Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([C:14]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])=[O:15])=[CH:12][C:11]([C:26]([F:29])([F:28])[F:27])=[N:10]2)[CH:6]=[CH:7][CH:8]=1.FC1C=CC2NC(=O)N([C:40](=[S:51])[C@H:41]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH3:42])C=2C=1>CN(C=O)C.O>[CH3:25][O:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][NH:16][C:14]([C:13]1[N:9]([C:5]2[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=2)[CH2:2][NH:1][C:40](=[S:51])[C@@H:41]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:48])([CH3:47])[CH3:49])[CH3:42])[N:10]=[C:11]([C:26]([F:28])([F:29])[F:27])[CH:12]=1)=[O:15]
Reactant: C[C@@H](NC(=O)OC(C)(C)C)C(=S)n1c(=O)[nH]c2ccc(F)cc21
Reactant: COc1ccccc1CNC(=O)c1cc(C(F)(F)F)nn1-c1cccc(CN)c1
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccccc1CNC(=O)c1cc(C(F)(F)F)nn1-c1cccc(CNC(=S)[C@H](C)NC(=O)OC(C)(C)C)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 38.6 %

Procedure:
To a solution of 58 (62 mg, 0.153 mmol) in dry DMF (0.3 mL) at 0° C. was added (R)-tert-butyl 1-(6-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-1-thioxopropan-2-ylcarbamate (57.2 mg, 0.169 mmol; J. Med. Chem.1999, 42, 2046-2052) in two equal portions over 10 minutes and the reaction was stirred at 0° C. for 2 hours and then at room temperature for 16 h. It was then diluted with water (˜15 mL) and extracted into dichloromethane using an “IST phase-separator.” The DCM extracts were combined and concentrated and the crude material purified by silica gel chromatography (Biotage 12M, 20% to 30% to 40% ethyl acetate in hexanes) to give 134 (35 mg, 0.059 mmol, 38.6% yield) as white solid. LRMS(ESI): (calc.) 529.3 (found) 614.3 (MNa)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.NN>CO.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(Cc2ccc([N+](=O)[O-])cc2)CC1
Agent: NN
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(Cc2ccc(N)cc2)CC1
Temperature: 25 °C
Yield: 97 %

Procedure:
To the solution of 1-tert-butoxycarbonyl-4-(4-nitrobenzyl)piperidine (4.53 g, 14.2 mmol) in methanol-tetrahydrofuran (1:1, 100 mL) were added activated carbon (2 g) and anhydrous ferric chloride (250 mg). To the mixture was added hydrazine monohydrate (5.64 mL), and the mixture was heated for 26 hours under ref lux. The reaction mixture was cooled to room temperature, the activated carbon was filtered off. The activated carbon was washed with methanol. The filtrate and washings were combined, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give the titled compound (4 g) as colorless powdery crystals.
Reaction SMILES: [CH2:1]([S:3][CH:4]1[NH:7][C:6](=[O:8])[CH2:5]1)[CH3:2].C([O:11][CH:12](O)[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1)=[O:14])C>C1C=CC=CC=1>[CH2:1]([S:3][CH:4]1[N:7]([CH:12]([OH:11])[C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)=[O:14])[C:6](=[O:8])[CH2:5]1)[CH3:2]
Reactant: CCOC(O)C(=O)OCc1ccc([N+](=O)[O-])cc1
Reactant: CCSC1CC(=O)N1
Solvent: c1ccccc1
Product: CCSC1CC(=O)N1C(O)C(=O)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 16 h

