Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:16])([O:10][CH2:11][C@@H:12]([OH:15])[CH2:13][OH:14])[CH3:9])=[CH:4][CH:3]=1.N1C=CN=C1.[C:22]([Si:26](Cl)([CH3:28])[CH3:27])([CH3:25])([CH3:24])[CH3:23].O>O1CCCC1.CN(C)C1C=CN=CC=1>[C:22]([Si:26]([CH3:28])([CH3:27])[O:14][CH2:13][C@H:12]([OH:15])[CH2:11][O:10][C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)([CH3:16])[CH3:9])([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(OC[C@@H](O)CO)c1ccc(F)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Agent: c1c[nH]cn1
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(OC[C@@H](O)CO[Si](C)(C)C(C)(C)C)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 82.6 %

Procedure:
To a solution of (S)-3-[1-(4-fluoro-phenyl)-1-methyl-ethoxy]-propane-1,2-diol (0.46 g) in tetrahydrofuran (6 ml) were added imidazole (0.32 g) and 4-dimethylaminopyridine (catalytic amount). The mixture was cooled to 0° C. and a solution of tert-butyl(chloro)dimethylsilane (0.32 g) in tetrahydrofuran (2 ml) was added dropwise. After 2 hours at 0° C., the reaction mixture was allowed to stir at room temperature for 16 hours. Water was added and the mixture was extracted twice with diethylether. The combined organic layers were dried (MgSO4) and evaporated. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 90:10->75:25) to give (R)-1-(tert-butyl-dimethyl-silanyloxy)-3-[1-(4-fluorophenyl)-1-methyl-ethoxy]-propan-2-ol (0.57 g, 83%) as a colorless liquid. 1H NMR (300 MHz, CDCl3, δ): 0.00 (s, 6H), 0.82 (s, 9H), 1.48 (s, 6H), 2.49 (bs, 1H), 3.15 (d, J=4 Hz, 2H), 3.56 (t, J=4 Hz, 2H), 3.68 (m, 1H)
Reaction SMILES: [O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[O:5][C@H:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@@H:3]1[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].Br[CH2:28][CH:29]1[CH2:31][CH2:30]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH:29]1([CH2:28][N:8]2[C:7]3[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=3[O:5][C@H:4]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C@H:3]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[C:2]2=[O:1])[CH2:31][CH2:30]1
Reactant: BrCC1CC1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C(=O)Nc2ccccc2O[C@@H]1c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H]1C(=O)N(CC2CC2)c2ccccc2O[C@@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.8 %

Procedure:
To a stirred solution of tert-butyl [(2R,3S)-4-oxo-2-phenyl-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]carbamate (67a) (190 mg, 0.536 mmol) in dry DMF (2 mL) under nitrogen was added (bromomethyl)cyclopropane (108 mg, 0.800 mmol) and powdered cesium carbonate (264 mg, 0.810 mmol). The mixture was stirred overnight at ambient temperature then diluted with ewater and extracted with ethyl acetate three times. The residue from the combined organic extracts was purified by flash chromatography on silica gel eluting with 6:1 (v/v) hexane:ethyl acetate to afford the title compound (201 mg, 92%) as a white solid. TLC Rf=0.31 (6:1 hexane:ethyl acetate). 1H NMR (300 MHz, CDCl3) δ0.19 (m, 1H), 0.35-0.62 (m, 3H), 1.15 (m, 1H), 1.37 (s, 9H), 3.50 and 3.55 (dd, 1H, J=7.0 Hz), 4.12 and 4.17 (dd, 1H, J=7.0 Hz), 4.93 (m, 2H), 5.65 (d, 1H, J=7.0 Hz), 7.29 (m, 4H), 7.41 (m, 5H). MS APCI, m/z=309 (M-BOC). LC/MS: 3.08 min.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[C:12]([F:13])=[C:11]([C:14]([NH2:16])=O)[C:10]([F:17])=[C:9]([F:18])[C:8]=1[CH3:19].Cl>C(Cl)Cl.N1C=CC=CC=1>[C:14]([C:11]1[C:10]([F:17])=[C:9]([F:18])[C:8]([CH3:19])=[C:7]([F:6])[C:12]=1[F:13])#[N:16]
Reactant: Cc1c(F)c(F)c(C(N)=O)c(F)c1F
Agent: Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1c(F)c(F)c(C#N)c(F)c1F
Temperature: 25 °C

