Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:7][C:8]3[C:13]([NH:14][C:15]=2[CH:16]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+].Br[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C(Cl)Cl>[C:37]1([N:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:16][C:15]2=3)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: COc1ccc2c(c1)Nc1ccccc1C2
Reactant: Brc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1ccc2c(c1)N(c1ccccc1)c1ccccc1C2
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.2 %

Procedure:
A mixture of 13.0 g of 3-methoxyacridan (57.7 mmol), 259 mg of Pd(OAc)2 (1.15 mmol), 187 g of tri-t-butylphosphine (0.92 mmol), 8.32 g of sodium t-butoxide (86.6 mmol), and 10.9 g of bromobenzene (69.2 mmol) in 100 mL of dry toluene was stirred under inert atmosphere at room temperature for 18 h. The reaction mixture was poured into a mixture of 300 mL of CH2Cl2 and 100 g of silica gel. The mixture was filtered, washed with an additional 500 mL of CH2Cl2, and the solids were discarded. The filtrate was concentrated in vacuo to afford a yellow solid. The solid was triturated in 100 mL of hexanes, filtered, washed with an additional 100 mL of hexanes, and dried to afford 13.8 g of N-phenyl-3-methoxyacridan, by NMR analysis (83%).
Reaction SMILES: [OH:1][N:2]=[C:3]([C:11](=O)[CH3:12])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(O)(=O)C.O>C1C=CC=CC=1>[OH:1][N:2]=[C:3]([C:11](=[N:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:12])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]
Reactant: Nc1ccccc1
Reactant: CC(=O)C(=NO)C(=O)OC(C)(C)C
Solvent: CC(=O)O
Solvent: c1ccccc1
Solvent: O
Product: CC(=Nc1ccccc1)C(=NO)C(=O)OC(C)(C)C
Reaction time: 5 h

Procedure:
A solution of tert-butyl 2-hydroxyimino-3-oxobutyrate (130 g), aniline (76 ml) and acetic acid (14 ml) in benzene (1.2 l) was refluxed with Dean Stark water separator for 5 hours. The resulting solution was cooled and washed with 5% aqueous sodium bicarbonate solution and water. After being dried over magnesium sulfate, the organic solvent was evaporated in vacuo. The residue was triturated with a mixture of n-hexane (300 ml) and diisopropyl ether (100 ml). The precipitate was collected by filtration, washed with n-hexane to give tert-butyl 2-hydroxyimino-3-phenyliminobutyrate (71.2 g).
Reaction SMILES: CS(C)=O.Cl.[NH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:30])[N:10]([C:17]1(CCCCN)[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:11]2=[O:16].C(N(CC)CC)C.C(CN)O>C(O)(C)C>[CH:14]1[CH:13]=[C:12]2[C:11](=[O:16])[N:10]([CH:17]3[C:18](=[O:24])[NH:19][C:20](=[O:23])[CH2:21][CH2:22]3)[C:9](=[O:30])[C:8]2=[C:7]([NH2:6])[CH:15]=1
Reactant: NCCCCC1(N2C(=O)c3cccc(N)c3C2=O)CCC(=O)NC1=O
Agent: Cl
Solvent: CC(C)O
Solvent: CS(C)=O
Solvent: NCCO
Product: Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reaction time: 16 h

