Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Si:4]([CH2:14][CH:15]=[CH2:16])([CH2:11][CH:12]=[CH2:13])[CH2:5][CH2:6][CH2:7][O:8]C=O)[CH:2]=[CH2:3].CO.C(=O)([O-])O.[K+]>O>[CH2:14]([Si:4]([CH2:1][CH:2]=[CH2:3])([CH2:11][CH:12]=[CH2:13])[CH2:5][CH2:6][CH2:7][OH:8])[CH:15]=[CH2:16]
Reactant: C=CC[Si](CC=C)(CC=C)CCCOC=O
Agent: O=C([O-])O
Agent: [K+]
Solvent: O
Solvent: CO
Product: C=CC[Si](CC=C)(CC=C)CCCO
Temperature: 50 °C
Reaction time: 5 h

Procedure:
The triallyl formyloxypropyl silane intermediate was converted to the hydroxylpropyl product by charging 5.0 grams of the intermediate, together with 50 ml of methanol (commercially available from Burdick and Jackson of Muskeegon, Mich.) and 10 ml of deionized water, in a 250 ml flask with stir bar. 1.0 gram (10 millimoles) of potassium hydrogen carbonate (commercially available from Aldrich Chemical Co.) was added to the solution, which was then stirred at 50° C. for five hours. The solution was filtered and was concentrated in vacuo. The sample was then taken up in cyclohexane and was washed with saturated aqueous sodium chloride before drying over anhydrous sodium sulfate (commercially available from Aldrich Chemical Co.). The sample was then purified using flash chromatography on silica with 99/1 cyclohexane/acetone eluent initially, followed by 80/20 cyclohexane/acetone. The recovered fractions were concentrated in vacuo to yield triallyl 3-hydroxypropyl silane, as shown by capillary GC/FID analysis using a 30 meter DB-5 column. Spectroscopic analysis using mass spectrometry, FTIR and NMR was consistent with triallyl-3-hydroxypropyl silane.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C@@H:13]1[CH2:18][CH2:17][C@H:16]([N:19]2[CH2:24][CH2:23][N:22]([C:25]3[CH:26]=[C:27]([C:35]([OH:37])=[O:36])[CH:28]=[C:29]4[C:34]=3[N:33]=[CH:32][CH:31]=[CH:30]4)[CH2:21][CH2:20]2)[CH2:15][CH2:14]1)#[N:2].[Si](C=[N+]=[N-])(C)(C)[CH3:39]>CO.C1(C)C=CC=CC=1.CCO>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C@@H:13]1[CH2:18][CH2:17][C@H:16]([N:19]2[CH2:20][CH2:21][N:22]([C:25]3[CH:26]=[C:27]([C:35]([O:37][CH3:39])=[O:36])[CH:28]=[C:29]4[C:34]=3[N:33]=[CH:32][CH:31]=[CH:30]4)[CH2:23][CH2:24]2)[CH2:15][CH2:14]1)#[N:2]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: Cn1cc([C@H]2CC[C@@H](N3CCN(c4cc(C(=O)O)cc5cccnc45)CC3)CC2)c2cc(C#N)ccc21
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: CO
Product: COC(=O)c1cc(N2CCN([C@H]3CC[C@@H](c4cn(C)c5ccc(C#N)cc54)CC3)CC2)c2ncccc2c1
Temperature: 23 °C
Reaction time: 12 h