Procedure:
A solution of phosphorus oxychloride (1.4 g) in methylene chloride (4 ml) was added slowly to a solution of 2,3,5,6-tetrafluoro-4-toluamide (1.0 g) in pyridine (8 ml) at -5° C. When the addition was complete the mixture was warmed to the ambient temperature over a period of 90 minutes, poured into a mixture of dilute hydrochloric acid and ice, and the resultant mixture was extracted with methylene chloride. After washing the extract with water (three times) and drying over anhydrous magnesium sulphate, the solvent was removed by evaporation under reduced pressure. The residual oil was purified by distillation under water pump pressure in a Kugelrohr apparatus to yield 4-cyano-2,3,5,6-tetrafluorotoluene, identified by infra red spectroscopy.
Reaction SMILES: [CH2:1]([C@H:8]([CH2:12][CH2:13][OH:14])C(O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:15]([O-])=O.[Na+]>OS(O)(=O)=O>[CH2:1]([C@@H:8]([NH2:15])[CH2:12][CH2:13][OH:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=N[O-]
Reactant: O=C(O)[C@@H](CCO)Cc1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: N[C@@H](CCO)Cc1ccccc1
Temperature: 2.5 °C

Procedure:
The hydrazide of (R)-2-benzyl-4hydroxybutanoic acid (0.5 gram) is reacted with a solution of 0.5 grams of sodium nitrite in 10 ml of 5% H2SO4. The reaction mixture is maintained for 1 hour at 0-5° C., followed extraction of the reaction mixture with ethyl acetate, followed by basification of the resulting aqueous solution with NaOH, extraction with methyl t-butyl ether, drying of the extracts over MgSO4, filtration, and the removal of solvent by rotary evaporation. The product (R)-1-benzyl-3-hydroxypropylamine is isolated as a light yellow oil.
Reaction SMILES: [NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[C:20]1([CH2:26][CH2:27][CH2:28][C:29](O)=[O:30])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:11][C:8]1[CH:7]=[CH:6][C:5]([CH:3]([OH:4])[CH:2]([NH:1][C:29](=[O:30])[CH2:28][CH2:27][CH2:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:12][C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)=[CH:10][CH:9]=1
Reactant: O=C(O)CCCc1ccccc1
Reactant: NC(Cc1ccc(F)cc1)C(O)c1ccc(F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CC#N
Product: O=C(CCCc1ccccc1)NC(Cc1ccc(F)cc1)C(O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.7 %

