Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:6][C:7]2[C:8]([CH3:21])=[C:9]([CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=2)[C:10]([O:12][CH3:13])=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:22](=O)([O-])[O-].[Cs+].[Cs+].CI>C(#N)C>[CH:1]1([N:6]([CH3:22])[C:7]2[C:8]([CH3:21])=[C:9]([CH:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[CH:16]=2)[C:10]([O:12][CH3:13])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COC(=O)c1cc(C(F)(F)F)cc(NC2CCCC2)c1C
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Solvent: CI
Product: COC(=O)c1cc(C(F)(F)F)cc(N(C)C2CCCC2)c1C
Temperature: 80 °C

Procedure:
To a stirred solution of methyl 3-(cyclopentylamino)-2-methyl-5-(trifluoromethyl)benzoate (1.6 g, 5.38 mmol) in acetonitrile (25 mL) was added cesium carbonate (3.5 g, 10.7 mmol) and methyl iodide (3.8 g, 26.8 mmol). The mixture was heated at 80° C. for 8 h. On completion, the reaction was cooled to room temperature and filtered. The residue was washed with ethyl acetate and the filtrate was concentrated to give methyl 3-(cyclopentyl(methyl)amino)-2-methyl-5-(trifluoromethyl)benzoate.
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C@@H:12]2[CH2:16][NH:15][C@H:14]([C:17]([N:19]3[CH2:23][CH2:22][S:21][CH2:20]3)=[O:18])[CH2:13]2)=[CH:7][CH:6]=1)([O-])=O.Cl.O1CCOCC1>C(O)C.[Pd]>[ClH:1].[NH2:2][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C@@H:12]2[CH2:16][NH:15][C@H:14]([C:17]([N:19]3[CH2:23][CH2:22][S:21][CH2:20]3)=[O:18])[CH2:13]2)=[CH:7][CH:6]=1
Reactant: O=C([C@@H]1C[C@H](Nc2ccc([N+](=O)[O-])cc2)CN1)N1CCSC1
Agent: [Pd]
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Product: Nc1ccc(N[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 7.1 %

Procedure:
The title compound (200 mg) of Example 55 was dissolved in ethanol (10 mL), and 4 mol/L hydrochloric acid-1,4-dioxane (0.28 mL) and 10% palladium/carbon (100 mg) were added. The mixture was stirred under a hydrogen atomosphere (1 atm) at room temperature for 18 hr. The reaction mixture was filtrated and the filtrate was concentrated under reduced pressure, and the obtained solid was washed with ethanol to give the title compound (13 mg) as a white powder.
Reaction SMILES: C(OC([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:16]2[CH:25]=[CH:24][CH:23]=[C:22]3[C:17]=2[C:18]([Br:26])=[CH:19][N:20]=[CH:21]3)[CH2:11][CH2:10]1)=O)(C)(C)C.[ClH:27].CO>>[ClH:27].[Br:26][C:18]1[C:17]2[C:22](=[CH:23][CH:24]=[CH:25][C:16]=2[NH:15][CH:12]2[CH2:13][CH2:14][CH:9]([NH2:8])[CH2:10][CH2:11]2)[CH:21]=[N:20][CH:19]=1
Reactant: CC(C)(C)OC(=O)NC1CCC(Nc2cccc3cncc(Br)c23)CC1
Agent: Cl
Solvent: CO
Product: NC1CCC(Nc2cccc3cncc(Br)c23)CC1
Temperature: 25 °C

Procedure:
According to the method of Example 1, Step C, deprotection was performed (50° C., 2 hours) by using Intermediate 76 (124 mg) and 10% hydrogen chloride/methanol solution (3 ml). The reaction mixture was cooled to room temperature, and then the solvent was evaporated under reduced pressure. The residue was added with methanol (2 ml) and diethyl ether (6 ml). The deposited precipitates were collected by filtration and washed with diethyl ether to obtain the title compound (107 mg).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([OH:11])[CH:5]=1.Br[CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:5]=[C:6]([O:11][CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:7]=[C:8]([O:10][CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:9]=1
Reactant: BrCCCOc1ccccc1-c1ccccc1
Reactant: COC(=O)c1cc(O)cc(O)c1
Product: COC(=O)c1cc(OCCCOc2ccccc2-c2ccccc2)cc(OCCCOc2ccccc2-c2ccccc2)c1

