Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([Si](C)(C)C)[O:10][C:3]=12.[F-].[K+].[I:17]C1CC(=O)NC1=O.C(OC(=O)C)C>C(#N)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([I:17])[O:10][C:3]=12
Reactant: C[Si](C)(C)c1cc2nccc(Cl)c2o1
Reactant: O=C1CC(I)C(=O)N1
Agent: [F-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: O
Product: Clc1ccnc2cc(I)oc12
Temperature: 60 °C
Reaction time: 14 h

Procedure:
7-Chloro-2-trimethylsilanyl-furo[3,2-b]pyridine (185 g, 0.23 mol) is dissolved in ACN under nitrogen atmosphere. Then KF (47.6 g, 0.82 mol) and Iodosuccinimide (553.1 g, 0.25 mol) are added. The reaction mixture is stirred at 60° C. for 14 h and then cooled to room temperature. To the reaction mixture is added acetic acid ethyl ester (5 l) and water (5 l). The organic layer is separated, washed with sodiumthiosulfate (5 l) solution, then extracted with NaHCO3 solution and washed with brine. The organic layer is dried over Na2SO4. The drying agent is filtered and the solvent is removed in vacuum; yield: 133 g 7-chloro-2-iodo-furo[3,2-b]pyridine; HPLC/MS: 2.34 min, [M+H]=280;
Reaction SMILES: C([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:50])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:49])[CH2:12][CH2:13][C@@:14]3([C:30]([NH:32][C@@H:33]4[CH2:36][C@H:35]([C:37]([O:39]CC5C=CC=CC=5)=[O:38])[C:34]4([CH3:48])[CH3:47])=[O:31])[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:52])[CH3:51])(=O)C.[OH-].[Na+]>CO.C1COCC1>[OH:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:50])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:49])[CH2:12][CH2:13][C@@:14]3([C:30]([NH:32][C@@H:33]4[CH2:36][C@H:35]([C:37]([OH:39])=[O:38])[C:34]4([CH3:48])[CH3:47])=[O:31])[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:52])[CH3:51]
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)N[C@@H]3C[C@H](C(=O)OCc4ccccc4)C3(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(C)=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)N[C@@H]3C[C@H](C(=O)O)C3(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 25 °C
Reaction time: 6 h
Yield: 92 %

Procedure:
To a solution of (1S,3R)-benzyl 3-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxamido)-2,2-dimethylcyclobutanecarboxylate (Example 2, about 0.140 g, 0.196 mmol) in MeOH:THF (2:1) (6 ml) at 0° C., 2N NaOH (2 ml) was added and allowed to stir at room temperature for about 6 hours. After completion of the reaction (monitored by TLC), the solvent was evaporated and acidified with 2N HCl, the aqueous layer was extracted with ethyl acetate and dried with Na2SO4. The solvent was evaporated and purified by silica gel column (100-200 mesh, elution 50% EtOAc in hexane) to afford the title compound as an off white solid. Wt: 0.105 g: Yield: 92%. 1H NMR (300 MHZ, CDCl3): δ 5.64 (d, 1H, J=7.8 Hz), 4.72 (s, 1H), 4.58 (s, 1H), 4.15 (q, 1H, J=9.3 Hz), 3.18 (dd, 1H, J=5.1, 10.8 Hz), 3.14-3.08 (m, 1H), 2.71-2.64 (m, 1H), 2.52-2.41 (m, 1H), 2.40-2.28 (m, 1H), 2.10-1.88 (m, 4H), 1.78-1.64 (m, 9H), 1.62-1.51 (m, 3H), 1.49-1.41 (m, 4H), 1.39-1.32 (m, 7H), 1.28-1.22 (m, 4H), 0.98 (s, 3H), 0.97 (s, 3H), 0.96 (s, 3H), 0.93 (s, 3H), 0.81 (s, 3H), 0.75 (s, 3H); Mass: [M+1]+ 582 (10%), [M+Na]+ 604 (100%); IR (KBr, cm−1): 3454, 3407, 2949, 2869, 1716, 1709, 1642, 1459, 1243, 1191, 1009, 885, 787; M.R: 174.6° C.-187.0° C.; HPLC: 90.33%.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][C:10]([Br:15])=[CH:9][CH:8]=3.[H-].[Na+].[Br:18][C:19]1[CH:20]=[CH:21][C:22]2[N:23]([CH2:33][CH:34]3[CH2:36][O:35]3)[C:24]3[C:29]([C:30]=2[CH:31]=1)=[CH:28][C:27]([Br:32])=[CH:26][CH:25]=3>CN(C=O)C>[Br:15][C:10]1[CH:9]=[CH:8][C:7]2[N:6]([CH2:36][CH:34]([OH:35])[CH2:33][N:23]3[C:24]4[CH:25]=[CH:26][C:27]([Br:32])=[CH:28][C:29]=4[C:30]4[C:22]3=[CH:21][CH:20]=[C:19]([Br:18])[CH:31]=4)[C:5]3[C:13]([C:12]=2[CH:11]=1)=[CH:14][C:2]([Br:1])=[CH:3][CH:4]=3
Reactant: Brc1ccc2[nH]c3ccc(Br)cc3c2c1
Reactant: Brc1ccc2c(c1)c1cc(Br)ccc1n2CC1CO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: OC(Cn1c2ccc(Br)cc2c2cc(Br)ccc21)Cn1c2ccc(Br)cc2c2cc(Br)ccc21
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 34 %

