Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].[C:2](=[O:5])([O-])[O-].[K+].[K+].[C:8]([Si:12]([CH3:28])([CH3:27])[O:13][CH2:14][CH2:15][NH:16][CH2:17][CH2:18][O:19][Si:20]([CH3:26])([CH3:25])[C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:11])([CH3:10])[CH3:9].[Cl:29][CH2:30]Cl>>[C:21]([Si:20]([CH3:25])([CH3:26])[O:19][CH2:18][CH2:17][N:16]([CH2:15][CH2:14][O:13][Si:12]([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:28])[CH3:27])[C:2](=[O:5])[CH2:30][Cl:29])([CH3:22])([CH3:24])[CH3:23]
Reactant: ClCCl
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)[Si](C)(C)OCCNCCO[Si](C)(C)C(C)(C)C
Agent: [Cl-]
Agent: [K+]
Product: CC(C)(C)[Si](C)(C)OCCN(CCO[Si](C)(C)C(C)(C)C)C(=O)CCl
Reaction time: 2 h
Yield: 87.4 %

Procedure:
Choloroacetyl chloride (1.1 g, 9.55 mmol) and potassium carbonate (2.638 g, 19.09 mmol) were dissolved in dry dichloromethane (80 mL) and cooled in an ice salt bath. To this was added bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]amine (3.353 g, 9.545 mmol) in dry dichloromethane (10 mL) over 10 minutes. The reaction mixture was stirred in an ice bath for 2 hours. The mixture was filtered and washed with dichloromethane, then washed with 1.5 N aqueous potassium hydrogen sulfate (2×100 mL) and brine (100 mL). The aqueous layers were back extracted with dichloromethane (2×100 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give N,N-bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-chloro-acetamide (3.8 g, 87.4%).
Reaction SMILES: FC(F)(F)C(O)=O.C([O:12][C:13](=[O:33])[C@@H:14]([N:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32])[CH3:15])(C)(C)C>ClCCl>[C:27]1([CH3:32])[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C@@H:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:24][CH2:25][N:16]1[C@@H:14]([CH3:15])[C:13]([OH:33])=[O:12].[C:27]1([CH3:32])[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C@H:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:24][CH2:25][N:16]1[C@@H:14]([CH3:15])[C:13]([OH:33])=[O:12]
Reactant: Cc1ccccc1C1c2ccccc2CCN1[C@@H](C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccccc1[C@@H]1c2ccccc2CCN1[C@@H](C)C(=O)O
Product: Cc1ccccc1[C@H]1c2ccccc2CCN1[C@@H](C)C(=O)O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Trifluoroacetic acid (5.0 mL, 64.9 mmol) is added to a solution of 2-(S)-(1-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl)-propionic acid tert-butyl ester (0.27 g, 0.768 mmol) in dichloromethane (5.0 mL). The reaction mixture is stirred at room temperature for 4 hours. All solvent is removed in vacuo, ethyl ether (50 mL) and saturated sodium bicarbonate (100 mL) are added and the organic layer is removed. The aqueous layer is acidified to pH 2.0 using 1M HCl and the crude product extracted into dichloromethane (100 mL), washed with water (2×50 mL) and brine (1×100 mL), and dried over magnesium sulfate. Filtration and concentration are followed by flash chromatography on SiO2 using 20:1 dichloromethane:methanol and afford 100 mg 2-(S)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid (Rf of 0.6) and 70 mg 2-(S)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid (Rf of 0.3) both as white foams. 2-(S)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid, 2-(R)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid and 2-(R)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid are prepared in similar fashion.
Reaction SMILES: [C:1]([O:5][C:6]([CH:8]1[CH2:14][CH2:13][C:12]2[CH:15]=[CH:16][C:17]([O:19][CH3:20])=[CH:18][C:11]=2[NH:10][C:9]1=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:29])C(=O)C1>C(O)(=O)C.C(Cl)(Cl)Cl.C(Cl)Cl>[Br:29][C:16]1[C:17]([O:19][CH3:20])=[CH:18][C:11]2[NH:10][C:9](=[O:21])[CH:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:14][CH2:13][C:12]=2[CH:15]=1
Reactant: COc1ccc2c(c1)NC(=O)C(C(=O)OC(C)(C)C)CC2
Reactant: O=C1CCC(=O)N1Br
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CC(=O)O
Product: COc1cc2c(cc1Br)CCC(C(=O)OC(C)(C)C)C(=O)N2

