Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(O[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:13]=2)[N:10]=[N:9][C:8]=1[C:23]([NH:25][CH:26]1[CH2:28][CH2:27]1)=[O:24])(=O)=O.C(=O)([O-])[O-].[K+].[K+].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>C(#N)C.C(OCC)(=O)C>[CH:26]1([NH:25][C:23]([C:8]2[N:9]=[N:10][N:11]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:13]=3)[C:7]=2[CH2:6][N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)=[O:24])[CH2:27][CH2:28]1
Reactant: CCNC(=O)c1ccc(-n2nnc(C(=O)NC3CC3)c2COS(C)(=O)=O)cc1
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCNC(=O)c1ccc(-n2nnc(C(=O)NC3CC3)c2CN2CCOCC2)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 74.3 %

Procedure:
(4-[(Cyclopropylamino)carbonyl]-1-{4-[(ethylamino)carbonyl]phenyl}-1H-1,2,3-triazol-5-yl)methyl methanesulfonate (195 mg, 0.479 mmol) obtained in Example 126a), potassium carbonate (66.1 mg, 0.479 mmol, 1.0 eq.) and morpholine (0.085 ml, 0.957 mmol, 2.0 eq.) were suspended in acetonitrile (4.0 ml), and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate (30 ml) and washed with 2% aqueous sodium carbonate solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine. The aqueous layers were each extracted with ethyl acetate (15 ml). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated. Diethyl ether was added and the precipitate was collected by filtration and crystallized from ethyl acetate. The precipitate was collected by filtration and crystallized from ethanol again to give the title compound as a white powder (142 mg, 0.356 mmol, 74.4%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH3:25])[CH:5]=[C:6]([NH:8][C:9]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([O:18][C:19]([C:22](O)=[O:23])([CH3:21])[CH3:20])=[CH:16][CH:17]=2)=[O:10])[CH:7]=1.Cl.C[O:28][C:29](=[O:42])[C@H:30]([CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35][CH:34]=1)[NH2:31].O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH3:25][C:4]1[CH:5]=[C:6]([NH:8][C:9]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]([CH3:20])([CH3:21])[C:22]([NH:31][CH:30]([CH2:32][C:33]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[NH:35][CH:34]=3)[C:29]([OH:28])=[O:42])=[O:23])=[CH:14][CH:13]=2)=[O:10])[CH:7]=[C:2]([CH3:1])[CH:3]=1
Reactant: COC(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Reactant: Cc1cc(C)cc(NC(=O)Cc2ccc(OC(C)(C)C(=O)O)cc2)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: CN1CCOCC1
Product: Cc1cc(C)cc(NC(=O)Cc2ccc(OC(C)(C)C(=O)NC(Cc3c[nH]c4ccccc34)C(=O)O)cc2)c1

Procedure:
Using RSR13 acid (1.5 g, 4.4 mmol), tryptophan methyl ester hydrochloride (1.12 mg, 4.4 mmol) and 1-hydroxybenzotriazole hydrate (653 mg, 4.8 mmol), N-methylmorpholine (666 mg, 7.5 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.01 g, 6.0 mmol) in dimethylformamide (30 mL), the product was prepared in 2.3 g yield (96%)
Reaction SMILES: CO[C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.[CH:26]([NH2:29])([CH3:28])[CH3:27]>>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:13]1[C:12]([CH2:11][O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([NH:29][CH:26]([CH3:28])[CH3:27])=[O:25])=[CH:5][N:6]=2)=[C:16]([CH3:17])[O:15][N:14]=1
Reactant: COC(=O)c1ccc(OCc2c(-c3ccccc3F)noc2C)nc1
Reactant: CC(C)N
Product: Cc1onc(-c2ccccc2F)c1COc1ccc(C(=O)NC(C)C)cn1
Yield: 83 %

