Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Li])CCC.[C:6]([C:8]1[CH:20]=[CH:19][C:11]([C:12]([C:14]2[S:18][CH:17]=[N:16][CH:15]=2)=O)=[CH:10][CH:9]=1)#[N:7].C(OCC)(=O)C>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC.CCOCC>[C:6]([C:8]1[CH:20]=[CH:19][C:11]([C:12]([C:14]2[S:18][CH:17]=[N:16][CH:15]=2)=[CH2:1])=[CH:10][CH:9]=1)#[N:7]
Reactant: [Li]CCCC
Reactant: N#Cc1ccc(C(=O)c2cncs2)cc1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: C=C(c1ccc(C#N)cc1)c1cncs1
Reaction time: 1.5 h

Procedure:
714 mg of methyltriphenylphosphonium bromide are introduced into 6.7 ml of ether, and 0.973 ml of 1.6M n-butyllithium in hexane is added at 7°. The orange suspension is stirred at the same temperature for 1.5 hours and then reacted with a suspension, cooled to 7°, of 5-(4-cyanobenzoyl)-thiazole (Example 8a) in 3 ml of ether. After stirring for 3 hours at RT, the ether is replaced by ethyl acetate and the mixture is stirred for a further 2 hours under reflux. The solid material is filtered off with suction and the mother liquor is concentrated. The residue is taken up in methylene chloride and the organic phase is washed in succession with 7 ml of 2N hydrochloric acid and with water, dried over sodium sulfate and concentrated. The crude product is purified by column chromatography (SiO2 0.04-0.06 mesh, 0.1 bar, hexane/ethyl acetate 2:1 to 1:1) and crystallised from hexane; m.p. 71°-73°; 1H-NMR (CDCl3): δ(ppm)=5.5 (s,1H), 5.73 (s,1H) 7.54 and 7.71 (m,4H), 7.69 (s,1H), 8.78 (s,1H).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:6]=[C:5]([I:13])[C:4]=1[OH:14].C[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[CH:25]1C=CC=CC=1>C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:12][C:9]([C:7]1[CH:6]=[C:5]([I:13])[C:4]2[O:14][C:25]3([CH:21]4[CH2:20][CH:19]5[CH2:24][CH:23]([CH2:16][CH:17]3[CH2:18]5)[CH2:22]4)[NH:1][CH2:2][C:3]=2[CH:8]=1)([CH3:11])[CH3:10]
Reactant: CC(C)(C)c1cc(I)c(O)c(CN)c1
Reactant: c1ccccc1
Reactant: CCCCCCCCCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CC(C)(C)c1cc(I)c2c(c1)CNC1(O2)C2CC3CC(C2)CC1C3

Procedure:
A mixture of 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol (1.5 g., 0.005 mole), 2-oxotricyclo(3.3.1.1.3,7)-decane (0.75 g., 0.005 mole) and p-toluenesulfonic acid (50 mg.) in benzene (25 ml.) is refluxed under a Dean-Stark trap for 2 hr. The solution is cooled, filtered, and evaporated to dryness. The residue is crystallized from ethanol to obtain 3,4-dihydro-6-(1,1-dimethylethyl)-8-iodospiro[2H-1,3-benzoxazine-2,2'-tricyclo(3.3.1.13,7)decane] (1.4 g.), m.p. 165°-166° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN.CCN=C=NCCCN(C)C.C1C=CC2N(O)[N:40]=[N:39]C=2C=1>O.C(N(CC)CC)C.C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:39][NH2:40])=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: On1nnc2ccccc21
Reactant: O=C(O)Cc1ccc(OCc2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: NN
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: NNC(=O)Cc1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 16.2 %

