Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1](Cl)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C@@H:19]1([N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[O:26][C@H:23]([CH2:24][OH:25])[C@@H:21]([OH:22])[CH2:20]1.N1C=CN=C1.C(Cl)Cl>CN(C)C=O.CO>[CH3:15][C:14]([Si:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[O:25][CH2:24][C@H:23]1[O:26][C@@H:19]([N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[CH2:20][C@@H:21]1[OH:22])([CH3:17])[CH3:16]
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CO
Solvent: ClCCl
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 2.33 h
Yield: 62.4 %

Procedure:
1.43 ml (5.5 mmol) of t-butyldiphenylsilyl chloride were added to a solution of 1.21 g (5 mmol) of thymidine and 0.749 g (11 mmol) of imidazole in 10 ml of dimethylformamide under an atmosphere of argon, and the resulting mixture was stirred at room temperature for 140 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure, and the resulting residue was dissolved in 100 ml of methylene chloride. The solution was then washed 5 times, each time with 100 ml of water. The solution was then dried over anhydrous magnesium sulfate, after which the solvent was distilled off under reduced pressure. The residue was purified by column chromatography through 100 g of silica gel (70-230 mesh) using a gradient elution method, with methylene chloride containing from 0.5 to 3% by volume of methanol as the eluent, to give 1.5 g (yield 62%) of the title compound.
Reaction SMILES: [OH-].[Li+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH:14]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[N:13]([CH2:24][C:25]([O:27]C)=[O:26])[C:12](=[O:29])[C@H:11]1[CH2:30][CH:31]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl>O.C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH:14]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[N:13]([CH2:24][C:25]([OH:27])=[O:26])[C:12](=[O:29])[C@H:11]1[CH2:30][CH:31]1[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: COC(=O)CN1C(=O)[C@@H](CC2CCCCCC2)N(C(=O)OC(C)(C)C)CC1c1cc(F)cc(F)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CC(c2cc(F)cc(F)c2)N(CC(=O)O)C(=O)[C@H]1CC1CCCCCC1

Procedure:
29 mg (1.2 mmol) lithium hydroxide in 1.0 ml of water were added to 0.53 g (1.1 mmol) (2R)-tert-butyl-2-(cycloheptylmethyl)-5-(3,5-difluorophenyl)-4-(2-methoxy-2-oxoethyl)-3-oxopiperazine-1-carboxylate (isomer 3.1.1) in 5 ml THF. After 2 h at RT the mixture was neutralised with 0.1 M hydrochloric acid solution. The reaction mixture was evaporated to dryness by rotary evaporation.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH2:7][O:8][C:9]2[N:14]=[N:13][C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=2)=[C:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[N:4]=[N:3]1.[CH:24]([NH2:27])([CH3:26])[CH3:25]>>[CH:24]([NH:27][C:15]([C:12]1[N:13]=[N:14][C:9]([O:8][CH2:7][C:6]2[N:2]([CH3:1])[N:3]=[N:4][C:5]=2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:10][CH:11]=1)=[O:17])([CH3:26])[CH3:25]
Reactant: Cn1nnc(-c2ccccn2)c1COc1ccc(C(=O)O)nn1
Reactant: CC(C)N
Product: CC(C)NC(=O)c1ccc(OCc2c(-c3ccccn3)nnn2C)nn1
Yield: 91 %