Procedure:
About 2 mL of a suspension of affigel-10 (15 μmol/mL of gel, 50% slurry) in isopropanol was transferred to a conical tube and centrifuged to a settled volume of 1.04 mL. The isopropanol was removed and the affigel-10 was washed with DMSO (3×5 mL). A DMSO (2.2 mL) solution of 7 (0.002 g, 0.00525 mmol) and triethylamine (0.007 mL, 0.0525 mmol) was subsequently added and the resulting mixture was sealed and tumbled on a rotator at room temperature. After 16 h, the conical tube was spun down and the DMSO supernatant was tested for the presence of 7 by LC-MS. 7 was not observed and therefore to the mixture was added triethylamine (0.015 mL, 0.105 mmol) and ethanolamine (0.006 mL, 0.10503 mmol) and the resulting mixture was tumbled on a rotator at room temperature. After 20 h, SS-0007896 was spun down, the solvent was removed, and the resin was washed with DMSO (3×5 mL) and isopropanol (3×5 mL) and stored in isopropanol at −20° C.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH:28]([CH3:30])[CH3:29])[CH:13]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH2:14][C:15](OCC)=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].C(O)C>C1COCC1.C(OCC)(=O)C>[Si:21]([O:20][CH:13]([CH2:14][CH2:15][OH:16])[C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:28]([CH3:30])[CH3:29])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]
Reactant: CCOC(=O)CC(O[Si](C)(C)C(C)(C)C)[C@@H](NC(=O)OCc1ccccc1)C(C)C
Agent: [BH4-]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)[C@H](NC(=O)OCc1ccccc1)C(CCO)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Yield: 93.1 %

Procedure:
Under an argon atmosphere, to a suspension (303 mL) of ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(dimethyl)silyl]oxy}-5-methylhexanoate (17.7 g), calcium chloride (6.73 g) and sodium borohydride (4.58 g) in dehydrated THF was added with stirring under ice-cooling dehydrated ethanol (152 mL), and the mixture was gradually warmed to room temperature and stirred for 15 hr. The reaction mixture was slowly poured into a mixture of ethyl acetate and ice water (containing 1 mol/L hydrochloric acid, 122 mL) and the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=19/1→1/1) to give benzyl ((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-1-isopropylbutyl)carbamate as colorless oil (yield: 14.9 g).
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][CH2:5][C:6]1[C:11]2[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=[CH:15][C:10]=2[O:9][CH2:8][CH:7]=1.[Br:18]Br.C(N(CC)CC)C>C(OCC)(=O)C>[NH2:2][CH2:3][CH2:4][CH:5]=[C:6]1[C:11]2[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=[CH:15][C:10]=2[O:9][CH2:8][CH:7]1[Br:18]
Reactant: BrBr
Reactant: COc1ccc2c(c1)C(CCCN)=CCO2
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COc1ccc2c(c1)C(=CCCN)C(Br)CO2

Procedure:
To a suspension of 20 g of 4-(3-aminopropyl)-6-methoxy-2H-[1]-benzopyran hydrochloride in 200 ml of ethyl acetate is added 12.5 g of bromine at room temperature. After 15 minutes at room temperature 24 g of triethylamine is added to yield 4-(3-aminopropylidene)-3-bromo-6-methoxy-2H-[1]-benzopyran and the reaction mixture is refluxed for 2 hours. After washing with water and drying the solvent is removed in vacuo. The residue is dissolved in ethanol and acidified with ethanolic hydrogen chloride to afford 9-methoxy-2,3,4a,5-tetrahydro-4H-[1]-benzopyrano[3,4-b]pyridine hydrochloride, m.p. 285°-286°.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]([OH:13])=[O:12])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].OS(O)(=O)=O.[CH3:19]O>>[CH3:19][O:12][C:11](=[O:13])[CH2:10][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=1
Reactant: COc1ccc(CC(=O)O)cc1F
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1ccc(OC)c(F)c1

Procedure:
(3-Fluoro-4-methoxyphenyl)acetic acid (5.0 g, 27.1 mmol) is dissolved in MeOH (100 mL). To it is added concentrated H2SO4 (5 mL) and the solution it warmed to reflux for 2 h. At that point, the solution is evaporated to dryness and taken up in EtOAc. The solution is washed with saturated aqueous NaHCO3, dried (Na2SO4) and evaporated to give (3-fluoro-4-methoxyphenyl)acetic acid methyl ester (cas#588-14-7) as a yellow oil. MS (ESI) m/z 199.3 (M+H).
Reaction SMILES: [K].[OH:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:9])=[N:7][CH:8]=1.Br[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1>CN(C)C=O.CO.[Cu]>[CH3:17][C:14]1[CH:15]=[CH:16][C:11]([O:2][C:3]2[CH:4]=[CH:5][C:6]([CH3:9])=[N:7][CH:8]=2)=[CH:12][CH:13]=1
Reactant: Cc1ccc(O)cn1
Reactant: Cc1ccc(Br)cc1
Agent: [Cu]
Agent: [K]
Solvent: CO
Solvent: CN(C)C=O
Product: Cc1ccc(Oc2ccc(C)nc2)cc1

