloromethane (3×5 mL). The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. The title compound was isolated as light brown solid (3.8 mg, 25%). MS: 297.4 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:4])[NH2:3].[CH3:5][O:6][CH2:7]/[CH:8]=[CH:9]/[CH:10]=O>>[CH3:1][N:2]([CH3:4])[N:3]=[CH:10]/[CH:9]=[CH:8]/[CH2:7][O:6][CH3:5]
Reactant: CN(C)N
Reactant: COC/C=C/C=O
Product: COC/C=C/C=NN(C)C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 78.2 %

Procedure:
N,N-Dimethylhydrazine (10.90 mL, 0.14 mol) was added dropwise over 15 min to (E)-4-methoxy-2-butenal (13.06 g, 0.13 mol) while cooling the reaction with an ice bath. The bath was then removed and the mixture stirred for 1.5 h at ambient temperature. Calcium chloride (20 g) was added to the reaction, let set for 15 min, and the product decanted. Distillation (bp 102°-110° C., 25 mm Hg) of the oil through a 10 cm Vigreaux column provided pure (E)-4-methoxy-2-butenal N,N-dimethylhydrazone (17) (14.45 g, 78%): IR (neat) 2850, 2820, 1560, 1465, 1445, 1375, 1270, 1120, 1030, 970 cm-1 ; 1H NMR (CDCl3) δ2.80 (s, 6 H), 3.26 (s, 3 H), 3.93 (dd, 2 H, J=6.2, 1.2 Hz), 5.74 (dr, 1 H, J=15.8, 6.2 Hz), 6.31 (ddt, 1 H, J=15.8, 8.9, 1.2 Hz), 6.92 (d, 1 H, J=8.9 Hz); Anal. calcd for C7H14N2O: C 59.05, H 10.07, N 19.52; found C 59.13, H 9.92, N 19.70.
Reaction SMILES: [N:1]1[C:14]2[C:5](=[C:6]3[C:11](=[CH:12][CH:13]=2)[CH2:10][CH2:9][C@H:8]([CH2:15][OH:16])[O:7]3)[CH:4]=[CH:3][CH:2]=1.[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>N1C=CC=CC=1>[N:1]1[C:14]2[C:5](=[C:6]3[C:11](=[CH:12][CH:13]=2)[CH2:10][CH2:9][C@H:8]([CH2:15][O:16][S:23]([C:20]2[CH:21]=[CH:22][C:17]([CH3:27])=[CH:18][CH:19]=2)(=[O:25])=[O:24])[O:7]3)[CH:4]=[CH:3][CH:2]=1
Reactant: OC[C@H]1CCc2ccc3ncccc3c2O1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@H]2CCc3ccc4ncccc4c3O2)cc1
Reaction time: 24 h
Yield: 93.2 %

Procedure:
A solution of (6R)-(7,8-dihydro-6H-5-oxa-1-aza-phenanthren-6-yl)-methanol (0.38 g, 1.8 mmole) and p-toluenesulfonyl chloride (0.67 g, 3.5 mmole) in anhydrous pyridine (50 mL) was allowed to stir for 24 hours and then the solvent was removed in vacuum. The residue was dissolved in ethyl acetate (50 mL) and washed with water (3×30 mL). The organic layer was dried over sodium sulfate and filtered, and the solvent was removed under vacuum. Column chromatography on silica gel (50% methylene chloride/hexane) afforded 0.62 g (95%) of the title compound as a solid, mp 123° C., [α]25D=−27.71° (c=5.0, CHCl3).
Reaction SMILES: [CH3:1][C:2](=[CH2:7])[C:3]#[C:4][CH2:5][OH:6].[CH3:8][SiH:9]([CH3:14])N[SiH](C)C.CC([O-])(C)C.[K+]>>[CH3:8][Si:9]1([CH3:14])[C:3]([C:2]([CH3:1])=[CH2:7])=[CH:4][CH2:5][O:6]1
Reactant: C[SiH](C)N[SiH](C)C
Reactant: C=C(C)C#CCO
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: C=C(C)C1=CCO[Si]1(C)C
Yield: 115.7 %

