Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[C:3](=[O:22])[NH:4][C:5](=[O:21])[N:6]([CH:20]=1)[C@@H:7]1[O:19][C@H:10]([CH2:11][O:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:9][CH2:8]1.[CH:23]1[C:40]2=[C:41]3[C:30]([C:31]4[C:42]5[C:35](=[CH:36][CH:37]=[CH:38][C:39]2=5)[CH:34]=[CH:33][CH:32]=4)=[CH:29][CH:28]=[CH:27][C:26]3=[C:25]([C:43]#[CH:44])[CH:24]=1.CCN(CC)CC>CN(C=O)C.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.[Cu]I>[CH:23]1[C:40]2=[C:41]3[C:30]([C:31]4[C:42]5[C:35](=[CH:36][CH:37]=[CH:38][C:39]2=5)[CH:34]=[CH:33][CH:32]=4)=[CH:29][CH:28]=[CH:27][C:26]3=[C:25]([C:43]#[C:44][C:2]2[C:3](=[O:22])[NH:4][C:5](=[O:21])[N:6]([CH:20]=2)[C@@H:7]2[O:19][C@H:10]([CH2:11][O:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:9][CH2:8]2)[CH:24]=1
Reactant: CC(C)(C)C(=O)OC[C@@H]1CC[C@H](n2cc(I)c(=O)[nH]c2=O)O1
Reactant: C#Cc1ccc2c3cccc4cccc(c5cccc1c52)c43
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)C(=O)OC[C@@H]1CC[C@H](n2cc(C#Cc3ccc4c5cccc6cccc(c7cccc3c74)c65)c(=O)[nH]c2=O)O1
Temperature: 25 °C
Reaction time: 43 h
Yield: 95.5 %

Procedure:
A solution of 5-iodo-5′-O-pivaloyl-2′,3′-dideoxyuridine (442 mg, 1 mmol) and 3-perylenylacetylene (345 mg, 1.25 mmol) in 10 mL of DMF was degassed three times by alternation between vacuum and argon. Then Pd(PPh3)4 (115 mg, 0.1 mmol), CuI (38 mg, 0.2 mmol) and Et3N (0.278 mL, 2 mmol) were added and the flask was degassed once again, filled with argon, and the mixture was stirred for 43 hours at ambient temperature. The mixture was diluted with 300 mL of EtOAc, washed 3×200 mL of water, dried with Na2SO4, and evaporated. Chromatography on a silica gel column using a 0 to 2% of EtOH/CHCl3 gradient gave rise to a chromatographically homogeneous (Rf 0.28, 5% EtOH/CHCl3) product as orange foam (545 mg, 96%). 1H-NMR (DMSO-d6): 11.85 (s, 1H, NH), 8.44 (d, 1H, J 7.8), 8.39-8.35 (m, 3H), 8.32 (d, 1H, J 8.2) (perylenyl), 8.06 (s, 1H, H-6), 7.83-7.81 (m, 2H), 7.69-7.60 (m, 2H), 7.58-7.53 (m, 2H) (perylenyl), 6.00 (dd, 1H, J1′,2′α 6.9 J1′,2′β 4.6, H-1′), 4.37-4.34 (m, 1H, H-4′), 4.32-4.26 (m, 2H, H-5′), 2.42-2.36 (m, 1H, H-2′), 2.17-2.12 (m, 1H, H-2′), 2.06-2.00 (m, 1H, H-3′), 1.90-1.83 (m, 1H, H-3′), 1.17 (s, 9H, tBu).
Reaction SMILES: [CH3:1][C:2](C)([O-])C.[K+].[CH3:7][S:8][C:9]1[N:10]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:11](=[O:20])[CH:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:13]=1.C(I)C>O1CCCC1.C(OCC)(=O)C>[CH2:1]([C:12]1([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:11](=[O:20])[N:10]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:9]([S:8][CH3:7])=[N:13]1)[CH3:2]
Reactant: CSC1=NC(c2ccccc2)C(=O)N1Nc1ccccc1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CCI
Solvent: C1CCOC1
Product: CCC1(c2ccccc2)N=C(SC)N(Nc2ccccc2)C1=O
Yield: 40.8 %