Procedure:
7.4 g of a potassium salt of 5-hydroxy-2-methylpyridine, 8.5 g of p-bromotoluene and 500 mg of a copper powder were suspended in 25 ml of dimethylformamide, and the mixture was allowed to react in a nitrogen gas stream at 130° C. for 14 hours under stirring. The reaction mixture was diluted with 70 ml of methanol and filtered. The filtrate was immediately concentrated, and to the residue was added 150 ml of chloroform. The mixture was washed with 100 ml of a 0.01 N aqueous sodium hydroxide solution, whereby the unreacted 5-hydroxy-2-methylpyridine shifted to the aqueous layer. The chloroform layer was washed with water, dried with anhydrous sodium sulfate and immediately dried to obtain 8.9 g of oily 5-(p-methylphenoxy)-2-methylpyridine.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:14]([C:15]([C:25]#[N:26])=[C:16]4[S:20][C:19]5[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=5[C:17]=24)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.O[C@@H:28]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:29]([O:31]C)=[O:30]>C(Cl)(Cl)Cl>[C:25]([C:15]1[C:16]2[S:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[C:17]=2[C:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][C@H:28]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:29]([OH:31])=[O:30])=[CH:7][CH:6]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][CH:11]=[CH:10]2)#[N:26]
Reactant: COC(=O)[C@@H](O)Cc1ccccc1
Reactant: N#Cc1c2ccccc2c(-c2ccc(O)cc2)c2c1sc1ccccc12
Solvent: ClC(Cl)Cl
Product: N#Cc1c2ccccc2c(-c2ccc(O[C@H](Cc3ccccc3)C(=O)O)cc2)c2c1sc1ccccc12

Procedure:
Prepared from 11-(4-hydroxy-phenyl)-benzo [b]naphtho[2,3-d]thiophene-6-carbonitrile (Example 44) and (S)-2-hydroxy-3-phenylpropionic acid, methyl ester (Example 96). White solid: mp 145-148° C.: [a]D25=-2.03° (7.883 mg/mL CHCl3); NMR (CDCl3); δ8.31 (ddd, J=8, 1, 1 Hz, 1 H), 7.78 (ddd., J=8, 1, 1 Hz, 1 H), 7.70 (ddd, J=8, 8, 1 Hz, 1 H), 7.56 (ddd, J=8, 1, 1 Hz, 1 H), 7.47-7.37 (m, 6 H), 7.32 (ddd, J=8, 7, 1 Hz, 1 H), 7.20 (dd., J=8, 2 Hz, 1 H),7.14-7.05 (m, 4 H), 6.62 (ddd, J=8, 1, 1 Hz, 1 H), 5.06 (dd, J=7, 5 Hz, 1 H), 3.44 (d, J=5 Hz, 1 H), 3.42 (d, J=7 Hz, 1 H); MS (EI): [M+], 499 (100%); Anal. Calc. for C32H21NO3S: C, 76.93, H, 4.24, N, 2.80. Found: C, 75.77, H, 4.22, N, 2.70.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[Li]CCCC.Cl[C:21]([O:23][CH2:24][CH3:25])=[O:22].O>C1COCC1>[CH3:1][O:2][C:3]1[C:12]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:11]([O:13][CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1
Reactant: COc1cc(OC)c2ccccc2n1
Reactant: CCOC(=O)Cl
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)c1c(OC)nc2ccccc2c1OC
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 60 %