Procedure:
As described for example 48b, 6-(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-ylmethoxy)-pyridazine-3-carboxylic acid (98 mg, 0.31 mmol) was converted, using isopropylamine instead of 4-aminotetrahydropyran, to the title compound (101 mg, 91%) which was obtained as an off white solid. MS: m/e=354.2 [M+H]+.
Reaction SMILES: [C:1]([CH2:3][CH2:4][O:5][C:6](=[O:23])[C:7](=[CH:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[C:8](=O)[CH2:9][CH2:10][CH3:11])#[N:2].[NH2:24][C:25]([CH2:37][CH2:38][CH3:39])=[CH:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>CCO>[CH2:30]([O:29][C:27]([C:26]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)[C:7]([C:6]([O:5][CH2:4][CH2:3][C:1]#[N:2])=[O:23])=[C:8]([CH2:9][CH2:10][CH3:11])[NH:24][C:25]=1[CH2:37][CH2:38][CH3:39])=[O:28])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: CCCC(N)=CC(=O)OCc1ccccc1
Reactant: CCCC(=O)C(=Cc1ccc([N+](=O)[O-])cc1)C(=O)OCCC#N
Solvent: CCO
Product: CCCC1=C(C(=O)OCCC#N)C(c2ccc([N+](=O)[O-])cc2)C(C(=O)OCc2ccccc2)=C(CCC)N1

Procedure:
A solution of 2-[(4-nitrophenyl)methylene]-3-oxohexanoic acid 2-cyanoethyl ester (9.80 g, 30 mmol) and benzyl 3-amino-2-hexenoate (7.24 g, 33 mmol) in 150 ml of EtOH was refluxed for 36 hrs. After the solvent was removed in vacuo, the residue was dissolved in 250 ml of CHCl3, washed with water (2×100 ml) and dried over Na2SO4. After filtration and evaporation of solvent, 5-benzyloxycarbonyl-3-(2-cyanoethoxy)carbonyl-1,4-dihydro-4-(4-nitrophenyl)-2,6-dipropylpyridine was obtained as a yellow oil (15.4 g, 97%).
Reaction SMILES: [CH3:1][N:2]([CH3:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)=[C:5]([CH3:15])[CH:4]=1.[CH3:17][I:18]>C(#N)C>[I-:18].[CH3:1][N:2]([CH3:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N+:12]([CH3:17])=[CH:11][CH:10]=2)=[C:5]([CH3:15])[CH:4]=1
Reactant: Cc1cc(N(C)C)ccc1-c1ccncc1
Reactant: CI
Solvent: CC#N
Product: Cc1cc(N(C)C)ccc1-c1cc[n+](C)cc1
Product: [I-]
Reaction time: 2 h

Procedure:
N,N,3-trimethyl-4-(pyridine-4-yl)aniline (0.2 g, 0.9 mmols) was dissolved in acetonitrile (50 ml) and methyl iodide (3 ml) was added. The mixture was heated at reflux with stirring for 2 hrs cooled and evaporated to a volume of 10 ml. Then diethyl ether (50 ml) was added and the product crystallized resulting in (0.068 g, 0.19 mmols) of 4-(4-(dimethylamino)-2-methylphenyl)-1-methylpyridinium iodide as a red solid. 1H NMR (DMSO-d6) δ 2.40 (s, 3H), 3.00 (s, 6H), 4.30 (s, 3H), 6.70 (m, 2H), 6.90 (d, 2H), 8.10 (d, 2H), 8.85 (d, 2H).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:21]([CH2:22][C:23]([O:25]CC)=[O:24])[N:20]=[C:19]([C:28]([F:31])([F:30])[F:29])[CH:18]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[OH-].[Li+]>C1COCC1.O>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:21]([CH2:22][C:23]([OH:25])=[O:24])[N:20]=[C:19]([C:28]([F:31])([F:29])[F:30])[CH:18]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])=[O:4]
Reactant: CCOC(=O)Cn1nc(C(F)(F)F)cc1-c1ccc(-c2cccc(S(C)(=O)=O)c2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CS(=O)(=O)c1cccc(-c2ccc(-c3cc(C(F)(F)F)nn3CC(=O)O)cc2)c1
Reaction time: 2 h
Yield: 117.8 %