Procedure:
To 50 mg (0.1 mmol) of 8-[4-[(Cis)-4-(5-cyano-1-methyl-1H-indole-3-yl)cyclohexyl]-1-piperazinyl]-6-quinolinecarboxylic acid in 1 mL of MeOH and 3 mL of C6H5CH3 at 23° C. was added 0.9 mL (0.39 mmol) of a 10% solution of (CH3)3SiCHN2 in hexanes. After stirring at 23° C. for 12 hours, the volatiles were removed by rotary evaporation. The crude product was chromatographed on silica gel eluting with 20:1 CH2Cl2:MeOH. The product fractions were pooled, stripped, and treated with 5 mg (0.05 mmol) of (CO2H)2 in absolute EtOH to give 20 mg (0.04 mmol, a 40% yield) of the oxalate salt of the title compound as a tan crystalline solid. mp: 153-155° C.; MS (ES) m/z: 599 (MH)+.
Reaction SMILES: [C:1]1([C@@H:7]([N:9]([CH2:14][C@H:15]2[CH2:20][N:19]([S:21]([C:24]3[S:25][CH:26]=[CH:27][CH:28]=3)(=[O:23])=[O:22])[CH2:18][CH2:17][N:16]2[C:29]2[CH:34]=[CH:33][C:32]([C@@:35]([OH:41])([CH3:40])[C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=2)[S:10]([CH3:13])(=[O:12])=[O:11])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1([C@H](N(C[C@H]2CN(S(C3SC=CC=3)(=O)=O)CCN2C2C=CC([C@](O)(C)C(F)(F)F)=CC=2)S(C)(=O)=O)C)C=CC=CC=1.C1([C@@H](N(C[C@H]2CN(S(C3SC=CC=3)(=O)=O)CCN2C2C=CC([C@](O)(C)C(F)(F)F)=CC=2)S(C)(=O)=O)C)C=CC=CC=1>>[C:1]1([C@H:7]([N:9]([CH2:14][C@H:15]2[CH2:20][N:19]([S:21]([C:24]3[S:25][CH:26]=[CH:27][CH:28]=3)(=[O:23])=[O:22])[CH2:18][CH2:17][N:16]2[C:29]2[CH:30]=[CH:31][C:32]([C@@:35]([OH:41])([CH3:40])[C:36]([F:38])([F:37])[F:39])=[CH:33][CH:34]=2)[S:10]([CH3:13])(=[O:12])=[O:11])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C[C@@H](c1ccccc1)N(C[C@H]1CN(S(=O)(=O)c2cccs2)CCN1c1ccc([C@](C)(O)C(F)(F)F)cc1)S(C)(=O)=O
Agent: C[C@@H](c1ccccc1)N(C[C@H]1CN(S(=O)(=O)c2cccs2)CCN1c1ccc([C@@](C)(O)C(F)(F)F)cc1)S(C)(=O)=O
Agent: C[C@H](c1ccccc1)N(C[C@H]1CN(S(=O)(=O)c2cccs2)CCN1c1ccc([C@@](C)(O)C(F)(F)F)cc1)S(C)(=O)=O
Product: C[C@H](c1ccccc1)N(C[C@H]1CN(S(=O)(=O)c2cccs2)CCN1c1ccc([C@](C)(O)C(F)(F)F)cc1)S(C)(=O)=O

Procedure:
N-((1S)-1-phenylethyl)-N-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-((1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)methanesulfonamide; N-((1R)-1-phenylethyl)-N-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-((1R)-2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)methanesulfonamide; and N-((1S)-1-phenylethyl)-N-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-((1R)-2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)methanesulfonamide
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([P:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:10]2[C:15]([CH3:16])=[CH:14][C:13]([Br:17])=[C:12]([CH3:18])[CH:11]=2)=[CH:4][C:3]=1[CH3:25].ClC1C=C(C=CC=1)C(OO)=[O:31]>C(Cl)Cl>[Br:17][C:13]1[CH:14]=[C:15]([CH3:16])[C:10]([P:9](=[O:31])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:5]2[C:6]([CH3:8])=[CH:7][C:2]([Br:1])=[C:3]([CH3:25])[CH:4]=2)=[CH:11][C:12]=1[CH3:18]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1cc(P(c2ccccc2)c2cc(C)c(Br)cc2C)c(C)cc1Br
Solvent: ClCCl
Product: Cc1cc(P(=O)(c2ccccc2)c2cc(C)c(Br)cc2C)c(C)cc1Br
Yield: 61.3 %