Procedure:
A suspension of 3-tert-butoxycarbonyl-8-methoxy-2,3,4,5-tetrahydro-1H-1-benzazepine-2-one (1.00 g, 3.43 mmol) and NBS (0.672 g, 3.78 mmol) in acetic acid (0.8 mL) and chloroform (8 mL) was heated at reflux for 3 hrs. Then, the reaction mixture was diluted with DCM (30 mL), washed with water, dried over Na2SO4, filtered and evaporated. The crude residue was purified by flash chromatography on silica column using gradient elution with EtOAc/DCM (from 5% ethyl acetate in DCM to 10% ethyl acetate in DCM). The title compound was obtained as a white powder (0.689 g, 54%).
Reaction SMILES: [CH2:1]([N:3]1[C:7]2[N:8]=[CH:9][C:10]3[C:15](=[O:16])[N:14]4[N:17]=[C:18]([CH2:20][CH3:21])[CH:19]=[C:13]4[NH:12][C:11]=3[C:6]=2[CH:5]=[N:4]1)[CH3:2].[C:22](Br)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[CH2:1]([N:3]1[C:7]2[N:8]=[CH:9][C:10]3[C:15](=[O:16])[N:14]4[N:17]=[C:18]([CH2:20][CH3:21])[CH:19]=[C:13]4[N:12]([C:22](=[O:29])[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:11]=3[C:6]=2[CH:5]=[N:4]1)[CH3:2]
Reactant: CCc1cc2[nH]c3c(cnc4c3cnn4CC)c(=O)n2n1
Reactant: O=C(Br)c1ccccc1
Product: CCc1cc2n(C(=O)c3ccccc3)c3c(cnc4c3cnn4CC)c(=O)n2n1

Procedure:
By treating the product of Example 25 with benzoyl bromide according to the procedure of Example 2, 3,9-diethyl-3,11-dihydro-11-benzoyl-6H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[4,3-d]pyrimidin-6-one is obtained.
Reaction SMILES: [CH:1]1([C:4]2[C:15]3[O:14][C:11]4([CH2:13][CH2:12]4)[CH2:10][C:9]([CH3:17])([CH3:16])[C:8]=3[CH:7]=[C:6]([C:18]#[CH:19])[CH:5]=2)[CH2:3][CH2:2]1.[CH3:20][O:21][C:22](=[O:32])[CH:23]([C:25]1[CH:30]=[CH:29][C:28](I)=[CH:27][CH:26]=1)[CH3:24]>C(N(CC)CC)C.C(OCC)C.[Cu]I.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>[CH3:20][O:21][C:22](=[O:32])[CH:23]([C:25]1[CH:26]=[CH:27][C:28]([C:19]#[C:18][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[C:15]3[O:14][C:11]4([CH2:13][CH2:12]4)[CH2:10][C:9]([CH3:16])([CH3:17])[C:8]=3[CH:7]=2)=[CH:29][CH:30]=1)[CH3:24]
Reactant: C#Cc1cc(C2CC2)c2c(c1)C(C)(C)CC1(CC1)O2
Reactant: COC(=O)C(C)c1ccc(I)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: COC(=O)C(C)c1ccc(C#Cc2cc(C3CC3)c3c(c2)C(C)(C)CC2(CC2)O3)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56 %