Procedure:
As described for example 84f, 6-[3--(2-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (200 mg, 0.58 mmol) was converted, using isopropylamine instead of 2,2,2-trifluoroethylamine, to the title compound (180 mg, 83%) which was obtained as a colourless oil. MS: m/e=370.1 [M+H]+.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[CH:16]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:22][C:23](C)([O-])[CH3:24].[K+].IC(C)C>CN(C)C=O.C(OCC)(=O)C>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH:23]([CH3:24])[CH3:22])[CH:17]=[CH:16]2)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCCCOc1ccc2[nH]ccc2c1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)I
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)n1ccc2cc(OCCCO[Si](C)(C)C(C)(C)C)ccc21
Reaction time: 0.17 h
Yield: 38 %

Procedure:
Dissolve 5-[3-(tert-butyldimethylsilyloxy)propoxy]-1H-indole (1.0 g, 0.327 mmol) in N,N-dimethylformamide (20 mL) under nitrogen. Add 3.6 mL potassium tert-butoxide (1M solution in THF, 1.1 equiv) and stir 10 minutes, then add 2-iodopropane (0.36 mL, 1.1 eq) and stir for 30 minutes. Dilute with ethyl acetate and wash with water then brine. Dry over magnesium sulfate, filter and concentrate. Purification by column chromography (hexanes to 4:1 hexanes:ethyl acetate) affords 0.43 g product (38%) as a clear oil. 1H NMR (400 MHz, DMSO-d6) δ 0.00 (s, 6H), 0.83 (s, 9H), 1.40 (d, J=6.83 Hz, 6H), 1.86 (m, 2H), 3.74 (m, 2H), 3.98 (m, 2H), 4.64 (m, 1H), 6.29 (d, J=2.93 Hz, 1H), 6.71 (m, 1H), 6.99 (d, J=1.95 Hz, 1H), 7.36 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([OH:12])=[O:11])[CH:5]=[CH:6][CH:7]=1.OS(O)(=O)=O.[C:18]([O-])([O-])=O.[Na+].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([O:12][CH3:18])=[O:11])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)/C=C/c1cccc(F)c1
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CO
Product: COC(=O)/C=C/c1cccc(F)c1
Yield: 339.2 %