Procedure:
To a solution of (1RS,2SR)-2-amino-1,3-bis(4-fluorophenyl)-1-propanol (450 mg, 1.71 mmol) in acetonitrile (30 ml) were added 4-phenyl-n-butyric acid (280 mg, 1.71 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (491 mg, 2.56 mmol) and 1-hydroxy-1H-benzotriazole (261 mg, 1.71 mmol) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). Recrystallization from ethyl acetate-hexane gave the title compound (523 mg, 75%).
Reaction SMILES: [NH2:1][C@@H:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([O:5][CH3:6])=[O:4].Cl.[OH:14][C@@H:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:16](O)=[O:17].CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>ClCCl>[OH:14][C@@H:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:16]([NH:1][C@@H:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([O:5][CH3:6])=[O:4])=[O:17]
Reactant: COC(=O)[C@@H](N)c1ccccc1
Reactant: CC(C)C[C@H](O)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COC(=O)[C@@H](NC(=O)[C@@H](O)CC(C)C)c1ccccc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a cooled (0° C.) solution of methyl (2S)-amino(phenyl)acetate (3.06 g), (2S)-2-hydroxy-4-methylpentanoic acid hydrochloride, NMM (1.85 ml), and HOBt (6.15 g) in dichloromethane (50 ml) was added EDAC-HCl (5.81 g). Additional NMM (2.31 ml) was then added. The mixture was stirred for 2 h at 0° C., then overnight at RT. The reaction was concentrated and the residue was taken up in Ethyl acetate washed with 0.1N hydrochloric acid, saturated sodium bicarbonate, brine, dried, filtered and evaporated to afford the title compound (4.20 g). 1H NMR (300 MHz, CDCl3) δ 0.92-0.95 (m, 6H), 1.47-1.67 (m, 2H), 1.76-2.04 (m, 1H), 2.63 (bs, 1H), 3.74 (s, 3H), 4.21 (d, 1H, J=9 Hz), 5.58 (d, 1H, J=8 Hz), 7.26-7.42 (m, 5H). MS APCI, m/z=280 (M+1). LC/MS: 1.95 min.
Reaction SMILES: [CH2:1]([N:3]([CH2:7][CH3:8])[CH2:4][CH2:5][NH2:6])[CH3:2].[C:9]1([S:15]([CH2:18][CH2:19][NH:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:29]([OH:34])(=[O:33])[C:30]([OH:32])=[O:31].[CH2:35]([O:37]CC)C>O1CCCC1.CO>[OH2:16].[C:29]([OH:34])(=[O:33])[C:30]([OH:32])=[O:31].[CH2:1]([N:3]([CH2:7][CH3:8])[CH2:4][CH2:5][NH:6][C:35](=[O:37])[N:20]([CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[CH2:19][CH2:18][S:15]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)(=[O:16])=[O:17])[CH3:2]
Reactant: CCOCC
Reactant: O=S(=O)(CCNCCN1CCOCC1)c1ccccc1
Reactant: CCN(CC)CCN
Agent: O=C(O)C(=O)O
Solvent: C1CCOC1
Solvent: CO
Product: CCN(CC)CCNC(=O)N(CCN1CCOCC1)CCS(=O)(=O)c1ccccc1
Product: O
Temperature: 25 °C
Reaction time: 1 h
Yield: 66.3 %

Procedure:
A mixture of 4.70 g (0.029 mole) of 1,1'-carboyldiimidazole and 3.14 g (0.027 mole) of N,N-diethylethylenediamine in 40 ml of tetrahydrofuran was stirred at room temperature for 1 hr. A solution of 7.28 g (0.0244 mole) of N-[2-(phenylsulfonyl)ethyl]-4-morpholineethanamine in 50 ml of tetrahydrofuran was added, and the mixture was refluxed for 16 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and water. The methylene chloride phase was dried over magnesium sulfate, and the solvent was removed in vacuo to give an oil. The oil was dissolved in methanol, 2 equivalents of oxalic acid were added, and diethyl ether was added. A white solid precipitated to give 10.33 g (66.3%) of the title compound, a white crystalline solid, m.p. 98°-100° C.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].N1C=CC=CC=1>ClCCl>[C:9]([O:8][C:6]([N:13]1[CH2:18][CH2:17][N:16]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:15][CH2:14]1)=[O:7])([CH3:12])([CH3:10])[CH3:11]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCN(S(C)(=O)=O)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1.3 mL of methanesulfonyl chloride was slowly added to a solution of 2 g of 1-Boc-piperazine and 1.3 mL of pyridine in 6 mL of dichloromethane at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h while being monitored by TLC. Upon completion, the mixture was diluted with dichloromethane, washed with H2O, dried (MgSO4) and evaporated. Purified by silica gel chromatograph (20-100% ethyl acetate/hexane) to afford tert-butyl-4-(methylsulfonyl)piperazine-1-carboxylate. 930 mg of tert-butyl-4-(methylsulfonyl)piperazine-1-carboxylate was treated with 4N HCl in dioxane for 2 h. The reaction mixture was evaporated to give the HCl salt of 1-(methylsulfonyl)piperazine. Procedure F was performed using 50 mg of 6-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-methylnicotinamide, 69 mg of 1-(methylsulfonyl)piperazine and DEPA (1 eq) in 0.5 mL of BuOH. Purified by reverse phase HPLC to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-methyl-6-(4-(methylsulfonyl)piperazin-1-yl)nicotinamide. MS (Q1) 486.3 (M)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11](Cl)=[CH:12][CH:13]=2)[N:8]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:7]=1)=[O:5])[CH3:2].[C:23]([O:27][C:28]([CH2:30][NH:31][C@H:32]1[C@H:36]([O:37][CH3:38])[CH2:35][NH:34][CH2:33]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>>[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11]([N:34]3[CH2:35][C@@H:36]([O:37][CH3:38])[C@H:32]([NH:31][CH2:30][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH2:33]3)=[CH:12][CH:13]=2)[N:8]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cn(-c2nccs2)c2nc(Cl)ccc2c1=O
Reactant: CO[C@@H]1CNC[C@H]1NCC(=O)OC(C)(C)C
Product: CCOC(=O)c1cn(-c2nccs2)c2nc(N3C[C@@H](NCC(=O)OC(C)(C)C)[C@H](OC)C3)ccc2c1=O