Procedure:
A solution of 8-cyclopropyl-6-ethynyl-3,4-dihydro-4,4-dimethylspiro[2H-1-benzopyran-2,1′-cyclopropane] (described in U.S. Pat. No. 6,252,090; 0.068 g, 0.27 mmol), and methyl-2-(4-iodo phenyl)propionate (Reagent 1, 0.086 g, 0.3 mmol) in triethyl amine (3 mL), was treated with copper(I)iodide (0.028 g, 0.15 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (0.057 g, 0.08 mmol) was added and the reaction mixture was stirred overnight at room temperature. It was diluted with diethyl ether and filtered over a bed of celite. The filtrate was evaporated in vacuo to brown oil that was subjected to flash column chromatography over silica gel (230-400 mesh) to afford the title compound as an oil (0.072 g, 56%).
Reaction SMILES: [Br:1][C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[Cl:9][C:10]1[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C.O>[Br:1][C:2]1[N:7]=[N:6][C:5]([NH:8][CH2:14][C:13]2[CH:16]=[CH:17][C:10]([Cl:9])=[CH:11][CH:12]=2)=[CH:4][CH:3]=1
Reactant: Nc1ccc(Br)nn1
Reactant: O=Cc1ccc(Cl)cc1
Agent: CC[SiH](CC)CC
Solvent: CC#N
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: Clc1ccc(CNc2ccc(Br)nn2)cc1

Procedure:
To 6-bromo-pyridazin-3-ylamine (521, 0.85 g, 0.0049 mol) in acetonitrile (30.0 mL) were added 4-chlorobenzaldehyde (40, 0.82 g, 0.0058 mol), triethylsilane (4.0 mL, 0.025 mol) and trifluoroacetic acid (2.0 mL, 0.026 mol). The reaction was heated to reflux for 4 hours, then poured into water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated and washed with ethyl acetate to give a white solid (522, 1.0 g). MS (ESI) [M+H+]+=298.3, 300.2.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1.[NH2:16][CH:17]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH:29]([NH2:33])[C:30]([OH:32])=[O:31])[CH:23]=1)[C:18]([OH:20])=[O:19]>>[C:12]([C:11]1[C:2]([NH:33][CH:29]([C:30]([OH:32])=[O:31])[CH2:28][C:24]2[CH:23]=[C:22]([CH2:21][CH:17]([NH:16][C:2]3[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]4[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=4)[N:3]=3)[C:18]([OH:20])=[O:19])[CH:27]=[CH:26][CH:25]=2)=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([Cl:15])=[CH:6][CH:5]=2)([OH:14])=[O:13]
Reactant: O=C(O)c1cc2cc(Cl)ccc2nc1Cl
Reactant: NC(Cc1cccc(CC(N)C(=O)O)c1)C(=O)O
Product: O=C(O)c1cc2cc(Cl)ccc2nc1NC(Cc1cccc(CC(Nc2nc3ccc(Cl)cc3cc2C(=O)O)C(=O)O)c1)C(=O)O

