Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[CH2:13]([N:20]1[CH2:25][CH2:24][CH:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[N:31]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[N:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>C1COCC1>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([N:31]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCOC(=O)C1CCN(Cc2ccccc2)CC1
Reactant: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C1(N(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)CCN(Cc2ccccc2)CC1
Temperature: -70 °C
Reaction time: 0.08 h
Yield: 73.3 %

Procedure:
To a solution of diisopropylamine (153 mg, 1.5 mmol) in THF (20 mL) was added n-BuLi (2.5 M, 0.6 mL) at −75° C. under N2. After 5 min, ethyl 1-benzylpiperidine-4-carboxylate (247 mg, 1.0 mmol) was added and the resulting mixture then stirred at −70° C. for 10 min, before adding di-tert-butyl azodicarboxylate (345 mg, 1.5 mmol). The reaction was stirred for 30 min, then quenched with aqueous NH4Cl (10 mL) and extracted with EA (10 mL×3). The combined organic layers were dried over Na2SO4 and concentrated to give the crude product (350 mg, 72%) as an off-white solid. MS (ESI, m/e) [M+1]+ 478.3.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:21][C:22]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=2[F:29])=[C:4]([Cl:20])[C:5]([NH:8][C:9]([NH:11]C(=O)C2C=CC=CC=2)=[S:10])=[N:6][CH:7]=1.[OH-].[Na+]>C(O)C>[Br:1][C:2]1[C:3]([O:21][C:22]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=2[F:29])=[C:4]([Cl:20])[C:5]([NH:8][C:9]([NH2:11])=[S:10])=[N:6][CH:7]=1
Reactant: O=C(NC(=S)Nc1ncc(Br)c(Oc2c(F)cccc2F)c1Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: NC(=S)Nc1ncc(Br)c(Oc2c(F)cccc2F)c1Cl

Procedure:
A mixture of N-(5-bromo-3-chloro-4-(2,6-difluorophenoxy)pyridin-2-ylcarbamothioyl)benzamide (474 mg, 0.95 mmol) and 3M NaOH (1 mL, 30 mmol) in ethanol (4 mL) is heated. The reaction mixture is cooled, concentrated to 2 mL, diluted with water, and filtered to afford 1-(5-bromo-3-chloro-4-(2,6-difluorophenoxy)pyridin-2-yl)thiourea.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:4][CH:3]=1.[C:13]([O-])(=O)/C=C/C([O-])=O>>[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH2:8][N:9]([CH3:13])[CH2:10][CH2:11][CH:12]=2)=[N:4][CH:3]=1
Reactant: O=C([O-])/C=C/C(=O)[O-]
Reactant: Cc1cnc(-c2cccnc2)s1
Product: Cc1cnc(C2=CCCN(C)C2)s1

Procedure:
The title compound was prepared from 88 (2.2 g, 0.013 mol) by the procedure described in Example 49. The crude free base obtained, 89, was converted to the title fumarate, 90. Yield: 0.8 g (0.0032 mol, 25%). M.P. 159°-160° C. Anal. (C12H16N2O2S)C, H, N.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15]([C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:13]=[CH:12]3)O1.Br[C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[CH:28][N:29]=[CH:30]2.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CCO>[CH:30]1[C:31]2[C:26](=[C:25]([C:9]3[CH:10]=[C:11]4[C:16](=[CH:17][CH:18]=3)[C:15]([C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:13]=[CH:12]4)[CH:34]=[CH:33][CH:32]=2)[CH:27]=[CH:28][N:29]=1
Reactant: COC(=O)c1cccc2cc(B3OC(C)(C)C(C)(C)O3)ccc12
Reactant: Brc1cccc2cnccc12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: COC(=O)c1cccc2cc(-c3cccc4cnccc34)ccc12
Yield: 70.9 %