Procedure:
Using this procedure, the reaction of 3,5-dihydroxybenzoic acid methyl ester with 2-(3-bromopropoxy)-1,1-biphenyl gave 3,5-bis[3-(1,1'-biphenyl-2-yloxy)propoxy]benzoic acid methyl ester, mp 77°-79°. Anal. Calcd for C38H36O6 : C, 77.53; H, 6.16. Found: C, 77.31; H, 6.15.
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)[CH:5]=[CH:4][C:3]1=2.[OH-].[Na+].Cl>CCO.C1COCC1>[CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccccc2C)=CCC3(C)C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1ccccc1C1=CCC(C)(C)c2ccc(C#Cc3ccc(C(=O)O)cc3)cc21
Temperature: 50 °C

Procedure:
To a solution of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(2-methylphenyl)-2-naphthalenyl)ethynyl]-benzoate (Compound 3) 80.0 mg (0.190 mmol) in 3 ml of EtOH and 2 ml of THF was added 60.0 mg (1.50 mmol, 1.50 ml) of NaOH (1.0M aqueous solution). The solution was heated to 50° C. for 2 hours, cooled to room temperature, and acidified with 10% HCl. Extraction with EtOAc, followed by drying over Na2SO4, and removal of the solvents under reduced pressure afforded the title compound as a colorless solid. 1H NMR (DMSO): δ 7.89(2H, d, J=8.4 Hz), 7.57 (2H, d, J=8.4 Hz), 7.46 (2H, s), 7.29-7.14 (4H, m), 6.59 (1H, s), 5.90 (1H, t, J=4.7 Hz), 2.39 (2H, m), 2.60 (3H, s), 1.39 (3H, s), 1.29 (3H, s).
Reaction SMILES: CC1[O:3][C:4]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[NH:23][N:22]=[N:21][N:20]=4)=[CH:15][CH:14]=3)[C:5]=2[CH:6]=1.C[OH:25]>CN(C)C=O>[CH:6]([C:5]1[C:4]([OH:3])=[CH:10][CH:9]=[CH:8][C:7]=1[O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[NH:20][N:21]=[N:22][N:23]=2)=[CH:15][CH:14]=1)=[O:25]
Reactant: Cc1cc2c(OCc3ccc(-c4nnn[nH]4)cc3)cccc2o1
Reactant: CO
Solvent: CN(C)C=O
Product: O=Cc1c(O)cccc1OCc1ccc(-c2nnn[nH]2)cc1
Temperature: -65 °C