Procedure:
3,6-Dibromocarbazole (0.050 g, 0.154 mmol) was dissolved in DMF (1.5 mL) and cooled to 0° C. NaH (60% dispersion in mineral oil, 0.007 g, 0.169 mmol) was added and the reaction was stirred for 45 min at 0° C. 3,6-Dibromo-9-(oxiran-2-ylmethyl)-9H-carbazole (0.059 g, 0.154 mmol) was added and the reaction was stirred at ambient temperature for 24 h. Upon consumption of the starting material by TLC, the reaction was partitioned between EtOAc and H2O. The aqueous layer was washed 3× with EtOAc, and the combined organics were washed with saturated aqueous NaCl, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by chromatography (SiO2, 0-50% EtOAc/Hexane) to afford the desired product (37 mg, 34%).
Reaction SMILES: I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:12])[CH2:6][CH2:5]2.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]#[CH:35])=[N:32][CH:33]=2)=[CH:24][CH:23]=1>>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]#[C:35][C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[N:7]([C:11]([O:13][CH2:14][CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:12])[CH2:6][CH2:5]4)=[N:32][CH:33]=2)=[CH:26][CH:27]=1
Reactant: O=C(OCCN1CCCC1)N1CCc2cc(I)ccc21
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Product: O=C(OCCN1CCCC1)N1CCc2cc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)ccc21

Procedure:
Prepared according to general working method I from 2-pyrrolidin-1-yl-ethyl 5-iodo-2,3-dihydro-indole-1-carboxylate (120 mg, 0.31 mmol) and 5-(4-chloro-phenyl)-2-ethynyl-pyridine (80 mg, 0.37 mmol).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:20]=[CH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]CCC.[OH2:30].[CH2:31]1[CH2:35][O:34][CH2:33][CH2:32]1>>[C:35]([OH:34])(=[O:30])[CH2:31][CH2:32][CH2:33][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: O
Reactant: C=CCCCCCCCC
Reactant: C1CCOC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCCCCCCCCCC(=O)O
Temperature: 50 °C
Reaction time: 8 h
Yield: 68 %

Procedure:
The [PdCl2 /CuCl2 /CO] complex was freshly prepared as described above. To this catalyst (0.16 mmol) was added a solution of triphenylphosphine (0.13 g, 0.50 mmol). The mixture was transferred to an autoclave (Hastelloy B, 100-mL). A solution of 1-decene (1.12 g, 8.0 mmol), H2O (1 mL), and THF (15 mL) was then added via syringe. The autoclave was purged with CO (2×500 psig) and was then pressurized with CO (500 psig). The reactor was agitated at 50° C. overnight. GC analysis of an aliquote showed a 1:1 mixture of 2-methyldecanoic acid and n-undecanoic acid in 70% conversion. The reactor was cooled to room temperature and CO pressure was released. Standard workup yielded undecanoic acid (1.0 g, 68% yield) as an oil.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][OH:12])=[N:9][CH:10]=1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>ClCCl>[CH3:22][S:23]([O:12][CH2:11][C:8]1[CH:7]=[CH:6][C:5]([O:4][CH2:3][C:2]([F:1])([F:13])[F:14])=[CH:10][N:9]=1)(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: OCc1ccc(OCC(F)(F)F)cn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCc1ccc(OCC(F)(F)F)cn1
Yield: 67.5 %

