Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C:5]1([O:11][CH2:12][CH2:13][CH2:14]Br)[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1)(C)(C)C.[OH:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][CH:22]=1>CN(C=O)C>[S:19]1[CH:20]=[CH:21][CH:22]=[C:18]1[CH2:17][O:16][CH2:14][CH2:13][CH2:12][O:11][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1
Reactant: OCc1cccs1
Reactant: CC(C)(C)C1(OCCCBr)CCCCO1
Solvent: CN(C)C=O
Product: c1csc(COCCCOC2CCCCO2)c1

Procedure:
In an analogous manner to that described in Example 1 (g), by alkylating tert-butyl (RS)-2-(3-bromo-propoxy)-tetrahydro-pyran with 2-hydroxymethyl-thiophene in DMF there was obtained (RS)-2-[3-(thiophen-2-ylmethoxy)-propoxy]-tetrahydro-pyran, which after cleavage of the THP group analogously to Example 53 (c), yielded 3-(thiophen-2-ylmethoxy)-propan-1-ol. Subsequent conversion into the mesylate according to a procedure known from the literature and alkylation effected with the latter analogously to Example 44 (e) of tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate gave tert-butyl (3RS,4RS)-3-hydroxy-4-[4-[3-(thiophen-2-ylmethoxy)-propoxy]-phenyl]-piperidine-1-carboxylate. By alkylation with 2-chloromethyl-1,4-dimethoxy-naphthalene analogously to Example 1 (g) there was obtained (3RS,4RS)-3-(1,4-dimethoxy-naphthalen-2-ylmethoxy)-4-{4-[3-(thiophen-2-ylmethoxy)-propoxy]-phenyl}-piperidine-1-carboxylate as a pale yellow resin; MS: 648 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH:11][C:12](=O)[CH3:13])=[CH:5][CH:4]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[C:6]([CH2:9][CH2:10][N:11]=[C:12]2[CH3:13])=[CH:5][CH:4]=1
Reactant: COc1ccc(CCNC(C)=O)cc1
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Product: COc1ccc2c(c1)C(C)=NCC2

Procedure:
In close analogy to the procedure described above, N-[2-(4-methoxy-phenyl)-ethyl]-acetamide is reacted with phosphorus pentoxide to provide the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]2.[CH3:13][N:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:15](Cl)=[O:16]>>[O:12]=[C:8]1[CH2:7][CH2:6][CH2:5][C:4]2[CH:3]=[C:2]([O:1][C:15](=[O:16])[N:14]([CH3:13])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:11]=[CH:10][C:9]1=2
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: O=C1CCCc2cc(O)ccc21
Product: CN(C(=O)Oc1ccc2c(c1)CCCC2=O)c1ccccc1

Procedure:
The title product was prepared from 6-hydroxy-1-tetralone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (49%, colorless oil). HPLC-MS: m/z=296.2 (M+1); Rt: 3.90 min.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2Cl)=[CH:6][N:5]=[C:4]([NH:15][C:16]2[N:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH:3]=1.CC(C)([O-])C.[Na+].N#N.[NH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C([O-])(=O)C.C([O-])(=O)C.[Pd+2].COCCOC>[C:44]1([N:43]2[C:9]3[CH:10]=[N:11][CH:12]=[CH:13][C:8]=3[C:7]3[CH:6]=[N:5][C:4]([NH:15][C:16]4[N:21]=[CH:20][C:19]([N:22]5[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:26][CH2:27]5)=[CH:18][CH:17]=4)=[CH:3][C:2]2=3)[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
Reactant: Nc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3cc(Cl)c(-c4ccncc4Cl)cn3)nc2)CC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3cc4c(cn3)c3ccncc3n4-c3ccccc3)nc2)CC1
Temperature: 100 °C
Reaction time: 20 h

