Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[OH:2].[C:3]([NH:16][C@@H:17]1[C:23](=[O:24])[O:22][C:20](=[O:21])[CH2:19][CH2:18]1)(=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]>C(Cl)Cl.N1C=CC=CC=1>[C:3]([NH:16][C@H:17]([C:23]([OH:22])=[O:24])[CH2:18][CH2:19][C:20]([OH:2])=[O:21])(=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCC(=O)N[C@H]1CCC(=O)OC1=O
Reactant: CO
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCCCCCCCCCC(=O)N[C@@H](CCC(=O)O)C(=O)O
Reaction time: 8 h
Yield: 84.4 %

Procedure:
10.00 g (0.00892 mol) of mono-terminal carbinol-modified silicone was dissolved in 10.00 g of methylene chloride and 1.00 g of pyridine. 4.67 g (0.0150 mol) of lauroylglutamic acid anhydride was added to the reaction mixture, and then the mixture was stirred overnight. The reaction liquid was concentrated and separated after adding hexane and a 90% methanol aqueous solution. The hexane layer was concentrated to obtain 10.64 g (0.00753 mol) of lauroylglutamic acid-modified silicone.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8](F)=[CH:7][CH:6]=1)[CH3:2].[OH:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([N:17]2[CH:18]=[CH:19][C:14](=[O:13])[CH:15]=[CH:16]2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: Oc1ccncc1
Reactant: CCOC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: CCOC(=O)c1ccc(-n2ccc(=O)cc2)cc1
Temperature: 140 °C
Reaction time: 3 h

Procedure:
In a 500 ml round bottom flask with stirbar was place 4-fluorobenzoic acid ethyl ester (16.8 g, 100 mmol), 4-hydroxypyridine (14.26 g, 150 mmol), potassium carbonate (20.7 g, 150 mmol) and N-methylpyrrolidinone (75 ml). This mixture was gradually warmed to 140° C. and kept at this temperature for three hours after which time all the starting aryl fluoride was consumed. The mixture was cooled to room temperature and with stirring ice and water was added in porions to bring the volume up to 500 ml. The precipitated product was isolated by suction filtration, washed well with water and air dried. This directly isolated material was very pure and suitable for further use. Material recrystallized from toluene had Mp 178°-180°.
Reaction SMILES: [C:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([CH:10]([NH:12]C(=O)OC(C)(C)C)[CH3:11])=[C:5]([O:20][CH2:21][CH3:22])[C:4]=1[C:23]1[CH:24]=[N:25][CH:26]=[C:27]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:28]=1)#[N:2]>Cl.O1CCOCC1>[NH2:12][CH:10]([C:6]1[CH:7]=[C:8]([CH3:9])[C:3]([C:1]#[N:2])=[C:4]([C:23]2[CH:24]=[N:25][CH:26]=[C:27]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:28]=2)[C:5]=1[O:20][CH2:21][CH3:22])[CH3:11]
Reactant: CCOc1c(C(C)NC(=O)OC(C)(C)C)cc(C)c(C#N)c1-c1cncc(S(C)(=O)=O)c1
Agent: Cl
Solvent: C1COCCO1
Product: CCOc1c(C(C)N)cc(C)c(C#N)c1-c1cncc(S(C)(=O)=O)c1
Reaction time: 1 h
Yield: 149.8 %