Procedure:
To a stirred solution of 36 (1.3 g, 2.0 mmol) in THF (10.0 mL) at room temperature, was added a solution of lithium hydroxide (103 mg, 4.0 mmol) in water (10.0 mL) and stirring continued for 2 h. On completion, the solvent was removed and the reaction mixture diluted with water (20 mL) and washed with ether (30 mL×3). The aqueous layer was acidified with 1N HCl and extracted with 10% methanol in dichloromethane (50 mL×3). Combined organic layer was washed brine, dried over sodium sulphate and concentrated. The crude product after ether and pentane washing afforded 38 (1 g, 83%). LCMS: 425.15 (M+1)+; 1H NMR (DMSO-ds, 400 MHz) δ 13.3 (s, 1H), 8.24 (s, 2H), 8.12 (d, 1H, J=8 Hz), 7.78 (t, 1H, J=8 Hz), 7.67 (d, 1H, J=8.4 Hz), 7.04 (s, 1H), 5.13 (s, 1H), 3.25 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([CH2:14][NH2:15])[CH:11]=[CH:12][CH:13]=2)=[N:6][CH:7]=1.CN(C1C=CC=CN=1)C.[C:25](OC([O-])=O)([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].O>ClCCl.C(N(CC)CC)C>[C:28]([O:27][C:25](=[O:26])[NH:15][CH2:14][C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)[CH:9]=1)([CH3:31])([CH3:30])[CH3:29]
Reactant: NCc1cccc(-c2ccc(Br)cn2)c1
Reactant: CC(C)(C)OC(=O)OC(=O)[O-]
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)OC(=O)NCc1cccc(-c2ccc(Br)cn2)c1
Temperature: 40 °C
Reaction time: 8 h
Yield: 81.2 %

Procedure:
1.07 g (4 mmol, 1 eq) of [3-(5-bromopyrid-2-yl)phenyl]methylamine are dissolved in 10 mL of dichloromethane in the presence of 1 mL of triethylamine and 200 mg of dimethylaminopyridine. 1.7 g (8 mmol, 2 eq) of tert-butyl dicarbonate are added and the reaction mixture is stirred overnight at 40° C. The reaction is stopped by adding 30 ml of water and is then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate). 1.18 g of tert-butyl[3-(5-bromopyrid-2-yl)phenyl}methylcarbamate are obtained. Yield=81%.
Reaction SMILES: [Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=O)[C:18]3[C:13]4=[C:14]([O:28][CH2:29][CH2:30][N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:52])=CC=1.C1(C)C=CC=CC=1>ClC(Cl)C.C(Cl)Cl>[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[S:52])[C:18]3[C:13]4=[C:14]([O:28][CH2:29][CH2:30][N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1
Reactant: O=C(NCc1ccc(Cl)cc1)c1cn2c3c(cc(CN4CCOCC4)cc3c1=O)OCC2
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: CC(Cl)Cl
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: O=C(NCc1ccc(Cl)cc1)c1cn2c3c(cc(CN4CCOCC4)cc3c1=S)OCC2
Temperature: 25 °C
Yield: 3.9 %

Procedure:
A mixture of N-(4-Chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide (1.20 g, 2.64 mmol) of preparation 6 is dissolved in dichloroethane (160 mL) followed by the addition of KHMDS (0.5 M, 5.3 mL, 2.64 mmol, 1 equiv.). Then Lawesson's reagent (2.1 g, 5.28 mmol, 2.0 equiv) and toluene (160 mL) is added and the resulting mixture is heated at reflux for 24 h. The reaction is cooled to room temperature, diluted with DCM, washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (heptane/EtOAc 4/1, 1/1, 1/4, 0/1 then DCM/MeOH 19/1) and then repurified by silica gel chromatography (DCM/MeOH 11/0, 45/1, 9/1) to afford 48 mg of the title compound as a solid.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][C:4]=1[O:10][CH3:11].Br[CH2:13][CH:14]([CH3:16])[CH3:15].[CH3:17][C:18]1([CH3:31])[C@@H:20]2[CH2:21][C:22]3[C:26]([C@H:19]12)=[C:25]([CH3:27])[S:24][C:23]=3[C:28](O)=[O:29]>>[CH2:13]([O:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][C:28]([C:23]2[S:24][C:25]([CH3:27])=[C:26]3[C:22]=2[CH2:21][C@H:20]2[C:18]([CH3:31])([CH3:17])[C@H:19]23)=[O:29])=[C:4]([O:10][CH3:11])[CH:5]=1)[CH:14]([CH3:16])[CH3:15]
Reactant: CC(C)CBr
Reactant: Cc1sc(C(=O)O)c2c1[C@H]1[C@@H](C2)C1(C)C
Reactant: COc1cc(O)ccc1CN
Product: COc1cc(OCC(C)C)ccc1CNC(=O)c1sc(C)c2c1C[C@@H]1[C@H]2C1(C)C