Procedure:
To a solution of THF (50 mL) of 4-benzyloxy-phenylacetic acid (7.0 g) were added hydrazine monohydrate (4.3 g), WSC (6.7 g), HOBt (4.7 g), and triethylamine (3.5 g), which was stirred for 15 hours at room temperature. Water was added to the reaction mixture, and the precipitated solids were filtered off to obtain the titled compound (1.2 g).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:20]=[CH:19][C:8]2[C:9]([C:12]3[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][CH:13]=3)=[N:10][S:11][C:7]=2[CH:6]=1.[CH3:21][O:22][CH2:23][CH2:24][NH:25][CH3:26]>>[Br:18][C:15]1[CH:16]=[CH:17][C:12]([C:9]2[C:8]3[CH:19]=[CH:20][C:5]([O:4][CH2:3][CH2:2][N:25]([CH2:24][CH2:23][O:22][CH3:21])[CH3:26])=[CH:6][C:7]=3[S:11][N:10]=2)=[CH:13][CH:14]=1
Reactant: BrCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1
Reactant: CNCCOC
Product: COCCN(C)CCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1

Procedure:
According to the method in example 4, 6-(2-Bromo-ethoxy)-3-(4-bromo-phenyl)-benzo[d]isothiazole and N-(2-methoxyethyl)methylamine were converted to yield [2-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-ethyl]-(2-methoxy-ethyl)-methyl-amine, MS: 422 (MH+, 1Br).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:12])[C:5]([N+:9]([O-:11])=[O:10])=[CH:6][C:7]=1[CH3:8].[CH3:13][CH2:14][CH2:15]CCC>CS(C)=O>[CH2:15]([O:12][C:4]1[CH:3]=[C:2]([Cl:1])[C:7]([CH3:8])=[CH:6][C:5]=1[N+:9]([O-:11])=[O:10])[CH:14]=[CH2:13]
Reactant: Cc1cc([N+](=O)[O-])c(O)cc1Cl
Reactant: CCCCCC
Solvent: CS(C)=O
Product: C=CCOc1cc(Cl)c(C)cc1[N+](=O)[O-]
Temperature: 70 °C
Reaction time: 5 h

Procedure:
A solution of 37.5 g of 4B in 200 ml of dimethyl sulfoxide (DMSO) was added drop-by-drop over 30 minutes to a stirred solution of 4.8 g of freshly hexane-washed sodium hydride in 200 ml of DMSO, the temperature being held at 30° C. Then 26.6 3-bromopropene was added drop-by-drop over 10 minutes, and the mixture was stirred at 70° C. for 5 hours. The mixture was mixed with 1 liter of cold water and the resulting mixture was extracted with methylene chloride. The extract was washed with water, dried (MgSO4) and the solvent was evaporated, to give 1-(2-propenyloxy)-5-chloro-4-methyl-2-nitrobenzene (7A), as brown solid, m.p.: not determined.
Reaction SMILES: C[O:2][CH:3]=[CH:4][CH:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1>C(O)=O>[O:2]=[CH:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1
Reactant: COC=CC1CCCN(C(=O)OC(C)(C)C)C1
Solvent: O=CO
Product: CC(C)(C)OC(=O)N1CCCC(CC=O)C1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 59.6 %

Procedure:
tert-Butyl 3-(2-methoxyethenyl)-1-piperidinecarboxylate (1.16 g, 4.81 mmol) was dissolved in 90% formic acid (2 mL). The mixture was stirred at room temperature for 40 min. The mixture was then partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The separated organic phase was washed with brine, dried over Na2SO4, filtered and evaporated. Purification by column chromatography (hexane/ethyl acetate=4/1) gave tert-butyl 3-(2-oxoethyl)-1-piperidinecarboxylate as a colorless oil (652 mg, yield; 60%). [Starting Compound 2H]
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C:5]1[C:13]2[S:12][N:11]=[N:10][C:9]=2[CH:8]=[CH:7][CH:6]=1.[H][H].[CH3:16]I.Cl>CS(C)=O.O1CCCC1>[CH3:16][O:3][CH2:4][C:5]1[C:13]2[S:12][N:11]=[N:10][C:9]=2[CH:8]=[CH:7][CH:6]=1
Reactant: OCc1cccc2nnsc12
Reactant: CI
Reactant: [H][H]
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CS(C)=O
Product: COCc1cccc2nnsc12
Temperature: 0 °C