Procedure:
In close analogy to the procedure described in Example 1, 2,6-dichloroquinoline-3-carboxylic acid is reacted with 2-amino-3-[3-(2-amino-2-carboxy-ethyl)-phenyl]-propionic acid to provide the title compound in good yield.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([N:14]3[CH:23]([CH3:24])[CH2:22][C:21]4[C:16](=[CH:17][C:18]([C:25]5[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=5)=[CH:19][CH:20]=4)[CH2:15]3)[N:11]=[C:10]([NH2:31])[N:9]=2)[CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.[N:41]([CH:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1)=[C:42]=[O:43]>CN(C)C=O.CO>[NH2:31][C:10]1[N:11]=[C:12]([N:14]2[CH:23]([CH3:24])[CH2:22][C:21]3[C:16](=[CH:17][C:18]([C:25]4[CH2:26][CH2:27][N:28]([C:42]([NH:41][CH:44]5[CH2:48][CH2:47][CH2:46][CH2:45]5)=[O:43])[CH2:29][CH:30]=4)=[CH:19][CH:20]=3)[CH2:15]2)[CH:13]=[C:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[N:9]=1
Reactant: CC1Cc2ccc(C3=CCNCC3)cc2CN1c1cc(N2CCN(C)CC2)nc(N)n1
Reactant: O=C=NC1CCCC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: CC1Cc2ccc(C3=CCN(C(=O)NC4CCCC4)CC3)cc2CN1c1cc(N2CCN(C)CC2)nc(N)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
4-(4-Methylpiperazin-1-yl)-6-[3-methyl-7-(1,2,3,6-tetrahydropyridin-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine (21.0 mg) HCl salt in N,N-dimethylformamide (1.0 mL) was treated with N,N-diisopropylethylamine (0.070 mL, 0.40 mmol). To the solution was added isocyanatocyclopentane (11.1 mg, 0.100 mmol). The mixture was stirred at r.t. for 2 h. The mixture was diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=531.2.
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:12]1(OB([O-])[O-])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=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.O.C(O)C>[C:12]1([C:8]2[CH:9]=[C:10]3[C:5]([CH2:4][CH2:3][CH2:2][C:1]3=[O:11])=[CH:6][CH:7]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C1CCCc2ccccc21
Reactant: [O-]B([O-])Oc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: O=C1CCCc2ccc(-c3ccccc3)cc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78.2 %

Procedure:
A mixture of 7- (trifluoromethanesulfoxy) -1-tetralone (23.3 g), phenylborate (11.8 g), potassiumcarbonate (21.9 g), toluene (500 ml), ethanol (50 ml) and water (50 ml) was stirred for 30 minutes at room temperature under argon atmosphere, and to the mixture was added tetrakis(triphenylphosphine)palladium (3.66 g). The mixture was refluxed for 20 hours and then cooled to room temperature. The organic layer was separated, washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/toluene/hexane=1/5/5) to give 7-phenyl-1-tetralone (15.1 g) as pale brown oil.
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C@@H:2]([C@H:4]([C:6]([OH:8])=O)[OH:5])[OH:3].[C:11](Cl)(=[O:15])[CH:12]([CH3:14])[CH3:13]>C1(C)C=CC=CC=1.CCOCC.CCCCCC>[O:10]=[C:1]1[C@H:2]([O:3][C:11](=[O:15])[CH:12]([CH3:14])[CH3:13])[C@@H:4]([O:5][C:11](=[O:15])[CH:12]([CH3:14])[CH3:13])[C:6](=[O:8])[O:9]1
Reactant: CC(C)C(=O)Cl
Reactant: O=C(O)[C@H](O)[C@@H](O)C(=O)O
Solvent: CCOCC
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: CC(C)C(=O)O[C@H]1C(=O)OC(=O)[C@@H]1OC(=O)C(C)C
Reaction time: 22 h
Yield: 70.6 %

Procedure:
To a suspension of L-tartaric acid (5.0 g, 33.3 mmol) in toluene (60 mL) was added isobutyryl chloride (11.3 mL, 107 mmol). The resulting suspension was heated to reflux and stirred for 22 h at reflux temperature. The reaction mixture was then concentrated in vacuo to afford a crystalline solid, which was suspended in a mixture of ether and hexane (1:3), filtered, washed with hexane and dried to afford the desired compound (27) as a white crystalline solid (6.4 g, 71%). 1H-NMR (400 MHz, CDCl3): δ 1.25 (d, J=6.8 Hz, 12H), 2.72 (hept, J=6.8 Hz, 2H), 5.63 (s, 2H).
Reaction SMILES: [CH:1]1([OH:6])[CH2:5][CH:4]=[CH:3][CH2:2]1.[Si:7](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[Si:7]([O:6][CH:1]1[CH2:5][CH:4]=[CH:3][CH2:2]1)([C:20]([CH3:23])([CH3:22])[CH3:21])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: OC1CC=CC1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Product: CC(C)(C)[Si](OC1CC=CC1)(c1ccccc1)c1ccccc1
Yield: 96.6 %