Procedure:
In a 10 mL single-necked round bottom flask were placed tert-butyl 4-(6-(4-chloro-5-(3-chloropyridin-4-yl)pyridin-2-ylamino)pyridin-3-yl)piperazine-1-carboxylate (371) (50 mg, 100 μmol), palladium diacetate (11 mg, 50 μmol), Josiphos (28 mg, 50 μmol), and sodium tert-butoxide (29 mg, 299 μmol). The flask was subjected to 3 cycles of evacuation and back-filling with N2. Aniline (36 μl, 399 μmol) was added under N2 followed by 1,2-dimethoxyethane (3 mL). The resulting mixture was stirred at 100° C. for 20 h. After the volatiles were removed, the residue was subjected to combi-flash column chromatography (methanol/DCM). The product containing compound 372 after concentration was used without further purification. LCMS-ESI (POS), M/Z, M+1: Found 522.2.
Reaction SMILES: [OH:1][CH:2]([CH2:16][CH:17]=[CH2:18])[C@@H:3]([NH:5][C:6](=[O:15])[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:4].N1C(C)=CC=CC=1C.FC(F)(F)S(O)(=O)=O.[C:35]([SiH:39]([CH3:41])[CH3:40])([CH3:38])([CH3:37])[CH3:36].O>O1CCCC1>[CH2:8]([O:7][C:6](=[O:15])[NH:5][C@@H:3]([CH3:4])[CH:2]([O:1][Si:39]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:41])[CH3:40])[CH2:16][CH:17]=[CH2:18])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: C=CCC(O)[C@H](C)NC(=O)OCc1ccccc1
Reactant: C[SiH](C)C(C)(C)C
Agent: O=S(=O)(O)C(F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Solvent: O
Product: C=CCC(O[Si](C)(C)C(C)(C)C)[C@H](C)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution (30 mL) of benzyl [(1S)-1-methyl-2-oxoethyl]carbamate (3.0 g) in tetrahydrofuran was added 1.0 mol/L solution (28.8 mL) of allylmagnesium bromide in tetrahydrofuran under ice-cooling, and the mixture was stirred at room temperature for 18 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→1:1) to give benzyl [(1S)-2-hydroxy-1-methylpent-4-en-1-yl]carbamate as a colorless oil. To a solution (10 mL) of the obtained benzyl [(1S)-2-hydroxy-1-methylpent-4-en-1-yl]carbamate in tetrahydrofuran were added 2,6-lutidine (0.629 mL) and tert-butyldimethylsilane trifluoromethanesulfonate (0.91 mL) and the mixture was stirred at room temperature for 30 min. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→2:1) to give the title compound as a colorless oil (yield: 610 mg).
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[Cl:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:13]2>CN(C)C=O>[Br:1][C:13]1[C:12]2[C:16](=[CH:17][CH:18]=[C:10]([Cl:9])[CH:11]=2)[NH:15][C:14]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20]
Reactant: CCOC(=O)c1cc2cc(Cl)ccc2[nH]1
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Product: CCOC(=O)c1[nH]c2ccc(Cl)cc2c1Br
Temperature: 25 °C
Reaction time: 18 h
Yield: 100.5 %

Procedure:
N-Bromosuccinimide (440 mg) was added to a solution of ethyl 5-chloroindole-2-carboxylate (500 mg) in N,N-dimethylformamide (10 ml). The reaction mixture was stirred at room temperature for 18 hours, and the solvent was distilled off under reduced pressure. The residue was partitioned in ethyl acetate and water, and a water layer was extracted with ethyl acetate. The resultant organic layers were combined, washed with saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:9), and white powder thus obtained was washed with hexane to obtain the title compound (680 mg).
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[O:14][CH3:15].[CH3:16][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:15][O:14][C:6]1[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=[CH:10][C:5]=1[O:4][CH2:3][CH2:2][N:20]1[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]1
Reactant: COc1cc([N+](=O)[O-])ccc1OCCCl
Reactant: CN1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1cc([N+](=O)[O-])ccc1OCCN1CCN(C)CC1