Procedure:
Monomer 1 (30 g, 63.0 mmol, 1 equiv.) was dissolved in methylene choride (200 ml) at room temperature. m-Chloroperoxybenzoic acid (MCPBA, 50 wt %, ca. 22 g, 63.0 mmol, 1 equiv) was then added portion wise. A small exotherm was noted. Once the addition was complete, thin layer chromatography revealed complete conversion after approximately 5 minutes. The crude product was extracted with aqueous sodium hydroxide (2 M) and the organic layer evaporated under reduced pressure to give the crude product as a white solid. Crystallisation from ethanol gave the title compound (19 g, 63%). GC-MS 99.6%, M+ 491 (expected M+ 491)); 31P-NMR (CDCl3) δ (ppm) 34.
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[C:9]([F:10])=[C:8]([F:11])[CH:7]=[CH:6][C:5]=1[CH2:12]Br.[Br:14][C:15]1[CH:23]=[C:22]2[C:18]([CH2:19][CH2:20][C:21]2=[O:24])=[CH:17][CH:16]=1.[H-].[Na+]>C1COCC1>[Br:14][C:15]1[CH:23]=[C:22]2[C:18]([CH2:19][C:20]3([C:21]2=[O:24])[CH2:2][CH2:3][C:4]2[C:5](=[CH:6][CH:7]=[C:8]([F:11])[C:9]=2[F:10])[CH2:12]3)=[CH:17][CH:16]=1
Reactant: O=C1CCc2ccc(Br)cc21
Reactant: Fc1ccc(CBr)c(CCBr)c1F
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1c2cc(Br)ccc2CC12CCc1c(ccc(F)c1F)C2
Yield: 45.8 %

Procedure:
To a solution of 2-(2-bromoethyl)-1-(bromomethyl)-3,4-difluorobenzene (3 g, 9.62 mmol) and 6-bromo-2,3-dihydro-1H-inden-1-one (2.03 mg, 9.62 mmol) in THF (20 mL) was added NaH (0.58 mg, 14.43 mmol), and the mixture was refluxed for 2 hour. The reaction was cooled and quenched with ice-water. The mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give the residue, which was purified by preparative TLC to afford 6-bromo-5′,6′-difluoro-3′,4′-dihydro-1′H-spiro[indene-2,2′-naphthalen]-1(3H)-one (1.6 g, 46%). 1H NMR (CDCl3): 1.68 (m, 1H), 2.01 (m, 1H), 2.47 (d, 1H), 2.72 (m, 2H), 2.89 (d, 1H), 3.07 (m, 2H), 6.71 (m, 1H), 6.86 (m, 1H), 7.22 (d, 1H), 7.63 (d, 1H), 7.92 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[NH:8][N:9]=[C:10]([OH:11])[C:5]2=[C:4]([CH3:12])[CH:3]=1.[N:13]([CH2:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)=[C:14]=[O:15]>C1COCC1>[S:19]1[CH:20]=[CH:21][CH:22]=[C:18]1[CH2:17][CH2:16][NH:13][C:14]([N:9]1[C:10](=[O:11])[C:5]2[C:6](=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:12])[NH:8]1)=[O:15]
Reactant: O=C=NCCc1cccs1
Reactant: Cc1cc(Cl)nc2[nH]nc(O)c12
Solvent: C1CCOC1
Product: Cc1cc(Cl)nc2[nH]n(C(=O)NCCc3cccs3)c(=O)c12

Procedure:
In analogy to example 1c, 200 mg (1.09 mmol) of 6-chloro-4-methyl-1H-pyrazolo-[3,4-b]pyridin-3-ol were reacted with 183.5 mg (1.19 mmol) of 2-(2-isocyanatoethyl)-thiophene in THF at room temperature. Yield: 184 mg (50%), M+H+: 337.09.
Reaction SMILES: N1C=CC=CC=1.[CH3:7][N:8]([O:19][CH3:20])[C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([NH2:17])[CH:11]=1.[CH:21]([S:24](Cl)(=[O:26])=[O:25])([CH3:23])[CH3:22].CCCCCC>ClCCl.C(OCC)(=O)C>[CH3:7][N:8]([O:19][CH3:20])[C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([NH:17][S:24]([CH:21]([CH3:23])[CH3:22])(=[O:26])=[O:25])[CH:11]=1
Reactant: CON(C)C(=O)c1ccc(N)c(N)c1
Reactant: CC(C)S(=O)(=O)Cl
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CON(C)C(=O)c1ccc(N)c(NS(=O)(=O)C(C)C)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 40 %