Procedure:
By using 2.2 g of 3-cyclopentenol prepared according to the method described in J. Org. Chem., 25, 26-29 (1960) and 9.2 g of t-butyldiphenylsilyl chloride and by the same procedures as in (1) of the intermediate preparation example 1, there was obtained 8.15 g of 3-cyclopenten-1-yl (t-butyldiphenylsilyl) ether. Yield 97%
Reaction SMILES: [CH3:1][C:2]([S:26]([CH3:29])(=[O:28])=[O:27])([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH:25]=[CH:24][CH:23]=[N:22]2)=[CH:17][CH:16]=1)[C:3]([NH:5][O:6]C1CCCCO1)=[O:4].Cl.CO>C(Cl)Cl>[OH:6][NH:5][C:3](=[O:4])[C:2]([CH3:1])([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH:25]=[CH:24][CH:23]=[N:22]2)=[CH:19][CH:20]=1
Reactant: CC(CCc1ccc(-n2cccn2)cc1)(C(=O)NOC1CCCCO1)S(C)(=O)=O
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CC(CCc1ccc(-n2cccn2)cc1)(C(=O)NO)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
2-Methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (302.9 mg, 0.719 mmol) was dissolved in methylene chloride (10 mL) at ambient temperature. To this solution was added HCl (4M in 1,4-dioxane, 5.39 mL, 21.6 mmol) and the solution was stirred at RT for 5 minutes. Methanol (500 uL) was added followed by silica gel and the mixture was concentrated to dryness. The crude material was purified via silica gel chromatography eluting with methylene chloride/methanol to afford N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]butanamide as a solid. 67.8 mg. LCMS: (M−1) 336.3 1H NMR (CD3OD) 8.16 (1H, d, J=2.54 Hz), 7.69 (1H, d, J=1.17 Hz), 7.64 (2H, d, J=8.59), 7.36 (2H, d, J=8.40) 6.50 (1H, t), 3.03 (3H, s), 2.80-2.72 (1H, m), 2.61-2.52 (2H, m), 2.11-2.03 (1H, m), 1.65 (3H, s) ppm.
Reaction SMILES: [ClH:1].[C:2](=[NH:10])(OC)[CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].[CH3:11][NH2:12].[CH3:13]CO>CO>[ClH:1].[CH3:11][NH:12][C:2](=[N:10][CH3:13])[CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7]
Reactant: CCO
Reactant: C=CCCCC(=N)OC
Reactant: CN
Agent: Cl
Solvent: CO
Product: C=CCCCC(=NC)NC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 5-hexenimidoate hydrochloride (4.63 g, 28 mmol, Prep. 1) in MeOH (20 ml) was added methylamine 8M in EtOH (142 mmol). The solution was heated to reflux for 6 h and stirred overnight at r.t. Volatiles were evaporated in vacuo to give 4.4 g of the title compound as pale yellow oil, which was used without further purification.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.C(N(CC)CC)C.[CH3:19][C:20]1[N:21]=[CH:22][N:23]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][C:26]=2[C:32]([F:35])([F:34])[F:33])[CH:24]=1>O=S(Cl)Cl.CN(C1C=CN=CC=1)C.C1COCC1>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([NH:29][C:28]1[CH:30]=[CH:31][C:25]([N:23]2[CH:24]=[C:20]([CH3:19])[N:21]=[CH:22]2)=[C:26]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)=[O:7]
Reactant: Cc1cn(-c2ccc(N)cc2C(F)(F)F)cn1
Reactant: Cc1ccc(C(=O)O)cc1I
Agent: CN(C)c1ccncc1
Solvent: O=S(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cc1cn(-c2ccc(NC(=O)c3ccc(C)c(I)c3)cc2C(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 40 h
Yield: 72.1 %