Procedure:
Methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-naphthoate (2.2 g, 7.0 mmol), 5-Bromoisoquinoline (1.33 g, 6.3 mmol), a 2M solution of sodium carbonate (9.6 mL) and palladium tetrakistriphenylphospine (0.37 g, 0.32 mmol) were heated in Toluene-EtOH (105 mL-21 mL) at 80° C. overnight. Solvent was evaporated and mixture was extracted with ethyl acetate. Organic phase was washed with brine, dried, filtered and evaporated. Residue was purified by chromatography (ethyl acetate-hexane 10:90->20:80->30:70->40:60->60-40. to give 1.4 g of the title compound as an off-white solid
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH2:12].[OH-].[Na+].C(O)(=O)CCC(O)=O>C(Cl)Cl>[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH:12][C:4](=[O:5])[CH2:3][CH2:2][C:1]([OH:6])=[O:7]
Reactant: O=C1CCC(=O)O1
Reactant: COC(CN)OC
Agent: O=C(O)CCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: COC(CNC(=O)CCC(=O)O)OC
Reaction time: 0.5 h

Procedure:
50.4 g (0.5 mol) of freshly distilled succinic anhydride are dispersed in 100 ml of methylene chloride. 52.75 g (0.5 mol) of aminoacetaldehyde dimethyl acetal are added, and the mixture is boiled under reflux. After 30 minutes, the homogeneous solution is evaporated in vacuo and freed from solvent at 60° C. under a high vacuum, giving a viscous oil which, according to titration with sodium hydroxide solution, has a purity of 99.4%. NMR data: 2.63 ppm (m) 4 methylene protons of succinic acid, 3.42 ppm (s) 6 methoxy protons, 4.42 ppm (t) 1 acetal proton, 3.6 ppm (d) 2 methylene protons, 6.60 ppm (t) 1 amide proton, 9.79 ppm 1 acid proton ##STR39##
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]([F:42])([F:41])[C:9]1[CH:10]=[C:11]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:12][NH:13][CH2:14][C:15]1[C:16]([N:25]([CH2:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH2:26][CH3:27])=[N:17][C:18]2[CH2:19][CH2:20][CH2:21][CH2:22][C:23]=2[CH:24]=1.Cl[C:44]([O:46][CH3:47])=[O:45]>C1COCC1>[CH3:47][O:46][C:44](=[O:45])[N:13]([CH2:12][C:11]1[CH:10]=[C:9]([C:8]([F:41])([F:7])[F:42])[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=1)[CH2:14][C:15]1[C:16]([N:25]([CH2:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH2:26][CH3:27])=[N:17][C:18]2[CH2:19][CH2:20][CH2:21][CH2:22][C:23]=2[CH:24]=1
Reactant: COC(=O)Cl
Reactant: CCN(CC1CCCC1)c1nc2c(cc1CNCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCCC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCN(CC1CCCC1)c1nc2c(cc1CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)OC)CCCC2
Reaction time: 1 h
Yield: 15 %

Procedure:
To a suspension of potassium carbonate (0.269 g, 1.949 mmol) in dry THF (5 mL) was added a THF solution (10 mL) of {3-[(3,5-bis-trifluoromethyl-benzylamino)-methyl]-5,6,7,8-tetrahydro-quinolin-2-yl}-cyclopentylmethyl-ethylamine (0.25 g, 0.3 mmol), which was then stirred for 1 h. Methyl chloroformate (0.137 g, 1.46 mmol) was then added and stirring was was continued at RT for 8 h. The solvent was then evaporated, water was added, and the product was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and the solvent was evaporated to afford a residue. This crude residue was purified over silica gel (100-200 mesh) and eluted with 2% ethyl acetate and petroleum ether to afford (3,5-bis-trifluoromethyl-benzyl)-[2-(cyclopentylmethyl-ethyl-amino)-5,6,7,8-tetrahydro-quinolin-3-ylmethyl]-carbamic acid methyl ester as light green, pasty compound (0.05 g), yield: 15%.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=O)[O:10][C:8](=[O:9])[C:7]2=[CH:13][CH:14]=1)([O-:3])=[O:2].[NH2:15][NH2:16].Cl>CC(O)C>[OH:9][C:8]1[C:7]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:14][CH:13]=2)[C:11]([OH:10])=[N:16][N:15]=1
Reactant: NN
Reactant: O=C1OC(=O)c2cc([N+](=O)[O-])ccc21
Agent: Cl
Solvent: CC(C)O
Product: O=[N+]([O-])c1ccc2c(O)nnc(O)c2c1
Temperature: 85 °C
Yield: 72.3 %