Procedure:
Add dry pyridine (234 mL, 2.94 moles) to a cold (0° C.) solution of N-[methyl] N-[methoxy] 3,4-diaminobenzamide (135 g, 0.69 moles) in 1 liter of dry dichloromethane under a nitrogen atomosphere. Add isopropylsulfonyl chloride (85.4 mL, 0.76 moles) at 0° C. over 30 minutes, stir the mixture 0° C. for another 30 minutes, and then at room temperature overnight. Concentrate the reaction mixture under reduced pressure and partition the residue with diethyl ether (1 L) and 5 N hydrochloric acid (1 L). Separate the layers, discard the diethyl ether layer, add ethyl acetate (1.5 L) to the aqueous layer and stir while adding solid sodium carbonate until pH=6.5. Extract the aqueous layer using ethyl acetate, wash the combined organic layers, dry over magnesium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography eluting with a gradient 65:3 ethyl acetate:hexane to 100% ethyl acetate to provide a 40% yield of the desired compound.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].C([Sn](CCCC)(CCCC)[C:17]([O:19]CC)=[CH2:18])CCC>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>[F:8][C:7]1[CH:6]=[CH:5][C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]=1[C:17](=[O:19])[CH3:18]
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Reactant: O=[N+]([O-])c1ccc(F)c(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CC(=O)c1cc([N+](=O)[O-])ccc1F
Temperature: 110 °C
Reaction time: 0.67 h

Procedure:
To a solution of 3-bromo-4-fluoronitrobenzene (696 mg, 3.16 mmol) and tributyl(1-ethoxyvinyl)tin (1.07 ml, 3.5 mmol) in 10 mL toluene, was added tetrakis(triphenylphosphine)palladium(0) (183 mg, 016 mmol). The mixture was purged with argon for 3 minutes, and then heated to 110° C. under argon for 2 days. The reaction mixture was cooled to room temperature, 3 mL 1 N HCl was added and stirred at room temperature for 40 minutes. Workup followed by column chromatographic purification (silica 10%-30% EtOAc/hexane) to give pure 1-(2-fluoro-5-nitro-phenyl)-ethanone.
Reaction SMILES: I.CO[C:4]1[C:9]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])=[CH:8][CH:7]=[CH:6][C:5]=1[CH:18]([CH2:22][CH3:23])[C:19]([OH:21])=[O:20].OC1C(OC2C=CC=CC=2C)=CC=CC=1C(CC)C(O)=O>C(OC(=O)C)(=O)C>[CH2:22]([CH:18]1[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([O:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH3:17])[C:4]=2[O:20][C:19]1=[O:21])[CH3:23]
Reactant: CCC(C(=O)O)c1cccc(Oc2ccccc2C)c1OC
Agent: CCC(C(=O)O)c1cccc(Oc2ccccc2C)c1O
Agent: I
Solvent: CC(=O)OC(C)=O
Product: CCC1C(=O)Oc2c(Oc3ccccc3C)cccc21
Yield: 33.1 %

Procedure:
Hydriodic acid (55-58%, 20 ml) and a solution of 2-[2-methoxy-3-(o-tolyloxy)phenyl]butyric acid (2.2 g) in acetic anhydride (10 ml) were treated in a similar manner to that of Example 10-(7). The resultant product, i.e. 2-[2-hydroxy-3-(o-tolyloxy)phenyl]butyric acid was treated with acetic anhydride (20 ml) in a similar manner to that of Example 10-(7) to give 3-ethyl-7-(o-tolyloxy)-2,3-dihydrobenzofuran-2-one (650 mg). mp 44°-45° C.
Reaction SMILES: [F:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH3:11])[CH:5]=[CH:4][C:3]=1[N+:12]([O-])=O>C(O)C.[Pt](=O)=O>[F:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH3:11])[CH:5]=[CH:4][C:3]=1[NH2:12]
Reactant: COc1ccc([N+](=O)[O-])c(F)c1OC
Agent: O=[Pt]=O
Solvent: CCO
Product: COc1ccc(N)c(F)c1OC
Yield: 94.6 %