Procedure:
A solution of 12.3 g. of 4-ethylthio-2-oxoazetidine and 25.5 g. of p-nitrobenzyl glyoxylate ethyl hemiacetal in 900 ml. of benzene was heated under reflux for 16 hours. During the heating for 16 hours, water and ethanol were removed from the reaction mixture by azeotropic distillation using a Dean-Stark trap. At this point, the benzene was removed by evaporation in vacuo, and the residue was dissolved in 700 ml. of dichloromethane. The dichloromethane solution was washed three times with water, and then dried with anhydrous sodium sulfate. Evaporation in vacuo afforded 32.5 g of the title compound as a yellow semi-solid. The IR spectrum of the product in chloroform showed an absorption at 5.65 microns. The NMR spectrum of the product in deuterochloroform showed peaks at 1.25 (t, 3H); 2.35-3.62 (m, 4H); 4.3 (s, 1H); 4.85 (m, 1H); 5.22 and 5.54 (ss, 1H); 5.38 (s, 2H); 7.5 (d, 2H); and 8.2 (d, 2H) ppm.
Reaction SMILES: CO.[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][Si:13](OC)(OC)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C(C1C=CC=CC=1)(=O)C>C(N(CC)CC)C>[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:11][CH2:12][SiH2:13][CH2:14][CH2:15]2)=[CH:6][CH:5]=1
Reactant: CO[Si]1(OC)CCC(c2ccc(F)cc2)CC1
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CC(=O)c1ccccc1
Product: Fc1ccc(C2CC[SiH2]CC2)cc1

Procedure:
In the same manner as in Example 9, 21.0 g of 4-(p-fluorophenyl)-1,1-dichloro-1-silacyclohexane was obtained from 4-(p-fluorophenyl)-1,1-diphenyl-1-silacyclohexane obtained in Preparatory Example 5. A mixture of 50.0 g of methanol and 30 g of triethylamine was added to the solution obtained above, followed by agitation under reflux for 1 hour. The resultant solution was concentrated, to which 200 ml of hexane was added thereby permitting secondarily produced hydrochloride to be precipitated. The precipitate was removed by filtration and the resulting filtrate was concentrated to obtain a mixture of 4-(p-fluorophenyl)-1,1-dimethoxy-1-silacyclohexane and acetophenone. The mixture was subjected to distillation under reduced pressure to remove the acetophenone therefrom. The resultant residue was dissolved in 100 ml of THF and added to a solution of 10.0 g of lithium aluminium hydride in 100 ml of THF. The reaction mixture was agitated under reflux for 1 hour, which was poured into 200 ml of 5% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried and concentrated by a usual manner, followed by purification through silica gel chromatography to obtain 14.7 g of 4-(p-fluorophenyl)-1-silacyclohexane. Subsequently, 14.0 g of 4-(p-fluorophenyl)-1-silacyclohexane was added to 100 ml of toluene, into which chlorine gas was blown to obtain 4-(p-fluorophenyl)-1-chloro-1-silacyclohexane. This solution was dropped in 100 ml of a THF solution of 1 mole/liter of trans-2-(4-n-propylcyclohexyl)ethylmagnesium bromide at room temperature. The reaction mixture was charged into 200 ml of 5% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried and concentrated, followed by purification through silica gel chromatography to obtain 20.8 g of the intended product. The thus obtained product exhibited nematic liquid crystal properties at a temperature between 49.1° C. and 62.9° C. and was found to be very useful as a liquid crystal substance.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]3([OH:26])[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.OS(O)(=O)=O>C(O)CCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]3([O:26][CH2:7][CH2:2][CH2:3][CH3:4])[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)[NH:11][C:12]=2[C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[CH:4][CH:3]=1
Reactant: CN1CCC(O)(c2nc(-c3ccc(F)cc3)c(-c3ccncc3)[nH]2)CC1
Agent: O=S(=O)(O)O
Solvent: CCCCO
Product: CCCCOC1(c2nc(-c3ccc(F)cc3)c(-c3ccncc3)[nH]2)CCN(C)CC1
Temperature: 40 °C
Yield: 120.5 %