Procedure:
A mixture of 4-nitrophthalic anhydride (10.0 g, 51.78 mmol) and IPA (180 mL) was stirred by a mechanical stirrer. Anhydrous hydrazine (2.77 mL, 56.96 mmol) was added dropwise and the reaction heated to 85° C. for 5 h. The reaction was cooled then acidified to pH 3 with conc. HCl. The solids were filtered and washed with IPA to afford the desired compound (7.76 g, 72%) as a pale yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:12]1[C:20]2[C:15](=[N:16][C:17]([CH:21]=[CH2:22])=[CH:18][CH:19]=2)[CH2:14][O:13]1.C[O:24][CH2:25][CH2:26][NH:27][CH3:28]>CC(O)=O.C(N(CC)CC)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:12]1[C:20]2[C:15](=[N:16][C:17]([CH2:21][CH2:22][N:27]([CH2:26][CH2:25][OH:24])[CH3:28])=[CH:18][CH:19]=2)[CH2:14][O:13]1
Reactant: CNCCOC
Reactant: C=Cc1ccc2c(n1)COC2=C1C(=O)Nc2ccc(F)cc21
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: CN(CCO)CCc1ccc2c(n1)COC2=C1C(=O)Nc2ccc(F)cc21
Temperature: 100 °C
Reaction time: 1 h
Yield: 65.2 %

Procedure:
Following the method described in Example 19, 5-fluoro-3-(2-vinyl-7H-furo[3,4-b]pyridin-5-ylidene)-1,3-dihydro-indol-2-one (65 mg, 0.22 mmol) and (2-methoxyethyl)methylamine (300 mg, 3.99 mmol) and AcOH (12 drops) are heated 100° C. for 2 h. Additional (2-methoxyethyl)methylamine is added and heating is continued for 1 hr. The reaction mixture is cooled and treated with triethylamine (10 drops). The reaction mixture is loaded onto silica gel and purified by chromatography (silica gel, MeOH-Chloroform). The product containing fractions are concentrated and the residue is triturated with EtOAc-hexane. The solid which formed is collected by filtration and dried under vacuum to provide the title compound (53 mg, 65%) as a yellow solid.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.[H-].[Na+].Br[CH2:9][CH2:10][CH2:11][N:12]1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2[C:13]1=[O:22].[I-].[K+]>CN(C)C=O.O>[N:1]1[N:2]([CH2:9][CH2:10][CH2:11][N:12]2[C:16](=[O:17])[C:15]3[C:14](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:13]2=[O:22])[N:3]=[CH:4][CH:5]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Reactant: c1c[nH]nn1
Agent: [H-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCn1nccn1
Reaction time: 0.5 h
Yield: 52.2 %

Procedure:
To a solution of 1H-1,2,3-triazole (2000 mg, 28.96 mmol) in N,N-dimethylformamide (60 mL) was added sodium hydride (1159 mg, 28.96 mmol, 60% in oil), which was stirred for 30 minutes. N-(3-Bromopropyl)phthalimide (7057 mg, 26.32 mmol) and potassium iodide (431 mg, 2.63 mmol) were added thereto, and the solution was stirred for 3 hours at 70°. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and then, concentrated in vacuo. The resulting residue was purified by silica gel chromatography (dichloromethane-ethyl acetate), and the title compound (3526 mg, 13.75 mmol, 47%) was obtained.
Reaction SMILES: [CH2:1]([O:8][NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[C:11]=1[O:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(O[CH:30]1[CH2:39][CH2:38][C:33]2([O:37][CH2:36][CH2:35][O:34]2)[CH2:32][CH2:31]1)(C1C=CC(C)=CC=1)(=O)=O>>[CH2:1]([O:8][N:9]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[C:11]=1[O:17][CH3:18])[CH:30]1[CH2:39][CH2:38][C:33]2([O:37][CH2:36][CH2:35][O:34]2)[CH2:32][CH2:31]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1c(NOCc2ccccc2)ccnc1C
Reactant: Cc1ccc(S(=O)(=O)OC2CCC3(CC2)OCCO3)cc1
Product: COc1c(N(OCc2ccccc2)C2CCC3(CC2)OCCO3)ccnc1C
Yield: 70 %