Procedure:
To a solution of (E)-3-(3-fluorophenyl)acrylic acid (5, 6.0 g, 32.7 mmol) in MeOH (150 mL) at 0° C. was added concentrated H2SO4 (3.0 mL) slowly. The reaction was heated under reflux for 24 h then cooled to room temperature and neutralized with Na2CO3 (1.0 g). The solvent was removed by rotary evaporation and the resulting yellow oil partitioned between EtOAc (300 mL) and saturated NaHCO3 (300 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (200 mL) and dried over Na2SO4. The solvent was removed by rotary evaporation to yield 6 as a low melting (<25° C.) white solid (32.0 mmol, 99%): 1H NMR (500 MHz, CDCl3) δ 3.79 (s, 3H), 6.39-6.43 (d, J=16.0 Hz, 1H), 7.04-7.07 (dt, J=2.0, 8.0 Hz, 1H), 7.18-7.20 (d, J=9.0 Hz, 1H), 7.25-7.26 (d, J=8.0 Hz, 1H), 7.30-7.35 (m, 1H), 7.60-7.64 (d, J=16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 52.0, 114.4, 114.6, 117.3, 117.4, 119.4, 124.29, 124.32, 130.6, 130.7, 136.8, 136.9, 143.6, 143.7, 162.2, 164.2, 167.2; LCQ-MS (M+H+) calcd for C10H10FO2 181. found 181.
Reaction SMILES: [CH2:1]([Li])CCC.C(NC(C)C)(C)C.[C:13]1([CH:19]2[CH2:22][CH:21]([C:23]([O:25][CH3:26])=[O:24])[CH2:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CI>CCCCCC.O1CCCC1>[CH3:1][C:21]1([C:23]([O:25][CH3:26])=[O:24])[CH2:20][CH:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:22]1
Reactant: [Li]CCCC
Reactant: COC(=O)C1CC(c2ccccc2)C1
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COC(=O)C1(C)CC(c2ccccc2)C1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
n-Butyl lithium (8.15ml. of a 1.23M solution in hexane) was added dropwise to a stirred solution of di-isopropylamine (1.40ml.) in dry tetrahydrofuran (15ml.) at -78° C. in an atmosphere of argon. The solution was warmed to 0° C. and a solution of methyl 3-phenylcyclobutanecarboxylate (1.90g.) in dry tetrahydrofuran (20ml.) was added dropwise and the reaction mixture was stirred at 0° C. for 1 hour. Methyl iodide (1.30ml.) was added and stirring was continued for 16 hours, allowing the reaction mixture to warm to room temperature. The tetrahydrofuran was evaporated under reduced pressure and the residue was partitioned between ethyl acetate (2 × 20ml.) and 0.5N hydrochloric acid (10ml.). The ethyl acetate solution was dried over sodium sulphate and the solvent was evaporated under reduced pressure to give the ester, methyl 1-methyl-3-phenylcyclobutanecarboxylate as a 2:1 mixture of isomers. The n.m.r. spectrum in deuteriochloroform showed the following characteristic features (δ values):
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:6]([C:8]1[CH:13]=[CH:12][C:11](OC)=[C:10](OC)[CH:9]=1)=[O:7].[C:23]1(OC)[C:24](=CC=[CH:29][CH:30]=1)OC.[Cl-].[Al+3].[Cl-].[Cl-].C1(C(Cl)=O)C2C(=CC=CC=2)C=CC=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:6]([C:8]1[C:9]2[C:10](=[CH:24][CH:23]=[CH:30][CH:29]=2)[CH:11]=[CH:12][CH:13]=1)=[O:7]
Reactant: COc1ccccc1OC
Reactant: COc1ccc(C(=O)c2ccc(OC)c(OC)c2)cc1OC
Agent: O=C(Cl)c1cccc2ccccc12
Agent: [Al+3]
Agent: [Cl-]
Product: COc1ccc(C(=O)c2cccc3ccccc23)cc1OC

Procedure:
1-(3,4-Dimethoxybenzoyl)naphthalene was prepared analogously to 3,4,3',4'-tetramethoxybenzophenone using veratrole (1.3 mL, 10 mmol), aluminum chloride (1.5 g, 11 mmol) and 1-naphthoyl chloride (1.5 mL, 10 mmol) with a reaction time of 24 hours at room temperature. The crude product was purified by flash column chromatography (silica gel, 2.5% ethyl acetate/methylene chloride) to afford 1.85 g (63%) of the product as a white solid: mp 92.5-94.5° C.; 1H NMR (CDCl3) δ 8.06-7.84 (m, 3 H), 7.80-7.39 (m, 5 H), 7.31-7.21 (m, 1 H), 6.84-6.74 (m, 1 H), 3.94 (s, 3 H), 3.91 (s, 3 H); 13C NMR (CDCl3) δ 196.6, 153.5, 149.0, 136.8, 133.6, 131.1, 130.9, 130.5, 128.2, 126.9, 126.7, 126.3, 126.3, 125.6, 124.3, 111.3, 109.7, 56.0, 55.9; Anal. Calcd for C19H16O3. Theoretical: C, 78.06; H, 5.52. Found: C, 77.97; H, 5.66.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]([OH:13])=[O:12])[N:8]([CH2:14][C:15]2[CH:19]=[C:18]([C:20]3[S:21][C:22]([Cl:25])=[CH:23][CH:24]=3)[O:17][N:16]=2)[N:7]=1)=O)C>C1COCC1>[Cl:25][C:22]1[S:21][C:20]([C:18]2[O:17][N:16]=[C:15]([CH2:14][N:8]3[C:9]([C:11]([OH:13])=[O:12])=[CH:10][C:6]([CH2:4][OH:3])=[N:7]3)[CH:19]=2)=[CH:24][CH:23]=1
Reactant: CCOC(=O)c1cc(C(=O)O)n(Cc2cc(-c3ccc(Cl)s3)on2)n1
Solvent: C1CCOC1
Product: O=C(O)c1cc(CO)nn1Cc1cc(-c2ccc(Cl)s2)on1
Reaction time: 16 h