Procedure:
The product of example 12, 4-(4-Fluorophenyl)-5-(4-pyridyl) 2-(4-hydroxy-1-methylpiperidin-4-yl)imidazole (22.2 g; 63 mmol) is dissolved in 1-butanol (1 l) upon warming to 40° C. H2SO4 conc (27.8 g; 283 mmol) is added dropwise and the initially resulting suspension is refluxed for 3.5 h, while distilling off ˜200 ml of 1-butanol. The reaction mixture is cooled to room temperature and poured on a saturated solution of Na2CO3 (500 ml). The aqueous phase is extracted with ethyl acetate and the combined organic phases dried over Na2SO4, filtered and evaporated to dryness. Purification by chromatography (SiO2; TBME/MeOH/NH3conc. 96/4/0.4 to 70/30/1) yields the title compound as yellow crystals (15.5 g; 60.3%). A sample is recrystallized from CH2Cl2/TBME to render colorless crystals: m.p. 177° C.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Br[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:22]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: O=Cc1ccc(O)cc1
Reactant: CCCCCCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCOc1ccc(C=O)cc1
Temperature: 65 °C
Reaction time: 18 h
Yield: 99.8 %

Procedure:
4-Hydroxybenzaldehyde (673 mg, 5.5 mmol), 1-bromododecane (1.25 g, 5 mmol) and potassium carbonate (859 mg, 6.22 mmol) were added to dimethylformamide (3 ml), and they were stirred at 65° C. for 18 hours. After the completion of the reaction followed by the extraction with ethyl acetate, 4-dodecyloxybenzaldehyde (yield: 1.45 g, 99%) was obtained in the form of white crystals.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[S:18](Cl)(=[O:20])=[O:19]>>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[S:18]([NH:1][CH2:2][CH2:3][C:4]1[N:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1)(=[O:20])=[O:19]
Reactant: COc1ccccc1S(=O)(=O)Cl
Reactant: Cn1cccc1CCN
Product: COc1ccccc1S(=O)(=O)NCCc1cccn1C

Procedure:
Prepared from 2-(2-aminoethyl)-1-methylpyrrol and 2-methoxybenzenesulphonylchloride analogously to Example A.
Reaction SMILES: [CH2:1]([C:4]1[NH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[C:7]([C:9]([O:11][CH3:12])=[O:10])[N:8]=1)[CH2:2][CH3:3].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([O:33][CH3:34])=[O:32])=[CH:21][CH:20]=1>>[C:31]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:22]1[CH:21]=[CH:20][C:19]([CH2:18][N:8]2[C:7]([C:9]([O:11][CH3:12])=[O:10])=[C:6]([C:13]([O:15][CH3:16])=[O:14])[N:5]=[C:4]2[CH2:1][CH2:2][CH3:3])=[CH:24][CH:23]=1)([O:33][CH3:34])=[O:32]
Reactant: CCCc1nc(C(=O)OC)c(C(=O)OC)[nH]1
Reactant: COC(=O)c1ccccc1-c1ccc(CBr)cc1
Product: CCCc1nc(C(=O)OC)c(C(=O)OC)n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
Yield: 97.6 %

Procedure:
2-n-Propyl-4,5-dicarbomethoxyimidazole (2.00 g, 8.8 mmol, 1 eq.) was alkylated with 4'-bromomethyl-2-carbomethoxybiphenyl (2.70 g, 8.8 mmol, 1 eq.) by the procedure described in Example 1, Part A. Obtained 3.87 g of a yellow oil which was suitable for further transformation. NMR (DMSO-d6): δ7.84-7.22 (m, 4H); 7.22 (d, 2H, J=9 Hz); 7.13 (d, 2H, J=9 Hz); 5.50 (s, 2H); 3.77 (s, 3H); 3.75 (s, 3H); 3.55 (s, 3H); 2.67 (t, 2H, J=7 Hz); 1.67 (t of q, 2H, J=7,7 Hz); 0.88 (t, 3H, J=7 Hz).
Reaction SMILES: [C:1]([CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([N:24](CC3C=CC(OC)=CC=3)[C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:23])=[O:22])[CH:19]=[CH:20][C:12]1=2)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:22])=[O:23])[CH:19]=[CH:20][C:12]1=2)#[N:2]
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3c2ccccc2OCC#N)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N#CCOc1ccccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)ccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 25 %