Procedure:
(1aS,5aR)-1,1,2-Trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-isobutoxy-2-methoxy-benzylamide is prepared starting from 4-aminomethyl-3-methoxy-phenol, 1-bromo-2-methyl-propane and (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid in analogy to the procedures given in Example 36. LC-MS: tR=1.16 min, [M+1]+=414.17.
Reaction SMILES: [CH2:1]([NH:13][CH2:14][CH2:15][CH2:16][NH2:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[C:18]1(=O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>>[CH:18]1([NH:17][CH2:16][CH2:15][CH2:14][NH:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: O=C1CCCCC1
Reactant: CCCCCCCCCCCCNCCCN
Product: CCCCCCCCCCCCNCCCNC1CCCCC1

Procedure:
Following the general procedure of Example 33, but starting with N-dodecyl-1,3-propanediamine and cyclohexanone, the title compound is produced; IR nmax (neat) 3292, 2925, 2854, 2810, 1466, 1450, 1367, 1130 and 721 cm-1. (PLA2)
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:12]3[N:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[F:21][C:22]1[CH:23]=[CH:24][C:25](B2OC(C)(C)C(C)(C)O2)=[C:26]([CH:29]=1)[C:27]#[N:28]>>[F:21][C:22]1[CH:23]=[CH:24][C:25]([C:2]2[CH:7]=[C:6]([C:8]3[N:12]4[N:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]4=[N:10][CH:9]=3)[CH:5]=[CH:4][N:3]=2)=[C:26]([CH:29]=1)[C:27]#[N:28]
Reactant: CC1(C)OB(c2ccc(F)cc2C#N)OC1(C)C
Reactant: FC(F)(F)c1cnn2c(-c3ccnc(Cl)c3)cnc2n1
Product: N#Cc1cc(F)ccc1-c1cc(-c2cnc3nc(C(F)(F)F)cnn23)ccn1
Yield: 24 %

Procedure:
7-(2-Chloropyridin-4-yl)-3-trifluoromethylimidazo[1,2-b][1,2,4]triazine was reacted with 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile by a similar procedure to that described in Example 1, step g, to give the title compound in 24% yield: 1H NMR (400 MHz, CD Cl3) δ 7.48 (1H, ddd, J 2.7, 7.8, 8.6), 7.57 (1H, dd, J 2.7, 8.2), 8.01 (1H, dd, J 5.3, 8.8), 8.08 (1H, dd, J 1.8, 5.3), 8.63 (1H, dd, J 1.0, 1.8), 8.82 (1H, s), 8.92 (1H, s), 8.95 (1H, dd, J 1.0, 5.3).
Reaction SMILES: [B:1]([O:10]C(C)C)([O:6]C(C)C)[O:2][CH:3]([CH3:5])[CH3:4].[OH:14][C:15]([C:18]([OH:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>>[B:1]([OH:10])([OH:6])[OH:2].[CH:3]([CH2:16][C:15]([C:18]([OH:21])([CH3:20])[CH3:19])([CH3:17])[OH:14])([CH3:5])[CH3:4]
Reactant: CC(C)(O)C(C)(C)O
Reactant: CC(C)OB(OC(C)C)OC(C)C
Product: CC(C)CC(C)(O)C(C)(C)O
Product: OB(O)O
Temperature: 90 °C