Procedure:
To a solution of 1 g 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-ethyl ester in 15 ml THF 314 mg LiBH4 were added cautiously. Then the reaction mixture was stirred for 16 h, quenched with diluted HCl and filtered through a chem elut® cartridge by elution with ethyl acetate and DCM. After concentration under reduced pressure the crude residue was directly subjected to the next reaction step. Yield: 800 mg.
Reaction SMILES: [C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][Cl:20])[C:12]=2[N+:21]([O-])=O)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.NN>C(O)C.[Pd]>[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][Cl:20])[C:12]=2[NH2:21])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl
Agent: [Pd]
Agent: NN
Solvent: O
Solvent: CCO
Product: Nc1c(CS(=O)(=O)c2ccccc2)cccc1OCCCl
Temperature: 60 °C

Procedure:
A mixture of 1-benzenesulfonylmethyl-3-(2-chloro-ethoxy)-2-nitrobenzene (0.57 g, 1.6 mmoles) in ethanol (10 mL) was stirred under nitrogen in a round bottom flask at 60° C. 10% Pd/C was added, and the temperature was increased to 80° C. Hydrazine hydrate (1.5 mL) was added dropwise and the mixture was stirred at reflux for 3 hours. Reaction mixture was filtered off through Celite, and the solution was washed with H2O (3×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (0.5 g, 1.53 mmoles).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:9]([C:10]([N:12]3[CH2:17][CH2:16][CH:15]([N:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)=[O:11])=[C:8](I)[N:7]=[C:6]2[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[CH2:3][CH2:2]1.[N:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1>>[CH:1]1([CH2:4][N:5]2[C:9]([C:10]([N:12]3[CH2:17][CH2:16][CH:15]([N:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)=[O:11])=[C:8]([C:37]3[CH:38]=[CH:39][N:34]=[CH:35][CH:36]=3)[N:7]=[C:6]2[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[CH2:3][CH2:2]1
Reactant: OB(O)c1ccncc1
Reactant: O=C(c1c(I)nc(-c2cccc(C(F)(F)F)c2)n1CC1CC1)N1CCC(N2CCCC2)CC1
Product: O=C(c1c(-c2ccncc2)nc(-c2cccc(C(F)(F)F)c2)n1CC1CC1)N1CCC(N2CCCC2)CC1

Procedure:
In analogy to the procedure described for example 7, [3-cyclopropylmethyl-5-iodo-2-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 56) was reacted with pyridin-4-yl-boronic acid to give the title compound light yellow amorphous solid. MS: 524.5 (MH+).
Reaction SMILES: [CH2:1]([N:3]([CH2:20][CH3:21])[CH2:4][CH2:5][N:6]1[CH2:12][CH2:11][CH2:10][C:9]2[NH:13][C:14]([CH:17]=O)=[C:15]([CH3:16])[C:8]=2[C:7]1=[O:19])[CH3:2].[Br:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[CH2:25][C:26](=[O:32])[NH:27]2>>[Br:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1/[C:25](=[CH:17]/[C:14]1[NH:13][C:9]3[CH2:10][CH2:11][CH2:12][N:6]([CH2:5][CH2:4][N:3]([CH2:20][CH3:21])[CH2:1][CH3:2])[C:7](=[O:19])[C:8]=3[C:15]=1[CH3:16])/[C:26](=[O:32])[NH:27]2
Reactant: CCN(CC)CCN1CCCc2[nH]c(C=O)c(C)c2C1=O
Reactant: O=C1Cc2c(Br)cccc2N1
Product: CCN(CC)CCN1CCCc2[nH]c(/C=C3\C(=O)Nc4cccc(Br)c43)c(C)c2C1=O
Yield: 45.5 %