Procedure:
A mixture of 1-(2-chloroethoxy)-2-methoxy-4-nitrobenzene (Step A, 1 eq), N-methylpiperazine (3 eq) and K2CO3 (2.5 eq) in CH3CN was stirred and heated under reflux until HPLC indicated the reaction was complete. The resulting solid was filtered, rinsed well with CH2Cl2 and the filtrate and washings were combined, concentrated and purified by column chromatography giving 1-[2-(2-methoxy-4-nitro-phenoxy)-ethyl]-4-methyl-piperazine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8](O)[CH3:9])=[N:6][CH:7]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:23]=[N+:24]=[N-:25].[Na+]>C(Cl)Cl.O>[N:23]([CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=1)[CH3:9])=[N+:24]=[N-:25]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(O)c1ccc(F)cn1
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(N=[N+]=[N-])c1ccc(F)cn1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1-(5-Fluoropyridin-2-yl)ethanol (Method 2; 7.5 g, 53.1 mmol) and triethyl amine (9.3 ml, 66.4 mmol) in anhydrous DCM (50 ml) was added methanesulfonyl chloride (4.5 ml, 58.5 mmol) at 0° C. After adding, the reaction was warmed to room temperature and stirred at room temperature for 2 hours. The solvent was removed. The residue was dissolved in anhydrous DMF (50 ml) and sodium azide (6.9 g, 106 mmol) was added. The reaction stirred at room temperature for 2 hours. Water (50 ml) was added and extracted with ether (2×75 ml).
Reaction SMILES: [OH-].[Na+].C[O:4][C:5](=[O:22])[C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[CH:8][C:7]=1[O:13][CH2:14][CH2:15][C:16]1[N:17]=[N:18][CH:19]=[CH:20][CH:21]=1.Cl>O>[F:12][C:10]1[CH:9]=[CH:8][C:7]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[C:6]([CH:11]=1)[C:5]([OH:22])=[O:4]
Reactant: COC(=O)c1cc(F)ccc1OCCc1cccnn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)c1cc(F)ccc1OCCc1cccnn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 98.8 %

Procedure:
NaOH (87 mg; 2.17 mmol; 10 eq.) was added to a solution of 5-fluoro-2-(2-pyridazin-3-yl-ethoxy)-benzoic acid methyl ester (60 mg; 0.22 mmol; 1 eq.) on THF (1 mL) and the reaction mixture was stirred at room temperature for 16 hours. The solution was diluted with water acidified with 0.1M HCl and extracted with DCM (3×). The combined organics were dried over magnesium sulfate and concentrated in vacuo to give the title compound (57 mg, quantitative) as a yellow solid which was used without further purification. UPLC/MS: (MS+) 263.2 ([M+H]+).
Reaction SMILES: [Cl:1][C:2]1[C:3]([OH:16])=[C:4]([C:11]([O:13]CC)=O)[C:5](=[O:10])[N:6]([CH3:9])[C:7]=1[CH3:8].[NH2:17][C:18]1[S:19][CH:20]=[CH:21][N:22]=1.BrC1C=CC=CC=1>CCCCCC>[Cl:1][C:2]1[C:3]([OH:16])=[C:4]([C:11]([NH:17][C:18]2[S:19][CH:20]=[CH:21][N:22]=2)=[O:13])[C:5](=[O:10])[N:6]([CH3:9])[C:7]=1[CH3:8]
Reactant: CCOC(=O)c1c(O)c(Cl)c(C)n(C)c1=O
Reactant: Nc1nccs1
Solvent: CCCCCC
Solvent: Brc1ccccc1
Product: Cc1c(Cl)c(O)c(C(=O)Nc2nccs2)c(=O)n1C
Temperature: 25 °C
Reaction time: 5 h
Yield: 75.7 %

Procedure:
160 mg of ethyl 5-chloro-1,6-dimethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate and 60 mg of 2-aminothiazole were added to 1.5 ml of bromobenzene, then, the mixture was stirred for 5 hours under heat refluxing condition. The reaction mixture was cooled to room temperature, then, hexane was added to this and the resultant mixture was allowed to stand still. The resulting solid was collected by filtration, and washed with a mixture of t-butyl methyl ether and n-hexane and dried to obtain 136 mg of 5-chloro-1,6-dimethyl-4-hydroxy-2-oxo-N-(2-thiazolyl)-1,2-dihydropyridine-3-carboxamide (hereinafter, referred to as present compound 30) represented by the formula:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[NH:5][C:6]1[C:7]2[S:14][C:13]3[CH:15]=[CH:16][C:17]([N+]([O-])=O)=[CH:18][C:12]=3[C:8]=2[N:9]=[CH:10][N:11]=1.NC1C=CC2SC3C(NC4C=CC=C(Br)C=4)=NC=NC=3C=2C=1.BrC1C=C(C=CC=1)NC1C2SC3C=CC(OC)=CC=3C=2N=CN=1>>[Br:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[NH:5][C:6]1[C:7]2[S:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[C:8]=2[N:9]=[CH:10][N:11]=1
Reactant: O=[N+]([O-])c1ccc2sc3c(Nc4cccc(Br)c4)ncnc3c2c1
Agent: COc1ccc2sc3c(Nc4cccc(Br)c4)ncnc3c2c1
Agent: Nc1ccc2sc3c(Nc4cccc(Br)c4)ncnc3c2c1
Product: Brc1cccc(Nc2ncnc3c2sc2ccccc23)c1