Procedure:
To a 20 L four-neck bottle tri-isopropyl borate (261.0 g, 1.388 mol) and pinacol (142.5 g, 1.207 mol) were added and heated to ˜90° C. for 12-16 h. The criteria for a reaction completion is pinacol<4.0% by GC. After completion, the reaction was converted to distillation, and the product fractions (boiling at 174-178° C.) collected. Thus the title product was obtained as a colourless oil in a yield range of 80-90% th across the six 20 L batches which were operated. GC records purity of 87-96%, but 1H NMR shows the product to be very pure. [discrepancy due to product instability to GC conditions.]
Reaction SMILES: CC(O)(CCC(C)([OH:8])C)C.[CH3:11][C:12]1([CH3:24])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](C)(C)[CH2:14][CH2:13]1.CC1(C)[C:39]2[C:30](=[CH:31][C:32]3[C:33]([CH3:43])([CH3:42])[CH2:34][CH2:35][C:36](C)(C)[C:37]=3[CH:38]=2)C(C)(C)CC1.[Al+3].[Cl-].[Cl-].[Cl-]>>[C:12]([CH2:13][CH:14]([CH3:15])[OH:8])([CH3:24])([CH3:11])[C:21]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1.[CH3:42][C:33]1([CH3:43])[C:32]2[C:31](=[CH:30][CH:39]=[CH:38][CH:37]=2)[CH:35]([CH3:36])[CH2:34]1
Reactant: CC(C)(O)CCC(C)(C)O
Reactant: CC1(C)CCC(C)(C)c2cc3c(cc21)C(C)(C)CCC3(C)C
Reactant: CC1(C)CCC(C)(C)c2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Product: CC(O)CC(C)(C)c1ccccc1
Product: CC1CC(C)(C)c2ccccc21
Yield: 25 %
Yield: 20 %

Procedure:
"C6H6 concenses with (Me2C(OH) 2 only if 2-2.5 moles AlCl3 are used at 80°, yielding 8% 1,1,2-trimethyl-indan and some 50% Me2CAc. CH2 (CMe2OH)2 with 1.5 moles AlCl3 at 50°-70° yields 52.5% 1,1,3,3-tetramethyl-indan and 18% 1,2,3,5,6,7-hexahydro-1,1,3,3,5,5,7,7-octamethyl-indacene, m. 214°, while 2,5-dimethyl-2,5-hexanediol similarly gives 57.3% 1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene and 1,1,4,4,5,5,8,8-octamethyl-1,2,3,4,5,6,7,8-octahydroanthracene (20%). Reaction with MeCH-(OH)CH2C(OH)Me2 with 1.5 moles AlCl3 at 50°-60° gave 20% Me2CPhCH2CH(OH)Me and 25% 1,1,3-trimethyl-indan. Me2C(OH)CH2COMe with 2 moles AlCl3 at 20° gave 61% PhCH2CHMeCH2COMe and a little unknown product, m. 127°. The mechanism is probably analogous to that given for ROH (Byull. Sredneaziat. Gosudarst. Univ. No. 25, 45(1947), with additional possibility of intermediate formation of oxido structures."
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])[CH2:23][CH2:22][C:21]([C:33]([O:35]C)=[O:34])=[CH:20][C:19]=3[CH:37]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+].O.Cl>O1CCCC1.CO>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])[CH2:23][CH2:22][C:21]([C:33]([OH:35])=[O:34])=[CH:20][C:19]=3[CH:37]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3Cc2ccccc2F)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3Cc2ccccc2F)cc1
Temperature: 25 °C
Reaction time: 96 h
Yield: 83.2 %