Procedure:
2-Fluoro-3,4-dimethoxy-1-nitrobenzene (52 g, 259 mmol) was hydrogenated on a Par shaker (30 psi) in Ethanol (300 mL) with platinum(IV) oxide (5 g, 22.02 mmol) at r.t. for 30 mins. LCMS indicated completion of the reaction. The catalyst was filtered off and the filtrate was concentrated to afford 2-fluoro-3,4-dimethoxyaniline (42 g, 245 mmol, 95% yield) as a brown oil. LCMS (M+H)+: 172.0.
Reaction SMILES: C[Si](C)(C)[NH:3][Si](C)(C)C.CO.[C:12]([O:16][C:17]([N:19]1[CH2:23][CH2:22][C:21]2([CH2:52][CH2:51][N:26]3[C:27]4[C:32]([C:33]([C:34]5[C:35](=[O:50])O[C:37](=[O:49])[C:38]=5[C:39]5[C:47]6[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=6)[N:41]([CH3:48])[CH:40]=5)=[C:25]3[CH2:24]2)=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].O>CN(C=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:23][CH2:22][C:21]2([CH2:52][CH2:51][N:26]3[C:27]4[C:32]([C:33]([C:34]5[C:35](=[O:50])[NH:3][C:37](=[O:49])[C:38]=5[C:39]5[C:47]6[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=6)[N:41]([CH3:48])[CH:40]=5)=[C:25]3[CH2:24]2)=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:20]1)=[O:18])([CH3:13])([CH3:14])[CH3:15]
Reactant: C[Si](C)(C)N[Si](C)(C)C
Reactant: Cn1cc(C2=C(c3c4n(c5ccccc35)CCC3(CCN(C(=O)OC(C)(C)C)C3)C4)C(=O)OC2=O)c2ccccc21
Solvent: CN(C)C=O
Solvent: CO
Solvent: O
Product: Cn1cc(C2=C(c3c4n(c5ccccc35)CCC3(CCN(C(=O)OC(C)(C)C)C3)C4)C(=O)NC2=O)c2ccccc21
Reaction time: 16 h
Yield: 58.7 %