Procedure:
4-(3-bromoanilino)-8-nitrobenzothieno[3,2-d]pyrimidine; 8-amino-4-(3-bromoanilino)benzothieno[3,2-d]pyrimidine; and 4-(3-bromoanilino)-8-methoxybenzothieno[3,2-d]pyrimidine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[OH:12][C:13]1[CH:37]=[CH:36][C:16]([C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]3[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=3)([CH3:28])[CH3:27])[CH:21]=2)([CH3:19])[CH3:18])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[N+:9]([C:4]1[CH:3]=[C:2]([F:1])[C:7]([O:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([CH3:27])([CH3:28])[C:29]4[CH:30]=[CH:31][C:32]([O:35][C:7]5[C:2]([F:1])=[CH:3][C:4]([N+:9]([O-:11])=[O:10])=[CH:5][CH:6]=5)=[CH:33][CH:34]=4)[CH:21]=3)([CH3:19])[CH3:18])=[CH:36][CH:37]=2)=[CH:6][CH:5]=1)([O-:11])=[O:10]
Reactant: CC(C)(c1ccc(O)cc1)c1cccc(C(C)(C)c2ccc(O)cc2)c1
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(c1ccc(Oc2ccc([N+](=O)[O-])cc2F)cc1)c1cccc(C(C)(C)c2ccc(Oc3ccc([N+](=O)[O-])cc3F)cc2)c1
Temperature: 80 °C
Yield: 104.1 %

Procedure:
To a reaction vessel equipped with a thermometer, reflux condenser and a stirrer, 200 g of N,N-dimethylformamide (DMF), 65 g (0.409 mol) of 3,4-difluoronitrobenzene, 69.1 g (0.199 mol) of 1,3-bis(4-hydroxycumyl) benzene and 33.1 g (0.239 mol) of potassium carbonate were charged and warmed to 80° C. with stirring. After aging the mixture at 80° C. for 6 hours, inorganic salts was removed by filtration. The filtrate was mixed with 50 ml of water and cooled to the room temperature. The precipitated crystal was filtered and slugged with isopropyl alcohol to obtain 129.4 g (97% yield) of 1,3-bis[4-(4-nitro-6-fluorophenoxy)-α, α-dimethylbenzyl]benzene having a melting point of 150.7°~151.8° C.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH:6]([NH:12][CH:13]=[O:14])[C:7]([Cl:11])([Cl:10])[CH2:8][Cl:9]>>[Cl:3][CH:6]([NH:12][CH:13]=[O:14])[C:7]([Cl:11])([Cl:10])[CH2:8][Cl:9]
Reactant: O=CNC(O)C(Cl)(Cl)CCl
Reactant: O=S(Cl)Cl
Product: O=CNC(Cl)C(Cl)(Cl)CCl

Procedure:
Thionyl chloride was poured over 20.6 gm of N-(1-hydroxy-2,2,3-trichloro-n-propyl)-formamide, and the mixture was refluxed for 15 minutes. Subsequently, the excess thionyl chloride was distilled off, and the residue was recrystallized from benzene/petroleum ether, m.p. 55°-57° C.
Reaction SMILES: [CH:1](=[N:8]/[OH:9])/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClN1[C:15](=[O:16])[CH2:14][CH2:13]C1=O.N1C=CC=CC=1.C(O)C#C.CCN(CC)CC>C1COCC1>[C:2]1([C:1]2[CH:13]=[C:14]([CH2:15][OH:16])[O:9][N:8]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O/N=C\c1ccccc1
Reactant: O=C1CCC(=O)N1Cl
Agent: C#CCO
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: OCc1cc(-c2ccccc2)no1
Temperature: 0 °C
Reaction time: 1 h
Yield: 36.4 %