Procedure:
With use of 7-chloro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid ethyl ester obtained in Example A-1 (4) and (-)-trans-3-(N-t-butoxycarbonylmethylamino)-4-methoxypyrrolidine obtained in Example B-3, there was obtained (+)-7-[trans-3-(N-t-butoxycarbonylmethylamino)-4-methoxy-1-pyrrolidinyl]-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid ethyl ester (amorphous) in the same manner as in Example C-1 (1).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:17][N:16]=[CH:15][N:14]=1)=[CH:9]2)([O-])=O.O1CCCC1.O.NN>O.O.O.O.O.O.[Fe](Cl)(Cl)Cl.CO>[S:17]1[C:13]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[CH:7][CH:6]=[CH:5][C:4]=3[NH2:1])=[N:14][CH:15]=[N:16]1
Reactant: O=[N+]([O-])c1cccc2cc(-c3ncns3)[nH]c12
Agent: Cl[Fe](Cl)Cl
Agent: NN
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Nc1cccc2cc(-c3ncns3)[nH]c12
Yield: 97.2 %

Procedure:
A mixture of 7-nitro-2-(1,2,4-thiadiazol-5-yl)-1H-indole (0.41 g), iron(III) chloride hexahydrate (33 mg), activated carbon (0.33 g), tetrahydrofuran (12 mL) and methanol (6 mL) was heated under reflux for 20 min. To the reaction mixture was added hydrazine monohydrate (0.50 g) over 10 min while heating under reflux. The reaction mixture was heated under reflux for 2 hr, filtrated, and the filtrate was concentrated. The resulting crystals were washed with water, and dried to give the title compound (0.35 g, yield 94%) as colorless crystals. melting point>223° C. (decomposition).
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)[C:4](=[O:20])[C:3]=1[CH2:21][CH2:22][CH2:23][CH2:24][OH:25].BrBr.N12CCCN=C1CCCCC2.O>C(Cl)Cl>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([N:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][N:7]=3)[C:2](=[O:1])[C:3]3([CH2:21][CH2:22][CH2:23][CH2:24][O:25]3)[C:4]2=[O:20])[CH:17]=[CH:16][CH:15]=1
Reactant: COc1cccc(-n2c(=O)c(CCCCO)c(O)c3cccnc32)c1
Agent: BrBr
Solvent: O
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: COc1cccc(N2C(=O)C3(CCCCO3)C(=O)c3cccnc32)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 4-Hydroxy-3-(4-hydroxybutyl)-1-(3-methoxyphenyl)(1,8)-naphthyridin-2(1H)-one (1 g.)in methylene chloride (10 ml),in an ice-acetone bath was added a solution of bromine (0.5 g.) in methylene chloride (5 ml.) over a period of 15 min. The resulting yellow-orange suspension was stirred overnight at room temperature. To the resulting clear yellow solution was added a solution of 1,8-diazabicyclo[5.4.0]undec-7-ene (1 g.), in methylene chloride (5 ml.) during 5 mins. The mixture was stirred at room temperature for 3 hrs after which time water (5 ml) was added. The organic layer was separated, dried and evaporated. To the residue was added 50% aqueous ethanol (10 ml.) and after some time the solid was filtered off and recrystallized from isopropanol to yield 1-(3-methoxyphenyl)-3', 4', 5', 6'-tetrahydrospiro[1,8-naphthyridine-3,2'-(2 H)pyran]-2, 4-dione, m.p. 181°-183° C.
Reaction SMILES: [CH2:1]([N:3]1[C:8](=[O:9])[CH:7]([CH2:10][CH3:11])[C:6](=O)[NH:5][C:4]1=[S:13])[CH3:2].P(Cl)(Cl)([Cl:16])=O>O>[CH2:1]([N:3]1[C:8](=[O:9])[C:7]([CH2:10][CH3:11])=[C:6]([Cl:16])[NH:5][C:4]1=[S:13])[CH3:2]
Reactant: CCC1C(=O)NC(=S)N(CC)C1=O
Reactant: O=P(Cl)(Cl)Cl
Solvent: O
Product: CCc1c(Cl)[nH]c(=S)n(CC)c1=O
Yield: 70 %