Procedure:
To a dichloromethane solution (2.8 mL) of [5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methanol (138 mg, 0.67 mmol), triethylamine (468 μL, 3.33 mmol) and methanesulfonyl chloride (77.4 μL, 1.00 mmol) were added at 0° C. and the resultant solution was stirred for 30 minutes. After completion of the reaction, the reaction solution was washed with saturated ammonium chloride aqueous solution and brine. The obtained organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a crude product (129 mg) of the title compound.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(OC([N:18]1[C:22]([NH2:23])=[CH:21][C:20]([CH2:24][CH2:25][C:26]2[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=2)=[N:19]1)=O)(C)(C)C.[F:36][CH:37]1[CH2:42][CH2:41][CH2:40][N:39]([CH2:43][C:44]2[CH:53]=[CH:52][C:47]([C:48](OC)=[O:49])=[CH:46][CH:45]=2)[CH2:38]1.C(=O)([O-])[O-]>C1COCC1.CC#N>[CH3:33][O:32][C:30]1[CH:31]=[C:26]([CH2:25][CH2:24][C:20]2[NH:19][N:18]=[C:22]([NH:23][C:48](=[O:49])[C:47]3[CH:46]=[CH:45][C:44]([CH2:43][N:39]4[CH2:40][CH2:41][CH2:42][CH:37]([F:36])[CH2:38]4)=[CH:53][CH:52]=3)[CH:21]=2)[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=1
Reactant: COc1cc(CCc2cc(N)n(C(=O)OC(C)(C)C)n2)cc(OC)c1
Reactant: COC(=O)c1ccc(CN2CCCC(F)C2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: C1CCOC1
Product: COc1cc(CCc2cc(NC(=O)c3ccc(CN4CCCC(F)C4)cc3)n[nH]2)cc(OC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 15.9 %

Procedure:
A solution of NaHMDS in THF (1 M, 0.86 ml, 0.86 mmol, 1.5 eq) was added dropwise at ambient temperature to a mixture of tert-butyl-5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate (200 mg, 0.58 mmol, 1 eq) and methyl 4-[(3-fluoro-1-piperidyl)methyl]benzoate (174 mg, 0.69 mmol, 1.2 eq) in THF (1 ml). The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was then concentrated and the crude product was purified by reverse-phase prep. HPLC (acidic) using a gradient of acetonitrile in water containing 0.1% TFA. The clean fractions were taken and evaporated. The residue was dissolved in 3:1 DCM:MeCN mixture (4 ml) and MP-carbonate (2.74 mmol/g, 1 g, 2.74 mmol) was added. The mixture was stirred for 4 h, filtered and the filtrate evaporated to afford the title compound as a pale yellow gum (43 mg, 16% yield); 1H NMR (399.902 MHz, DMSO) δ□ 1.46-1.34 (2H, m), 1.82-1.61 (2H, m), 2.36-2.28 (2H, m), 2.66-2.56 (2H, m), 2.81 (4H, s), 3.50 (2H, s), 3.65 (6H, s), 4.66-4.47 (1H, m), 6.26-6.24 (1H, m), 6.35 (2H, d), 6.40 (1H, s), 7.32 (2H, d), 7.88 (2H, d), 10.51 (1H, br.s), 12.07 (1H, br.s). MS: m/z 467 (MH+)
Reaction SMILES: [C:1](PCC1C(CPC(C)(C)C)=CC=CC=1)(C)(C)C.CS(O)(=O)=O.[C:24]([O-:44])(=[O:43])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][C@@H:35]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[OH:36]>CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:24]([O:44][CH3:1])(=[O:43])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][C@@H:35]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[OH:36]
Reactant: CC(C)(C)PCc1ccccc1CPC(C)(C)C
Reactant: CCCCCC[C@@H](O)C/C=C\CCCCCCCC(=O)[O-]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CS(=O)(=O)O
Solvent: CO
Product: CCCCCC[C@@H](O)C/C=C\CCCCCCCC(=O)OC
Temperature: 65 °C