Procedure:
(Z)-Benzaldehyde oxime (3.4 g, 28.2 mmol) was dissolved in anhydrous THF (50 mL) and cooled to 0° C. N-Chlorosuccinimide (5.63 g, 42.3 mmol) and pyridine (221 mg, 2.8 mmol) were added and the mixture was stirred at room temperature for 1 hour. Prop-2-yn-1-ol (1.89 g, 33.4 mmol) and NEt3 (286 mg, 2.8 mmol) were added and the mixture was heated at reflux for 2 hours. The reaction was cooled and quenched with water, extracted with EtOAc and dried over anhydrous sodium sulfate. The solution was concentrated under vacuum to give a crude product, which was purified by column chromatography to afford (3-phenylisoxazol-5-yl)methanol as a white solid (1.8 g).
Reaction SMILES: [CH2:1]1[C:10](=[O:11])[CH2:9][C:8]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:2]1.C(N(CC)CC)C.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Si:19]([O:11][C:10]1[CH2:1][CH2:2][C:3]2[C:8](=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH:9]=1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1CCc2ccccc2C1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OC1=Cc2ccccc2CC1
Reaction time: 72 h

Procedure:
Charge an oven dried, nitrogen flushed 125-mL round bottomed flask equipped with a stirring bar with β-tetralone (4.977 grams, 0.0340 moles), triethylamine (6.970 grams, 0.0689 moles), 4-dimethylamino pyridine (0.217 grams, 0.0018 moles), t-butyldimethylsilyl chloride (10.701 grams, 0.0709 moles) and 40 mL methylene chloride. Stir for 72 hours, filter, wash the filtrate with 1×5 mL saturated sodium bicarbonate solution, 1×5 mL water, dry over magnesium sulfate, concentrate using a Buchi rotavapor and distill (142°-145° C., 1 Torr) to obtain the named compound
Reaction SMILES: C([O:8][CH2:9][CH2:10][C@H:11]([OH:17])[C:12]([CH3:16])([CH3:15])[C:13]#[N:14])C1C=CC=CC=1>[OH-].[OH-].[Pd+2].O1CCCC1>[OH:8][CH2:9][CH2:10][C@H:11]([OH:17])[C:12]([CH3:16])([CH3:15])[C:13]#[N:14]
Reactant: CC(C)(C#N)[C@@H](O)CCOCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)(C#N)[C@@H](O)CCO
Reaction time: 7.5 h

Procedure:
16 g of Pearlman's catalyst (Pd(OH)2 on carbon, 20%) is added to 11.13 g (47.70 mmol) of 5-benzyloxy-2,2-dimethyl-3 (S)-hydroxy-pentane-nitrile of the title compound of Example 1c, dissolved in 110 ml of tetrahydrofuran. It is now hydrogenated for 7.5 hours at 10 bar and at room temperature. Catalyst is filtered out, and the filtrate is evaporated to the dry state in a vacuum.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[CH:12]=[CH:11][N:10]2[CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:15]=[C:9]2[CH:8]=1)=[O:6].Cl>C(O)C.O>[C:16]1([C:14]2[N:15]=[C:9]3[CH:8]=[C:7]([C:5]([OH:6])=[O:4])[CH:12]=[CH:11][N:10]3[CH:13]=2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)c1ccn2cc(-c3ccccc3)nc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1ccn2cc(-c3ccccc3)nc2c1
Temperature: 0 °C