Procedure:
5-[4-(2-Methyl-4-benzofuranyloxymethyl)phenyl]tetrazole (1.224 g, 0.004 M) was dissolved in a mixture of dry methanol (130 ml) and dry dimethylformamide (20 ml), and cooled to -65° C. with stirring and exclusion of moisture. Ozonised air was bubbled through the solution at a rate of 20 liters/hr for 1 hr. Nitrogen was then bubbled through the solution (5 mins). to remove excess ozone before the addition of dimethyl sulphide (1.2 ml). The mixture was allowed to warm to room temperature overnight (16 hr). The solvent was removed in vacuo and the residual oil dissolved in ethyl acetate and washed with 2 N hydrochloric acid, water, and extracted with sodium bicarbonate solution. The combined extracts were acidified with 2 N hydrochloric acid to give a solid which was filtered off and dried. This mixture of 5-[4-(2-formyl-3-hydroxyphenoxymethyl)phenyl]tetrazole and 5-[4-(3-acetoxy-2-formylphenoxymethyl)phenyl]tetrazole was suspended in 95% ethanol (20 ml) and 1N sodium hydroxide (20 ml) and stirred at room temperature (1 hr). The solution was evaporated and the residue diluted with water and acidified. The resulting solid was filtered off, washed with water, dried and recrystallised form ethanol/water to give 5-[4-(2-formyl-3-hydroxyphenoxymethyl)phenyl]tetrazole as the 0.5 hydrate, m.p. 206°-206.5° C. (Found: C, 59.00; H, 4.29; N, 18.46. C15H12N4O3 0.5H2O requires C, 59.01; H, 4.29; N, 18.35%).
Reaction SMILES: [O:1]1[CH:5]=[C:4]([CH2:6][O:7][N:8]=[C:9]2[CH2:18][CH2:17][CH:16]([O:19][C:20](=[O:25])[CH:21]([CH3:24])[CH2:22][CH3:23])[CH:15]3[C:10]2=[CH:11][C:12](=[O:38])[CH:13]([CH3:37])[CH:14]3[CH2:26][CH2:27][C:28](=[O:36])[CH2:29][CH:30]([OH:35])[CH2:31][C:32]([OH:34])=[O:33])[CH:3]=[N:2]1.O1CCOCC1.[OH-].[Na+:46]>O>[O:1]1[CH:5]=[C:4]([CH2:6][O:7][N:8]=[C:9]2[CH2:18][CH2:17][CH:16]([O:19][C:20](=[O:25])[CH:21]([CH3:24])[CH2:22][CH3:23])[CH:15]3[C:10]2=[CH:11][C:12](=[O:38])[CH:13]([CH3:37])[CH:14]3[CH2:26][CH2:27][C:28](=[O:36])[CH2:29][CH:30]([OH:35])[CH2:31][C:32]([O-:34])=[O:33])[CH:3]=[N:2]1.[Na+:46]
Reactant: CCC(C)C(=O)OC1CCC(=NOCc2cnoc2)C2=CC(=O)C(C)C(CCC(=O)CC(O)CC(=O)O)C21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CCC(C)C(=O)OC1CCC(=NOCc2cnoc2)C2=CC(=O)C(C)C(CCC(=O)CC(O)CC(=O)[O-])C21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
151 mg of 7-[5-(isoxazol-4-yl)methoxyimino-2-methyl-8-(2-methylbutyryloxy)-3-oxo-1,2,3,5,6,7,8,8a -octahydro-1-naphthyl]-3-hydroxy-5-oxoheptanoic acid (prepared as described in Example 9b) were dissolved in 2.5 ml of a 1:1 by volume. mixture of dioxane and water. 2.7 ml of a 0.1N aqueous solution of sodium hydroxide were then added dropwise over a period of 5 minutes at 0° C. to the solution, and the resulting mixture was stirred for 1 hour at room temperature. At the end of this time, the solution was freeze-dried, to obtain 153 mg of the title compound as a colorless moisture sensitive powder.
Reaction SMILES: [CH:1]([NH:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=1)=O.P(Cl)(Cl)(Cl)(Cl)Cl.CCCCCC>ClCCl>[CH3:13][O:12][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[CH:1]=[N:3][CH2:4][CH2:5]2
Reactant: COc1cccc(CCNC=O)c1
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: CCCCCC
Solvent: ClCCl
Product: COc1ccc2c(c1)CCN=C2
Temperature: 0 °C
Yield: 87 %

Procedure:
A solution of 29.4 Kg of N-formyl-3-methoxyphenethylamine in 30 litres of dichloromethane was added over 90 minutes to a well-stirred slurry of 38.4 Kg of phosphorus pentachloride in 30 litres of dichloromethane. An exothermic reaction ensued, causing the solvent to reflux at 35°-38° C. After addition was complete, the reaction mixture was hydrolysed by the addition of a mixture of 90 Kg of ice and 30 litres of hexane. After cooling the aqueous layer was separated, made basic with 144 Kg of 45% potassium hydroxide and extracted twice with 50 Kg of dichloromethane. After drying the organic layer with sodium sulfate the solvent was removed under reduced pressure to give 23 Kg of 6-methoxy-3,4-dihydroisoquinoline as an oil.
Reaction SMILES: [CH2:1]([O:8][N:9]([CH2:17][CH3:18])C(=O)OC(C)(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][NH:9][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(OCc1ccccc1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCNOCc1ccccc1
Reaction time: 1 h
Yield: 87.4 %

Procedure:
151 (616 mg) was dissolved in 4 ml of DCM and 4 ml of TFA was added then the reaction mixture was let 1 h at room temperature. The reaction mixture is concentrated and 50 ml of AcOEt are added. The organic phase are washed with saturated NaHCO3 and brine then dried over Na2SO4, filtered and concentrated to afford 152 as an oil (324 mg, 88%). 1H NMR (DMSO): δ 0.99 (t, 3H, J=7.3 Hz), 2.82 (m, 2H), 4.61 (s, 2H), 6.50 (t, 1H, J=5.8 Hz), 7.32 (m, 5H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]2[OH:15])=[CH:5][CH:4]=1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+].O.S(=O)(=O)(O)O>C(OCC)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]2=[O:15])=[CH:7][CH:8]=1
Reactant: COc1ccc(C2CCCCC2O)cc1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: COc1ccc(C2CCCCC2=O)cc1