Procedure:
To a solution of 4-(2-(cyanomethoxy)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (200 mg, 0.364 mmol) in DCM (30 mL) was added TFA (0.5 mL) at 0° C. The reaction mixture was stirred at ambient temperature for 2 h. After completion, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude product which was purified by prep HPLC purification to obtain 4-(2-(cyanomethoxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a white solid (39 mg, 25%). MS (ESI, positive ion) m/z; 429.0 (M+1). 1H NMR (400 MHz, DMSO) δ 12.50 (s, 1H), 7.42-7.36 (m, 2H), 7.36-7.30 (m, 1H), 7.23-7.15 (m, 2H), 7.12 (d, J=2.0 Hz, 1H), 7.08 (dd, J=8.5, 2.1 Hz, 1H), 6.77 (d, J=4.5 Hz, 1H), 6.19 (d, J=8.5 Hz, 1H), 5.18 (s, 2H), 4.32 (t, J=4.2 Hz, 2H), 3.64 (t, J=4.2 Hz, 2H).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[N:5][CH:6]=[C:7]3[CH2:12][CH2:11][C:10](=[CH:13][C:14]#[N:15])[C:8]3=2)[O:3][CH2:2]1.N.C(O)C.C(N(CC)CC)C.[C:27](Cl)(=[O:30])[CH2:28][CH3:29]>C(O)C.C(=O)([O-])O.[Na+].[Co]>[CH2:1]1[C:9]2[C:4](=[N:5][CH:6]=[C:7]3[CH2:12][CH2:11][C:10](=[CH:13][CH2:14][NH:15][C:27](=[O:30])[CH2:28][CH3:29])[C:8]3=2)[O:3][CH2:2]1
Reactant: CCC(=O)Cl
Reactant: N#CC=C1CCc2cnc3c(c21)CCO3
Agent: [Co]
Agent: N
Agent: O=C([O-])O
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCC(=O)NCC=C1CCc2cnc3c(c21)CCO3
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 1,2,6,7-tetrahydro-8H-cyclopenta[d]furo[2,3-b]pyridin-8-ylideneacetonitrile (700 mg, 3.53 mmol) in ethanol (24 mL) were added Raney cobalt (4 g) and 2M ammonia/ethanol solution (12 mL), and the mixture was stirred at room temperature for 4 hr under a hydrogen atmosphere. The catalyst was filtered through celite, and the filtrate was evaporated under reduced pressure. The residue was dissolved in dichloromethane (35 mL), triethylamine (984 μL, 7.06 mmol) and propionyl chloride (337 μL, 3.88 mmol) were added under ice-cooling, and the mixture was stirred for 5 min. The reaction solution was diluted with saturated aqueous sodium hydrogen carbonate solution, the mixture was extracted with ethyl acetate, and the extract was washed with saturated brine. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) to give the title compound. The obtained title compound was used for the reaction of Example 22 without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:7][CH:8]=1.C(Cl)(=O)C(Cl)=O.[CH2:19]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([N:29]2[CH2:30][CH2:31][N:26]([CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:27][CH2:28]2)=[O:12])[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(CC(=O)O)c1
Reactant: c1ccc(CN2CCNCC2)cc1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cccc(CC(=O)N2CCN(Cc3ccccc3)CC2)c1
Reaction time: 4 h

Procedure:
3-Methoxyphenylacetic acid (100 g, 600 mmole) was dissolved in methylene chloride (600 mL) and treated with oxalyl chloride (60 mL) and DMF (1 mL) at room temperature. The mixture was stirred for four hours until gas evolution ceased. The solvent was evaporated and the residue dried under vacuum to remove excess oxalyl chloride. The oil obtained was dissolved in methylene chloride (400 mL). Half of this solution (200 mL, approx. 300 mmole) was cooled in ice and treated with a solution of 1-benzylpiperazine (60 mL, 350 mmole) and triethylamine (30 mL) in methylene chloride (100 mL) dropwise. The mixture was stirred at room temperature for 16 hours. Sodium bicarbonate solution was added and the mixture stirred for 15 minutes. The layers were separated. The organic phase was washed with water, brine, dried over K2CO3 and evaporated to an oil. Wt. 90 g. A small portion was characterized as the hydrochloride, m.p. 229°-231° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[NH2:12][C:13]1[N:18]=[CH:17][CH:16]=[C:15](Cl)[N:14]=1.C(N(CC)CC)C>COCCO.C(Cl)Cl>[NH2:12][C:13]1[N:18]=[C:17]([NH:1][CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:10])[CH3:9])[CH:16]=[CH:15][N:14]=1
Reactant: CC(C)(C)OC(=O)NCCN
Reactant: Nc1nccc(Cl)n1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: COCCO
Product: CC(C)(C)OC(=O)NCCNc1ccnc(N)n1
Temperature: 130 °C