Procedure:
To a solution of 2,4-dimethoxyquinoline (11.5 g, 60.8 mmol) in anhydrous THF was added dropwise n-BuLi (2.5 M in hexane, 48.6 mL, 122 mmol) at 0° C. After stirring for 1.5 h at 0° C., the mixture was added to a solution of ethyl chloroformate in anhydrous THF and stirred at 0° C. for additional 30 min and then at room temperature overnight. The reaction mixture was poured into water and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrated under vacuum. The resulting residue was purified by column chromatography (petroleum ether/EtOAc=50/1) to give ethyl 2,4-dimethoxyquinoline-3-carboxylate (9.6 g, 60%).
Reaction SMILES: [NH2:1][C@@H:2]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)[CH3:3].FC1C(F)=C(F)C(F)=C(F)C=1O[C:21]1[N:26]=[C:25]([C:27]2[C:35]3[C:30](=[N:31][CH:32]=[C:33]([C:36]([F:39])([F:38])[F:37])[CH:34]=3)[N:29]([S:40]([C:43]3[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=3)(=[O:42])=[O:41])[CH:28]=2)[C:24]([C:50]#[N:51])=[CH:23][N:22]=1>>[C:50]([C:24]1[C:25]([C:27]2[C:35]3[C:30](=[N:31][CH:32]=[C:33]([C:36]([F:38])([F:37])[F:39])[CH:34]=3)[N:29]([S:40]([C:43]3[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=3)(=[O:42])=[O:41])[CH:28]=2)=[N:26][C:21]([NH:1][C@@H:2]([CH:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:8][CH2:9]2)[CH3:3])=[N:22][CH:23]=1)#[N:51]
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3nc(Oc4c(F)c(F)c(F)c(F)c4F)ncc3C#N)c3cc(C(F)(F)F)cnc32)cc1
Reactant: C[C@@H](N)C1CCN(C(=O)OC(C)(C)C)CC1
Product: Cc1ccc(S(=O)(=O)n2cc(-c3nc(N[C@H](C)C4CCN(C(=O)OC(C)(C)C)CC4)ncc3C#N)c3cc(C(F)(F)F)cnc32)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 65.3 %

Procedure:
(R)-tert-butyl 4-(1-aminoethyl)piperidine-1-carboxylate (43.82 mg, 0.19 mmol) was added to a solution of 2-(perfluorophenoxy)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (100 mg, 0.16 mmol) and the reaction mixture was stirred at room temperature for 2 hours. The crude mixture was concentrated to dryness and the resulting residue was purified on silica gel by flash column chromatography to afford the title compound (70 mg, 65% yield).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.C(N(CC)CC)C.[CH2:19]([OH:22])[C:20]#[CH:21]>CN(C=O)C.[Cu](I)I.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>[OH:22][CH2:19][C:20]#[C:21][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2
Reactant: O=C1CCc2cc(Br)ccc21
Reactant: C#CCO
Agent: I[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: O=C1CCc2cc(C#CCO)ccc21
Yield: 71.2 %