Procedure:
Prepared analogously to Example 5 from 4-(O-benzylhydroxylamino)-3-methoxy-2-methylpyridine and 8-tosyloxy-1,4-dioxaspiro[4.5]decane. Yield: 70%
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:28](OCC)=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:25])[F:26])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:28][OH:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc2cc(-c3ccc(OC(F)(F)F)cc3)ccc2n1Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: OCc1cc2cc(-c3ccc(OC(F)(F)F)cc3)ccc2n1Cc1ccccc1

Procedure:
The title compound was prepared from Ethyl 1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indole-2-carboxylate (Step 2 of Example 25) and lithium aluminum hydride in substantially the same manner, as described in Step 1 of Example 21. The product was obtained as a white solid, mp: 108-109° C. Mass spectrum (ESI, [M+H]+) m/z 398. 1HNMR (400 MHz, DMSO-d6): δ 7.82 (s, 1H), 7.76 (d, 2H, J=8.86 Hz), 7.42-7.36 (m, 4H), 7.29 (d, 1H, J=7.03 Hz), 7.27 (d, 1H, J=7.63 Hz), 7.23-7.20 (m, 1H), 7.06 (d, 2H, J=7.03 Hz), 6.52 (s, 1H), 5.50 (s, 2H), 5.36 (t, 1H), and 4.60 ppm (d, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][N:9]=[CH:10][CH3:11])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[O-:15][C:16]#[N:17].[K+].Cl[O-].[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:15])[NH:17][C:10]([CH3:11])=[N:9]2)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]
Reactant: N#C[O-]
Reactant: CC=NNc1ccc(Cl)c([N+](=O)[O-])c1
Agent: [K+]
Agent: [Na+]
Agent: [O-]Cl
Solvent: O
Solvent: CC(=O)O
Product: Cc1nn(-c2ccc(Cl)c([N+](=O)[O-])c2)c(=O)[nH]1
Reaction time: 0.5 h
Yield: 86.3 %

Procedure:
To a stirred solution of 5.25 g (00246 mole) of acetaldehyde 4-chloro-3-nitrophenylhydrazone in 25 ml of acetic acid was added dropwise a solution of 2.0 g (0.0246 mole) of potassium cyanate in 5 ml of water. After complete addition, 50 ml of an aqueous 5% sodium hypochlorite solution was added dropwise, forming a precipitate. After about 1/2 hour, the solid was collected by filtration and dried to yield 5.4 g of 1-(4-chloro-3-nitrophenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[O:7]=[C:8]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C:10]([CH2:11][CH2:12][C@@H:13]3[C@@H:22]2[CH2:21][CH2:20][C@@:18]2([CH3:19])[C@H:14]3[CH2:15][CH2:16][C@@H:17]2[CH2:27][OH:28])=[CH:9]1.CI>C(O)(C)(C)C>[O:7]=[C:8]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C:10]([CH2:11][CH2:12][C@@H:13]3[C@@H:22]2[CH2:21][CH2:20][C@@:18]2([CH3:19])[C@H:14]3[CH2:15][CH2:16][C@@H:17]2[CH2:27][OH:28])=[C:9]1[CH3:1]
Reactant: CC(C)(C)[O-]
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43C)[C@@H]1CC[C@@H]2CO
Agent: [K+]
Solvent: CI
Solvent: CC(C)(C)O
Product: CC1=C2CC[C@H]3[C@@H]4CC[C@H](CO)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Reaction time: 3 h