Procedure:
tert-Butyl 2-aminoethylcarbamate (3.27 g, 20.4 mmol) and 2-amino-6-chloropyrimidine (2.38 g, 18.4 mmol) were combined in 2-methoxyethanol with triethylamine (4.3 mL, 30.3 mmol) and heated to 130° C. overnight. The mixture was diluted with methylene chloride and washed with 1 N sodium hydroxide. The aqueous layer was extracted with methylene chloride followed by ethyl acetate. The organic layers were combined, absorbed on silica gel, and purified using silica gel chromatography, eluting with a gradient of methanol in methylene chloride (1-12%) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.44 (s, 9H) 3.32 (q, J=5.31 Hz, 2H) 3.38-3.50 (m, 2H) 4.70 (s, 2H) 4.91-5.19 (m, 2H) 5.78 (d, J=5.76 Hz, 1H) 7.81 (d, J=5.76 Hz, 1H); MS (ESI+) m/z 253.9 (M+H)+.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:15][SiH:16]([CH:18]([SiH:23]([Cl:25])[Cl:24])[Si:19]([Cl:22])([Cl:21])[Cl:20])[Cl:17]>C1C=CC=CC=1.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>[Cl:17][Si:16]1([Cl:15])[CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[Si:23]([Cl:24])([Cl:25])[CH:18]1[Si:19]([Cl:22])([Cl:20])[Cl:21]
Reactant: Cl[SiH](Cl)C([SiH](Cl)Cl)[Si](Cl)(Cl)Cl
Reactant: C(#Cc1ccccc1)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: Cl[Si](Cl)(Cl)C1[Si](Cl)(Cl)C(c2ccccc2)C(c2ccccc2)[Si]1(Cl)Cl
Yield: 25 %

Procedure:
Hydrosilation of diphenylacetylene with bis(dichlorosilyl)trichlorosilylmethane in the presence of Pd(PPh3)4. Into the same apparatus as described in Example 1 were add 0.98 g of bis(dichlorosilyl)trichlorosilylmethane, 0.101 g of Pd(PPh3)4, and 25 ml of dried benzene to form a mixture. The mixture was brought to reflux temperature and 0.52 g of diphenylacetylene in 10 ml of benzene were added over a 30 minute period. The mixture was stirred at reflux temperature for an additional 18 hours and then the solvent removed at atmospheric pressure. The residue was vacuum distilled to yield a mixture comprising 0.417 g of 1,1,3,3-tetrachloro-2-trichlorosilyl-4,5-diphenyl-1,3-disilacyclopentane (TCD-GC area 25%).
Reaction SMILES: [C:1]1([O:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:11][C:12]1[CH:26]=[CH:25][CH:24]=[CH:23][C:13]=1[C:14]([CH:16]1[CH2:21][CH2:20][N:19](C)[CH2:18][CH2:17]1)=[O:15]>C1(C)C=CC=CC=1>[O:7]([C:8]([N:19]1[CH2:20][CH2:21][CH:16]([C:14](=[O:15])[C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=2[F:11])[CH2:17][CH2:18]1)=[O:9])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CN1CCC(C(=O)c2ccccc2F)CC1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: Cc1ccccc1
Product: O=C(c1ccccc1F)C1CCN(C(=O)Oc2ccccc2)CC1
Temperature: 25 °C