Procedure:
1.4 g of sodium hydride (50% dispersion in oil) in 15 ml of absolute dimethyl sulfoxide are introduced into a reaction vessel, and a solution of 4.15 g of 7-hydroxymethylbenzo-1,2,3-thiadiazole in 15 ml of tetrahydrofuran is added dropwise at 0°-5° C. under a nitrogen atmosphere and with stirring, during which process hydrogen is evolved. After 20 minutes of stirring at 10° C., the mixture is cooled down to 0°-5° C., and a solution of 4 g of methyl iodide in 15 ml of tetrahydrofuran is added dropwise. Stirring is continued for another hour at room temperature, and the mixture is cooled, treated with ice-water, neutralised with dilute hydrochloric acid and extracted with ethyl acetate. The extracts are washed with water, dried over sodium sulfate and evaporated, and the residue is dried in a high vacuum, resulting in the title compound in the form of a yellow oil, nD27 =1.5912.
Reaction SMILES: CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][CH2:13][C:14]2=[O:17])=[CH:10][CH:9]=1.Br[CH2:19][CH2:20][O:21][CH2:22][CH2:23]Br>CC(O)(C)C.CC1CCCO1>[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][C:13]3([C:14]2=[O:17])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:10][CH:9]=1
Reactant: BrCCOCCBr
Reactant: O=C1CCc2ccc(Br)cc21
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: CC1CCCO1
Product: O=C1c2cc(Br)ccc2CC12CCOCC2
Temperature: 25 °C
Reaction time: 5 h
Yield: 24.2 %

Procedure:
A solution of potassium tert-butoxide (3.94 g, 35.1 mmol) in t-BuOH (35 mL) was added dropwise over 15 min to a solution of 6-bromo-1-indanone (3.53 g, 16.73 mmol) in 2-methyl-tetrahydrofuran (350 mL) at r.t. under a nitrogen atmosphere. After 15 min bis(2-bromoethyl)ether (2.102 mL, 16.73 mmol) was added and the resulting mixture was stirred at r.t. for 5 h. Potassium tert-butoxide (0.938 g, 8.36 mmol) was added and the mixture was stirred at r.t. overnight. The mixture was quenched with saturated aq. NH4Cl (150 mL) and the organic layer was separated. The aqueous layer was extracted with EtOAc (3×50 mL) and Et2O (50 mL). The combined organics were washed with brine (100 mL), dried over MgSO4, filtered and concentrated. The resulting residue was taken up in DCM, concentrated onto silica gel and purified on a silica gel column eluted with 0-40% EtOAc in heptane to give 1.14 g (24% yield) of the title compound; MS (ES+) m/z 281 [M+H]+.
Reaction SMILES: C([N:3]([CH2:6]C)CC)C.[OH:8][CH2:9][CH:10]([N:12]1[C:25]2[C:24](C#N)=[CH:23][CH:22]=[CH:21][C:20]=2[S:19][C:18]2[C:13]1=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH3:11].[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[CH3:28][S:29]([O:8][CH2:9][CH:10]([N:12]1[C:25]2[CH:24]=[C:23]([C:6]#[N:3])[CH:22]=[CH:21][C:20]=2[S:19][C:18]2[C:13]1=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH3:11])(=[O:31])=[O:30]
Reactant: CC(CO)N1c2ccccc2Sc2cccc(C#N)c21
Reactant: CCN(CC)CC
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CC(COS(C)(=O)=O)N1c2ccccc2Sc2ccc(C#N)cc21
Reaction time: 0.83 h