Procedure:
The tert-butyl (1-{4-cyano-2-ethoxy-5-methyl-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate (0.030 gm, 0.065 mmol) was dissolved in 4.0 M HCl in dioxane (2 mL) and was stirred for 1 hour. The reaction was concentrated in vacuo to give 4-(1-aminoethyl)-3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]benzonitrile as a semi-solid (0.035 g, 100%). LCMS calculated for C18H22N3O3S (M+H)+: m/z=360.1. found: 360.2.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([OH:20])[CH2:11][C@H:12]([CH2:16][CH2:17][CH2:18][CH3:19])[C:13]([OH:15])=[O:14])=[CH:6][CH:5]=1.[CH3:21]I>C1COCC1>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C@H:10]([O:20][CH3:21])[CH2:11][C@H:12]([CH2:16][CH2:17][CH2:18][CH3:19])[C:13]([OH:15])=[O:14])=[CH:8][CH:9]=1
Reactant: CCCC[C@@H](C[C@@H](O)c1ccc(F)cc1)C(=O)O
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCC[C@@H](C[C@@H](OC)c1ccc(F)cc1)C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a suspension of NaH (129 mg, 60% oil dispersion) in 20 mL THF was slowly added at room temperature the crude (S)-2-((R)-2-(4-fluorophenyl)-2-hydroxyethyl)hexanoic acid isolated above as a solution in 10 mL THF. To this mixture was added dropwise methyl iodide (164 mL, 373.9 mg, 2.6 mmol) and the resulting stirred for 3 h at room temperature. The reaction was quenched by the slow addition of 15 mL 1M aqueous HCl and the mixture extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (2×20 mL) and dried over sodium sulfate. Evaporation of solvent afforded the product as an oil which was used directly in the next reaction without further purification.
Reaction SMILES: CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:34]2[N:38]([CH2:39][CH3:40])[N:37]=[C:36]([CH:41]3[CH2:46][CH2:45][N:44]([C:47](=[O:57])[CH2:48][CH2:49][O:50]C4CCCCO4)[CH2:43][CH2:42]3)[N:35]=2)=[N:23][C:24]=1[C:25]1[O:26][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[N:28][N:29]=1>CO>[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:34]2[N:38]([CH2:39][CH3:40])[N:37]=[C:36]([CH:41]3[CH2:42][CH2:43][N:44]([C:47](=[O:57])[CH2:48][CH2:49][OH:50])[CH2:45][CH2:46]3)[N:35]=2)=[N:23][C:24]=1[C:25]1[O:26][C:27]([C:30]([CH3:33])([CH3:31])[CH3:32])=[N:28][N:29]=1
Reactant: CCn1nc(C2CCN(C(=O)CCOC3CCCCO3)CC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccncc1
Solvent: CO
Product: CCn1nc(C2CCN(C(=O)CCO)CC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 84.8 %

Procedure:
Pyridine 4-methylbenzenesulfonate (11.62 g, 46.24 mmol) was added to a suspension of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (128 g, 231.19 mmol) in methanol (1 L) under nitrogen. The mixture was stirred at 60° C. for 1.5 hours. The mixture was soluble after 5 minutes. The mixture was held at 50° C. overnight during which time a precipitate formed. The solid material was isolated by filtration and washed with water and acetonitrile. This material still contained minor impurities from the previous stage and required further purification. The material was dissolved in dichloromethane and purified by flash chromatography on silica gel (0% methanol/DCM to 10% methanol/DCM). The desired product, 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (Example 3) (92 g, 85%), was thus isolated as a cream solid (Form A): 1H NMR Spectrum: (DMSO-d6) 1.4-1.51 (12H, m), 1.51-1.78 (2H, m), 1.89-2.05 (2H, m), 2.72-2.86 (1H, m), 2.91-3.05 (1H, m), 3.12-3.24 (1H, m), 3.64 (2H, q), 3.83-4.01 (1H, m), 4.29-4.41 (1H, m), 4.47 (1H, t), 4.58 (2H, q), 8.26 (2H, s), 8.85 (1H, s); Mass Spectrum [M+H]+=470.
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH:6]=[CH:7][CH2:8][NH:9][CH2:10][CH2:11][NH:12][S:13]([C:16]2[C:17]3[CH:18]=[CH:19][N:20]=[CH:21][C:22]=3[CH:23]=[CH:24][CH:25]=2)(=[O:15])=[O:14])=[CH:4][CH:3]=1.[OH:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][CH:30]=1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[CH:7][CH2:8][N:9]([CH2:10][CH2:11][NH:12][S:13]([C:16]2[C:17]3[CH:18]=[CH:19][N:20]=[CH:21][C:22]=3[CH:23]=[CH:24][CH:25]=2)(=[O:14])=[O:15])[CH2:33][C:32]2[CH:35]=[CH:36][C:29]([OH:28])=[CH:30][CH:31]=2)=[CH:26][CH:27]=1
Reactant: O=S(=O)(NCCNCC=Cc1ccc(Cl)cc1)c1cccc2cnccc12
Reactant: O=Cc1ccc(O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: O=S(=O)(NCCN(CC=Cc1ccc(Cl)cc1)Cc1ccc(O)cc1)c1cccc2cnccc12
Temperature: 25 °C
Reaction time: 48 h
Yield: 59.3 %