Procedure:
In a second experiment, Pd(OAc)2 (6.5 mg, 0.029 mmol) and α,α′-di-tert-butylphosphino-o-xylene (59 mg, 0.15 mmol) were dissolved in 30 mL of dry methanol. Subsequently, methanesulfonic acid (20 μL, 0.3 mmol) and ricinoleate (290 mmol). The reaction was allowed to proceed at reflux (i.e. at a temperature of around 65° C.) for 24 h (conv. 80%), and then an identical amount of freshly prepared catalyst was added to the reaction mixture. After another 24 h of reflux, the reaction had reached completion and the mixture was allowed to cool down to room temperature and the crystals were filtered off and washed with methanol. The reaction mixture was analyzed with GC and showed only methyl-12-oxo-stearate.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]3=[C:7]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[NH:8][C:9]([CH:10]=1)=[C:5]23.[CH3:22][C:23]1[N:24]=[N:25][S:26][C:27]=1[C:28](O)=[O:29].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O.C(OCC)C>[O:21]=[C:20]1[C:4]2[C:5]3[C:6](=[C:7]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[NH:8][C:9]=3[CH:10]=[C:2]([NH:1][C:28]([C:27]3[S:26][N:25]=[N:24][C:23]=3[CH3:22])=[O:29])[CH:3]=2)[CH:17]=[N:18][NH:19]1
Reactant: Cc1nnsc1C(=O)O
Reactant: Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: Cc1nnsc1C(=O)Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
Yield: 31.5 %

Procedure:
Preparation of example 16 from the title compound of Example 7 (15 mg, 0.054 mmol), 4-methyl-[1,2,3]thiadiazole-5-carboxylic acid (8 mg, 0.062 mmol), triethylamine (0.030 mL, 0.22 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (25 mg, 0.065 mmol) in N,N-dimethylformamide (1.0 mL) was carried out analogously to Example 11. Additional 4-methyl-[1,2,3]thiadiazole-5-carboxylic acid (1.0 mg, 0.006 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.0 mg, 0.006 mmol) were added after c.a. 18 hours to drive the reaction to completion. Silica gel chromatography, also in an analogous manner, followed by diethyl ether trituration afforded the title compound (7 mg, 0.017 mmol) as a yellow powder in 32% yield.
Reaction SMILES: [OH:1][CH2:2][CH2:3][P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6].Cl[CH2:11][CH2:12][S:13](Cl)(=[O:15])=[O:14]>N1C=CC=CC=1>[CH:12]([S:13]([O:1][CH2:2][CH2:3][P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6])(=[O:15])=[O:14])=[CH2:11]
Reactant: O=S(=O)(Cl)CCCl
Reactant: COP(=O)(CCO)OC
Solvent: c1ccncc1
Product: C=CS(=O)(=O)OCCP(=O)(OC)OC

Procedure:
Dimethyl 2-vinylsulfonyloxyethylphosphonate was prepared in the same way as in Example 1 from 3.8 g of dimethyl 2-hydroxyethylphosphonate, 1.9 g of pyridine and 4.0 g of 2-chloroethylsulfonyl chloride. The yield was 20 mol%. The NMR spectrum (CDCl3) of this product was as follows:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[CH:9])=[CH:4][CH:3]=1.[CH:10]([C@@H:12]1[N:16]([CH3:17])[C:15](=[O:18])[CH2:14][C@@H:13]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:11].N1C=CC=CC=1>[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C@H:10]([C@@H:12]2[N:16]([CH3:17])[C:15](=[O:18])[CH2:14][C@@H:13]2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[OH:11])=[CH:4][CH:3]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]\[C@H:10]([C@@H:12]2[N:16]([CH3:17])[C:15](=[O:18])[CH2:14][C@@H:13]2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[OH:11])=[CH:4][CH:3]=1
Reactant: CN1C(=O)C[C@H](c2ccccc2)[C@@H]1C=O
Reactant: C#Cc1ccc(F)cc1
Agent: [Pd]
Solvent: c1ccncc1
Product: CN1C(=O)C[C@H](c2ccccc2)[C@@H]1[C@H](O)/C=C\c1ccc(F)cc1
Product: CN1C(=O)C[C@H](c2ccccc2)[C@@H]1[C@H](O)C#Cc1ccc(F)cc1
Reaction time: 8 h
Yield: 100 %