Procedure:
A mixture of potassium t-butoxide (5 g) in 100 ml t-butanol is heated to reflux. A solution of 3-oxo-17β-(hydroxymethyl)-4-androstene (10 g) in t-butanol is added followed by a solution of methyl iodide (2.7 g) in t-butanol. Heating is continued for 3 hours. The mixture is then cooled, acidified, and extracted with dichloromethane. The dichloromethane solution is washed with brine, dried, and concentrated to yield 3-oxo-17β-(hydroxymethyl)-4-methyl-4-androstene.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[F:14][C:15]([F:26])([F:25])[C:16]1[C:24]2[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=2[NH:18][N:17]=1.N[C@@H]1CCCC[C@H]1N.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Cu]I>[CH3:12][N:11]([CH3:13])[S:8]([C:5]1[CH:6]=[CH:7][C:2]([N:18]2[C:19]3[CH2:20][CH2:21][CH2:22][CH2:23][C:24]=3[C:16]([C:15]([F:14])([F:26])[F:25])=[N:17]2)=[CH:3][CH:4]=1)(=[O:10])=[O:9]
Reactant: FC(F)(F)c1n[nH]c2c1CCCC2
Reactant: CN(C)S(=O)(=O)c1ccc(I)cc1
Agent: [Cu]I
Agent: N[C@@H]1CCCC[C@H]1N
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CN(C)S(=O)(=O)c1ccc(-n2nc(C(F)(F)F)c3c2CCCC3)cc1
Temperature: 180 °C
Reaction time: 0.75 h
Yield: 34.8 %

Procedure:
A mixture of 4-iodo-N,N-dimethylbenzenesulfonamide (156 mg, 0.5 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (105 mg, 0.55 mmol), copper (I) iodide (1 mol %, 1 mg, 0.005 mmol), trans-1,2-diaminocyclohexane (10 mol %, 6 mg, 0.05 mmol) and potassium carbonate (145 mg, 1.05 mmol) in 1,4-dioxane (1 ml) was stirred at 180° C. in a microwave reactor for 45 minutes. The reaction mix was cooled and added to a 5 g pre-packed silica column which was then eluted from ethyl acetate, the product was further purified by mass directed auto-prep to give a crop of the title compound as a pale beige solid (65 mg, 35%).
Reaction SMILES: C([O:3][C:4](=[O:31])[C:5]1[CH:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]2([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][C:20]3[C:19]([CH3:23])([CH3:22])[CH2:18][CH2:17][C:16]([CH3:25])([CH3:24])[C:15]=3[CH2:14]2)=[CH:7][CH:6]=1)C.[OH-].[K+].C1COCC1>C(O)C.O>[CH3:23][C:19]1([CH3:22])[CH2:18][CH2:17][C:16]([CH3:24])([CH3:25])[C:15]2[CH2:14][C:13]([CH:12]=[CH:11][C:8]3[CH:7]=[CH:6][C:5]([C:4]([OH:31])=[O:3])=[CH:10][CH:9]=3)([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][C:20]1=2
Reactant: CCCCCC1(/C=C/c2ccc(C(=O)OCC)cc2)CC2=C(C1)C(C)(C)CCC2(C)C
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: CCCCCC1(C=Cc2ccc(C(=O)O)cc2)CC2=C(C1)C(C)(C)CCC2(C)C
Yield: 61.2 %

Procedure:
The ester (0.7 g) was dissolved in 10 ml of ethanol and treated with a solution of 1.8 g of KOH in 5 ml of water. After having added 4 ml of THF, the reaction mixture was reacted for 3 hours at 40° C., poured on ice/water, acidified with 2N HCL and extracted with ethyl acetate. The organic phase was dried (Na2SO4), the solvent evaporated, and the crystalline residue recrystallized from pentane to give 0.4 g of 4-[2-(4,4,7,7-tetramethyl-2-pentyl-2,3,4,5,6,7-hexahydro-1H-indene-2-yl)-vinyl]-benzoic acid as colorless crystals, m.p. 121-123° C.
Reaction SMILES: [CH3:1][C:2](=[O:7])[CH2:3][C:4](=[O:6])[CH3:5].Br[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:4]([CH:3]([C:2](=[O:7])[CH3:1])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(=[O:6])[CH3:5]
Reactant: CCOC(=O)CBr
Reactant: CC(=O)CC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)CC(C(C)=O)C(C)=O
Reaction time: 18 h
Yield: 56.9 %