Procedure:
0.2 g of the product of Example 172 and 0.13 g of p-hydroxybenzaldehyde were dissolved in 10 ml of methanol, to the solution were added 60 mg of sodium cyanoborohydride and two drops of acetic acid, and the mixture was stirred for 2 days at a room temperature. The reaction mixture was concentrated under a reduced pressure, and after adding a saturated sodium chloride aqueous solution, extracted three times with 20 ml of ethyl acetate. The extracts were combined, washed with sodium chloride, dried over magnesium sulfate, filtered and concentrated under a reduced pressure. The resulting residue was purified on a silica gel column (silica gel 10 g, eluant: 2% methanol in chloroform), to obtain 150 mg of the title compound in a colorless amorphous form.
Reaction SMILES: [F:1][B-](F)(F)F.[C:6]([C:8]1[CH:13]=[C:12]([S:14][C:15]#[N:16])[CH:11]=[CH:10][C:9]=1[N+]#N)#[N:7]>O>[F:1][C:9]1[CH:10]=[CH:11][C:12]([S:14][C:15]#[N:16])=[CH:13][C:8]=1[C:6]#[N:7]
Reactant: F[B-](F)(F)F
Reactant: N#CSc1ccc([N+]#N)c(C#N)c1
Solvent: O
Product: N#CSc1ccc(F)c(C#N)c1
Temperature: 200 °C
Yield: 14.9 %

Procedure:
2-Cyano-4-(thiocyanato)benzenediazonium fluoroborate (2.98 g (10.9 mmol)) was decomposed by first heating with a heat-gun until until the whole mass became black and then by heating to 200° C. in an oil bath for 30 minutes. After cooling, water was added and the resulting mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was then distilled by means of a glass tube oven under reduced pressure, and a fraction which boiled at 180-240 ° C./0.2 mmHg was collected to give 0.29 g (15%) of 2-fluoro-5-(thiocyanato)benzonitrile as a pale yellow-white crystals.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][N:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([C:18]([O:20]CC)=[O:19])[C:12]3=[O:23])[CH2:4][CH2:3]1.[OH-].[Na+].[ClH:26]>C1COCC1>[ClH:26].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][N:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([C:18]([OH:20])=[O:19])[C:12]3=[O:23])[CH2:4][CH2:3]1
Reactant: CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
Temperature: 75 °C
Reaction time: 8 h

Procedure:
A mixture of 0.865 g (2.75 mmol) of ethyl 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate, from Step 1, in 12 mL of THF and 16.5 mL of a 0.5N aqueous solution of sodium hydroxide was heated, with stirring, at 75° C. for 8 hours. The THF was removed from the reaction mixture by distillation during the reaction. The concentrated reaction mixture was cooled to ambient temperature and adjusted to pH 2.0 with 10.5 mL of 1N aqueous hydrochloric acid solution. The aqueous solution was concentrated in vacuo to remove ~80% of the water and the concentrate was diluted with 50 mL of 95% ethyl alcohol. The solid was collected by filtration, washed with 2 X 5 mL of ethyl alcohol and dried in vacuo to afford the desired product. The product was recrystallized from ethyl alcohol/water (3:1 v/v) to afford 0.332 g (37% yield) of the title compound, m.p.257°-258° C.; MS DCI-NH3 : 288 (M-Cl)+ 90%, 244 ((M-Cl)--CO2H)+ base, 270 (M-Cl--H2O)+ ; IR (KBr): 3420 (OH), 1645 (C=O) cm-1 ; 1H NMR (TFA) d 3.20 (m, 3H), 3.52 (dd, 2H, J=10 Hz), 4.02 (m, 4H), 4.63 (d, 2H, J=12 Hz), 7.41 (m, 2H), 7.65 (d, 1H, J=7.5 Hz), 8.26 (d, 1H, J=9 Hz), 9.18 (d, 1H, J=7.5 Hz). Analysis calculated for C15H18ClN3O3 +0.5H2O: C, 54.14; H, 5.75; N, 12.62. Found: C, 54.23; H, 5.54; N, 12.64.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:8]([CH2:11][CH2:12][CH3:13])(=[O:10])=[O:9])[CH:3]=1.[C:14]([O:18][C:19](=[O:31])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=1[C:29]#[CH:30])([CH3:17])([CH3:16])[CH3:15].N1CCCCC1>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:14]([O:18][C:19](=[O:31])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=1[C:29]#[C:30][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:8]([CH2:11][CH2:12][CH3:13])(=[O:10])=[O:9])[CH:3]=1)([CH3:17])([CH3:16])[CH3:15]
Reactant: CCCS(=O)(=O)c1cccc(Br)c1
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCNCC1
Solvent: CCOC(C)=O
Product: CCCS(=O)(=O)c1cccc(C#Cc2cc(Cl)ccc2OCC(=O)OC(C)(C)C)c1
Temperature: 70 °C