Procedure:
(±)-(4R*,5R*)-5-[(1R*)-3-(4-Fluorophenyl)-1-hydroxyprop-2-ynyl]-1-methyl-4-phenylpyrrolidin-2-one was prepared from 4-fluorophenylacetylene and Intermediate Z using a method analogous to that described for Example 8. To a 300 mg (0.93 mmol)slurry of this compound in hexanes (60 mL) was added Pd on CaCO3 (80 Mg), followed by pyridine (0.23 mL, 2.8 mmol). The reaction mixture was stir-red overnight, then filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure to give (±)-(4R*,5R*)-5-[(2Z)(1R*)-3-(4-fluorophenyl)-1-hydroxyprop-2-enyl]-1-methyl-4-phenylpyrrolidin-2-one (302 mg, 100%) as a white solid: mp 163-165° C.; 1H NMR (CD3OD) δ 2.36 (dd, J=15.8, 7.8 Hz, 1H), 3.01-3.17 (m, 4H), 3.80-3.90 (m, 2H), 4.33 (d, J=8.7 Hz, 1H), 5.74 (dd, J=11.6, 8.8 Hz, 1H), 6.34 (d, J=11.6 Hz, 1H), 6.85-6.97 (m, 4H), 7.18-7.36 (m, 5H).
Reaction SMILES: [OH:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([O:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][C:3]1([CH3:20])[CH3:19].[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[C:11]([O:10][CH:5]1[CH2:6][C:7]([CH3:9])([CH3:8])[N:2]([O:1][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:3]([CH3:20])([CH3:19])[CH2:4]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1O
Product: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1OC(=O)c1ccccc1
Yield: 83 %

Procedure:
Using 1-hydroxy-4-benzoyloxy-2,2,6,6-tetramethylpiperidine, prepared as described by: Kurumada T. et. al., loc. cit., and benzoyl chloride in a procedure otherwise similar to that for preparing the compound 101 gives an 83% yield of the compound 111 which is obtained in the form of colourless crystals; melting point. 138-140° C. (toluene/hexane).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1)=O.N1([C:20]2[CH2:24][CH2:23][CH2:22][CH:21]=2)CCCC1.Cl.[OH2:26]>C1C=CC=CC=1>[O:26]=[C:20]1[CH2:24][CH2:23][CH2:22][C:21]1=[CH:1][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1
Reactant: CCOC(=O)Cc1ccc(C=O)cc1
Reactant: C1=C(N2CCCC2)CCC1
Reactant: O
Agent: Cl
Solvent: c1ccccc1
Product: CCOC(=O)Cc1ccc(C=C2CCCC2=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3.7 g of ethyl p-formylphenylacetate, 5.2 g of pyrrolidinocyclopentene and 20 ml of benzene was heated under reflux for 13 hours. After cooling, 5 ml of conc. hydrochloric acid and 5 ml of water were added to the reaction mixture and the resulting mixture was stirred at room temperature overnight. To the mixture added 100 ml of benzene, a benzene layer was separated, washed with water and dried over anhydrous sodium sulfate. Thereafter, the benzene was distilled off and the residue was subjected to a silica gel column chromatography. Elution was effected with benzene-ethyl acetate 50:1 to give an oily substance, which was then distilled under reduced pressure to afford 0.5 g of an oily substance having a boiling point of 175°-180° C./0.3 mmHg (bath temp.).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1.[NH:18]1[CH:22]=[CH:21][N:20]=[CH:19]1.C1C=CC=CC=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O.CC1C=CC=CC=1C>[N:18]1([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=2)[CH:22]=[CH:21][N:20]=[CH:19]1
Reactant: c1c[nH]cn1
Reactant: CC(C)(C)OC(=O)NCCc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: O
Solvent: Cc1ccccc1C
Solvent: c1ccccc1
Product: CC(C)(C)OC(=O)NCCc1ccc(-n2ccnc2)cc1
Temperature: 120 °C
Reaction time: 96 h

Procedure:
Tert-butyl 2-(4-bromophenyl)ethylcarbamate (500 mg, 1.67 mmol), imidazole (170 mg, 2.50 mmol), (CuOTf)2.PhH (84 mg, 0.17 mmol), 1,10-Phenanthroline (360 mg, 2.00 mmol), dba (39 mg, 0.17 mmol), and Cs2CO3 (650 mg, 1.99 mmol) were mixed together in a flask and o-xylene (10 mL) was added. Resulting solution was heated to 120° C. and stirred for four days. Reaction mixture was then cooled, poured into water (20 mL) and extracted with EtOAc (3×20 mL). Combined organics were washed with water (1×20 mL) and brine (2×20 mL), dried over sodium sulfate, filtered, and concentrated Crude product was purified by flash chromatography eluting with 25% Hexanes in EtOAC to pure EtOAc to give tert-butyl 2-[4-(1H-imidazol-1-yl)phenyl]ethylcarbamate.
Reaction SMILES: [C:1]1(=[O:11])C2C(=CC=CC=2)C=[CH:3][CH2:2]1.[C:12]1([OH:23])[C:21]2[CH2:20][CH2:19][CH:18]([OH:22])[CH2:17][C:16]=2[CH:15]=[CH:14][CH:13]=1>>[O:11]1[CH2:1][CH:2]1[CH2:3][O:23][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[CH2:20][CH2:19][CH:18]([OH:22])[CH2:17]2
Reactant: O=C1CC=Cc2ccccc21
Reactant: Oc1cccc2c1CCC(O)C2
Product: OC1CCc2c(cccc2OCC2CO2)C1