Procedure:
0.55 g of potassium tert-butoxide is added to a solution of 1.5 g (5.05 mmol) of 2-methylthio-4-phenyl-1-phenylamino-2-imidazolin-5-one (Compound 5) in 50 ml of anhydrous tetrahydrofuran. The mixture is left to react for 30 minutes at room temperature and then 0.8 g (5.05 mmol) of ethyl iodide is added. The mixture is left to react for 1 hour at room temperature. The mixture is diluted with 150 ml of ethyl acetate. The solution is washed with water and then concentrated under reduced pressure. The product is purified by chromatography on a silica column (Merck 60H silica; eluent: 25% ethyl acetate/75% heptane). 0.65 g of Compound 48 is obtained in the form of a beige powder melting at 147° C.
Reaction SMILES: O1[C@H:3]2[CH2:4][C@H:5]3[C@:18]([CH3:20])([CH2:19][C@H:2]12)[C@@H:17]1[C@H:8]([C@H:9]2[C@@:13]([CH2:15][CH2:16]1)([CH3:14])[C@H:12]([OH:21])[C@@H:11]([N+:22]1([CH3:27])[CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:10]2)[CH2:7][CH2:6]3.[C:28]1([S:34]([O-:37])(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[CH2:26]([N+:22]([CH2:23][CH3:24])([CH3:27])[C@H:11]1[CH2:10][C@H:9]2[C@H:8]3[C@H:17]([CH2:16][CH2:15][C@:13]2([CH3:14])[C@@H:12]1[OH:21])[C@:18]1([CH3:20])[C@H:5]([CH2:4][CH:3]=[CH:2][CH2:19]1)[CH2:6][CH2:7]3)[CH3:25].[CH3:2][C:31]1[CH:32]=[CH:33][C:28]([S:34]([O-:37])(=[O:36])=[O:35])=[CH:29][CH:30]=1
Reactant: O=S(=O)([O-])c1ccccc1
Reactant: C[C@]12C[C@@H]3O[C@H]3C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@H](O)[C@@H]([N+]3(C)CCCC3)C[C@@H]12
Product: CC[N+](C)(CC)[C@H]1C[C@H]2[C@@H]3CC[C@H]4CC=CC[C@]4(C)[C@H]3CC[C@]2(C)[C@@H]1O
Product: Cc1ccc(S(=O)(=O)[O-])cc1