Procedure:
The title compound was prepared under the same conditions as described in step 10 of Example 1 with 5-(2-diethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 1j obtained from step 9 of Example 1 and 4-bromo-1,3-dihydro-indol-2-one as starting materials to obtain (Z)-2-(4-bromo-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-diethylamino-ethyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 13 (30 mg, yield 45.5%) as an orange solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:10]([CH3:18])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:19]([O:27][CH2:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[CH2:37][O:38][C:39](=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:32]Br)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>>[C:20]1([C:19]([O:27][CH2:28][C:29]2[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=2[CH2:37][O:38][C:39]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:46])[CH2:32][O:1][C:2]2[CH:3]=[C:4]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:10]([CH3:18])[CH:9]=3)[CH:5]=[CH:6][CH:7]=2)=[O:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: COC(=O)c1ccc(-c2cccc(O)c2)cc1C
Reactant: O=C(OCc1ccc(CBr)cc1COC(=O)c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COC(=O)c1ccc(-c2cccc(OCc3ccc(COC(=O)c4ccccc4)c(COC(=O)c4ccccc4)c3)c2)cc1C

Procedure:
In a manner similar to that of Example 1(i), by reaction of 1.5 g (6.2 mmol) of methyl 3′-hydroxy-3-methylbiphenyl-4-carboxylate with 3 g (6.88 mmol) of 3,4-bis(benzoyloxymethyl)benzyl bromide and 900 mg (6.4 mmol) of potassium carbonate, the desired product is obtained in the form of a yellow oil (m=3.69 g; Y=99%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]N=C2CCCC(=O)C2)=[CH:4][CH:3]=1.F[C:18](F)(F)[C:19]([OH:21])=O>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[NH:8][C:2]1[CH2:7][CH2:6][CH2:18][C:19](=[O:21])[C:3]2=1
Reactant: O=C1CCCC(=NNc2ccc(Cl)cc2)C1
Reactant: O=C(O)C(F)(F)F
Product: O=C1CCCc2[nH]c3ccc(Cl)cc3c21
Temperature: 80 °C
Yield: 42 %

Procedure:
A mixture of cyclohexane-1,3-dione mono-(4-chlorophenyl) hydrazone (45 mmol) obtained in Example 131 and trifluoroacetic acid (30 mL) is heated to 80° C. for 16 h, cooled to room temperature, poured over ice water and filtered. The filtercake is dried and recrystallized from ethanol/water to afford the title product, 4.2 g (42% yield), identified by HPLC and mass spectral analyses.
Reaction SMILES: [CH3:1][S:2][CH2:3][C@@H:4]([C:9]([OH:11])=O)[NH:5][C:6](=[O:8])[CH3:7].[CH2:12]([N:14](CC)CC)[CH3:13].ClC(OCCCC)=O.C(N)C>O1CCCC1>[CH2:12]([NH:14][C:9](=[O:11])[C@H:4]([CH2:3][S:2][CH3:1])[NH:5][C:6](=[O:8])[CH3:7])[CH3:13]
Reactant: CCN(CC)CC
Reactant: CSC[C@H](NC(C)=O)C(=O)O
Agent: CCCCOC(=O)Cl
Agent: CCN
Solvent: C1CCOC1
Product: CCNC(=O)[C@H](CSC)NC(C)=O
Temperature: -15 °C
Reaction time: 0.33 h
Yield: 53.8 %