Procedure:
A mixture of 1-bromo-3-(propane-1-sulfonyl)-benzene (Intermediate 5; 493 mg, 1.87 mmol), tert-butyl(4-chloro-2-ethynylphenoxy)acetate (Intermediate 3, 500 mg; 1.87 mmol), dichlorobis(triphenylphosphine)palladium(II) (52 mg; 0.07 mmol) and piperidine (550 μL; 5.6 mmol) was heated at 70° C. for 18 hours. The reaction mixture was taken up in EtOAc, washed twice with citric acid (0.5 M aqueous solution) and once with brine. The organic phase was dried over MgSO4, filtered and concentrated to dryness affording a crude, which was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc. The title compound was obtained as a dark orange sticky solid (640 mg, 76%).
Reaction SMILES: CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N:15]2[C:19]([NH:20][C:21](=[O:50])[NH:22][C@@H:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C@H:26]([O:33][C:34]4[CH:35]=[CH:36][C:37]5[N:38]([C:40]([N:43]6[CH2:48][CH2:47][CH2:46][CH2:45][C@@H:44]6[CH3:49])=[N:41][N:42]=5)[CH:39]=4)[CH2:25][CH2:24]3)=[CH:18][C:17]([C:51]([CH3:72])([CH3:71])[CH2:52][O:53][Si:54]([C:67]([CH3:70])([CH3:69])[CH3:68])([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[N:16]2)[CH:10]=1)(=O)=O.[CH3:73][NH:74][CH3:75]>C1COCC1>[Si:54]([O:53][CH2:52][C:51]([C:17]1[CH:18]=[C:19]([NH:20][C:21]([NH:22][C@@H:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C@H:26]([O:33][C:34]3[CH:35]=[CH:36][C:37]4[N:38]([C:40]([N:43]5[CH2:48][CH2:47][CH2:46][CH2:45][C@@H:44]5[CH3:49])=[N:41][N:42]=4)[CH:39]=3)[CH2:25][CH2:24]2)=[O:50])[N:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:7][CH2:6][N:74]([CH3:75])[CH3:73])[CH:10]=2)[N:16]=1)([CH3:71])[CH3:72])([C:67]([CH3:68])([CH3:69])[CH3:70])([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1
Reactant: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)CO[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)nn4-c4cccc(OCCOS(C)(=O)=O)c4)c4ccccc43)cn12
Reactant: CNC
Solvent: C1CCOC1
Product: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)CO[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)nn4-c4cccc(OCCN(C)C)c4)c4ccccc43)cn12
Temperature: 60 °C
Reaction time: 18 h
Yield: 75 %