Procedure:
To a solution of methyl 7-(4-butoxyethoxyphenyl)-1-(2-fluorobenzyl)-2,3-dihydro-1-benzazepine-4-carboxylate (382 mg) in a mixture of tetrahydrofuran (24 ml) and methanol (24 ml) was added 1N sodium hydroxide solution (8 ml), and the mixture was stirred at room temperature for 4 days. Then, to the mixture was added water at 0° C., and 1N hydrochloric acid was further added to make acidic (pH=4), and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, which was recrystallized from hexane-ethyl acetate to give 7-(4-butoxyethoxyphenyl)-1-(2-fluorobenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (309 mg) as yellow crystals.
Reaction SMILES: [ClH:1].Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([C:13]2[S:23][C:22]3[N:24]4[C:15](=[CH:16][N:17]=[C:18]4[CH:19]=[CH:20][CH:21]=3)[CH:14]=2)=[O:12])[CH2:5][CH2:4]1.C(N(CC)CC)C.S(O[CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)(=O)(=O)C>C(O)C>[ClH:1].[ClH:1].[O:39]([CH2:38][CH2:37][N:3]1[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([C:13]2[S:23][C:22]3[N:24]4[C:15](=[CH:16][N:17]=[C:18]4[CH:19]=[CH:20][CH:21]=3)[CH:14]=2)=[O:12])[CH2:5][CH2:4]1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
Reactant: CS(=O)(=O)OCCOc1ccccc1
Reactant: O=C(NCC1CCNCC1)C1=Cc2cnc3cccc(n23)S1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: O=C(NCC1CCN(CCOc2ccccc2)CC1)C1=Cc2cnc3cccc(n23)S1

Procedure:
Synthesis of N-[1-(2-phenoxyethan-1-yl)piperidin-4-ylmethyl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide Under nitrogen gas, 0.37 ml (4.78 mM) of methanesulfonyl chloride was added to a solution of 0.44 g (3.18 mM) of phenoxyethanol and 0.89 ml (6.39 mM) of triethylamine in methylene chloride (6 ml) at 0° C. and the mixture was stirred at the prevailing temperature for 35 minutes. The reaction was stopped by adding saturated aqueous solution of sodium hydrogen carbonate and the reaction mixture was extracted with diethyl ether. The organic layer was washed serially with water and saturated aqueous solution of sodium chloride and dried over MgSO4. The solvent was then distilled off under reduced pressure to provide 0.6989 g (<3.18 mM) of phenoxyethyl mesylate. To a solution of 0.58 g (1.5 mM) of N-(piperidin-4-ylmethyl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride and 1.0 ml (7.2 mM) of triethylamine in ethanol (6.0 ml) was added 0.6989 g (<3.18 mM) of the above phenoxyethyl mesylate at room temperature and the mixture was refluxed under nitrogen for 17 hours. The solvent was then distilled off under reduced pressure and the residue was diluted with water and extracted with chloroform. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4. The resulting crude product was purified by column chromatography (methanol/ethyl acetate 30-40%) to provide the title compound.
Reaction SMILES: [C:1]1([CH:7]([C:9]2[CH:10]=[N:11][C:12]3[C:17]([C:18]=2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:16][CH:15]=[CH:14][C:13]=3[C:25]([F:28])([F:27])[F:26])[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:36](Cl)(=[O:38])[CH3:37]>C(Cl)Cl>[C:36]([O:8][CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[C:25]([F:28])([F:26])[F:27])(=[O:38])[CH3:37]
Reactant: OC(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1ccccc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OC(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1ccccc1
Reaction time: 2 h
Yield: 79.1 %