Procedure:
S-Methyl-N-acetyl-L-cysteine (3.54 g, 20 mmole) was dissolved in 25 ml of tetrahydrofuran and 2.8 ml (20 mmole) of triethylamine was added thereto. Upon cooling to -15° C., 2.7 ml (20 mmole) of butyl chloroformate was added dropwise and the mixture was stirred for 20 minutes at that temperature. After cooling to -40° C., 3.0 ml (46.6 mmole) of aqueous 70% ethylamine solution was added in one portion and stirred for 3 hours under ice cooling. The reaction mixture was extracted with 100 ml of ethyl acetate three times and the extracts were washed successively with 2×30 ml of aqueous 5% sodium bicarbonate and 2×30 ml of saturated saline, dried over anhydrous magnesium sulfate and then concentrated in vacuo. The resulting crystals were collected and washed with ethyl ether to give 2.20 g (53.8% yield) of S-methyl-N-acetyl-L-cysteine ethylamide.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:23]=[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]([C:32]([CH3:34])=[CH2:33])=[CH:20][C:10]=1[C:11]([N:13]([CH2:17][C:18]#[CH:19])[CH2:14][C:15]#[CH:16])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:35]([OH:39])[CH2:36][C:37]#[CH:38].CCCCCCC>C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:23]=[C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:21]([C:32]([CH3:34])=[CH2:33])=[CH:20][C:10]=1[C:11]([N:13]1[CH2:17][C:18]2[C:15](=[CH:16][CH:38]=[C:37]([CH2:36][CH2:35][OH:39])[CH:19]=2)[CH2:14]1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#CCN(CC#C)C(=O)c1cc(C(=C)C)c(OCc2ccccc2)cc1OCc1ccccc1
Reactant: C#CCCO
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: C=C(C)c1cc(C(=O)N2Cc3ccc(CCO)cc3C2)c(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 40.7 %

Procedure:
To a solution of 2,4-bis-benzyloxy-5-isopropenyl-N,N-di-prop-2-ynyl-benzamide (0.940 g, 2.1 mmol) in ethyl acetate (2 mL) was added 3-butyn-1-ol (0.30 mL, 4.0 mmol) and RhCl(PPh3)3 (0.162 g, 0.17 mmol). The mixture was stirred at room temperature for 24 hours, then loaded directly onto a silica gel column, eluting with 7:3 ethyl acetate:heptane to give the desired product (0.444 g, 38% yield). LC/MS: m/z 520.25 [M+H]+
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[C:11]([N+:16]([O-])=O)[CH:10]=1)#[N:2]>C(O)C.[Pd]>[NH2:16][C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:1]#[N:2])[CH:15]=[CH:14][C:12]=1[NH2:13]
Reactant: N#Cc1ccccc1-c1ccc(N)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CCO
Product: N#Cc1ccccc1-c1ccc(N)c(N)c1

Procedure:
4-(2-Cyanophenyl)-2-nitroaniline (0.042 moles,10 g.) was dissolved in 200 ml ethanol and hydrogenated at 40 psi over 10 g of 10% Pd/C. The solution was filtered, concentrated, and purified by HPLC eluted with a gradient of 0-50% ethyl acetate in toluene. (MS)
Reaction SMILES: [C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]([CH:30]=[O:31])[CH2:26][C:27]([OH:29])=[O:28])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:32])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]1(C)[CH:38]=CC(S(O)(=O)=O)=C[CH:34]=1.C([O-])(O)=O.[Na+]>C(O)(C)C>[C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]3[CH2:26][C:27](=[O:29])[O:28][CH:30]3[O:31][CH:33]([CH3:38])[CH3:34])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:32])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=CC(CC(=O)O)NC(=O)C1CCCN2C(=O)CCC(NC(=O)c3ccccc3)C(=O)N12
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Product: CC(C)OC1OC(=O)CC1NC(=O)C1CCCN2C(=O)CCC(NC(=O)c3ccccc3)C(=O)N12
Reaction time: 1.25 h
Yield: 198.2 %