Procedure:
Triethylamine (16.2 cc) is added with stirring to a solution, cooled to a temperature in the region of 5° C., of 10-(1-hydroxy-2-propyl)phenothiazinecarbonitrile, D series (20 g) in methylene chloride (200 cc), a solution of methanesulphonyl chloride (8.9 cc) in methylene chloride (89 cc) is then introduced dropwise during 25 minutes, and stirring is continued for 50 minutes at a temperature in the region of 10° C. The reaction mixture is washed successively with distilled water (2×100 cc) and with saturated aqueous sodium chloride solution (100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. 2-(2--Cyano-10-phenothiazinyl)-1-propyl methanesulphonate, D series (25.8 g) is thereby obtained in the form of an orange gum, which is used without further purification for the next stage of the synthesis.
Reaction SMILES: Br[C:2]12[CH2:24][C:6]3([CH3:25])[CH2:7][C:8]([C:11]45[CH2:21][C:15]6([CH3:22])[CH2:16][C:17](Br)([CH2:19][C:13]([CH3:23])([CH2:14]6)[CH2:12]4)[CH2:18]5)([CH2:10][C:4]([CH3:26])([CH2:5]3)[CH2:3]1)[CH2:9]2.Br[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([Br:34])[CH:29]=1.[Br-:35].[Al+3].[Br-:37].[Br-:38].Cl>>[Br:35][C:2]1[CH:3]=[C:4]([C:2]23[CH2:3][C:4]4([CH3:26])[CH2:10][C:8]([C:11]56[CH2:21][C:15]7([CH3:22])[CH2:16][C:17]([C:28]8[CH:33]=[C:32]([Br:38])[CH:31]=[C:30]([Br:34])[CH:29]=8)([CH2:19][C:13]([CH3:23])([CH2:14]7)[CH2:12]5)[CH2:18]6)([CH2:7][C:6]([CH3:25])([CH2:5]4)[CH2:24]2)[CH2:9]3)[CH:5]=[C:6]([Br:37])[CH:24]=1
Reactant: CC12CC3(C)CC(Br)(C1)CC(C14CC5(C)CC(C)(CC(Br)(C5)C1)C4)(C2)C3
Reactant: [Br-]
Reactant: Brc1cccc(Br)c1
Agent: Cl
Agent: [Al+3]
Product: CC12CC3(C)CC(c4cc(Br)cc(Br)c4)(C1)CC(C14CC5(C)CC(C)(CC(c6cc(Br)cc(Br)c6)(C5)C1)C4)(C2)C3
Temperature: 25 °C
Yield: 180 %

Procedure:
In a 1 L recovery flask, 48.4 g of 7,7′-dibromo-3,3′,5,5′-tetramethyl-1,1′-biadamantane (100 mmol), 1,180 g of 1,3-dibromobenzene (5.00 mol) and a stirrer were charged. Under nitrogen flow, 26.7 g of aluminum bromide (100 mmol) was gradually added thereto with agitating at room temperature. After the addition, the mixture was agitated at 50° C. for seven hours. Reaction solution was added to 2 L of 1 mol/L hydrochloric acid aqueous solution. After an aqueous layer was separated and removed therefrom, 1 L of acetone was added. Solid thus precipitated was collected by filtration and dried under reduced pressure, thus obtaining 71.5 g of 7,7′-bis(3,5-dibromophenyl)-3,3′,5,5′-tetramethyl-1,1′-biadamantane (90.0 mmol; yield: 90.0%).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].CCN(C(C)C)C(C)C.[CH2:22]([NH2:34])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>C(Cl)Cl>[CH2:22]([NH:34][C:8](=[O:9])[C:7]1[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: CCCCCCCCCCCCN
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCCCCCCCCCCCNC(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 100.8 %