Procedure:
10 G. OF 3,5-DIETHYL-2-THIOBARBITURIC ACID IS CHLORINATED, AFTER THE ADDITION OF A FEW DROPS OF WATER, WITH EXCESS PHOSPHORUS OXYCHLORIDE (APPROXIMATELY 100 ML.) UNDER HEATING FOR 3/4 HOUR. The excess phosphorus oxychloride is distilled off, and the residue is poured on ice. The desired reaction product is crystallized during this step and melts, after recrystallization from aqueous ethanol, completely at 228° C. Yield: 70%
Reaction SMILES: [C:1]([Li])([CH3:4])([CH3:3])[CH3:2].Br[C:7]1[C:12]([CH3:13])=[CH:11][C:10]([CH3:14])=[CH:9][C:8]=1[CH3:15].Br[B:17](Br)[C:18]1[CH:23]=[CH:22][C:21]([B:24](Br)Br)=[CH:20][CH:19]=1.O>CCCCC.CCCCCC>[C:1]1([CH3:4])[CH:3]=[C:12]([CH3:11])[CH:7]=[C:8]([CH3:9])[C:2]=1[B:17]([C:7]1[C:12]([CH3:13])=[CH:11][C:10]([CH3:14])=[CH:9][C:8]=1[CH3:15])[C:18]1[CH:23]=[CH:22][C:21]([B:24]([C:7]2[C:12]([CH3:13])=[CH:11][C:10]([CH3:14])=[CH:9][C:8]=2[CH3:15])[C:7]2[C:12]([CH3:13])=[CH:11][C:10]([CH3:14])=[CH:9][C:8]=2[CH3:15])=[CH:20][CH:19]=1
Reactant: BrB(Br)c1ccc(B(Br)Br)cc1
Reactant: Cc1cc(C)c(Br)c(C)c1
Reactant: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: CCCCCC
Solvent: O
Product: Cc1cc(C)c(B(c2ccc(B(c3c(C)cc(C)cc3C)c3c(C)cc(C)cc3C)cc2)c2c(C)cc(C)cc2C)c(C)c1
Temperature: 0 °C
Yield: 52.2 %