Procedure:
A mixture of 4.09 g of 1,1,1,3,3,3-hexamethyldisilazane and 0.41 g of methanol was added to a solution of 1.40 g of 3-[1'-(tert.butoxycarbonyl)-7,9-dihydrospiro[pyrido[1,2-a]indole-8(6H),3'-pyrrolidin]-10-yl]-4-(1-methyl-3-indolyl)furan-2,5-dione in 25 ml of dry DMF and stirred for 16 hours. The mixture was poured into 100 ml of water and extracted with ethyl acetate. The ethyl acetate extracts were washed with sodium chloride solution, dried and concentrated. There were obtained 820 mg of 3-[1'-(tert.butoxycarbonyl)-7,9-dihydrospiro[pyrido-[1,2-a]indole-8(6H).3'-pyrrolidin]-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione after chromatography on silica gel using dichloromethane/methanol (9:1) for the elution.
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.CC(C)([O-])C.[K+].Br[CH2:14][CH2:15][CH2:16][Cl:17].O>CN(C=O)C>[Cl:17][CH2:16][CH2:15][CH2:14][N:4]1[CH:3]=[C:2]([I:1])[CH:6]=[N:5]1
Reactant: Ic1cn[nH]c1
Reactant: ClCCCBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: ClCCCn1cc(I)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
2.0 g (10.31 mmol) 4-iodopyrazole were dissolved in 20 ml DMF and 1.22 g (10.8 mmol) potassium t-butoxide was added. The mixture was stirred for 1 hour at room temperature and 1.06 ml (10.83 mmol) 1-bromo-3-chloropropane were added. A white precipitate appeared rapidly. After 30 minutes 50 ml water was added and the reaction mixture was extracted twice with 100 ml hexane. The combined organic layers were dried over MgSO4 and the solvent was removed to give 2.65 g of the desired product as a colourless oil. MS (ISP): 270.1 (MH+). 1H-NMR (CDCl3): 2.31 (quint, 2H), 3.47 (t, 2H), 4.32 (t, 2H), 7.48 (s, 1H), 7.53 (s, 1H).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][C:12]=3[O:19][CH3:20])=[CH:9][C:4]=2[N:3]=[CH:2]1.COC(OC)C1C=CC(OC2C=CC3NC=NC=3C=2)=C(OC)C=1.[NH2:44][CH:45]1[CH2:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:46]1>>[NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:18]=[CH:17][C:14]([CH2:15][NH:44][CH:45]4[CH2:53][C:52]5[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=5)[CH2:46]4)=[CH:13][C:12]=3[O:19][CH3:20])=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: NC1Cc2ccccc2C1
Reactant: COc1cc(C=O)ccc1Oc1ccc2[nH]cnc2c1
Agent: COc1cc(C(OC)OC)ccc1Oc1ccc2[nH]cnc2c1
Product: COc1cc(CNC2Cc3ccccc3C2)ccc1Oc1ccc2[nH]cnc2c1

Procedure:
N-{[4-(1H-Benzimidazol-5-yloxy)-3-(methyloxy)phenyl]methyl}-2,3-dihydro-1H-inden-2-amine was prepared using a mixture of 4-(1H-benzimidazol-5-yloxy)-3-(methyloxy)benzaldehyde and 5-{[4-[bis(methyloxy)methyl]-2-(methyloxy)phenyl]oxy}-1H-benzimidazole and the procedure of General method 1, step 5 where 2-aminoindane is the amine.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-])=O)[C:6]([N:12]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:5]([CH3:27])[CH:4]=1)#[N:2].S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)(O)[O-].[Na+].CO>C1COCC1.O>[NH2:9][C:7]1[CH:8]=[C:3]([C:1]#[N:2])[CH:4]=[C:5]([CH3:27])[C:6]=1[N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21]
Reactant: Cc1cc(C#N)cc([N+](=O)[O-])c1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(C#N)cc(N)c1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Di-t-butyl (4-cyano-2-methyl-6-nitrophenyl)imidodicarbonate obtained in Step 1 (3.77 g, 10 mmol) was dissolved in THF (0.2 M, 50 mL), and a solution prepared by dissolving sodium hydrosulfite (15.7 g, 9 eq, 90 mmol) and sodium bicarbonate (7.56 g, 90 mmol) in H2O (0.1 M, 100 mL) was added thereto. Subsequently, MeOH (17 mL) was added to the mixture, which was then stirred at room temperature for 1 hour. Upon completion of the reaction, THF and MeOH were removed under reduced pressure, and the residue was added with brine and extracted with ethyl acetate. The organic layer thus obtained was dried over MgSO4 and concentrated under reduced pressure. Then, the residue was purified by silica gel column chromatography (EA:Hex=1:2) to obtain the title compound in a white solid (2.90 g, yield: 83%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:20])=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH:7]=1.[CH3:21][C:22]1[N:23]=[CH:24][S:25][CH:26]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Ag+2].O.C(#N)C>[CH3:20][C:5]1[CH:4]=[CH:3][C:2]([C:24]2[S:25][CH:26]=[C:22]([CH3:21])[N:23]=2)=[CH:7][C:6]=1[CH:8]1[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]1=[O:19]
Reactant: Cc1ccc(Br)cc1C1C(=O)C(C)(C)OC(C)(C)C1=O
Reactant: Cc1cscn1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CC#N
Product: Cc1csc(-c2ccc(C)c(C3C(=O)C(C)(C)OC(C)(C)C3=O)c2)n1
Temperature: 65 °C
Yield: 17.1 %