Procedure:
5-Bromo-2,3-dihydro-1H-inden-1-one (1.68 g, 7.99 mmol) was dissolved in DMF and treated with triethylamine (1.61 g, 15.98 mmol), copper iodide (152 mg, 0.79 mmol) and prop-2-yn-1-ol (2.24 g, 39.96 mmol) in the presence of Pd(PPh3)4 (462 mg, 0.39 mmol) at ambient temperature. After being refluxed for 16 h, the reaction mixture was extracted with ethyl acetate (100 mL×3) and washed with brine. The combined organic layers were dried over MgSO4. Solvent removal under vacuum gave crude tan oil. Purification by preparative thin-layer chromatography afforded 5-(hydroxyprop-1-yn-1-yl)-2,3-dihydro-1H-indene-1-one (1.06 g, 72% yield): 1H NMR (400 MHz, CD3OD): δ 7.63 (d, 1H), 7.59 (s, 1H), 7.42 (d, 1H), 4.45 (s, 2H), 3.18 (m, 2H), 2.69 (m, 2H); MS (EI) for C12H10O2: 187.20 (MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH3:24]>C1COCC1.CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH2:24])=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N
Reactant: O=C(O)c1ccc(OCc2ccccc2)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: NC(=O)c1ccc(OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a suspension of 4.565 g (20 mmol) 4-benzyloxybenzoic acid in 25 ml THF and 0.3 ml N,N-dimethylformamide was added dropwise at 0° C. a solution of 2.6 ml oxalyl chloride in 5 ml THF. Stirring was continued for 3 hours at room temperature, then the suspension was added slowly to a stirred ice-cold solution of concentrated aqueous ammonia. The organic solvent was evaporated, 100 ml water added and the precipitate isolated and dried in vacuo at 50° C. Yield: 4.29 g (94%) white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]([CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:9][CH2:10][CH2:11][C:12](O)=[O:13])=[O:7])=[CH:4][CH:3]=1.[CH2:25]([NH:32][CH2:33][CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[OH-].[K+]>C(O)C>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]([CH:15]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16])[CH2:9][CH2:10][CH2:11][C:12]([N:32]([CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[O:13])=[O:7])=[CH:4][CH:3]=1
Reactant: CCOC(=O)CCCNCc1ccccc1
Reactant: CC(c1ccccc1)N(CCCC(=O)O)C(=O)c1ccc(Cl)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CC(c1ccccc1)N(CCCC(=O)N(CCCC(=O)O)Cc1ccccc1)C(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Analogously to Example 1, by using equivalent quantities, reacting N-(p-chlorobenzoyl)-4-(1-phenylethylamino)butyric acid and ethyl 4-benzylaminobutyrate and suitable processing, dissolving the evaporation residue in ethanol, adding an ethanolic solution of potassium hydroxide, stirring for 12 hours at room temperature and further processing yields N-[N-(p-chorobenzoyl)-4-(1-phenylethylamino)butyryl]-4-benzylaminobutyric acid.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:12]12(O)[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]3)[CH2:13]1)[CH2:19]2.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>ClCCl.O.C(O)(=O)C>[C:12]12([C:8]3[C:9]([OH:11])=[CH:10][C:2]([OH:1])=[C:3]([CH:7]=3)[C:4]([OH:6])=[O:5])[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]3)[CH2:13]1)[CH2:19]2
Reactant: O=C(O)c1ccc(O)cc1O
Reactant: OC12CC3CC(CC(C3)C1)C2
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: O
Product: O=C(O)c1cc(C23CC4CC(CC(C4)C2)C3)c(O)cc1O
Yield: 51 %

Procedure:
2,4-Dihydroxybenzoic acid (9.24 g) and 1-adamantanol (9.14 g) are dissolved in dichloromethane (200 mL) and then stirred. After adding acetic acid (17.1 mL) mixed with concentrated sulfuric acid (3.3 mL) dropwise, the mixture is stirred at room temperature for 12 hours. After adding water (200 mL), sodium bicarbonate is added until the pH of the solution becomes 6. The produced solid is filtered to obtain 8.82 g of 5-adamantan-1-yl-2,4-dihydroxybenzoic acid as solid of a light color.
Reaction SMILES: [CH:1]1([CH2:4][O:5][CH:6]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[CH2:3][CH2:2]1.Cl[CH2:13][CH2:14][CH2:15][N:16]1[C:21]2[C:22]([F:27])=[CH:23][CH:24]=[C:25]([F:26])[C:20]=2[O:19][CH2:18][C:17]1=[O:28].C([O-])([O-])=O.[K+].[K+]>>[CH:1]1([CH2:4][O:5][CH:6]2[CH2:11][CH2:10][N:9]([CH2:13][CH2:14][CH2:15][N:16]3[C:21]4[C:22]([F:27])=[CH:23][CH:24]=[C:25]([F:26])[C:20]=4[O:19][CH2:18][C:17]3=[O:28])[CH2:8][CH2:7]2)[CH2:2][CH2:3]1
Reactant: O=C1COc2c(F)ccc(F)c2N1CCCCl
Reactant: C1CC(OCC2CC2)CCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: O=C1COc2c(F)ccc(F)c2N1CCCN1CCC(OCC2CC2)CC1
Yield: 37.3 %