Procedure:
At 0° C., to a solution of 4-nitro-benzoyl chloride (12.664 g, 68.25 mmol) and DIEA (9.7 g, 75.05 mmol) in anhydrous DCM (200 mL) was added dropwise a solution of dodecylamine (12.650 g, 68.25 mmol in 50 mL of DCM). The reaction mixture was stirred at 0° C. for 30 min, then 1.5 h at rt. The solvents were evaporated and the residue dissolved in boiling AcOEt, washed with water, a 10% aqueous solution of HCl, water, dried over MgSO4 and filtered. The solvents were evaporated to give a yellow solid (23.02 g). This residue was washed twice with diethylether (50 mL) to give after evaporation of the solvent the title compound as a pale yellow powder (20.31 g, 89%). 1H NMR (DMSO-d6, 300 MHz) δ 8.77 (t, 1H, J=5.5 Hz), 8.30 (d, 2H, J=9.0 Hz), 8.04 (d, 2H, J=9.0 Hz), 3.25 (q, 2H, J=6.3 Hz), 1.43-1.58 (m, 2H), 1.12-1.35 (m, 18H), 0.83 (t, 3H, J=6.7 Hz). HPLC (Condition A), Rt: 6.55 min (HPLC purity: 93.2%).
Reaction SMILES: [CH3:1][CH:2]([CH3:33])[CH2:3][C@H:4]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:5][O:6][C:7]1[C:8]([CH:23]=[CH2:24])=[CH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[CH:22]=1.[H][H]>[Pd].CO.C(OCC)(=O)C>[CH2:23]([C:8]1[C:7]([O:6][CH2:5][C@@H:4]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:3][CH:2]([CH3:1])[CH3:33])=[CH:22][C:11]2[N:12]([CH3:21])[C:13](=[O:20])[C:14]3[C:19]([C:10]=2[CH:9]=1)=[CH:18][CH:17]=[N:16][CH:15]=3)[CH3:24]
Reactant: C=Cc1cc2c3ccncc3c(=O)n(C)c2cc1OC[C@H](CC(C)C)NC(=O)OC(C)(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCc1cc2c3ccncc3c(=O)n(C)c2cc1OC[C@H](CC(C)C)NC(=O)OC(C)(C)C
Yield: 40.1 %

Procedure:
A mixture of (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (0.15 g, 0.332 mmol) and palladium on carbon (0.075 g, 0.070 mmol) in MeOH (3 mL) and ethyl acetate (3 mL) was stirred at RT under a balloon of hydrogen gas for 24 h. The reaction mixture was filtered through diatomaceous earth (Celite®) and the filtrate was concentrated under reduced pressure. The residue was purified by prep TLC (60% ethyl acetate and petroleum ether) to afford (S)-tert-butyl (1-((9-ethyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan 2-yl)carbamate (0.11 g, 0.133 mmol, 40% yield) as a yellow semi solid. LC/MS (ESI) m/e 454.4, [(M+H)+, calcd for C26H36N3O4, 454.3]; LC/MS retention time (method D): tR=0.96 min.
Reaction SMILES: [CH2:1]([N:4]([CH2:17][CH2:18][CH3:19])[CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([CH2:15][NH2:16])[CH:9]=[CH:10][CH:11]=2)[CH2:6]1)[CH2:2][CH3:3].[CH3:20][N:21]=[C:22]=[O:23]>C1(C)C=CC=CC=1>[CH2:17]([N:4]([CH2:1][CH2:2][CH3:3])[CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([CH2:15][NH:16][C:22]([NH:21][CH3:20])=[O:23])[CH:9]=[CH:10][CH:11]=2)[CH2:6]1)[CH2:18][CH3:19]
Reactant: CN=C=O
Reactant: CCCN(CCC)C1CCc2cccc(CN)c2C1
Solvent: Cc1ccccc1
Product: CCCN(CCC)C1CCc2cccc(CNC(=O)NC)c2C1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
1.6 g (6 mmol) of 2-dipropylamino-8-aminomethyl-1,2,3,4-tetrahydronaphthalene were dissolved in 16 ml of toluene under nitrogen. 0.34 g (6 mmol) of methyl isocyanate was added dropwise at a maximum of +25° C. The batch was subsequently stirred for a further 1.5 h at room temperature. The reaction product which crystallized out was then filtered off under suction and dried at +40° C. in vacuo.
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[CH:4][C:3]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].O=[C:13]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:14][C:15](OCC)=[O:16]>C(O)(=O)C>[OH:16][C:15]1[N:6]2[N:5]=[CH:4][C:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]2[N:1]=[C:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:14]=1
Reactant: CCOC(=O)c1cn[nH]c1N
Reactant: CCOC(=O)CC(=O)c1ccccc1
Solvent: CC(=O)O
Product: CCOC(=O)c1cnn2c(O)cc(-c3ccccc3)nc12
Temperature: 25 °C
Yield: 34.2 %