Procedure:
A solution of 214e (101 mg, 0.23 mmol) in isopropanol (10 ml) was stirred at room temperature with a catalytic amount of p-toluenesulfonic acid (10 mg). After 75 minutes, the reaction mixture was poured into saturated NaHCO3 and extracted with CH2Cl2. The combined extracts were dried over Na2SO4 and concentrated. Flash chromatography (SiO2, CH2CHl2to EtOAc) afforded 56 mg (51%) of 2100a as a white solid: 1H NMR (CDCl3; mixture of diastereomers) δ 7.9-7.8 (2H,m), 7.6-7.5 (1H, m), 7.5-7.4 (2H, m), 7.1 (0.5H, d), 6.9 (0.5H, d), 6.4 (0.5H,d), 5.6 (0.5H, d), 5.3 (0.5H, s), 5.2-5.1 (1H, m), 4.95 (0.5H, m), 4.75-4.5 (1.5H, m), 4.35 (0.5H, t), 4.1 (0.5H, m), 3.98 (0.5H, m), 3.3-2.75 (4H, m), 2.5-2.4 (2H,m), 2.25 (1H, m), 2.1-1.9 (3H,m) 1.75-1.55 (2H,m).
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH:8]2[O:9][C:10]([CH3:13])([CH3:12])[O:11][CH:7]2[CH:6]([O:14][CH:15]([O:17][CH2:18][CH3:19])[CH3:16])[CH2:5][C:4]1=[O:20].C(N(CC)CC)C.[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].Cl>C(Cl)Cl>[Si:28]([O:1][CH2:2][CH:3]1[CH:8]2[O:9][C:10]([CH3:12])([CH3:13])[O:11][CH:7]2[CH:6]([O:14][CH:15]([O:17][CH2:18][CH3:19])[CH3:16])[CH2:5][C:4]1=[O:20])([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]
Reactant: CCOC(C)OC1CC(=O)C(CO)C2OC(C)(C)OC12
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(C)OC1CC(=O)C(CO[Si](C)(C)C(C)(C)C)C2OC(C)(C)OC12
Temperature: 0 °C
Reaction time: 13 h
Yield: 97.4 %

Procedure:
2-Hydroxymethyl-3,4-(dimethylmethylenedioxy)-5-(1-ethoxyethoxy)cyclohexanone (765 mg) was dissolved in 7 ml of dry methylene chloride, and 1.2 ml of triethylamine, 55.6 mg of N,N-dimethylaminopyridine and 520 mg of tert-butyldimethylsilyl chloride were added at 0° C., followed by stirring the mixture at 0° C. for 13 hours. The obtained reaction mixture was poured into 1N hydrochloric acid, and extracted with diethyl ether. The extract was washed with a saturated sodium hydrogen carbonate aqueous solution and then with a saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 1.04 g of 2-(tert-butyldimethylsilyloxymethyl)-3,4-(dimethylmethylenedioxy)-5-(1-ethoxyethoxy)cyclohexanone having the following properties.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([CH2:25][OH:26])=[CH:21][CH:20]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:9]([C:19]3[CH:20]=[CH:21][C:22]([CH2:25][O:26][S:35]([CH3:34])(=[O:37])=[O:36])=[CH:23][CH:24]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCc1ccc(-c2nc(-c3ccccc3)cc(-c3ccccc3)n2)cc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCc1ccc(-c2nc(-c3ccccc3)cc(-c3ccccc3)n2)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of [4-(4,6-diphenylpyrimidin-2-yl)-phenyl]methanol, 0.38 g (1.11 mmol), triethylamine, 0.34 mL (2.45 mmol), and 6 mL of methylene chloride was cooled to 0° C. via ice-water bath. Methanesulfonyl chloride, 0.10 mL (1.23 mmol) was added dropwise over minutes. The solution stirred for 2 h at 0° C. The solution was quenched with 20 mL of water and diluted with 20 mL of ethyl acetate. The organic layer was washed with water, sat. aq. NaCl, and dried (MgSO4). After the solution was concentrated, the residue was recrystallized with EtOAc-Heptane (1:2) to afford the desired product in 0.44 g (95%) as a yellow solid. 1H NMR (DMSO-d6) 8.77 (d, 2H, J=9.0), 8.44-8.41 (m, 4H), 8.30 (s, 1H), 7.68-7.61 (m, 8H), 5.37 (s, 2H), 3.11 (s, 3H).