Procedure:
A solution of 3-iodo-4-methylbenzoic acid (0.26 g, 1 mmol) in SOCl2 (5 mL) was refluxed for 3 hrs, then evaporated in vacuo to remove residual SOCl2. The residue was dissolved in 5 mL anhydrous THF and added to a solution of triethylamine (0.12 g, 1 mmol), 4-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)aniline (0.24 g, 1 mmol) and DMAP (12 mg) in 5 mL anhydrous THF in dropwise. The result mixture was stirred at rt for 40 hrs, and evaporated in vacuo. To the residue water was added and extracted with EtOAc (20 mL×3), the organic layer was washed with brine, dried with Na2SO4, after filtration, the filtrate was purified by chromatography on silica gel (CH2Cl2/CH3OH 97:3) to give 0.4 g crude product. The crude product was triturated with PE/EtOAc to give the title compound 0.35 g as pale yellow solid (72.2%). 1H NMR (300 MHz, CDCl3) δ: 8.91 (1H, s), 8.37 (1H, s), 8.08-8.12 (2H, m), 7.86-7.83 (1H, d, J=8.4 Hz), 7.54 (1H, s), 7.34-7.36 (2H, m), 6.84 (1H, s), 2.50 (3H, s), 2.29 (3H, s). LCMS: m/z [M+H]+ 486.0493.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([I:9])=[CH:5][CH:4]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1>C(OCC)(=O)C>[I:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:5]=1
Reactant: BrCc1ccc(I)cc1
Reactant: C1COCCN1
Solvent: CCOC(C)=O
Product: Ic1ccc(CN2CCOCC2)cc1
Temperature: 70 °C
Yield: 91.6 %

Procedure:
1-Bromomethyl-4-iodo-benzene (320 mg, 1.08 mmol) and morpholine (1 mL, 11.47 mmol) were combined. The reaction mixture was heated at 70° C. for 4 hours and then diluted with ethyl acetate. The resulting mixture was filtered and the filtrate was concentrated and dried. The residue was then dissolved in dichloromethane (10 mL), washed with water (4 mL), washed with brine (4 mL), dried over sodium sulfate and concentrated to give the product as an off-white solid (300 mg, 92%). 1H NMR (300 MHz, CDCl3): δ 7.64 (d, 2H), 7.09 (d, 2H), 3.7 (t, 4H), 3.43 (s, 2H), 2.43 (t, 4H).
Reaction SMILES: Cl[C:2](OCC)=O.C[C:8]1[NH:12][N:11]=[C:10]([C:13]([OH:15])=O)[CH:9]=1.Cl.[NH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])=[CH:22][CH:21]=1.[OH-].[Na+]>C(O)C.C(N(CC)CC)C.O1CCCC1>[CH3:2][C:10]1([C:13]([NH:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:22][CH:21]=2)=[O:15])[N:11]=[N:12][CH:8]=[CH:9]1
Reactant: Cc1cc(C(=O)O)n[nH]1
Reactant: CCOC(=O)CCc1ccc(CCN)cc1
Reactant: CCOC(=O)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC1(C(=O)NCCc2ccc(CCC(=O)O)cc2)C=CN=N1
Reaction time: 0.25 h
Yield: 22 %