Procedure:
A solution of Intermediate 153i (131 mg, 0.13 mmol) in THF (0.8 mL) was treated with a 2M solution of dimethylamine in THF (1.3 mL, 2.6 mmol) and the mixture was stirred at 60° C. for 18 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown gum. The gum was purified by FCC, using 0-8% (2N NH3MeOH) in DCM, to give the title compound as a white foam (93 mg, 75%). LCMS (Method 3): Rt 3.91 min, m/z 960.6 [MH+].
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[C:6](F)[CH:7]=1.[CH2:13]([OH:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[CH2:13]([O:20][C:6]1[CH:5]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:3]=[C:2]([Cl:1])[CH:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: OCc1ccccc1
Reactant: O=C(O)Cc1cc(F)cc(Cl)c1
Product: O=C(O)Cc1cc(Cl)cc(OCc2ccccc2)c1

Procedure:
Prepared according to the procedure described in Example 185, Step 1, using the following starting materials: 3-chloro-5-fluorophenylacetic acid and benzyl alcohol.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]([O:16]C)=[O:15])=[CH:13][C:8]=3[O:7][C:6]=2[CH:18]=1.C1COCC1.[OH-].[Na+]>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]([OH:16])=[O:15])=[CH:13][C:8]=3[O:7][C:6]=2[CH:18]=1
Reactant: COC(=O)c1ccc2c(c1)oc1cc(Br)ccc12
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1ccc2c(c1)oc1cc(Br)ccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 101.4 %

Procedure:
To a mixture of methyl 3-bromo-dibenzofuran 7-carboxylate (3.2 g, 10.5 mmol) in 2:1 THF:methanol (90 ml) was added 2.5N NaOH (60 ml). After stirring at room temperature for 1 hour, the reaction was complete. Nearly all the THF:methanol was evaporated off and then the mixture was adjusted to pH=1 with concentrated HCl and extracted with ethyl acetate. Drying (MgSO4) and evaporation yielded 3.1 g (100%) of the title compound which was used in the next reaction without purification.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[C:7]#[N:8].[C:9]1([N:15]=[C:16]=[O:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(C(C)=O)C.C(O)C.C1(C)C=CC=CC=1>[C:9]1([NH:15][C:16]([NH:1][C:2]2[N:3]=[CH:4][NH:5][C:6]=2[C:7]#[N:8])=[O:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: N#Cc1[nH]cnc1N
Reactant: O=C=Nc1ccccc1
Solvent: CCC(C)=O
Solvent: Cc1ccccc1
Solvent: CCO
Product: N#Cc1[nH]cnc1NC(=O)Nc1ccccc1
Yield: 40.9 %

Procedure:
Under a nitrogen atmosphere a stirred solution of 4-amino-1H-imidazole-5-carbonitrile (1.1 g, 0.01 mole) and phenyl isocyanate (1.3 g, 0.011 mole) in 30 ml of dry methyl ethyl ketone was heated under reflux for 10 hours. The solvent was removed, and the residue was stirred with 50 ml of boiling tetrahydrofuran. The mixture was filtered hot, and the filtrate was concentrated under reduced pressure. The residual solid was slurried in 50 ml of diethyl ether and the solid was collected by filtration, washed three times with diethyl ether, and dried to give a solid (1.2 g; mp, 165° d). The solid was dissolved in hot ethanol/toluene and an insoluble material removed by filtration. The filtrate was concentrated under reduced pressure to give N-phenyl-N'-(5-cyano-1H-imidazol-4-yl)urea (0.93 g; mp, >300°).
Reaction SMILES: [CH:1]1([C:11]([O:13][CH3:14])=[O:12])[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:10])=[O:8])[CH:3]=[CH:2]1>C1CCCCC1.[Pt]>[C:7]([O:9][CH3:10])(=[O:8])[C:4]1[CH:5]=[CH:6][C:1]([C:11]([O:13][CH3:14])=[O:12])=[CH:2][CH:3]=1
Reactant: COC(=O)C1C=CC(C(=O)OC)CC1
Agent: [Pt]
Solvent: C1CCCCC1
Product: COC(=O)c1ccc(C(=O)OC)cc1
Temperature: 150 °C