Procedure:
47.0 g of phenylchloroformate are added to a stirring solution of 57.5 g of 4-(2-fluorobenzoyl)-1-methyl piperidine in 750 ml of toluene. The reaction mixture is refluxed for 5 hours, cooled to ambient temperature, filtered, and the solvent is removed leaving a light colored oil. Theoil is triturated with hexane to give a crystalline material which is recrystallized twice from an ethanol-water mixture and once from ethanol The oil give the compound, mp 95°-96° C., 1-phenoxycarbonyl-4-(2-fluorobenzoyl)piperidine.
Reaction SMILES: [CH3:1][CH:2]([C:4]1[S:8][CH:7]=[N:6][C:5]=1[C:9]1[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=1)[CH3:3].CN(C)CCN(C)C.C([Li])CCC.[F:30][C:31]([F:39])([F:38])[C:32]([C:34]([F:37])([F:36])[F:35])=[O:33]>O1CCCC1>[CH3:3][CH:2]([C:4]1[S:8][C:7]([C:32]([C:34]([F:37])([F:36])[F:35])([C:31]([F:39])([F:38])[F:30])[OH:33])=[N:6][C:5]=1[C:9]1[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=1)[CH3:1]
Reactant: O=C(C(F)(F)F)C(F)(F)F
Reactant: CSc1ccc(-c2ncsc2C(C)C)cc1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CSc1ccc(-c2nc(C(O)(C(F)(F)F)C(F)(F)F)sc2C(C)C)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 78.9 %

Procedure:
To a solution of 4.50 g (18.0 mmol) of 5-(1-methylethyl)-4-(4-methylthiophenyl)thiazole and 3.15 ml (20.9 mmol) of tetramethylethylenediamine in 85 ml of tetrahydrofuran at -78° C. was added dropwise 20.0 ml (32.0 mmol) of n-butyl lithium (1.6M in hexane). The resulting solution was stirred for 1 hour at -78° C., and then 5.6 ml (50 mmol) of hexafluoroacetone was added dropwise. The mixture was stirred for 1 hour at -78° C. and then quenched by the rapid addition of 50 ml of sodium bicarbonate solution. After warming to 25° C., the organic and aqueous phases were separated and the aqueous phase was extracted with tetrahydrofuran. The combined organic phases were then washed with brine, dried over anhydrous potassium carbonate, filtered, and concentrated. The residue was dissolved in a mixture of 150 ml of ethanol and 30 ml of 4N hydrochloric acid; and the solution was stirred overnight at 25° C. The solution was concentrated in vacuo to remove the ethanol and the resulting aqueous mixture was extracted with diethyl ether. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (elution-benzene) to provide 5.9 g of 5-(1-methylethyl)-4-(4-methylthiophenyl)-α,α-bis(trifluoromethyl)thiazole-2-methanol as a light orange oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[O:13][C:12]([CH:14]3[CH2:16][CH2:15]3)=[N:11][C:10]=2[C:17]2[CH:18]=[CH:19][C:20]([C:23](=[O:25])[CH3:24])=[N:21][CH:22]=2)=[N:6][CH:7]=1.[BH4-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[O:13][C:12]([CH:14]3[CH2:16][CH2:15]3)=[N:11][C:10]=2[C:17]2[CH:18]=[CH:19][C:20]([CH:23]([OH:25])[CH3:24])=[N:21][CH:22]=2)=[N:6][CH:7]=1
Reactant: CC(=O)c1ccc(-c2nc(C3CC3)oc2Sc2ccc(Cl)cn2)cn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(O)c1ccc(-c2nc(C3CC3)oc2Sc2ccc(Cl)cn2)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80.2 %

Procedure:
To a solution of Example 88 (16 mg, 0.04 mmol) in MeOH (10 mL) at rt was added NaBH4 (1.6 mg, 0.04 mmol). The resulting solution was stirred at rt for 1 h. Upon completion of the reaction as judged by TLC analysis, the reaction was concentrated to dryness and purified on silica gel to afford the titled compound (12 mg). LC/MS: m/e 373.9 (M+H)+.