Procedure:
1.27 ml. triethylamino and 0.85 ml. ethyl chloroformate are added at -10° C. to a solution of 1.12 g. 5-methylpyrazole-3-carboxylic acid in 25 ml. anhydrous tetrahydrofuran. After 15 minutes, a further 1.27 ml. triethylamine is added and then 2.57 g. ethyl β-[4-(2-aminoethyl)-phenyl]-propionate hydrochloride. The reaction mixture is stirred for 1 hour at +20° C., filtered with suction and the filtered is evaporated and the residue taken up in methylene chloride. After extraction with 2% hydrochloric acid, 2 N aqueous sodium hydroxide solution and neutralization, the solution is dried and evaporated. The crude ester thus obtained is heated under reflux for 1 hour with 0.6 g. sodium hydroxide in 30 ml. ethanol. After cooling, the precipitated sodium salt is filtered off with suction, dissolved in water and carefully acidified. The precipitate obtained is filtered off and recrystallized from 20% ethanol. There is obtained β-{4-[2-(5-methylpyrazole- 5-carboxamido)-ethyl]-phenyl}-propionic acid in a yield of 22% of theory; m.p. 202°-205° C.
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]([CH2:18][SiH:19]([Cl:21])[Cl:20])[Cl:17]>C1C=CC=CC=1>[Cl:15][Si:16]1([Cl:17])[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:19]([Cl:21])([Cl:20])[CH2:18]1.[Cl:15][Si:16]([Cl:17])([CH2:18][Si:19]([Cl:21])([Cl:20])[C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[CH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:8]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[CH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cl[SiH](Cl)C[SiH](Cl)Cl
Reactant: C(#Cc1ccccc1)c1ccccc1
Solvent: c1ccccc1
Product: Cl[Si](Cl)(C[Si](Cl)(Cl)C(=Cc1ccccc1)c1ccccc1)C(=Cc1ccccc1)c1ccccc1
Product: Cl[Si]1(Cl)C[Si](Cl)(Cl)C(c2ccccc2)C1c1ccccc1
Reaction time: 12 h
Yield: 4 %
Yield: 71 %

Procedure:
Hydrosilation of diphenylacetylene in the presence Into the same apparatus as described in Example 1 were added 6.1 g of bis(dichlorosilyl)methane, 6.1 g of diphenylacetylene, 28.3 μI of 0.1 M H2PtCl6 /IPA, and 20 ml of dried benzene. The flask content was refluxed, with stirring, for 12 hours and then the solvent removed at atmospheric pressure. The products were vacuum distilled at 67 Pa to give a crude product mixture. Crystallization from benzene gave 7.83 g of 1,1,3,3-tetrachloro-4,5-diphenyl-1,3-disilacyclopentane (yield 71 %) and 0.7 g of 3,3,5,5-tetrachloro-1,2,6,7-tetraphenyl-3,5-disilahepta-1,6-diene (yield 4%). 1,1,3,3-Tetrachloro-4,5-diphenyl-1,3-disilacyclopentane=1H-NMR (CDCl3, ppm): 1.51 (s, 2H, SiCH2Si), 3.50 (s, 2H, CHCH), 7.12-7.28 (m, 1OH, ArH) and 3,3,5,5-tetrachloro-1,2,6,7-tetraphenyl-3,5-disilahepta-1,6-diene=1H-NMR (CDCl3, ppm): 1.28 (s, 2H, SiCH2Si), 7.07 (s, 1H, CHPh), 7.16-7.41 (m, 20H, ArH).
Reaction SMILES: [NH2:1][C@H:2]([C:6]([O:8][CH2:9][C@@H:10]([C:18]([OH:20])=[O:19])[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])=[O:7])[C@@H:3]([CH3:5])[OH:4].ClCC(O)=O.[N:26]([O-])=O.[K+]>>[N+:1](=[C:2]([C@H:3]([OH:4])[CH3:5])[C:6]([O:8][CH2:9][C@@H:10]([C:18]([OH:20])=[O:19])[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])=[O:7])=[N-:26]
Reactant: O=N[O-]
Reactant: C[C@@H](O)[C@H](N)C(=O)OC[C@H](NC(=O)C(F)(F)F)C(=O)O
Agent: O=C(O)CCl
Agent: [K+]
Product: C[C@@H](O)C(=[N+]=[N-])C(=O)OC[C@H](NC(=O)C(F)(F)F)C(=O)O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of O-(L-threonyl)-N-(trifluoroacetyl)-L-serine (109 mg) were added aqueous 4M chloroacetic acid (20 μl) and aqueous 6M potassium nitrite (120 μl) and the solution was stirred at room temperature for 15 minutes.