Procedure:
2 equivalents (0.08 mol) of t-butyllithium in pentane are added over the course of one hour at 0° C. to a solution of 8 g (0.04 mol) of bromomesitylene in 100 ml of hexane. The mixture is refluxed for 3 hours. After cooling to 0° C., a solution of 4.17 g (0.01 mol) of 1,4-bis(dibromoboryl)benzene in 80 ml of hexan is added to the mixture and the batch is refluxed overnight. The thick suspension produced is poured into 200 ml of water and subjected twice to extraction with 50 ml of hexane. The combined organic phases are dried over magnesium sulphate, filtered and concentrated. A yellow solid is formed which is recrystallized from hexane, giving 3.0 g (52% of theory) of 1,4-bis(dimesitylboryl)benzene.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=O)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][C:20]#[N:21])[CH:14]=1.C[O-].[Na+]>C(O)C>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=[C:19]([C:15]3[CH:14]=[N:13][CH:18]=[CH:17][CH:16]=3)[C:20]#[N:21])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: N#CCc1cccnc1
Reactant: O=Cc1ccc2c(c1)OCCO2
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: N#CC(=Cc1ccc2c(c1)OCCO2)c1cccnc1
Reaction time: 18 h
Yield: 88.3 %

Procedure:
To the solution of 2,3-dihydro-benzo[1,4]dioxin-6-carboxaldehyde (4.92 g; 0.03 mol) and 3-pyridylacetonitrile (3.54 g; 0.03 mol) in ethanol (100 mL) was added sodium methoxide (6.48 g, of 25% methanol solution, 0.03 mol). The mixture was allowed to stand at ambient temperature for 18 hours. The mixture was concentrated to half volume. The solid was collected by filtration and dried to give 7.0 g (88.4% yield) of the title compound as an off-white solid, m.p. 158°-159° C. Anal. Calcd. for C16H12N2O2 : C, 72.72; H, 4.58; N, 10.60. Found: C, 72.53; H, 4.48; N, 10.97. Mass spectrum (DEI; M+) m/z 264. 1 H-NMR (DMSO-d6 ; 400 MHz) δ 8.91 (d, 1H), 8.59 (d, 1H), 8.08 (d, 1H), 8.00 (s, 1H), 7.57 (d, 1H), 7.47-7.53 (m, 2H), 7.02 (d, 2H), and 4.31 ppm (m, 4H).
Reaction SMILES: [CH2:1]([NH:4][C:5]([C:7]1[N:8]=[N:9][C:10]2[C:15]([C:16]=1[NH2:17])=[CH:14][CH:13]=[CH:12][C:11]=2Br)=[O:6])[CH:2]=[CH2:3].[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=1B(O)O>>[CH2:1]([NH:4][C:5]([C:7]1[N:8]=[N:9][C:10]2[C:15]([C:16]=1[NH2:17])=[CH:14][CH:13]=[CH:12][C:11]=2[C:25]1[CH:26]=[C:21]([O:20][CH3:19])[CH:22]=[CH:23][C:24]=1[O:27][CH3:28])=[O:6])[CH:2]=[CH2:3]
Reactant: COc1ccc(OC)c(B(O)O)c1
Reactant: C=CCNC(=O)c1nnc2c(Br)cccc2c1N
Product: C=CCNC(=O)c1nnc2c(-c3cc(OC)ccc3OC)cccc2c1N