Procedure:
In a Parr pressure reactor, dimethyl cyclohex-2-ene-1,4-dicarboxylate (2.42 g, 12.2 mmol) is dissolved in cyclohexane (120 ml, 0.10 M) and a catalytic amount of platinum on carbon (476 mg, 5 percent Pt/C, 1 mole percent platinum) powder is added. The reactor is pressurized with air (240 psi (1.65 MPa) at 23° C. after saturation of the solution) and its contents are heated at a 150° C. set-point temperature for 3 days under rapid stirring (160 rpm). After opening the cooled Parr reactor, a suspension of black platinum on carbon (Pt/C) in a near colorless solution is present. All solvent is removed from a sample of the suspension, and the entire residue is dissolved in CDCl3 for 1H NMR analysis. Integration of the respective resonances shows the presence of about 23 percent unreacted dimethyl cyclohex-2-ene-1,4-dicarboxylate starting material, of about 59 percent dimethyl terephthalate oxidation product, and of about 18 percent dimethyl cyclohexane-1,4-dicarboxylate disproportionation by-product. Column chromatography (Si35, SF40-150g, AnaLogix column with 10 percent ethyl acetate/hexane isocratic eluent) provides pure dimethyl terephthalate.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:7]=1[CH3:14])=[O:5].[N+:20]([O-])([OH:22])=[O:21]>O>[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([N+:20]([O-:22])=[O:21])[C:9]([O:12][CH3:13])=[CH:8][C:7]=1[CH3:14])=[O:5]
Reactant: O=[N+]([O-])O
Reactant: COc1ccc(C(=O)c2c(Cl)cccc2Cl)c(C)c1
Solvent: O
Product: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)cc1[N+](=O)[O-]
Temperature: 80 °C
Reaction time: 1 h

Procedure:
2,6-Dichloro-4'-methoxy-2'-methyl-benzophenone (0.75 g; 2.5 mmol) is added to nitric acid (10 ml; 65%). The mixture is stirred at 80° C. for 1 hour. After addition of water the reaction product crystallises and is chromatographically purified (flash column filled with 30 g of silicagel, elution with toluene). White crystalls (0.35 g; 41% y); mp. 156-160° C.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Cl.O.[NH:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1>[Pt](=O)=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:16]3[CH2:17][CH2:18][NH:13][CH2:14][CH2:15]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C1CCNCC1
Reactant: Fc1ccc2cc[nH]c2c1
Agent: O=[Pt]=O
Agent: Cl
Solvent: O
Product: Fc1ccc2c(C3CCNCC3)c[nH]c2c1
Yield: 39.6 %

Procedure:
This compound was prepared following the procedure described in example 1 (parts A and B) starting with 1 g (7.4 mmol) of 6-fluoroindol and 2.84 g (18.5 mmol) of 4-piperidone monohydrate hydrochloride. In this case, the hydrogenation step took place for 1 hour at 30 psi and the catalyst used was platinum (IV) oxide. 0.640 g (51% yield) of 6-fluoro-3-piperidin-4-yl-1H-indole were obtained.
Reaction SMILES: [OH:1][CH:2]([CH3:7])[CH2:3][C:4]([OH:6])=[O:5].[Br:8][CH2:9][C:10](Cl)=[O:11].C(N(CC)CC)C>C(OCC)C>[Br:8][CH2:9][C:10]([O:1][CH:2]([CH3:7])[CH2:3][C:4]([OH:6])=[O:5])=[O:11]
Reactant: O=C(Cl)CBr
Reactant: CC(O)CC(=O)O
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CC(CC(=O)O)OC(=O)CBr
Temperature: 5 °C
Yield: 70 %

Procedure:
5 g (0.048 mol) of 3-hydroxybutyric acid and 0.062 mol of bromoacetyl chloride were dissolved in 100 ml of diethyl ether. This solution was stirred in an ice bath, and while maintaining the solution at a level of not higher than 5° C., 20 ml of diethyl ether containing 5.35 g (0.053 mol) of triethylamine was dropwise added over a period of 30 minutes. After the dropwise addition, the mixture was stirred at room temperature for 10 hours. Then, triethylamine hydrochloride was filtered off from the reaction solution, and the filtrate was washed three times with distilled water. The ether solution thereby obtained was dried over anhydrous sodium sulfate, and then diethyl ether was distilled off. As a result, a slightly yellow desired compound was obtained in a yield of 70%.