Procedure:
Phenyl[4-phenyl-8-(trifluoromethyl)quinolin-3-yl]methanol (Example 34, 0.050 g, 0.132 mmol) was taken into CH2Cl2 (3 mL). Next, triethylamine (0.1 mL, 0.70 mmol) was added followed by acetyl chloride (0.05 mL, 0.70 mmol). The reaction was allowed to stir for 2 hours. The solvent was removed and the resulting material was taken up into an Ether/water/5% HCl solution. The layers were separated and the organic layer was washed once more with 5% HCl, dried over magnesium sulfate and concentrated. The product was purified via column chromatography using 7% ethyl acetate in hexane as the eluent to afford the product as a white solid (0.044 g, 79.4%). MS (ESI) m/z 422 ([M+H]+); Anal. Calcd. for C25H18F3NO2: C, 71.25; H, 4.31; N, 3.32. Found: C, 71.15; H, 4.11; N, 3.21.
Reaction SMILES: Cl.[NH2:2][O:3][CH2:4][CH3:5].[C:6]([CH:9]1[CH2:12][N:11]([C:13](=[O:27])/[CH:14]=[CH:15]/[C:16]2[CH:17]=[C:18]3[C:23](=[N:24][CH:25]=2)[NH:22][C:21](=[O:26])[CH2:20][CH2:19]3)[CH2:10]1)(=O)[CH3:7]>CO.ClCCl>[CH2:4]([O:3]/[N:2]=[C:6](\[CH:9]1[CH2:12][N:11]([C:13](=[O:27])/[CH:14]=[CH:15]/[C:16]2[CH:17]=[C:18]3[C:23](=[N:24][CH:25]=2)[NH:22][C:21](=[O:26])[CH2:20][CH2:19]3)[CH2:10]1)/[CH3:7])[CH3:5]
Reactant: CCON
Reactant: CC(=O)C1CN(C(=O)/C=C/c2cnc3c(c2)CCC(=O)N3)C1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CCO/N=C(/C)C1CN(C(=O)/C=C/c2cnc3c(c2)CCC(=O)N3)C1
Reaction time: 8 h

Procedure:
1-(Aminooxy)ethane hydrochloride (23 mg, 0.23 mmol) was added to a solution of (E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (50.0 mg, 0.16 mmol) in a mixture methanol/dichloromethane (8:2, 3.5 mL) at room temperature. The reaction mixture was stirred overnight. After concentration to dryness, the residue was purified by chromatography on silica gel using ethyl acetate/methanol (95:5) as eluent. The title product was obtained as a white solid (20 mg, 35%).
Reaction SMILES: [CH3:1][CH:2]([Si:4]([CH:16]([CH3:18])[CH3:17])([O:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1)[CH:5]([CH3:7])[CH3:6])[CH3:3].CN[C:21]1[N:26]=[C:25]([CH2:27][CH2:28]O)[CH:24]=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:49]([C:56](OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:7][CH:5]([Si:4]([CH:16]([CH3:18])[CH3:17])([O:8][C:9]1[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=1)[O:15][CH2:28][CH2:27][C:25]1[N:26]=[C:21]([CH2:56][NH2:49])[CH:22]=[CH:23][CH:24]=1)[CH:2]([CH3:1])[CH3:3])[CH3:6]
Reactant: CCOC(=O)N=NC(=O)OCC
Reactant: CNc1cccc(CCO)n1
Reactant: CC(C)[Si](Oc1cccc(O)c1)(C(C)C)C(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)[Si](Oc1cccc(OCCc2cccc(CN)n2)c1)(C(C)C)C(C)C
Reaction time: 8 h
Yield: 27.9 %

Procedure:
To a stirring solution of 3-[1,1-bis(methylethyl)-2-methyl-1-silapropoxy]phenol (200 mg,0.75 mmol),2-[6-(methylamino)-2-pyridyl]ethan-1-ol (104 mg, 0.68 mmol), triphenylphosphine (199 mg, 0.75 mmol) and THF (25 ml), was added diethyl azodicarboxylate (0.12 ml, 0.75 mmol) at 0° C. The reaction was stirred overnight under argon. The solvent was removed under vaccum and the crude product was chromatographed over silica gel to yield 76 mg (28%) of [6-(2-{3-[1,1-bis(Methylethyl)-2-methyl-1-silapropoxy]phenoxy}ethyl)(2-pyridyl)]methylamine. NMR 1H Cl3CD δ: 7.39 (m, 1H), 7.07 (t, 1H, J=8.0 Hz), 6.5 (m, 3H), 6.25 (d, 1H, J=8 Hz), 4.27 (t, 2H, J=6.8 Hz), 3.06 (t, 2H, J=6.8 Hz), 2.90 (d, 3H, J=8 Hz), 1.28 (m, 3H), 1.10 (d, 18H, J=7.0 Hz).