Procedure:
Commercially available ethyl 5-amino-1H-pyrazole-4-carboxylate (5.0 g, 32 mmol) was taken into glacial acetic acid (3.2 mL) followed by addition of ethyl 3-oxo-3-phenylpropanoate (6.1 mL, 35 mmol) and the mixture was refluxed for 12 h. The mixture was allowed to cool to room temperature and concentrated in vacuo. The crude solid was recrystallized (ethanol) and collected to yield 3.1 g (61%) of crystalline ethyl 7-hydroxy-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate. 1H NMR (400 MHz, d6-DMSO): 11.75 (s, 1H), 8.28 (s, 1H), 7.80 (m, 2H), 7.61 (m, 3H), 6.28 (s, 1H), 4.31 (q, 2H), 1.34 (t, 3H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)=[CH:6][C:5](Br)=[CH:4][C:3]=1[S:14]([O-:17])(=[O:16])=[O:15].[Na+:18].[OH-].[Na+].C(O)C>[Zn].CO>[NH2:1][C:2]1[C:7]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[S:14]([O-:17])(=[O:16])=[O:15].[Na+:18]
Reactant: Nc1c(-c2cccs2)cc(Br)cc1S(=O)(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Agent: [Zn]
Solvent: CCO
Solvent: CO
Product: Nc1c(-c2cccs2)cccc1S(=O)(=O)[O-]

Procedure:
21 g (59 mmol) of sodium 2-amino-5-bromo-3-(2-thienyl)benzenesulphonate are heated at 100° C. for 1 hour in the presence of 350 ml of 10% sodium hydroxide solution, 15 ml of ethanol and 7.4 g of zinc. The temperature of the reaction medium is allowed to return to room temperature and 300 ml of methanol are added. The mixture is filtered through Celite, the filtrate is concentrated and the residue is taken up in 1N sodium hydroxide solution at 0° C. and dried under vacuum.
Reaction SMILES: [H-].[Na+].CN(C)C=O.[CH3:8][C:9]1[O:13][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:11][C:10]=1[CH2:20][O:21][C:22]1[CH:42]=[CH:41][C:25]([CH2:26][N:27]2[C:39]3[CH:38]=[CH:37][CH:36]=[C:35]([OH:40])[C:34]=3[C:33]3[C:28]2=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:24][C:23]=1[O:43][CH3:44].Br[C@H:46]([CH2:52][CH3:53])[C:47]([O:49][CH2:50][CH3:51])=[O:48]>O>[CH3:44][O:43][C:23]1[CH:24]=[C:25]([CH:41]=[CH:42][C:22]=1[O:21][CH2:20][C:10]1[N:11]=[C:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[O:13][C:9]=1[CH3:8])[CH2:26][N:27]1[C:39]2[CH:38]=[CH:37][CH:36]=[C:35]([O:40][C@@H:46]([CH2:52][CH3:53])[C:47]([O:49][CH2:50][CH3:51])=[O:48])[C:34]=2[C:33]2[C:28]1=[CH:29][CH:30]=[CH:31][CH:32]=2
Reactant: CCOC(=O)[C@H](Br)CC
Reactant: COc1cc(Cn2c3ccccc3c3c(O)cccc32)ccc1OCc1nc(-c2ccccc2)oc1C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)[C@H](CC)Oc1cccc2c1c1ccccc1n2Cc1ccc(OCc2nc(-c3ccccc3)oc2C)c(OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
41 mg of sodium hydride (60%) was added to N,N-dimethylformamide (2.5 mL) solution of 500 mg of 9-{4-[(5-methyl-2-phenyloxazole-4-yl)methoxy]-3-methoxybenzyl}-9H-carbazole-4-ol while being cooled in an ice bath, and stirred at room temperature for 1 hour. Thereafter, 239 mg of ethyl (R)-2-bromobutyrate was added thereto dropwise at −5° C., and was stirred for 30 minutes. Water was added to the reaction mixture, and extracted twice with ethyl acetate. The combined extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residue was purified by NH silica gel chromatography (ethyl acetate:n-hexane=1:4), and 650 mg of the subject compound was prepared. Optical purity 95% ee (HPLC).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[CH:7]=[CH:6][C:5]1=[O:10].C(N(CC)CC)C.Cl[Si:19]([CH3:22])([CH3:21])[CH3:20]>ClCCl>[CH3:20][Si:19]([CH3:22])([CH3:21])[O:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[CH:7]=[CH:6][C:5]1=[O:10]
Reactant: O=C1C=CC(=O)N1CCO
Reactant: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[Si](C)(C)OCCN1C(=O)C=CC1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
To a solution of N-(2-hydroxyethyl)maleimide (0.2 g, 1.41 mmol) in dry dichloromethane (10 ml) and triethylamine (0.22 ml, 1.57 mmol) at 0° C. was added chlorotrimethylsilane (TMS-C1, 0.2 ml, 1.57 mmol). After stirring for 1 hour at room temperature, TLC analysis (ethyl acetate/petroleum ether 1:1) indicated one spot (Rf=0.67). Solvent was removed in vacuo and the residue was dissolved in dichloromethane and filtered through a small silica gel column eluting with dichloromethane. The fractions containing product were pooled and evaporated in vacuo to afford N-(2-trimethylsiloxyethyl)-maleimide (formula H) as colorless flakes (0.3 g; 100% yield).
Reaction SMILES: [CH:1]1[C:6]2[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][CH2:10][CH2:11][C:5]=2C(C#N)=[CH:3][CH:2]=1.[OH-:18].[K+].[CH2:20]([OH:23])[CH2:21]O>O>[CH:1]1[C:6]2[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][CH2:10][CH2:11][C:5]=2[C:21]([C:20]([OH:23])=[O:18])=[CH:3][CH:2]=1
Reactant: OCCO
Reactant: N#Cc1cccc2c1CCCc1ccccc1-2
Reactant: [OH-]
Agent: [K+]
Solvent: O
Product: O=C(O)c1cccc2c1CCCc1ccccc1-2