Procedure:
146 g (0.71 mole) of 2-(4-methoxyphenyl)-cyclohexanol from the 1st stage were dissolved in 600 ml of diethyl ether. A solution consisting of 69.9 g (0.23 mole) of sodium dichromate (as dihydrate), 355 ml of water and 53.2 ml of conc. sulfuric acid was added dropwise while stirring vigorously and cooling in an ice bath so that the internal temperature did not exceed 10° C. After completion of the addition the reaction mixture was stirred overnight at room temperature. After separating the phases the aqueous phase was then extracted twice with 200 ml of diethyl ether. The combined organic phases were washed twice with 200 ml of saturated sodium hydrogen carbonate solution and dried over sodium sulfate. After removing the solvent by distillation the remaining oil was distilled and the fraction passing over at 128–134° C./0.05 bar was collected. After crystallisation from n-hexane 130 g of colourless crystals with a melting point of 90° C. were obtained (90% of theory).
Reaction SMILES: Cl.[CH2:2]([O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]=[C:15]([N+]([O-])=O)[CH3:16])=[CH:10][N:9]=1)[CH3:3].C[OH:21]>[Fe]>[CH2:2]([O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15](=[O:21])[CH3:16])=[CH:10][N:9]=1)[CH3:3]
Reactant: CCOCCOc1ccc(C=C(C)[N+](=O)[O-])cn1
Reactant: CO
Agent: [Fe]
Agent: Cl
Product: CCOCCOc1ccc(CC(C)=O)cn1

Procedure:
6.5 ml of concentrated hydrochloric acid are added dropwise to a boiling suspension of 800 mg (3.2 mmol) of 1-[2-(2-ethoxyethoxy)-5-pyridyl]-2-nitro-1-propene and 710 mg of iron filings in 10 ml of methanol. After 30 minutes the mixture is filtered and diluted with water. It is washed with ether, adjusted to pH 7 and extracted with ether. The organic phase is washed with 1% strength aqueous sodium hydroxide solution and then with water, dried over sodium sulphate and evaporated.
Reaction SMILES: N#N.Br[C:4]1[CH:5]=[C:6]([N+:11]([O-:13])=[O:12])[C:7]([CH3:10])=[N:8][CH:9]=1.CCN(CC)CC.[CH3:21][N:22]([CH3:26])[CH2:23][C:24]#[CH:25]>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:21][N:22]([CH3:26])[CH2:23][C:24]#[C:25][C:4]1[CH:9]=[N:8][C:7]([CH3:10])=[C:6]([N+:11]([O-:13])=[O:12])[CH:5]=1
Reactant: C#CCN(C)C
Reactant: Cc1ncc(Br)cc1[N+](=O)[O-]
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: N#N
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: Cc1ncc(C#CCN(C)C)cc1[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 3 h

Procedure:
A 12 L reactor equipped with an overhead stirrer and N2 bubbler was charged with a solution of 5-bromo-2-methyl-3-nitropyridine (945 g, 4.35 mol) in EtOAc (5.7 L, 6 vol). To the reaction mixture, Pd(PPh3)2Cl2 (15.4 g, 0.022 mol, 0.005 equiv), CuI (8.28 g, 0.0435 mol, 0.01 equiv) and Et3N (3 L, 21.75 mol, 5 equiv) were added. Nitrogen was bubbled through the solution for 15 min and 3-dimethylamino-1-propyne (556 mL, 5.22 mol, 1.2 equiv) was added. The reaction-temperature setting was increased to 60° C. stepwise. The maximum temperature attained was 66° C. The reaction was continued for 3 h at this temperature (60° C.) and was judged complete by HPLC analysis. The reaction was cooled to ambient temperature and the inorganic salts were filtered off by passing the reaction mixture through a pad of celite. The filter cake was washed with EtOAc (2 L, 2 vol). The filtrate was transferred into a 20 L separatory funnel. The EtOAc layer was washed with 5% aqueous Na2CO3 solution (2×5 L, 5 vol). The layers were separated. The EtOAc layer was then washed with 10% brine in water (5 L, 5 vol). The layers were separated and the EtOAc layer was pumped down to a low volume (ca. 2 L, 2 vol) under reduced pressure. IPA (5 L, 5 vol) was added to the solution and the solvent was again evaporated to a low volume (ca. 2 L, 2 vol). The solution of N,N-dimethyl-3-(6-methyl-5-nitropyridin-3-yl)prop-2-yn-1-amine was subjected to hydrogenation in two batches using the procedure described in step 2, below.
Reaction SMILES: CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[O:19][C:18](=[O:21])[C:17]([C:22]([OH:24])=O)=[CH:16]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:49]([O:53][C:54]([N:56]1[CH:60]=[CH:59][CH:58]=[C:57]1[C:61]1[CH:66]=[CH:65][CH:64]=[C:63]([NH2:67])[CH:62]=1)=[O:55])([CH3:52])([CH3:51])[CH3:50]>CN(C=O)C>[C:49]([O:53][C:54]([N:56]1[CH:60]=[CH:59][CH:58]=[C:57]1[C:61]1[CH:66]=[CH:65][CH:64]=[C:63]([NH:67][C:22]([C:17]2[C:18](=[O:21])[O:19][C:20]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][C:11]=3[OH:10])=[O:24])[CH:62]=1)=[O:55])([CH3:52])([CH3:50])[CH3:51]
Reactant: CC(C)(C)OC(=O)n1cccc1-c1cccc(N)c1
Reactant: O=C(O)c1cc2cccc(O)c2oc1=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)n1cccc1-c1cccc(NC(=O)c2cc3cccc(O)c3oc2=O)c1
Temperature: 25 °C
Yield: 65.3 %