Procedure:
A solution of NaOH in water (1N, 54 ml, 54 mmol) was added to a suspension of 2-phenyl-imidazo[1,2-a]pyridine-7-carboxylic acid methyl ester (6.8 g, 27 mmol) in a mixture of ethanol (50 ml) and water (25 ml). The mixture was heated to reflux (2 h). The obtained clear solution was cooled, poured onto crushed ice (50 g); HCl (25%, 10 ml) was added. The mixture was then filtered, and the precipitate was washed (ethanol) and dried under vacuum. The obtained solid (6.36 g, 99%) was used in the next step without further purification. MS (m/e)=239.1 [M+H+].
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][N:10]=[C:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1>C1COCC1.C1C=CC=CC=1>[C:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NCc1ccccn1
Reactant: O=C=NCCCc1ccccc1
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: O=C(NCCCc1ccccc1)NCc1ccccn1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 92 %

Procedure:
To a solution of 3-phenylpropyl isocyanate (1.8 mmol) in anhydrous THF (10 mL) at 0° C. under an argon atmosphere was added 2-aminomethyl-pyridine (1.8 mmol). The reaction mixture was stirred at 0° C. for 10 min, the solvent was evaporated under reduced pressure, and the resultant solid was recrystallized from CH2Cl2/Et2O to give pure 59.1 in 92% yield. White solid. m p 89-90° C. When anhydrous benzene was used as solvent the product was directly crystallized out and isolated by filtration (93% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]([OH:15])([C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[CH2:17]([N:25]1[CH2:29]C[C@@H:27](O)[CH2:26]1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:17]([N:25]1[CH2:26][CH2:27][C@@H:1]([O:2][C:3](=[O:16])[C:4]([OH:15])([C:5]2[S:6][CH:7]=[CH:8][CH:9]=2)[C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[CH2:29]1)[CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: COC(=O)C(O)(c1cccs1)c1cccs1
Reactant: O[C@@H]1CCN(CCc2ccccc2)C1
Product: O=C(O[C@@H]1CCN(CCc2ccccc2)C1)C(O)(c1cccs1)c1cccs1
Yield: 50.5 %

Procedure:
Prepared as described in Intermediate I-1 from 2-Hydroxy-2,2-dithien-2-ylacetic acid methyl ester and (3R)-1-phenethylpyrrolidin-3-ol (Intermediate I-18). The yield was 0.98 g (50.5%) of the title product.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]2[OH:16])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C:11]2=[O:16])[CH:5]=[C:6]([F:9])[C:7]=1[F:8]
Reactant: OC1CCCCC1c1cc(F)c(F)c(F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C1CCCCC1c1cc(F)c(F)c(F)c1
Temperature: 25 °C
Yield: 95.2 %

Procedure:
To a solution of 2-(3,4,5-trifluoro-phenyl)-cyclohexanol (215 mg, 0.93 mmol) dissolved in methylene chloride (15 mL) was added under nitrogen Dess-Martin reagent (475 mg, 1.1 mmol, 15 weight-percent in methylene chloride). The reaction was stirred at room temperature over night. The same amount of Des-Martin reagent was added and the reaction was stirred at room temperature over night. The reaction was poured onto a saturated sodium bicarbonate solution. The organic layer was washed with 10% aqueous sodium thiosulfate solution and brine, dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was stirred with heptane/ethyl acetate (7:3 v/v) and the solid was filtered off to yield the title compound (202 mg, 95%) as a yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.10-7.20 (m, 2H), 3.84 (dd, 1H), 2.28-2.33 (m, 2H), 1.65-2.12 (m, 6H).
Reaction SMILES: [NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.[CH3:21][O:22][C:23](=[O:28])[CH2:24][CH2:25][CH2:26][NH2:27].CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[C:16]([O:15][C:13]([NH:1][C@H:2]([C:10]([CH2:21][O:22][C:23](=[O:28])[CH2:24][CH2:25][CH2:26][NH2:27])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:14])([CH3:19])([CH3:18])[CH3:17]
Reactant: COC(=O)CCCN
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)COC(=O)CCCN

Procedure:
The title compound was prepared in the idential manner as in Example 1 from 2.65 of Boc-Phe, 1.69 g (11.0 mmole) of methyl-γ-aminobutyrate hydrochloride salt, 1.25 ml of N-methylmorpholine and 2.27 g (11.0 mmole) of dicyclohexylcarbodiimide in 25 ml of methylene chloride, reacted for 24 hours, to provide a quantitative yield of product (TLC in the above solvent system, Rf 0.84).