Procedure:
Employing the procedure of Example 3a, but substituting a 6-alkoxy-1-tetralone as shown in the left hand (first) column of Table II for 6-methoxy-1-tetralone, a 6-alkoxy-1-naphthol is produced, which is converted as per Example 3b to the corresponding 5-hydroxy-3,4-dihydro-2(1H)-naphthalenenone shown in the middle column of Table II; employing the procedure of Example 3c the naphthalenone is converted to the corresponding 5,6,7,8-tetrahydro-1,6-naphthalenediol which is reacted with an epoxide of the structure ##STR52## in accordance with the procedure of Example 3d to form the corresponding 1,2,3,4-tetrahydro-5-[2,3-epoxy-propoxy]-2-naphthol which is reacted with an amine of the structure ##STR53## in accordance with the procedure of Example 3e to form the corresponding 1,2,3,4-tetrahydro-5-[2-hydroxy-3-(R1, R2 -substituted amino)propoxy]-2-naphthol (formula I) as shown in the right hand (third) column of Table II.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][CH:5]=[C:6](Cl)[C:7]=1[Cl:8].C(N(C(C)C)C(C)C)C.[NH:19]1[CH2:22][CH:21]([C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH:35]3[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]3)(=[O:34])=[O:33])=[CH:28][CH:27]=2)=[O:24])[CH2:20]1>CN(C)C=O.O>[Cl:8][C:7]1[C:6]([N:19]2[CH2:22][CH:21]([C:23]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([S:32]([CH:35]4[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH2:40]4)(=[O:34])=[O:33])=[CH:30][CH:31]=3)=[O:24])[CH2:20]2)=[CH:5][N:4]=[N:3][C:2]=1[Cl:1]
Reactant: Clc1cnnc(Cl)c1Cl
Reactant: CC(C)(C)OC(=O)N1CCC(S(=O)(=O)c2ccc(NC(=O)C3CNC3)cc2)CC1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(S(=O)(=O)c2ccc(NC(=O)C3CN(c4cnnc(Cl)c4Cl)C3)cc2)CC1
Reaction time: 8 h

Procedure:
To 3,4,5-trichloropyridazine (1.624 g, 8.85 mmol) and N-ethyl-N-isopropylpropan-2-amine (2.289 g, 17.71 mmol) in 50 mL N,N-dimethylformamide at 0° C. was added tert-butyl 4-(4-(azetidine-3-carboxamido)phenylsulfonyl)piperidine-1-carboxylate (2.5 g, 5.90 mmol) in 10 ml N,N-dimethylformamide, dropwise. The reaction mixture was stirred from 0° C. to room temperature overnight, diluted with water and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, concentrated and purified by flash chromatography to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][C:5]2[C:6]3[C:21](=[O:22])[NH:20][C:19]([CH3:23])=[N:18][C:7]=3[CH2:8][N+:9]([O-])=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.[C:26]([O:29]C(=O)C)(=[O:28])[CH3:27]>>[C:26]([O:29][CH:8]1[C:7]2[N:18]=[C:19]([CH3:23])[NH:20][C:21](=[O:22])[C:6]=2[C:5]2[CH:24]=[CH:25][C:2]([Cl:1])=[CH:3][C:4]=2[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:9]1)(=[O:28])[CH3:27]
Reactant: Cc1nc2c(c(=O)[nH]1)-c1ccc(Cl)cc1C(c1ccccc1)=[N+]([O-])C2
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OC1N=C(c2ccccc2)c2cc(Cl)ccc2-c2c1nc(C)[nH]c2=O

Procedure:
A mixture of 0.5 g (1.4 mmol) of 9-chloro-3-methyl-7-phenyl-5H-pyrimido[4,5-d][2]benzazepin-1(2H)-one 6-oxide and 10 mL of acetic anhydride was heated on a steam bath for 3 hr. The reaction mixture was concentrated at reduced pressure and the crystalline product separated. Recrystallization from methylene chloride gave the product as cream colored crystals, mp >320°.