Procedure:
A solution of 28.2 ml (0.275 moles) of 2,4-pentanedione and 27.7 ml (0.25 moles) of ethyl bromoacetate in 50 ml of acetone was stirred under nitrogen while 38.0 g (0.275 moles) of dry potassium carbonate, predried at 100° C. under vacuum for 18 hours, was added. The mixture was heated to reflux for 4.5 hours. After cooling, the mixture was separated by filtration and the solid was washed with two portions of 50 ml of acetone. The filtrate was concentrated to dryness, dissolved in methylene chloride, filtered through Fluorosil, concentrated under vacuum to dryness, leaving a residual oil which was distilled. The fraction distilling at 48°-52° C. at 0.05 mm pressure was collected and 26.5 g of ethyl 3-acetyl-4-oxopentanoate were obtained.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]#[CH:6])[CH3:3].C(=O)([O-])[O-].[Na+].[Na+].Br[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1>C(O)C.C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH3:1][N:2]([CH3:3])[CH2:4][C:5]#[C:6][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1
Reactant: C#CCN(C)C
Reactant: Brc1cccnc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: COCCOC
Product: CN(C)CC#Cc1cccnc1
Temperature: 90 °C
Reaction time: 1 h
Yield: 4.1 %

Procedure:
To a pressure tube containing a magnetic stir bar was added N,N-dimethylpropargylamine (333 mg, 4 mmol) and the vial was purged with argon. To the tube is added a solution of tetrakis(triphenylphosphine)palladium(0) (139 mg, 0.12 mmol) in ethanol/dimethoxyethane (1:1, 2 mL), sodium carbonate(aq) (2 M, 4 mL, 4 mmol), copper(I)iodide (46 mg, 0.24 mmol) and the vial was once again purged with argon. The resultant solution was stirred at room temperature for 5 min when 3-bromopyridine (483 μL, 5 mmol) was added as a neat oil. The tube was purged with argon, capped, heated to 90° C. and stirred for 1 h. The solution was cooled to room temperature and poured into a flask containing anhydrous sodium sulfate (5 g). The solution was dried for 10 min, filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH3OH/CHCl3, 10/90, Rf=0.13) to afford the title compound 51 (26 mg, 4% yield) as a brown oil: 1H NMR (CDCl3) δ 8.67 (br s, 1H), 8.52 (m, 1H), 7.72 (m, 1H), 7.24 (m, 1H), 3.49 (s, 2H), 2.37 (s, 6H); LRMS (ESI) m/z calcd for C10H12N2 [M+H]+ 161. found 161; LRMS (ESI) m/z calcd for C8H6N [M−N(CH3)2]+ 116. found 116; HRMS (ESI) m/z calcd for C10H12N2 [M+H]+ 161.1079. found 161.1090; HPLC>98% (tR=9.38 min, 60 (A):40 (B): 0.02 (C); tR=4.70 min, 60 (A):40 (B): 0.07 (C)).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[O:17][C:16](=[O:18])[NH:15][C:14]2=[O:19])=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:23][C:24]1[N:25]=[C:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:27][C:28]=1[CH3:29].Cl>CN(C)C=O.O>[CH3:29][C:28]1[O:27][C:26]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[N:25][C:24]=1[CH2:23][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[O:17][C:16](=[O:18])[NH:15][C:14]2=[O:19])=[CH:4][CH:3]=1
Reactant: O=C1NC(=O)C(CCCCCc2ccc(O)cc2)O1
Reactant: Cc1oc(-c2ccccc2)nc1CCl
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CCCCCC2OC(=O)NC2=O)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 57.9 %

Procedure:
To a solution of 5-[5-(4-hydroxyphenyl)pentyl]-2,4-oxazolidinedione (0.9 g) in N,N-dimethylformamide (DMF) (40 ml) was added sodium hydride (60% in oil, 0.28 g). The mixture was stirred for 15 minutes at room temperature, to which was then added 4-chloromethyl-5-methyl-2-phenyloxazole (0.85 g), and the mixture was stirred for 2 hours at 70° C. The reaction mixture was poured into water, acidified with 2N HCl, and subjected to extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and then the solvent was distilled off. The oily residue was subjected to a silica gel column chromatography. From the fractions eluted with ethyl acetate-chloroform (.1:5, v/v) was obtained 5-[5-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]pentyl]-2,4-oxazolidinedione (0.86 g, 58%). Recrystallization from dichloromethane-isopropyl ether gave colorless prisms, m.p.120-121° C.