Procedure:
1-[(2β, 3α, 5α, 16β, 17α)-2,3-epoxy-17-hydroxy-androstan16-yl]- 1-methylpyrrolidinium 4-methy)benzenesulphonate and
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[CH:9]([NH:17][S:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19])[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1.CI.[CH2:26](N(CC)CC)C>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[CH:9]([N:17]([CH3:26])[S:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19])[C:10]1[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=1
Reactant: CCN(CC)CC
Reactant: CC(C)(C)S(=O)NC(c1ccc(Cl)cc1)c1cc(Br)ccc1N
Solvent: CN(C)C=O
Solvent: CI
Product: CN(C(c1ccc(Cl)cc1)c1cc(Br)ccc1N)S(=O)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2-Methyl-propane-2-sulfinic acid [(2-amino-5-bromo-phenyl)-(4-chloro-phenyl)-methyl]-amide (9.73 g, 0.024 mmol) solved in 150 mL DMF is added LiHNDS (1.06M, 24.5 mL) at −30° C. After 1 h, methyl iodide (3.4 g, 0.024 mol) and triethylamine (33.5 mL, 0.24 mol) is added. The mixture is stirred at RT for 2 h. The mixture is then quenched with H2O, extracted with CH3O(CH3)3, dried over Na2SO4, concentrated. This produces the desired compound.
Reaction SMILES: [N+:1]([C:4]1[CH:38]=[CH:37][C:7]([CH2:8][O:9][C:10]([O:12][C@@H:13]([C@H:15]2[C:21](=[O:22])[N:20]3[C@@H:16]2[CH2:17][C:18](=O)[C@@H:19]3[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=2)=[O:24])[CH3:14])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(C(C)C)CC)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[SH:63][C@@H:64]1[CH2:68][N:67]([C:69]([O:71][CH2:72][C:73]2[CH:78]=[CH:77][C:76]([N+:79]([O-:81])=[O:80])=[CH:75][CH:74]=2)=[O:70])[C@H:66]([CH2:82][S:83][C:84]2[CH:89]=[CH:88][N:87]=[CH:86][CH:85]=2)[CH2:65]1>ClCCl>[N+:79]([C:76]1[CH:75]=[CH:74][C:73]([CH2:72][O:71][C:69]([N:67]2[CH2:68][C@@H:64]([S:63][C:18]3[CH2:17][C@H:16]4[N:20]([C:21](=[O:22])[C@@H:15]4[C@H:13]([O:12][C:10]([O:9][CH2:8][C:7]4[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:38][CH:37]=4)=[O:11])[CH3:14])[C:19]=3[C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=3)=[O:24])[CH2:65][C@H:66]2[CH2:82][S:83][C:84]2[CH:89]=[CH:88][N:87]=[CH:86][CH:85]=2)=[O:70])=[CH:78][CH:77]=1)([O-:81])=[O:80]
Reactant: C[C@@H](OC(=O)OCc1ccc([N+](=O)[O-])cc1)[C@H]1C(=O)N2[C@@H](C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)C[C@H]12
Reactant: O=C(OCc1ccc([N+](=O)[O-])cc1)N1C[C@@H](S)C[C@H]1CSc1ccncc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C[C@@H](OC(=O)OCc1ccc([N+](=O)[O-])cc1)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](CSc4ccncc4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)C[C@H]12
Reaction time: 0.25 h
Yield: 45.2 %

Procedure:
To a solution of 4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (1.2 g) in dry dichloromethane (40 ml) were added N,N-diisopropyl-N-ethylamine (0.44 ml) and trifluoromethanesulfonic anhydride (0.40 ml) at -40° C., and the solution was stirred at the same temperature for 15 minutes. To this solution were added N,N-diisopropyl-N-ethylamine (0.63 ml) and a solution of (2S,4S)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)-2-(pyridin-4-ylthiomethyl)pyrrolidine (1.38 g) in dry dichloromethane (5 ml) successively at the same temperature under an atmosphere of nitrogen, and stirred at ambient temperature for 2 hours. The reaction mixture was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo to give a residue. The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (4:1 V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give 4-nitrobenzyl (5R,6S)-3-[(2S,4S)-1-(4-nitrobenzyloxycarbonyl)-2-(pyridin-4-ylthiomethyl)pyrrolidin-4-ylthio]-6-[(1R)-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.94 g).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[CH2:11]O)=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:35].O>CC(N(C)C)=O>[Br:35][CH2:11]/[CH:10]=[CH:9]/[C:6]1[CH:7]=[CH:8][C:3]([C:2]([F:14])([F:13])[F:1])=[CH:4][CH:5]=1
Reactant: BrC(Br)(Br)Br
Reactant: OC/C=C/c1ccc(C(F)(F)F)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)N(C)C
Solvent: O
Product: FC(F)(F)c1ccc(/C=C/CBr)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.2 %

Procedure:
To a solution of the alcohol obtained in step 2 (10 g) in dimethylacetamide (100 ml) at room temperature were added triphenylphosphine (23 g) and carbon tetrabromide (29 g). The resulting solution was stirred at room temperature for 1 h, poured into water and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate and filtered over silica gel to give 13 g of the desired product as a white solid (95%) which was characterized by its mass and NMR spectra.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:13][C:14]([N:16]2[CH:21]=[CH:20][C:19](=[O:22])[CH2:18][C@H:17]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[O:15])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7](O)=[O:8].C[N:31](C)C=O.C(Cl)(=O)C(Cl)=O.N>ClCCl.O1CCOCC1>[Br:1][C:2]1[C:3]([NH:13][C:14]([N:16]2[CH:21]=[CH:20][C:19](=[O:22])[CH2:18][C@H:17]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[O:15])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([NH2:31])=[O:8]
Reactant: COc1cc(NC(=O)N2C=CC(=O)C[C@H]2c2ccc(F)cc2)c(Br)cc1C(=O)O
Reactant: CN(C)C=O
Agent: N
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: COc1cc(NC(=O)N2C=CC(=O)C[C@H]2c2ccc(F)cc2)c(Br)cc1C(N)=O
Reaction time: 3 h

Procedure:
(S)-5-Bromo-4-{[2-(4-fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carbonyl]-amino}-2-methoxy-benzoic acid (72 mg) was dissolved in 2 ml dichloromethane and 0.001 ml dimethylformamide under argon. To this solution was added 0.02 ml oxalyl chloride and the solution was stirred for three hours. The solution was then slowly added at 0° C. to 0.5M NH3 in dioxane. After stirring for 10 minutes, the mixture was concentrated in vacuo and chromatographed (dichloromethane) to yield 26 mg (S)-5-bromo-4-{[2-(4-fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carbonyl]-amino}-2-methoxy-benzamide. MS (M+H) 463.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][N:9]3[C:12]([C:15]([O:17]CC)=[O:16])=[CH:13][N:14]=[C:8]3[CH:7]=2)=[N:2]1.[Li+].[OH-].Cl>C1COCC1.CO.O>[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][N:9]3[C:12]([C:15]([OH:17])=[O:16])=[CH:13][N:14]=[C:8]3[CH:7]=2)=[N:2]1
Reactant: CCOC(=O)c1cnc2cc(-c3cc[nH]n3)ccn12
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cnc2cc(-c3cc[nH]n3)ccn12
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a stirring solution of ethyl 7-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-carboxylate (62) (103 mg, 0.4 mmol) in THF:MeOH:H2O (3:2:1, 1.6 mL) was added 6N LiOH (0.035 mL). The reaction was stirred at room temperature for 20 minutes. The pH was adjusted between 4-5 with 3N HCl. The resulting mixture was concentrated to yield 7-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-carboxylic acid (63). MS (m/z) 229.2 (M+1)+.
Reaction SMILES: C(O[BH-](O[C:11](=O)[CH3:12])OC(=O)C)(=O)C.[Na+].[N:15]1([C:22]2[S:26][C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:24][CH:23]=2)[CH2:21][CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[C:32](O)(=O)C>CC(C)=O>[CH:11]([N:18]1[CH2:19][CH2:20][CH2:21][N:15]([C:22]2[S:26][C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:24][CH:23]=2)[CH2:16][CH2:17]1)([CH3:12])[CH3:32]
Reactant: CCOC(=O)c1ccc(N2CCCNCC2)s1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: CC(=O)O
Agent: [Na+]
Solvent: CC(C)=O
Product: CCOC(=O)c1ccc(N2CCCN(C(C)C)CC2)s1
Temperature: 25 °C
Reaction time: 18 h
Yield: 81.4 %

Procedure:
Sodium triacetoxyborohydride (396 mg, 1.87 mmol) was added portionwise to ethyl 5-(1,4-diazepan-1-yl)thiophene-2-carboxylate (190 mg, 0.75 mmol) and acetic acid (0.086 ml, 1.49 mmol) in acetone (1.917 ml) at room temperature. The resulting solution was stirred at ambient temperature for 18 h under nitrogen. The reaction mixture was concentrated and diluted with water (200 mL) and basified with 2M NaOH. The aqueous was extracted with diethyl ether (3×100 mL) and washed sequentially with water (200 mL) and saturated brine (200 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford desired product ethyl 5-(4-isopropyl-1,4-diazepan-1-yl)thiophene-2-carboxylate (181 mg, 82%). This was used directly with no further purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([OH:19])=O)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[CH2:24]([N:26](CC)[CH2:27][CH3:28])[CH3:25].N1CCCC1>C(Cl)Cl.C1C=NC2N(O)N=NC=2C=1>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([N:26]3[CH2:27][CH2:28][CH2:25][CH2:24]3)=[O:19])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1Cc2ccc(C(=O)O)cc2C1
Reactant: CCN(CC)CC
Agent: On1nnc2cccnc21
Solvent: ClCCCl
Solvent: ClCCl
Solvent: C1CCNC1
Product: CC(C)(C)OC(=O)N1Cc2ccc(C(=O)N3CCCC3)cc2C1
Reaction time: 8 h

Procedure:
A mixture of N-t-butoxycarbonyl-5-carboxyisoindoline (D13) (300 mg), EDC (440 mg), HOAT (10 mg), triethylamine (0.4 ml) and pyrrolidine (0.11 ml) in DCM (10 ml) was stirred overnight and then evaporated. The residue was redissolved in EtOAc (10 ml), washed with saturated NaHCO3 solution (10 ml), water (10 ml), brine (10 ml), dried (MgSO4) and evaporated. The residue was chromatographed on a silica gel flash column [step gradient 70-90% EtOAc in light petroleum 40-60] to give the tiUe compound (D17) (314 mg). MS electrospray (+ion) 317 (MH+). 1H NMR δ (CDCl3): 7.42 (2H, m), 7.27 (1H, m), 4.70 (2H, m), 4.67 (2H, m), 3.65 (2H, m), 3.42 (2H, m), 1.92 (4H, m), 1.52
Reaction SMILES: [Si]([O:8][C@H:9]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])(C(C)(C)C)(C)C>O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[OH:8][C@H:9]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:21]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]
Reactant: COC(=O)c1ccc(C[C@@H]2CC[C@H]([C@H](O[Si](C)(C)C(C)(C)C)c3cccnc3)N2C(=O)OC(C)(C)C)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C[C@@H]2CC[C@H]([C@H](O)c3cccnc3)N2C(=O)OC(C)(C)C)cc1
Yield: 98.3 %

Procedure:
A solution of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(pyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (11.0 g, 20.3 mmol) in 100 mL of 2 M tetrabutylammonium fluoride tetrahydrofuran solution was stirred at RT overnight. The mixture was then diluted with water and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with water, brine, dried over Na2SO4, and concentrated to afford 8.51 g (98%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 2H), 7.93 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 1H), 7.34-7.28 (m, 3H), 6.36 (s, 1H), 4.54 (d, J=8.5 Hz, 1H), 4.18-4.09 (m, 2H), 3.92 (s, 3H), 3.23 (s, 1H), 3.13-3.10 (m, 1H), 2.61-2.52 (m, 1H), 1.78-1.60 (m, 2H), 1.49 (s, 9H). MS: m/z (ESI) 427 (M+1).
Reaction SMILES: [C:1]([CH:4]([CH2:16][CH2:17][CH2:18][CH:19]1[O:21][CH2:20]1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])(=[O:3])[CH3:2].[C:22]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23].[OH-].[Na+]>O.O1CCCC1>[C:1]([CH:4]([CH2:16][CH2:17][CH2:18][CH:19]([OH:21])[CH2:20][O:32][C:29]1[CH:30]=[CH:31][C:26]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:27][CH:28]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])(=[O:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(O)cc1
Reactant: CCOC(=O)CCCCCCC(CCCC1CO1)C(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(=O)C(CCCCCCC(=O)O)CCCC(O)COc1ccc(C(C)(C)C)cc1
Reaction time: 1 h

Procedure:
A mixture of ethyl 8-acetyl-12,13-epoxytridecanoate (14.9 g., 0.05 mole), 4-tert-butylphenol (11.2 g., 0.075 mole), sodium hydroxide (7.0 g., 0.175 mole), water (30 ml.) and tetrahydrofuran (200 ml.) is stirred 4 hours at 40°-45°, 17 hours at 25° and one hour on the steam bath letting the tetrahydrofuran slowly boil away. The residue is treated with water and extracted with ether. The aqueous solution is acidified with hydrochloric acid. The oily product is taken up in ether. The ether is evaporated and the residue treated with a solution of 16.8 g. sodium bicarbonate in 275 ml. of water. The resulting solution is extracted twice with ether to remove the excess weakly acidic phenol. The aqueous solution is acidified, the product taken up in ether, washed with water and dried over sodium sulfate. The ether is evaporated leaving 10.2 g. of the crude title compound as a yellow viscous oil.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[O:6][C:7]=1[CH3:8].[O:18]=[CH:19][C:20]1[CH:28]=[CH:27][C:25]([OH:26])=[C:22]([O:23][CH3:24])[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:24][O:23][C:22]1[CH:21]=[C:20]([CH:28]=[CH:27][C:25]=1[O:26][CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[O:6][C:7]=1[CH3:8])[CH:19]=[O:18]
Reactant: Cc1oc(-c2cccc([N+](=O)[O-])c2)nc1CCl
Reactant: COc1cc(C=O)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(C=O)ccc1OCc1nc(-c2cccc([N+](=O)[O-])c2)oc1C
Temperature: 90 °C
Reaction time: 2 h
Yield: 97.3 %

Procedure:
A mixture of 4-chloromethyl-5-methyl-2-(3-nitrophenyl)-1,3-oxazole (2.67 g), vanillin (1.52 g), anhydrous potassium carbonate (1.38 g) and N,N-dimethylformamide (30 mL) was stirred at 90° C. for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was dried over anhydrous magnesium sulfate, and filtered through a silica gel column. The filtrate was concentrated and the residue was washed with diethyl ether-hexane to give 3-methoxy-4-{[5-methyl-2-(3-nitrophenyl)-1,3-oxazol-4-yl]methoxy}benzaldehyde as colorless crystals (3.58 g, yield 97%). Recrystallization from ethyl acetate-hexane gave pale-yellow prism crystals. melting point: 179-180° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5]/[C:4](=[C:12]2/[C:13](C)=[N:14][NH:15][C:16]/2=[O:17])/[CH:3]=1.[SH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[OH:26]>>[OH:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[S:19][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5]/[C:4](=[C:12]2/[CH:13]=[N:14][NH:15][C:16]/2=[O:17])/[CH:3]=1
Reactant: Oc1ccccc1S
Reactant: CC1=NNC(=O)/C1=C1/C=C(Cl)c2ccccc2N1
Product: O=C1NN=C/C1=C1\C=C(Sc2ccccc2O)c2ccccc2N1

Procedure:
The title compound was prepared from (Z)-4-(4-chloroquinolin-2(1H)-ylidene)-3-methyl-1H-pyrazol-5(4H)-one and 2-mercaptophenol using a procedure analogous to the one described in Example 6. 1H NMR (400 MHz, DMSO-D6) δ ppm 2.08 (s, 3H) 7.08 (s, 1H) 7.38-7.68 (m, 3H) 7.76-7.88 (m, 3H) 7.92 (d, J=8.14 Hz, 1H) 8.18 (d, J=8.24 Hz, 1H) 10.38 (s, 1H) 13.10 (bs, 1H); ESI-MS: m/z calc'd for C19H15N3O2S 349.09. found 350.3 (M+H)+.
Reaction SMILES: C=[CH:2][C@@H:3]1[C@:20]2([CH3:21])[C@H:6]([C@H:7]3[C@H:17]([CH2:18][CH2:19]2)[C@:15]2([CH3:16])[C:10](=[CH:11][C:12](=[O:22])[CH2:13][CH2:14]2)[C:9](=O)[CH2:8]3)[CH2:5][CH2:4]1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[Na].O>O1CCOCC1.C(OC)(C)(C)C>[CH2:2]=[C:3]1[CH2:4][CH2:5][C@H:6]2[C@H:7]3[C@H:17]([CH2:18][CH2:19][C@:20]12[CH3:21])[C@:15]1([CH3:16])[C:10](=[CH:11][C:12](=[O:22])[CH:13]=[CH:14]1)[CH2:9][CH2:8]3
Reactant: C=C[C@H]1CC[C@H]2[C@@H]3CC(=O)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Agent: [Na]
Solvent: O
Solvent: COC(C)(C)C
Solvent: C1COCCO1
Product: C=C1CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@H]3CC[C@]12C
Yield: 50.3 %