Procedure:
DIEA (0.009 mL, 0.053 mmol) was added to 8-hydroxy-3-carboxy-coumarin (0.010 g, 0.048 mmol) and HATU (0.02 g, 0.053 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 2-(3-Amino-phenyl)-pyrrole-1-carboxylic acid tert-butyl ester (0.013 g, 0.048 mmol) was added and allowed to react overnight. DMF was removed under vacuum and the reaction was resuspended in DMSO. The crude product was purified on a Parallex Flex parallel preparative reverse phase HPLC instrument (Biotage) using a solvent gradient of 10-95% ACN/H2O with 0.05% TFA at a flow rate of 20 mL/min. UV absorbance was monitored at 254 nm and the fractions corresponding to the product peak were collected and the solvent removed under vacuum to give 0.014 g of product in 62% yield: LCMS (ESI) m/z 447 (MH+).
Reaction SMILES: Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:11]2[CH2:15][CH2:14][NH:13][CH2:12]2)=[CH:5][CH:4]=1.[O:23]([CH2:30][CH2:31][CH2:32]Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[F:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][CH:10]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[CH:11]2[CH2:15][CH2:14][N:13]([CH2:32][CH2:31][CH2:30][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:12]2)=[CH:7][CH:8]=1
Reactant: Fc1ccc(NC(c2ccc(F)cc2)C2CCNC2)cc1
Reactant: BrCCCOc1ccccc1
Agent: Cl
Product: Fc1ccc(NC(c2ccc(F)cc2)C2CCN(CCCOc3ccccc3)C2)cc1

Procedure:
The title compound is prepared from N,α-bis(4-fluorophenyl)-3-pyrrolidinemethanamine hydrochloride and 3-phenoxypropylbromide according to the procedure of Example 8.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2([CH2:29][CH2:30][N:31]3[C@H:36]4[CH2:37][CH2:38][C@@H:32]3[CH2:33][CH:34]([N:39]3[C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=5[N:41]=[C:40]3[CH3:48])[CH2:35]4)[CH2:13][CH2:12][N:11]([C:14]([C:16]3([NH:21]C(=O)OC(C)(C)C)[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2([CH2:29][CH2:30][N:31]3[C@H:32]4[CH2:38][CH2:37][C@@H:36]3[CH2:35][CH:34]([N:39]3[C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=5[N:41]=[C:40]3[CH3:48])[CH2:33]4)[CH2:13][CH2:12][N:11]([C:14]([C:16]3([NH2:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1nc2ccccc2n1C1C[C@H]2CC[C@@H](C1)N2CCC1(c2cccc(F)c2)CCN(C(=O)C2(NC(=O)OC(C)(C)C)CCCC2)CC1
Agent: Cl
Product: Cc1nc2ccccc2n1C1C[C@H]2CC[C@@H](C1)N2CCC1(c2cccc(F)c2)CCN(C(=O)C2(N)CCCC2)CC1
Yield: 99.6 %