Procedure:
Using 4-methylpent-4-en-2-yn-1-ol (1.792 g, 18.64 mmol), 1,1,3,3-tetramethyldisilazane (1.504 g, 11.28 mmol) and KOtBu (0.217 g, 1.934 mmol) according to the above general procedure resulted a clear brown colored crude reaction mixture which upon purification by column chromatography yielded 10a as a clear colorless oil (2.014 g, 13.05 mmol, 70.0%): Rf 0.68 (pentane/Et2O, 3:1); 1H NMR (500 MHz, CDCl3) δ 6.60 (as, 1H, H-4), 4.99 (s, 1H, H-8′), 4.82 (s, 1H, H-8″), 4.66 (s, 2H, H-5), 1.93 (s, 3H, H-9), 0.33 (as, 6H, H-6); 13C NMR (300 MHz, CDCl3) δ 142.2 (C-3), 141.3 (C-7), 141.2 (C-4), 115.7 (C-8), 71.9 (C-5), 20.4 (C-9), 0.45 (C-6); HRMS calcd for C8H14OSi (M+) 154.0814. found 154.0813.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[N:19]=[C:18]([CH3:20])[C:17]([CH3:21])=[N:16][C:15]=1[CH3:22].[CH3:23][C:24](=[O:30])[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>CCOCC>[OH:30][C:24]([CH3:23])([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][C:15]1[C:14]([CH3:13])=[N:19][C:18]([CH3:20])=[C:17]([CH3:21])[N:16]=1
Reactant: CCCCCC(C)=O
Reactant: Cc1nc(C)c(C)nc1C
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: CCOCC
Product: CCCCCC(C)(O)Cc1nc(C)c(C)nc1C

Procedure:
The preparation is carried out in the manner described in Example VII using 10.1 grams (0.1 mole) of diisopropylamine in 80 milliliters of ether, 0.95 mole of butyllithium, 13.6 grams (0.1 mole) of tetramethylpyrazine, and 12.8 grams (0.1 mole) of 2-heptanone. The reaction is worked up as before, and the product is isolated by chromatography on silica gel.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl.[NH:8]1[CH2:11][CH2:10][CH2:9]1.CN1CCCC1=O.[CH2:19]([O:26][C:27]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH2:54]Br)=[CH:48][C:28]=1[C:29]([NH:31][C:32]1[CH:41]=[C:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:39]=[CH:38][C:33]=1[C:34]([O:36][CH3:37])=[O:35])=[O:30])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(OCC)(=O)C.O>[N:8]1([CH2:54][CH2:53][O:52][C:49]2[CH:50]=[CH:51][C:27]([O:26][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[C:28]([CH:48]=2)[C:29]([NH:31][C:32]2[CH:41]=[C:40]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:39]=[CH:38][C:33]=2[C:34]([O:36][CH3:37])=[O:35])=[O:30])[CH2:11][CH2:10][CH2:9]1
Reactant: C1CNC1
Reactant: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(OCCBr)ccc1OCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN1CCCC1=O
Product: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(OCCN2CCC2)ccc1OCc1ccccc1
Temperature: 90 °C
Reaction time: 0.75 h
Yield: 36.8 %

Procedure:
Potassium carbonate (0.15 g) and azetidine hydrochloride (0.046 g) were added to a 1-methyl-2-pyrrolidone (1.3 mL) solution of methyl 2-(2-(benzyloxy)-5-(2-bromoethoxy)benzamido)-4-phenylbenzoate (0.25 g), followed by stirring at 90° C. for 45 minutes. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-90% chloroform/methanol] to obtain 0.088 g of methyl 2-(5-(2-(azetidin-1-yl)ethoxy)-2-(benzyloxy)benzamido)-4-phenylbenzoate as a light yellow oily substance.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)C=O)([OH:3])=[O:2].C(C#N)[CH2:13][OH:14].CCN=C=[N:21][CH2:22][CH2:23][CH2:24]N(C)C.Cl.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.Cl>ClCCl>[C:22]([CH2:23][CH2:24][O:3][C:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:6][C:5]=1[CH:13]=[O:14])=[O:2])#[N:21]
Reactant: N#CCCO
Reactant: CCN=C=NCCCN(C)C
Reactant: O=Cc1cccc(C(=O)O)c1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N#CCCOC(=O)c1ccccc1C=O

Procedure:
1.51 g (10.0 mmol) of 3-carboxybenzaldehyde, 1.85 g (26.0 mmol) of ethylene cyanohydrin, 4.99 g (26.2 mmol) of WSC hydrochloride, 1.82 ml (13.1 mmol) of triethylamine and 1.49 g (11.0 mmol) of HOBt were stirred in 20 ml of dichloromethane at room temperature overnight. 1 N hydrochloric acid was added to the reaction mixture. After extraction with dichloromethane, the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound.