Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1Cl.P>CC(C)=O.C(Cl)C=CC1C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:4][C:3](=[O:2])[CH3:8]
Reactant: COc1ccccc1Cl
Agent: [Pd]
Agent: ClCC=Cc1ccccc1
Agent: P
Solvent: CC(C)=O
Product: COc1ccccc1CC(C)=O
Yield: 179.9 %

Procedure:
This reaction is carried out in the same manner as the reaction in example 3. The difference is that, the reactants are o-methoxyphenyl chloride (142.3 mg, 1.0 mmol), palladium cinnamyl chloride (7.9 mg, 0.015 mmol), 2-Methoxy-6-(N-methyl-N-phenyl-amino) henyldicyclohexyl)phosphine (24.5 mg, 0.060 mmol), CS2CO3 (653.0 mg, 2.0 mmol) in 4.0 mL acetone at 90° C. for 16 h. 1-(2′-Methoxyphenyl)-2-propanone (147.7 mg) was obtained with a yield of 89% as liquid. 1H NMR (300 MHz, CDCl3) δ 7.29-7.22 (m, 1H, ArH), 7.14-7.09 (m, 1H, ArH), 6.94-6.84 (m, 2H, ArH), 3.79 (s, 3H, OCH3), 3.66 (s, 2H, CH2), 2.12 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 206.9, 157.2, 131.0, 128.4, 123.5, 120.5, 110.3, 55.2, 45.4, 29.1; IR (neat) v (cm−1) 3003, 2941, 2905, 2837, 1713, 1602, 1589, 1496, 1464, 1439, 1356, 1322, 1290, 1247, 1176, 1160, 1115, 1050, 1030; MS (70 eV, EI) m/z (%): 165 (M++1, 6.45), 164 (M+, 50.19), 91 (100).
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:21].[F:22][C:23]1[CH:24]=[C:25]([CH2:30][C:31](O)=[O:32])[CH:26]=[C:27]([F:29])[CH:28]=1>>[F:22][C:23]1[CH:24]=[C:25]([CH2:30][C:31]([NH:1][N:2]2[N:11]=[C:10]([S:12]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)(=[O:14])=[O:13])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]2=[O:21])=[O:32])[CH:26]=[C:27]([F:29])[CH:28]=1
Reactant: O=C(O)Cc1cc(F)cc(F)c1
Reactant: Nn1nc(S(=O)(=O)c2ccccc2)c2ccccc2c1=O
Product: O=C(Cc1cc(F)cc(F)c1)Nn1nc(S(=O)(=O)c2ccccc2)c2ccccc2c1=O

Procedure:
The product from Example 68B and 2-(3,5-difluorophenyl)acetic acid were processed using a method similar to that described in Example 10C to afford the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 8.69-8.72 (m, 1H), 8.44-8.47 (m, 1H), 8.31-8.35 (bs, 1H), 8.00-8.06 (m, 2H), 7.93-7.98 (m, 1H), 7.85-7.90 (m, 1H), 7.66-7.70 (m, 1H), 7.55-7.61 (m, 2H), 6.82-6.91 (m, 2H), 6.74-6.81 (m, 1H), 3.69-3.74 (bs, 2H); MS (APCI+) M/Z 456 (M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:25])[C:4](=[O:24])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[CH:7][CH:6]=1>CO.[OH-].[Na+]>[N+:21]([C:18]1[CH:17]=[CH:16][C:15]([O:14][CH2:13][CH2:12][O:11][C:8]2[CH:9]=[CH:10][C:5]([C:4](=[O:24])[C:3]([OH:25])=[O:2])=[CH:6][CH:7]=2)=[CH:20][CH:19]=1)([O-:23])=[O:22]
Reactant: COC(=O)C(=O)c1ccc(OCCOc2ccc([N+](=O)[O-])cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)C(=O)c1ccc(OCCOc2ccc([N+](=O)[O-])cc2)cc1

Procedure:
A mixture of 4-[[2-(4-nitrophenoxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester (4:1) molar hydrate (0.65 g) in methanol and 0.5N sodium hydroxide (8 mL) was treated as in Example 19. Extraction provided 0.6 g of crude product which solidified and was crystallized from dichloromethane-hexane to give 0.55 g of colorless 4-[[2-(4nitrophenoxy)ethyl]oxy]-alpha-oxobenzeneacetic acid, mp 129°-130° C.
Reaction SMILES: [OH:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].OS(O)(=O)=O.[CH3:19]O>>[OH:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O:7][CH3:19])=[O:6]
Reactant: O=C(O)c1cccc(O)c1[N+](=O)[O-]
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1cccc(O)c1[N+](=O)[O-]

Procedure:
A solution of 3-hydroxy-2-nitrobenzoic acid (51 g) and con.H2SO4 (5 mL) in anhydrous methanol (450 mL) was heated to reflux for 48 hr. The mixture was concentrated to remove methanol, and the residue was partitioned between water (500 mL) and ethyl acetate (800 mL). The organic layer was washed with brine (300 mL), dried over anhydrous sodium sulfate, and concentrated to give crude compound. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=40:1 to 5:1) to give methyl 3-hydroxy-2-nitrobenzoate (28 g) 1H-NMR (400 MHz, CDCl3) δ 3.8 (s, 3H), 7.32-7.34 (d, J=8.4 Hz, 1H), 7.39-7.41 (d, J=8.0 Hz, 1H), 7.48-7.52 (t, J=8.0 Hz, 1H), 11.37 (s, 1H); LC-MS (m/z) 198 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[C:3]=1[C:4]([OH:6])=[O:5].[C:14](OC(=O)C)(=O)[CH3:15]>>[CH3:14][C:15]1[O:5][C:4](=[O:6])[C:3]2[C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=[CH:10][C:2]=2[N:1]=1
Reactant: Nc1cccc([N+](=O)[O-])c1C(=O)O
Reactant: CC(=O)OC(C)=O
Product: Cc1nc2cccc([N+](=O)[O-])c2c(=O)o1
Temperature: 200 °C
Reaction time: 2 h
Yield: 85 %

Procedure:
A mixture of 2-amino-6-nitro-benzoic acid (1.5 g, 8.2 mmol) in acetic anhydride (15 mL) was heated at 200° C. for 30 minutes in a microwave oven. The mixture was filtered and washed with ethyl acetate (20 mL). The filtrate was concentrated in vacuo. The solid was stirred in ether (20 mL) for 2 hrs. The suspension was filtered and washed with ether (20 mL) to give 2-methyl-5-nitro-benzo[d][1,3]oxazin-4-one as a light brown solid (1.4 g, 85% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, CH3CN/0.1% H3PO4, 5% grad 95% in 5 min, 5.36 min (92%); 1H NMR (DMSO-d6) δ 2.42 (s, 3H, CH3), 7.79 (dd, J=1, 8 Hz, 1H, Ar), 7.93 (dd, J=1, 8 Hz, 1H, Ar), 8.06 (t, J=8 Hz, 1H, Ar); 13C NMR (DMSO-d6) δ 20.87, 107.79, 121.54, 128.87, 137.19, 147.12, 148.46, 155.18, 161.78; LCMS: MH=207.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C@@H:14]([NH:22][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].C(=O)([O-])[O-].[K+].[K+].[CH2:37](I)[CH3:38]>CN(C=O)C.O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C@@H:14]([NH:22][C:23](=[O:30])[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:12]([CH2:37][CH3:38])[CH:13]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: CCI
Reactant: N#Cc1ccc(-c2c[nH]c([C@H](Cc3ccccc3)NC(=O)c3ccccc3)n2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCn1cc(-c2ccc(C#N)cc2)nc1[C@H](Cc1ccccc1)NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76 %

Procedure:
The compound of Example 182 Part A (60 mg, 0.15 mmol) was dissolved in DMF (2.5 mL) and potassium carbonate (32 mg, 0.23 mmol) was added followed by ethyl iodide (0.015 mL, 0.19 mmol), and the resulting mixture was stirred overnight at room temperature. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined extracts were washed with water and brine, then dried over Na2SO4, filtered and evaporated. The residue was chromatographed on silica gel to provide the product (48 mg, 76%). 1H NMR (400 MHz, DMSO-D6) δ 1.17 (t, J=7.25 Hz, 3H) 3.34-3.48 (m, 2H) 3.89-4.05 (m, 2H) 5.46 (d, J=7.03 Hz, 1H) 7.14 (d, J=7.03 Hz, 1H) 7.21 (t, J=7.47 Hz, 2H) 7.31 (d, J=7.47 Hz, 2H) 7.41 (t, J=7.25 Hz, 2H) 7.48 (d, J=7.03 Hz, 1H) 7.76-7.84 (m, 3H) 7.88 (s, 1H) 7.94 (d, J=8.79 Hz, 2H) 9.08 (d, J=8.35 Hz, 1H). m/z 421.2 (M+H)+.
Reaction SMILES: CC([O:4][C@@H:5]1[C@@:9]2([CH3:24])[CH2:10][CH2:11][C@@H:12]3[C@:22]4([CH3:23])[C:16](=[CH:17][C:18]([CH2:20][CH2:21]4)=[O:19])[CH2:15][CH2:14][C@H:13]3[C@@H:8]2[CH2:7][CH2:6]1)=O.C=O.[C:27]1(S)C=CC=CC=1>N(CCO)(CCO)CCO.[Cl-].[Na+].O>[CH3:27][C:17]1[C:18](=[O:19])[CH2:20][CH2:21][C@@:22]2([CH3:23])[C:16]=1[CH2:15][CH2:14][C@@H:13]1[C@@H:12]2[CH2:11][CH2:10][C@@:9]2([CH3:24])[C@H:8]1[CH2:7][CH2:6][C:5]2=[O:4]
Reactant: Sc1ccccc1
Reactant: CC(=O)O[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: C=O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: OCCN(CCO)CCO
Product: CC1=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@@]2(C)CCC1=O
Reaction time: 0.25 h

Procedure:
A mixture of Testosterone acetate (available from Steraloids Inc, Wilton, N.H. USA) (3.3 g, 10 mmol.), aqueous formaldehyde (1 mL) and thiophenol (0.9 g, 8 mmol ) is stirred in triethanolamine (30 mL) for 10 h under an atmosphere of argon at 110° C. After 4 h. additional aqueous formaldehyde (0.7 mL) and thiophenol (0.5 mg) are added. After cooling, the mixture is poured in brine and extracted with methylene chloride. The organic phase is washed with dilute sodium hydroxide solution and with water, dried and evaporated. The residue is purified by chromatography on "flash" silica gel using mixtures of ethyl acetate and hexane as eluant. The purified residue in acetone (15 mL) is added to Raney nickel (35 g) in acetone (60 mL) which is heated at reflux since 1 h. The reflux is continued for 15 min. The hot organic phase is decanted and the metal is washed with hot acetone. The combined filtrates were concentrated and purified by chromatography on "flash" silica gel using a mixture of ethyl acetate and hexane as eluant. The purified residue is dissolved in methanolic potassium hydroxide solution (50 mL, 3%) and kept at room temperature for 4 h. under an atmosphere of argon. After concentration, the mixture is poured in water and extracted with methylene chloride. The organic phase is washed with brine, dried and evaporated to dryness. The residue, purified by chromatography on "flash" silica gel using a mixture of ethyl acetate and hexane as eluant, is dissolved in acetone (30 mL) and treated at 0° C. with a slight excess of Jones' reagent (8N chromium trioxide)(until a red color). After 15 min., isopropanol (1 mL) is added and the mixture is poured in brine and extracted with ethyl acetate. The organic phase is washed with brine, dried and evaporated to dryness. Purification of the residue by chromatography on "flash" silica gel using a mixture of ethyl acetate and hexane as eluant give pure 4-methyl-4-androsten-3,17-dione.
Reaction SMILES: [NH4+].[Cl-].C1C=CC2N(O)N=[N:9]C=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[CH2:33]([O:40][N:41]([C@H:54]1[CH2:59][N:58]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C@H:57]([C:67](O)=[O:68])[CH2:56][CH2:55]1)[S:42]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[N+:51]([O-:53])=[O:52])(=[O:44])=[O:43])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C=O)C.CCOC(C)=O>[CH2:33]([O:40][N:41]([C@H:54]1[CH2:59][N:58]([C:60]([O:62][C:63]([CH3:64])([CH3:65])[CH3:66])=[O:61])[C@H:57]([C:67](=[O:68])[NH2:9])[CH2:56][CH2:55]1)[S:42]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[N+:51]([O-:53])=[O:52])(=[O:44])=[O:43])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: On1nnc2ccccc21
Reactant: CC(C)(C)OC(=O)N1C[C@H](N(OCc2ccccc2)S(=O)(=O)c2ccccc2[N+](=O)[O-])CC[C@H]1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1C[C@H](N(OCc2ccccc2)S(=O)(=O)c2ccccc2[N+](=O)[O-])CC[C@H]1C(N)=O
Temperature: 25 °C
Reaction time: 17 h
Yield: 99 %

Procedure:
NH4Cl (1.39 g, 26.18 mmol), HOBt (3.53 g, 26.18 mmol), EDCI (5 g, 26.18 mmol), and DIPEA (8.44 g, 65.45 mmol) were added to a solution of (2S,5R)-5-(N-(benzyloxy)-2-nitrophenylsulfonamido)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (10 g, 18.7 mmol) in DMF (90 mL) The mixture was stirred at rt for 17 hrs, then, EtOAc (500 mL) was added. he mixture was washed with saturated sodium chloride (6×), dried over Na2SO4, and concentrated. The residue was washed with petroleum ether/EtOAc (95:5, 200 mL) to give (2S,5R)-tert-butyl 5-(N-(benzyloxy)-2-nitrophenylsulfonamido)-2-carbamoylpiperidine-1-carboxylate (9.9 g, 99%) which was used in the next step. ESI-MS (EI+, m/z): 535.0 [M+H]+.
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:13].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22](O)=[O:23])=[CH:17][CH:16]=1>>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH:1][N:2]2[N:11]=[C:10]([CH3:12])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]2=[O:13])=[O:23])=[CH:17][CH:16]=1
Reactant: Cc1nn(N)c(=O)c2ccccc12
Reactant: O=C(O)Cc1ccc(Cl)cc1
Product: Cc1nn(NC(=O)Cc2ccc(Cl)cc2)c(=O)c2ccccc12

Procedure:
The product from Example 28A and 2-(4-chlorophenyl)acetic acid were processed using a method similar to that described in Example 17C to afford the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 2.54 (s, 3H) 3.74 (s, 2H) 6.94-7.09 (m, 1H) 7.10-7.20 (m, 3H) 7.85-7.98 (m, 1H) 7.95-8.11 (m, 2H) 8.32 (d, J=7.93 Hz, 1H) 11.47-11.69 (m, 1H); MS (ESI) m/z 328 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH2:15][CH:16]([N+:18]([O-])=O)[CH3:17])[CH:12]=[CH:11][C:10]=1[O:21][CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN>[Ni].CO>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH2:15][CH:16]([NH2:18])[CH3:17])[CH:12]=[CH:11][C:10]=1[O:21][CH3:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(CC(C)[N+](=O)[O-])cc1OCc1ccccc1
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CO
Product: COc1ccc(CC(C)N)cc1OCc1ccccc1
Temperature: 40 °C
Yield: 75.7 %

Procedure:
Raney nickel (50%, slurry in water, 2.0 g) was washed with MeOH (3×). To this was added MeOH (70 ml) and 209 (3.05 g, 10.1 mmol). The mixture was cooled (ice-bath) and hydrazine hydrate (2.53 g, 50.5 mmol) was added dropwise. The mixture was heated to 40° C. for 1 h, then further Raney nickel (50% slurry in water, 1.0 g) was added as a suspension in MeOH (10 ml). The reaction mixture was heated at 40° C. for a further 18 h. The resulting solution was cooled to rt and filtered through celite, washing through with MeOH (200 ml). The filtrate was concentrated in vacuo and purification (flashmaster: 50 g, EtOAc/MeOH) afforded the title compound (2.074 g, 76%) as a pale yellow oil. 1H NMR (270 MHz; CDCl3) 1.04 (3H, d, J=6.4 Hz, CH3), 2.36 (1H, dd, J=13.3, 8.2 Hz, CHH), 2.58 (1H, dd, J=13.3, 5.2 Hz, CHH), 2.98-3.1 (1H, m, CH), 3.86 (3H, s, OCH3), 5.13 (2H, s, CH2), 6.67-6.83 (3H, m, 3×CH), 7.25-7.43 (5H, m, 5×CH, phenyl). LC/MS (ES+) tr=1.82 min, m/z 272.19 (M++H).
Reaction SMILES: CC[O:3][C:4]([C:6]1[N:7](C(OC(C)(C)C)=O)[C:8]2[C:13]([CH:14]=1)=[C:12]([O:15][CH2:16][C:17]1[C:21]3[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:20]=3[O:19][CH:18]=1)[CH:11]=[CH:10][CH:9]=2)=[O:5].[OH-].[K+]>C1COCC1.C(O)C.O>[F:26][C:24]1[CH:23]=[CH:22][C:21]2[C:17]([CH2:16][O:15][C:12]3[CH:11]=[CH:10][CH:9]=[C:8]4[C:13]=3[CH:14]=[C:6]([C:4]([OH:5])=[O:3])[NH:7]4)=[CH:18][O:19][C:20]=2[CH:25]=1
Reactant: CCOC(=O)c1cc2c(OCc3coc4cc(F)ccc34)cccc2n1C(=O)OC(C)(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cc2c(OCc3coc4cc(F)ccc34)cccc2[nH]1
Temperature: 85 °C
Reaction time: 2 h

Procedure:
112 (1.2 g, 2.6 mmol) is dissolved in 30 ml of a 1:1:1 mixture of THF, ethanol and water. And after addition of KOH pellets (742 mg, 13.2 mmol) the mixture is stirred for 2 h (TLC control) at 85° C. Then the organic solvent are removed under reduced pressure. The residue is cooled to 0° C. and treated with 2M HCl. The crude product is filtered off and dried under high vacuum. The crude product (800 mg) is recrystallized from ethyl acetate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4](=[CH:9][NH:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[CH2:25](I)[CH2:26][CH2:27][CH3:28].O>CN(C)C=O>[CH3:8][O:7][C:5](=[O:6])[C:4](=[CH:9][NH:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:15][CH:16]=1)[C:3]([O:2][CH3:1])=[O:18]
Reactant: CCCCI
Reactant: COC(=O)C(=CNc1ccc(O)cc1)C(=O)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCOc1ccc(NC=C(C(=O)OC)C(=O)OC)cc1
Temperature: 25 °C
Yield: 52.3 %

Procedure:
To a mixture of 7 g (28 mMol) of 2-(4-Hydroxy-anilinomethylene)-propanedioic acid dimethyl ester, 3.9 g (28 mMol) of Potassium carbonate in 50 ml of dimethylformamide, 7.3 g (28 mMol) of Butyl iodide were added dropwise with stirring at room temperature. The reaction mixture was heated at 80° C. for 24 hours. Then the reaction mixture was poured into 50 ml of water and extracted three times with ethyl acetate. The organic layer was washed with a solution of sodium hydroxyde (15%) and thereafter with water, dried and evaporated and gave 4.5 g of the title compound which is a white solid melting at 46-47° C., UV 328 nm (E=685).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=2)[CH2:4]1.CSC1C=CC(N)=CC=1.C(OC[C@@H]1OC1)(=O)CCC.O[C:37]1[CH:41]=[CH:40][O:39][N:38]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[O:39]1[CH:40]=[CH:41][C:37]([O:1][CH2:2][C@@H:3]2[O:7][C:6](=[O:8])[N:5]([C:9]3[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=3)[CH2:4]2)=[N:38]1
Reactant: CSc1ccc(N2C[C@H](CO)OC2=O)cc1
Reactant: Oc1ccon1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: CCCC(=O)OC[C@H]1CO1
Agent: CSc1ccc(N)cc1
Solvent: C1CCOC1
Product: CSc1ccc(N2C[C@H](COc3ccon3)OC2=O)cc1
Yield: 61 %

Procedure:
Prepared by the general method of Example 1 using 5(R)-hydroxymethyl-3-(4-methylthiophenyl)oxazolidin-2-one (650 mg, 2.72 mmol ; prepared from the reaction of 4-methylthioaniline and (R)-glycidyl butyrate), 3-hydroxyisoxazole (243 mg, 2.86 mmol), diisopropylazodicarboxylate (577 mg, 2.86 mmol) and triphenylphosphine (770 mg, 2.94 mmol) in THF (10 ml). Purified by flash chromatography (Merck 9385 silica, EtOAc/isohexane (1/1)) to give the title compound 507 mg, 61%) as a colourless solid. MS: ESP+ (M+H)+=307.
Reaction SMILES: [CH2:1]1[C:7]2=[C:8]3[C:12](=[CH:13][CH:14]=[C:6]2[O:5][CH2:4][CH2:3][N:2]1C(OC(C)(C)C)=O)[NH:11][CH:10]=[CH:9]3.[H-].[Na+].CN(C=O)C.[CH3:29][C:30]1[S:31][C:32]([CH3:39])=[CH:33][C:34]=1[S:35](Cl)(=[O:37])=[O:36]>N.CO>[CH3:29][C:30]1[S:31][C:32]([CH3:39])=[CH:33][C:34]=1[S:35]([N:11]1[C:12]2[C:8](=[C:7]3[CH2:1][NH:2][CH2:3][CH2:4][O:5][C:6]3=[CH:14][CH:13]=2)[CH:9]=[CH:10]1)(=[O:37])=[O:36]
Reactant: Cc1cc(S(=O)(=O)Cl)c(C)s1
Reactant: CC(C)(C)OC(=O)N1CCOc2ccc3[nH]ccc3c2C1
Agent: N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1cc(S(=O)(=O)n2ccc3c4c(ccc32)OCCNC4)c(C)s1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 17.7 %

Procedure:
tert-Butyl 1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate (Intermediate 18, 14 mg, 0.050 mmol), NaH (60% in mineral oil, 6.4 mg, 0.10 mmol) and dry DMF (0.2 mL) were shaken at room temperature for 10 minutes. 2,5-Dimethylthiophene-3-sulfonyl chloride (21 mg, 0.10 mmol, in 0.15 mL of dry DMF) was added to the solution. The reaction mixture was shaken at room temperature for another 20 minutes and a mixture of MeOH/1 M HCl (3:1, 1 mL) was added. The reaction mixture was stirred overnight and evaporated. The residue was dissolved in 1 M NH3 in MeOH (1 mL, 1 mmol) and MeOH (1 mL). The crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give the title compound as an off-white solid (3.2 mg). MS m/z 363 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[Cl:10][CH2:11][CH2:12][CH2:13][C:14](Cl)=[O:15].FC(Br)C1C=CC=CC=1.C1(C(Cl)=O)CCC1>>[Cl:10][CH2:11][CH2:12][CH2:13][C:14](=[O:15])[CH2:4][C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[Cl:1]
Reactant: O=C(Cl)CCCCl
Reactant: Clc1ccccc1CBr
Agent: FC(Br)c1ccccc1
Agent: O=C(Cl)C1CCC1
Product: O=C(CCCCl)Cc1ccccc1Cl
Yield: 79 %

Procedure:
Following a procedure similar to that described in Preparation 13, except that equivalent amounts of 2-chlorobenzyl bromide and 4-chlorobutyryl chloride were used in place of the 2 fluorobenzyl bromide and cyclobutanecarbonyl chloride, the title compound was obtained as a yellow oil in a yield of 79%.
Reaction SMILES: [C:1](=[S:3])=[S:2].OS(O[CH2:9][CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11]1)(=O)=O>[OH-].[Na+]>[CH2:9]1[CH:10]2[CH2:18][C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]2[C:1](=[S:3])[S:2]1
Reactant: O=S(=O)(O)OCC1Cc2ccccc2N1
Reactant: S=C=S
Agent: [Na+]
Agent: [OH-]
Product: S=C1SCC2Cc3ccccc3N12
Temperature: 20 °C
Reaction time: 2 h

Procedure:
Carbon disulphide (65 cc) is added to a suspension of (RS)-2-hydroxysulphonyloxymethylindoline (45.8 g) in 1.5 N aqueous sodium hydroxide solution (400 cc). After stirring for 2 hours at a temperature of about 20° C., a solution is obtained and the formation of beige crystals is then observed; stirring is continued for 12 hours. The crystals formed are filtered off, washed with water and then recrystallised from ethanol (850 cc). (RS)-9,9a-dihydrothiazolo[3,4-a]indole-3-thione (31.3 g) is thus obtained in the form of white crystals melting at 132° C.
Reaction SMILES: [NH2:1][C:2]([CH3:16])([CH2:5][N:6]1[N:10]=[C:9]2[CH:11]=[CH:12][CH:13]=[C:14]([Cl:15])[C:8]2=[N:7]1)[C:3]#[N:4].[O:17]([C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[Cl:15][C:14]1[C:8]2[C:9](=[N:10][N:6]([CH2:5][C:2]([NH:1][C:28](=[O:29])[C:27]3[CH:26]=[CH:25][C:24]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:32][CH:31]=3)([C:3]#[N:4])[CH3:16])[N:7]=2)[CH:11]=[CH:12][CH:13]=1
Reactant: CC(N)(C#N)Cn1nc2cccc(Cl)c2n1
Reactant: O=C(Cl)c1ccc(Oc2ccccc2)cc1
Product: CC(C#N)(Cn1nc2cccc(Cl)c2n1)NC(=O)c1ccc(Oc2ccccc2)cc1

Procedure:
Using a procedure similar to that described in Example 1, except using 2-amino-3-(4-chloro-2H-benzotriazol-2-yl)-2-methylpropionitrile (100 mg, described in Example 35) and 4-phenoxybenzoyl chloride (0.10 mL), the title compound was isolated as a white solid (70 mg, 38%). Rf=0.7 (1:1 EA/heptane). MS (ES): M/Z [M+H]=432. NMR: (400 MHz, DMSO-d6): 1.75 (s, 3H), 5.43 (d, J=13.3 Hz, 1H), 5.50 (d, J=13.3 Hz, 1H), 7.04-7.10 (m, 4H), 7.22 (t, J=7.4 Hz, 1H), 7.43-7.48 (m, 3H), 7.59 (d, J=6.6 Hz, 1H), 7.84 (d, J=8.9 Hz, 2H), 7.94 (d, J=8.0 Hz, 1H) and 8.73 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[C:3]([O:16][S:17](=[O:31])(=[O:30])[O:18][C:19]2[CH:29]=[CH:28][C:22]([C:23]([O:25]CC)=[O:24])=[CH:21][CH:20]=2)=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.[Li+].[OH-].CO>O1CCCC1>[CH3:1][C:2]1[C:3]([O:16][S:17](=[O:31])(=[O:30])[O:18][C:19]2[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:28][CH:29]=2)=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:12])([CH3:13])[C:10]=2[CH:11]=1
Reactant: CCOC(=O)c1ccc(OS(=O)(=O)Oc2cc3c(cc2C)C(C)(C)CCC3(C)C)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc2c(cc1OS(=O)(=O)Oc1ccc(C(=O)O)cc1)C(C)(C)CCC2(C)C
Temperature: 55 °C
Reaction time: 8 h
Yield: 0.6 %

Procedure:
To a solution of 58 mg (0.15 mmol) of ethyl 4-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthylsulfoxy)benzoate (Compound 8) in 4.0 mL of tetrahydrofuran was added 1.0 mL of LiOH (2N aqueous solution) and 2.0 ml of MeOH. The solution was heated at 55° C. for 2 h and stirred at room temperature for 8 h. The reaction mixture was then concentrated in vacuo. The residue was diluted with brine and 10% HCl and extracted with diethyl ether (2×). The combined ether layers were dried (MgSO4), filtered, and the solvents removed in vacuo to give the title compound as a white solid (0.39 mg, 72%):
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]1([CH2:13]N2C=NC=N2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:19]1([CH:25]=NC2C=CC=CC=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[C:7]1([C:13]#[C:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: c1ccc(Cn2cncn2)cc1
Reactant: C(=Nc1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C(#Cc1ccccc1)c1ccccc1
Temperature: 0 °C
Yield: 11 %

Procedure:
To potassium t-butoxide (5.6 g, 50 mmol) in DMF (40 mL) at 75° C. was added N-(phenylmethyl)-1H-1,2,4-triazole (1.59 g, 10 mmol) and N-(phenylmethylene)benzenamine (1.81 g, 10 mmol) dissolved in DMF (10 mL). After 30 minutes the solution is poured into ice-cold water (150 mL), extracted with CHCl3 (3×50 mL) and chromatographed (PE). Diphenylacetylene was obtained in 11% yield.