Procedure:
N-{1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]cyclopentyl}-2,2-dimethylpropanamide was obtained from treating 1,1-dimethylethyl {1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]cyclopentyl}carbamate (0.627 g, 0.95 mmol) with HCl as outlined in the procedure for Example 890 to form 1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]cyclopentanamine (0.528 g, 99%). 1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]cyclopentanamine (0.050 g, 0.09 mmol), 2,2-Dimethyl-propionyl chloride (0.011 g, 0.09 mmol) and DIEA (0.034 g, 0.534 mmol) were reacted following the procedure outlined in Example 890 to give the title compound, N-{1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]cyclopentyl}-2,2-dimethylpropanamide (0.031 g, 54%) as an oil. ES-LCMS m/z 642 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]([C:12]([O:14][CH3:15])=[O:13])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:6].CO[CH:19](OC)[N:20]([CH3:22])[CH3:21].CN(C=O)C>C1C=CC=CC=1>[CH3:15][O:14][C:12](=[O:13])[C:4]([C:3]([O:2][CH3:1])=[O:16])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:6]=[CH:19][N:20]([CH3:22])[CH3:21]
Reactant: CCOC(=O)C(C)=C(C(=O)OC)C(=O)OC
Reactant: COC(OC)N(C)C
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: CCOC(=O)C(C=CN(C)C)=C(C(=O)OC)C(=O)OC
Temperature: 80 °C
Yield: 85.4 %

Procedure:
A mixture of 3-ethoxycarbonyl-2-methoxycarbonyl-but-2-enoic acid methyl ester (10 g, 43.5 mmol), dimethylformamide dimethyl acetal (6.1 mL, 45.7 mmol) and DMF (8 mL) was heated at 80° C. for 3 h. The slightly cooled solution was poured into 100 mL of benzene, and the resulting mixture was washed several times with water. The organic layer was dried over MgSO4 and concentrated to give a dark yellow solid, which was recrystallized from CCl4 to give 10.6 g of the title compound as a bright yellow solid. 1H NMR (CDCl3, 200 MHz): δ=6.77 (d, 1H, J=12.8 Hz), 5.74 (d, 1H, J=13.2 Hz), 4.34 (q, 2H, J=7.0 Hz), 3.80 (s, 3H), 3.71 (s, 3H), 2.97 (br s, 6H), 1.36 (t, 3H, J=7.0 Hz).
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>[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
Solvent: c1ccccc1
Product: Cl[Si](Cl)(Cl)C1[Si](Cl)(Cl)C(c2ccccc2)C(c2ccccc2)[Si]1(Cl)Cl
Yield: 71.2 %

Procedure:
Hydrosilation of diphenylacetylene with bis(dichlorosilyl)trichlorosilylmethane in the presence of H2PtCl6 /IPA. Into the same apparatus as described in Example 1 were placed 0.60 g of diphenylacetylene, 1.06 g of bis(dichlorosilyl)trichlorosilylmethane, 31 μl of 0.1 M H2PtCl6/IPA, and 25 ml of dried benzene forming a mixture. The resulting mixture, with stirring, was refluxed for 5 hours and then the solvent removed at atmospheric pressure. The residue was vacuum distilled at 67 Pa to yield a mixture comprising 1.42 g of 1,1,3,3-tetrachloro-2-trichlorosilyl-4,5-diphenyl-1,3-disilacyclopentane (TCD-GC area 71.2%) and 3,3,5,5-tetrachloro-4-trichlorosilyl-1,2,6,7-tetraphenyl-3,5-disilahepta-1,6-diene (TCD-GC area 5.9%). 1,1,3,3-Tetrachloro-2-trichlorosilyl-4,5-diphenyl- 1,3-disilacyclopentane=1H-NMR (CDCl3, ppm): 1.82 (s, 1H, SiCHSi), 3.35-3.44 (m, 2H, CHPh), 7.06-7.18 (m, 5H, ArH).
Reaction SMILES: [C:1]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:6])[CH2:2][C:3]([CH3:5])=O.[CH3:15][NH2:16]>C(O)C>[CH2:8]([O:7][C:1](=[O:6])[CH:2]=[C:3]([NH:16][CH3:15])[CH3:5])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CN
Reactant: CC(=O)CC(=O)OCc1ccccc1
Solvent: CCO
Product: CNC(C)=CC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.8 %

Procedure:
To benzyl acetoacetate (29 g, 151 mmol) in ethanol (30 mL) was added methyl amine (33% in ethanol, 7.02 g, 226 mmol). The solution was stirred for 2 hours at room temperature followed by evaporation to yield a yellow oil (˜30 g).