Procedure:
4-Cyclopropylmethoxypiperidine (0.085 g, 0.55 mmol), 4-(3-chloropropyl)-5,8-difluoro-4H-benzo[1,4]oxazin-3-one (0.146 g, 0.56 mmol), K2CO3 (0.152 g, 1.1 mmol), and KI (0.164 g, 1.1 mmol) were mixed according to GP3. Purified by prep TLC (SiO2; Heptanes/EtOAc 1:1) to give the title compound (0.078 g, 37%). 1H NMR (CDCl3) d 6.82-6.69 (m, 2H), 4.57 (s, 2H), 4.07-4.03 (m, 2H), 3.31-3.22 (m, 3H), 2.72-2.64 (m, 2H), 2.32 (t, J=7.2 Hz, 2H), 2.02 (t, J=10.4 Hz, 2H), 1.88-1.76 (m, 4H), 1.59-1.48 (m, 2H), 1.07-0.95 (m, 2H), 0.53-0.47 (m, 2H), 0.19-0.14 (m, 2H); 13C NMR (CDCl3) d 164.6, 148.3 (dd, J=243.3 Hz, J=2.7 Hz), 147.7 (dd, J=243.9, J=2.8 Hz), 136.6 (dd, J=11.2Hz, J=4.9Hz), 120.0 (d, J=11.1 Hz), 111.2 (dd, J=20.4Hz, J=9.6 Hz), 110.3 (dd, J=24.8 Hz, J=7.7 Hz), 75.0, 72.6, 68.6, 55.6, 51.5, 42.7 (d, J=10.8 Hz), 31.5, 25.7 (d, J=2.7 Hz), 11.1, 3.2.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[N+:6]([O-])=[N:7][C:8]3[CH:9]=[CH:10][C:11]([Cl:14])=[CH:12][C:13]=3[C:4]=2[CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]2[N:7]=[N:6][C:5]3[CH:16]=[CH:17][C:2]([Cl:1])=[CH:3][C:4]=3[C:13]=2[CH:12]=1
Reactant: [O-][n+]1nc2ccc(Cl)cc2c2cc(Cl)ccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: Clc1ccc2nnc3ccc(Cl)cc3c2c1

Procedure:
Furthermore, 2,9-dichloro-benzo-[c]-cinnoline is prepared according to the process described by J. F. Corbett, P. F. Holt, A. N. Hughes, M. Vickery (J. Chem. Soc. 1962, 1823) by the reduction of 2,9-dichloro-benzo-[c]-cinnoline-N-oxide with lithium aluminium hydride.
Reaction SMILES: [F:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Br:33]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:33][CH2:8][C:7]1[C:2]([F:1])=[C:3]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:4]=[CH:5][CH:6]=1
Reactant: Cc1cccc(-c2ccccc2)c1F
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: Fc1c(CBr)cccc1-c1ccccc1
Yield: 95.1 %

Procedure:
A stirred solution of 2-fluoro-3-methyl-[1,1'-biphenyl] (1.5 g, 0.00805 mole) in 25 ml of carbon tetrachloride was irradiated and heated at reflux with a 250 watt brooder lamp. Benzoyl peroxide (0.2 g) was added to the reaction mixture, followed by N-bromosuccinimide (1.46 g, 0.00805 mole). After a total of 21 hours of irradiation, the reaction mixture was cooled, filtered, and the filter cake rinsed with carbon tetrachloride. The combined filtrates were washed with saturated aqueous sodium chloride solution. The organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to give 3-bromomethyl-2-fluoro-[1,1'-biphenyl] (2.03 g) as an oil.
Reaction SMILES: [C:1]([NH:4][NH:5][C:6](=[O:26])[CH2:7][N:8]1[C:12]([CH2:13][CH3:14])=[C:11]([O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)[C:10]([CH2:24][CH3:25])=[N:9]1)(=[O:3])C.C(C1C=CC(OC2C(CC)=NN(CC(O)=O)C=2CC)=CC=1)#N.C(NN)=O>>[C:22]([C:19]1[CH:18]=[CH:17][C:16]([O:15][C:11]2[C:10]([CH2:24][CH3:25])=[N:9][N:8]([CH2:7][C:6]([NH:5][NH:4][CH:1]=[O:3])=[O:26])[C:12]=2[CH2:13][CH3:14])=[CH:21][CH:20]=1)#[N:23]
Reactant: CCc1nn(CC(=O)NNC(C)=O)c(CC)c1Oc1ccc(C#N)cc1
Agent: CCc1nn(CC(=O)O)c(CC)c1Oc1ccc(C#N)cc1
Agent: NNC=O
Product: CCc1nn(CC(=O)NNC=O)c(CC)c1Oc1ccc(C#N)cc1
Yield: 51 %