Procedure:
To a mixture of 4-(5-bromo-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (200 mg, 0.589 mmol), 4-methylthiazole (70 mg, 0.707 mmol), silver carbonate (814 mg, 2.94 mmol), triphenylphosphine (15 mg, 0.0589 mmol) and [1,1-bis(diphenylphosphino)-ferrocene]palladium(II)chloride (24 mg, 0.0294 mmol) is added a degassed solvent mixture of water/acetonitrile (1.5 ml, 1:1 ratio), followed by subsequent purging with nitrogen then heating at 65° C. for 65 hours with shaking. After cooling to room temperature the reaction mixture is then partitioned between 2M aqueous hydrochloric acid and dichloromethane, and the organic phase is separated. The aqueous layer is washed with a further aliquot of dichloromethane, and the combined organic layers are evaporated under reduced pressure to give a brown solid which is purified by preparative reverse phase HPLC to give 4-[2-methyl-5-(4-methylthiazol-2-yl)phenyl]-2,2,6,6-tetramethylpyran-3,5-dione as a pale yellow solid (36 mg).
Reaction SMILES: [CH2:1]([C@@H:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([OH:10])[CH2:5]1)[CH:2]=[CH2:3].[Si:11](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CN=C1.CC1C=CN=C(N)C=1C>CN(C)C=O.C(OC)(C)(C)C>[CH2:1]([C@@H:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:5]1)[CH:2]=[CH2:3]
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: C=CC[C@@H]1CCC[C@H](O)C1
Agent: Cc1ccnc(N)c1C
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: COC(C)(C)C
Product: C=CC[C@@H]1CCC[C@H](O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
6.8 g of cis-3-allylcyclohexanol are, together with 15 ml of tert-butyl-diphenylsilyl chloride, 5 g of imidazole and 200 mg of dimethyl-aminopyridine, dissolved in 100 ml of dimethylformamide, and the mixture is stirred at room temperature for 12 h. 400 ml of methyl tert-butyl ether are added to the reaction mixture, and the mixture is washed three times with water. The organic phase is dried over MgSO4 and the solvent is then removed under reduced pressure. This gives 20.5 g of (cis-3-allylcyclohexyloxy)-tert-butyl-diphenyl-silane as an oil. C25H340Si (378.64), MS(ESI): 379 (M+H+), Rf(n-heptane:ethyl acetate=2:1)=0.93.
Reaction SMILES: [C:1]([N:8](C)[C@H:9]([C:14]([NH:16][C@H:17]([C:21]([N:23]([CH3:43])[C@H:24]([C:29]([NH:31][C@H:32]([C:34]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:35])[CH3:33])=[O:30])[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])(OC(C)(C)C)=O>FC(F)(F)C(O)=O>[NH:8]([CH3:1])[C@H:9]([C:14]([NH:16][C@H:17]([C:21]([N:23]([CH3:43])[C@H:24]([C:29]([NH:31][C@H:32]([C:34]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:35])[CH3:33])=[O:30])[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:22])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH2:10][CH:11]([CH3:12])[CH3:13]
Reactant: CC(C)C[C@@H](C(=O)N[C@H](C(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)Cc1ccccc1)C(C)C)N(C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CN[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)Cc1ccccc1)C(C)C
Reaction time: 2 h

Procedure:
31.27 g (49.5 mMol) BOC-MeLeu-Val-MeLeu-Ala-Bzl dissolved in 100 ml trifluoroacetic acid are stirred for 21/2 hrs. at room temperature and the product solution concentrated under vacuum. The residue is diluted with 500 ml methylene carbonate solution, ice being added and the aqueous phases extracted with 200 ml methylene chloride. The combined organic phases are dried over potassium carbonate, filtered and concentrated to yield the title compound: rotation [α]D22 =-114.4° (c=1.0 in chloroform), M.P. on re-crystallisation from ether/petrol ether=66°-67°