Procedure:
Refer to FIG. 190. A solution of 17-methylenandrost-4-en-3-one (9, 1.0001 g, 3.5160 mmol) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 2.43 g, 10.7 mmol) in dioxane (60 ml, freshly distilled after overnight reflux over sodium) was refluxed 6 h and then cooled with swirling in tap water. Methyl t-butyl ether (MTBE, 50 ml) was added and the suspension was filtered through diatomaceous earth. The residue was washed with two 50 ml portions of MTBE and the combined filtrates were concentrated under reduced pressure. Flash chromatography of the residue (20% ethyl acetate/hexanes on silica gel) followed by recrystallization from 95% ethanol gave off-white crystals (498.9 mg, 1.767 mmol, 50%), m.p. 155-157° C.
Reaction SMILES: C([N:8]1[CH2:12][C@H:11]2[C@H:13]([NH:16][C:17](=[O:32])[C@@H:18]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C@@H:19]([CH3:22])[CH2:20][CH3:21])[CH2:14][CH2:15][C@H:10]2[CH2:9]1)C1C=CC=CC=1.C(N1C[C@H]2[C@H](NC(=O)[C@@H](N3CCOCC3)CC(C)C)CC[C@H]2C1)C1C=CC=CC=1.[F:62][C:63]([F:75])([F:74])[C:64]1[CH:69]=[CH:68][C:67]([S:70](Cl)(=[O:72])=[O:71])=[CH:66][CH:65]=1.FC(F)(F)C1C=C(S(Cl)(=O)=O)C=CC=1>>[CH3:31][N:23]([C@@H:18]([C@@H:19]([CH3:22])[CH2:20][CH3:21])[C:17](=[O:32])[NH:16][C@H:13]1[C@H:11]2[C@H:10]([CH2:9][N:8]([S:70]([C:67]3[CH:66]=[CH:65][C:64]([C:63]([F:62])([F:74])[F:75])=[CH:69][CH:68]=3)(=[O:72])=[O:71])[CH2:12]2)[CH2:15][CH2:14]1)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27]
Reactant: O=S(=O)(Cl)c1ccc(C(F)(F)F)cc1
Reactant: CC[C@H](C)[C@@H](C(=O)N[C@@H]1CC[C@H]2CN(Cc3ccccc3)C[C@H]21)N(C)C(=O)OC(C)(C)C
Agent: CC(C)C[C@@H](C(=O)N[C@@H]1CC[C@H]2CN(Cc3ccccc3)C[C@H]21)N1CCOCC1
Agent: O=S(=O)(Cl)c1cccc(C(F)(F)F)c1
Product: CC[C@H](C)[C@@H](C(=O)N[C@@H]1CC[C@H]2CN(S(=O)(=O)c3ccc(C(F)(F)F)cc3)C[C@H]21)N(C)C(=O)OC(C)(C)C

Procedure:
The title compound was prepared by substituting tert-butyl(2S,3S)-1-(3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylamino)-3-methyl-1-oxopentan-2-yl(methyl)carbamate from Step A of Example 334 for (S)—N-((3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl)-4-methyl-2-morpholinopentanamide and 4-(trifluoromethyl)benzene-1-sulfonyl chloride for 3-(trifluoromethyl)benzene-1-sulfonyl chloride in the procedures described in Example 319: 1H NMR (400 MHz, pyridine-d5) δ ppm 8.66-8.72 (m, 1H), 8.05-8.13 (m, 2H), 7.88-7.91 (m, 2H), 4.69 (d, J=11.3 Hz, 1H), 4.15-4.22 (m, 1H), 3.73-3.87 (m, 1H), 3.16-3.23 (m, 1H), 3.11-3.18 (bs, 3H), 3.00 (t, J=8.3 Hz, 1H), 2.90 (t, J=8.4 Hz, 1H), 2.42-2.56 (m, 2H), 2.21-2.28 (m, 1H), 1.88-2.03 (m, 1H), 1.73-1.88 (m, 1H), 1.52-1.66 (m, 1H), 1.48 (s, 9H), 1.34-1.46 (m, 1H), 1.21-1.34 (m, 1H), 0.98-1.13 (m, 1H), 0.94 (d, J=6.3 Hz, 3H), 0.76-0.81 (m, 3H); MS (ESI+) m/z 562 (M+H)+.