Procedure:
The title compound was prepared from 4-amino-8-bromo-cinnoline-3-carboxylic acid allylamide (273 mg, 0.89 mmol) and 2,5-dimethoxyphenyl boronic acid (201.1 mg, 1.11 mmol) according to Method A to afford an off-white solid (105 mg, 32%). 1H NMR (300.132 MHz, CDCl3) δ 8.64 (bs, 1H), 7.87 (d, J=7.3 Hz, 1H), 7.77-7.69 (m, 2H), 6.96 (t, J=2.8 Hz, 1H), 6.96 (s, 1H), 6.93 (d, J=1.8 Hz, 1H), 6.00-5.88 (m, 1H), 5.29 (dq, J=17.2, 1.6 Hz, 1H), 5.17 (dq, J=10.2, 1.4 Hz, 1H), 4.12 (tt, J=5.7, 1.6 Hz, 2H), 3.79 (s, 3H), 3.64 (s, 3H). MS APCI, m/z=365 (M+H). HPLC 1.76 min.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[CH2:29]=[CH:30]CCCC.CC(CCC[C@H]([C@@H]1[C@]2(C)[C@H]([C@H]3[C@H](CC2)[C@]2(C)C(=CC(=O)CC2)CC3)CC1)C)C.C[C@@H]([C@@H]1[C@@]2(C)CC[C@@H]3[C@@]4(C)CCC(C[C@@H]4CC[C@H]3[C@@H]2CC1)=O)CCCC(C)C.CC(C(=O)CC[C@H]([C@@H]1[C@]2(C)[C@H]([C@H]3[C@H](CC2)[C@]2(C)C(CCCC2)CC3)CC1)C)C>C(C(C)=O)C>[CH3:29][CH2:30][C@@H:4]([CH:2]([CH3:1])[CH3:3])[CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@@:27]2([CH3:28])[CH2:26][CH2:25][C@@H:24]3[C@@:22]4([CH3:23])[CH2:21][CH2:20][C@H:18]([OH:19])[CH2:17][C:16]4=[CH:15][CH2:14][C@H:13]3[C@@H:12]2[CH2:11][CH2:10]1)[CH3:8]
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: C=CCCCC
Agent: CC(C)C(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4CCCC[C@]4(C)[C@H]3CC[C@]12C
Agent: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Solvent: CCC(C)=O
Product: CC[C@H](CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C
Reaction time: 4 h

Procedure:
Cholesterol (20 g), methyl ethyl ketone (150 ml), and Girdler G65-S-RS catalyst (10.0 g) and 1-hexene (13 g) were heated and rocked at 250° C. for 4 hours. An analysis by gas chromatography indicated conversion to a mixture of 4-cholesten-3-one (78 parts), cholesterol (4 parts), coprostanone (8 parts), and cholestanone (6 parts). Similar results are obtained when sitosterol is used in place of cholesterol.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:8]([CH3:16])[O:7][CH2:6][N:5]1[C:17]([CH3:27])([CH3:26])[C:18]([CH:20]1[CH2:24][CH2:23][CH2:22][C:21]1=[CH2:25])=[O:19].IC.[C:30](OCC)(=O)C>O>[CH2:16]([C:8]1[O:7][CH2:6][N:5]([C:17]([CH3:27])([CH3:26])[C:18]([CH:20]2[CH2:24][CH2:23][CH2:22][C:21]2=[CH2:25])=[O:19])[C:4](=[O:3])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:30]
Reactant: CCOC(C)=O
Reactant: C=C1CCCC1C(=O)C(C)(C)N1COC(C)=C(c2ccccc2)C1=O
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: C=C1CCCC1C(=O)C(C)(C)N1COC(CC)=C(c2ccccc2)C1=O
Reaction time: 0.17 h

Procedure:
Sodium hydride (60%, 0.06 g) was added to a stirred solution of 2-(2,3-dihydro-4-oxo-6-methyl-5-phenyl-4H-1,3-oxazin-3-yl)-2-methyl-1-(2-methylenecyclopentyl)propan-1-one (0.45 g) at 20° C. After 10 minutes, iodomethane (0.1 ml) was added and stirring continued for 3 hours. Ethyl acetate and water were added and the organic phase dried (magnesium sulphate), evaporated and purified by silica gel column chromatography eluting with n-hexane/ethyl acetate (3:1) to give 2-(2,3-dihydro-6-ethyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methyl-1-(2-methylenecyclopentyl)propan-1-one (Compound 1075, 0.15 g), NMR: 1.09(t,3H), 1.49(s,3H), 1.55(s,3H), 1.80-2.00(3H), 2.21(q,2H), 2.25-2.50(3H), 3.89(1H), 4.86(s,1H), 4.98(s,1H), 5.26(d,1H), 5.32(d,1H), 7.20-7.38(5H).