Procedure:
The title compound (290 mg, 51%) was prepared by a similar method to that describe for the acetohydrazide of step (b) of Example 140 using the acid of step (a) of Example 140 and formic hydrazide as the starting materials.
Reaction SMILES: CC1OC(C)=CC=1.[OH:8][CH2:9][C:10]1[O:16][C:13]([CH:14]=[O:15])=[CH:12][CH:11]=1>>[OH:15][CH2:14][C:13]1[O:16][C:10]([CH2:9][OH:8])=[CH:11][CH:12]=1
Reactant: O=Cc1ccc(CO)o1
Agent: Cc1ccc(C)o1
Product: OCc1ccc(CO)o1

Procedure:
In another aspect, the present disclosure provides a method C for preparing 2,5-dimethylfuran, which includes the steps of: a) combining 5-(hydroxymethyl)furfural (HMF) with H2, a first catalyst, and an aprotic solvent; b) reacting the mixture of step (a) to form 2,5-bis(hydroxymethyl)furan (BHMF); c) adding a carboxylic acid, and a second catalyst to the reaction mixture of step (b) to form an ester of BHMF; and d) adding H2 to the reaction mixture that includes the ester of BHMF of step (c) to form 2,5-dimethylfuran.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:33]=[CH:32][C:8]2[N:9]=[C:10]([C:12]([C:17]3[CH:22]=[CH:21][C:20]([O:23]CC4C=CC=CC=4)=[C:19]([CH3:31])[CH:18]=3)([CH2:15][CH3:16])[CH2:13][CH3:14])[O:11][C:7]=2[CH:6]=1)=[O:4]>CO.C1COCC1.[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:33]=[CH:32][C:8]2[N:9]=[C:10]([C:12]([CH2:13][CH3:14])([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH3:31])[CH:18]=3)[CH2:15][CH3:16])[O:11][C:7]=2[CH:6]=1)=[O:4]
Reactant: CCC(CC)(c1ccc(OCc2ccccc2)c(C)c1)c1nc2ccc(C(=O)OC)cc2o1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CCC(CC)(c1ccc(O)c(C)c1)c1nc2ccc(C(=O)OC)cc2o1
Reaction time: 12 h
Yield: 100.5 %

Procedure:
A solution of 2-[1-(4-benzyloxy-3-methyl-phenyl)-1-ethyl-propyl]-benzooxazole-6-carboxylic acid methyl ester (1.50 g, 3.38 mmol) in MeOH (20 mL) is added a slurry of Pd—C (150 mg, 10%) in THF (20 mL) at RT. The resulting mixture is stirred under hydrogen balloon pressure for 12 h. The mixture is filtered through a pad of celite, and the filtrate is concentrated. The residue is purified with 20% EtOAc/Hex to afford the title compound (1.20 g, 100%). H-NMR (ppm, CDCl3) δ: 8.11 (1H, s), 8.03 (1H, dd, J=1.8, 8.4 Hz), 7.73 (1H, d, J=8.4 Hz), 6.97 (1H, d, J=2.2 Hz), 6.92 (1H, dd, J=2.2, 8.4 Hz), 6.70 (1H, d, J=8.4 Hz), 3.93 (3H, s), 2.40 (2H, q, J=7.5 Hz), 2.30 (2H, q, J=7.5 Hz), 2.20 (3H, s), 0.76 (6H, t, J=7.5 Hz).