Procedure:
Under a dry nitrogen atmosphere a solution of 6,7-dihydro-5H-dibenzo[a,c]cycloheptene-4-carbonitrile (2.95 grams, 0.0134 mole), potassium hydroxide (4 grams, 0.085 mole), ethylene glycol (40 ml) and water (3 ml) was heated at reflux for approximately 24 hours. The mixture was cooled, diluted with water, and the solution was washed with diethyl ether. The aqueous solution was acidified and extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to give a white solid. The solid was combined with similar material prepared in a separate experiment, and the combined solids were recrystallized from n-hexane to give 6,7-dihydro-5H-dibenzo[a,c]cycloheptene-4-carboxylic acid (mp 137°-139°) as nearly white crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[C:3]=1[C:4]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13](=[O:15])[CH3:14])[CH:8]=1)=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:32][C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34]>C1COCC1.CN1C(=O)N(C)CCC1.C(OCC)(=O)C>[CH3:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[C:3]=1[C:4]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13](=[O:15])[CH2:14][CH2:32][C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34])[CH:8]=1)=[O:5]
Reactant: CC(=O)c1cccc(OC(=O)c2c(C)cccc2C)c1
Reactant: O=C(CBr)OCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CN1CCCN(C)C1=O
Product: Cc1cccc(C)c1C(=O)Oc1cccc(C(=O)CCC(=O)OCc2ccccc2)c1
Temperature: -65 °C
Reaction time: 0.17 h

Procedure:
To a stirred solution of 3-Acetylphenyl 2,6-dimethylbenzoate (Step B, 2.90 g, 10.8 mmol) in dry THF (50 ml) and DMPU (17 ml) was added a solution of lithium bis(trimethylsilyl) amide (1.0M, 11.89 ml) at −65° C. under argon. After 10 minutes of stirring at −65° C., benzyl bromoacetate (3.72 g, 16.24 mmol) was added rapidly. The reaction mixture was stirred for an additional 10 minutes and then warmed to room temperature for 4 hours. The crude mixture was taken in ethyl acetate and washed with water and brine. The aqueous layer was extracted one more time with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (hex: ethyl acetate, 4:1) to provide the title compound.