Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:14][CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[NH:8][N:7]=[CH:6]2.P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:9]1[C:10]2[C:5](=[C:4]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)[C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[CH:6]=[N:7][N:8]=1
Reactant: COc1ccc2c(=O)[nH]ncc2c1OCC1CCCCO1
Reactant: O=P(Cl)(Cl)Cl
Product: COc1ccc2c(Cl)nncc2c1OCC1CCCCO1

Procedure:
Operating analogously to example 7 staring from 6-methoxy-5-(tetrahydropyran-2-yl-methoxy)-2H-phthalazin-1-one (1.48 g, 5.12 mmoles), obtained as described in example 42, and phosphoryl chloride (6 ml) 1.65 g of the title product as a crude were obtained and used as such in the next step.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=O)=[CH:5][CH:4]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:23])=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[S:23])=[CH:5][CH:4]=1
Reactant: NC(=O)c1ccc(C(F)(F)F)cc1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: NC(=S)c1ccc(C(F)(F)F)cc1

Procedure:
A mixture of 4-trifluoromethylbenzamide (79 mM) and Lawesson's reagent (39 mM) in toluene (200 mL) was heated at reflux for 4 hours under N2. The reaction mixture was cooled and the resulting precipitate was isolated by filtration to give 4-trifluoromethylthiobenzamide as a solid: mp 125° C. (The following general procedure was used to synthesize the various substituted thiobenzamides (Tetrahedron 35,2433, (1979)):
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[C@@H:14]1[CH2:23][CH2:22][C:21]2[CH:20]=[C:19]([O:24]C(=O)C(C)(C)C)[CH:18]=[CH:17][C:16]=2[CH2:15]1)[CH3:2].[F:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[O:40][CH:41]1[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]1)[CH:35]=O>>[CH2:1]([N:3]([CH2:35][C:34]1[CH:37]=[CH:38][C:39]([O:40][CH:41]2[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]2)=[C:32]([F:31])[CH:33]=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[C@@H:14]1[CH2:23][CH2:22][C:21]2[CH:20]=[C:19]([OH:24])[CH:18]=[CH:17][C:16]=2[CH2:15]1)[CH3:2]
Reactant: CCNc1cc(OC)c(OC)cc1[C@@H]1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Reactant: CN1CCC(Oc2ccc(C=O)cc2F)CC1
Product: CCN(Cc1ccc(OC2CCN(C)CC2)c(F)c1)c1cc(OC)c(OC)cc1[C@@H]1CCc2cc(O)ccc2C1
Yield: 34.5 %

Procedure:
Synthesized from pivalic acid (R)-6-(2-ethylamino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl ester (20 mg) and 3-fluoro-4-(1-methylpiperidin-4-yloxy)benzaldehyde (55 mg) according to an analogous synthetic method to Example 264 and purified by LC-MS, the title compound (9.2 mg) was obtained.
Reaction SMILES: [CH2:1](I)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:10]([C:14]1[N:15]([CH2:23][C:24]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:25]=2[CH:26]=[CH:27][N:28]3[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[C:39]#[N:40])[C:16]([C:20]([OH:22])=[O:21])=[C:17]([Cl:19])[N:18]=1)[CH2:11][CH2:12][CH3:13]>CN(C)C=O.C(OCC)(=O)C>[CH2:10]([C:14]1[N:15]([CH2:23][C:24]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:25]=2[CH:26]=[CH:27][N:28]3[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[C:39]#[N:40])[C:16]([C:20]([O:22][CH2:1][CH3:2])=[O:21])=[C:17]([Cl:19])[N:18]=1)[CH2:11][CH2:12][CH3:13]
Reactant: CCI
Reactant: CCCCc1nc(Cl)c(C(=O)O)n1Cc1cccc2c1ccn2-c1ccccc1C#N
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCCc1nc(Cl)c(C(=O)OCC)n1Cc1cccc2c1ccn2-c1ccccc1C#N
Reaction time: 1.5 h

Procedure:
Ethyl iodide (561.5 mg, 3.60 mmol) and cesium carbonate (1.5g, 4.5 mmol) were added to a solution of 2-butyl-4-chloro-1-[[1-(2-cyanophenyl)-1H-indol-4-yl]methyl]-1H-imidazole-5carboxylic acid (779.2 mg, 1.80 mmol, prepared as described in part C of Example 9) in dimethylformamide (3.72 ml). After 1.5 hours at room temperature, the reaction was diluted with ethyl acetate and filtered to remove the cesium carbonate. The ethyl acetate was washed with pH=4 buffer (2×20 ml), pH=7 buffer (2×25 ml), saturated sodium chloride (20 mL) and dried over anhydrous magnesium sulfate, filtered and concentrated to a yellow oil (890 mg). Purification by flash chromatography (83 g Merck silica gel, 8:2 hexane/ethyl acetate) gave 662 mg of the title A compound.
Reaction SMILES: [CH3:1][OH:2].[NH2:3][C:4]1[C:11]([F:12])=[CH:10][C:7]([C:8]#[N:9])=[C:6](F)[CH:5]=1>O1CCCC1>[NH2:3][C:4]1[C:11]([F:12])=[CH:10][C:7]([C:8]#[N:9])=[C:6]([O:2][CH3:1])[CH:5]=1
Reactant: N#Cc1cc(F)c(N)cc1F
Reactant: CO
Solvent: C1CCOC1
Product: COc1cc(N)c(F)cc1C#N
Temperature: 25 °C
Yield: 97 %

Procedure:
To a mixture of methanol (10.48 mL, 0.25 mol) and anh. tetrahydrofuran (60 mL) was added dropwise a solution of potassium tert-butilate (6.76 g, 0.05 mol) in anh. tetrahydrofuran (52 mL) at 0° C. under nitrogen atmosphere. The mixture was stirred for minutes at room temperature and then 4-amino-2,5-difluorobenzonitrile (4 g, 0.02 mol) was added. The reaction mixture was stirred at 70° C. for 3 hours. The solvent was partially removed and ether was added into the mixture. The organic layer was washed with bicarbonate and brine, dried and filtered. The organic solvent was removed under reduced pressure to give the title compound as a yellow solid (97%), which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C@H:9]([NH:11][S@](C(C)(C)C)=O)[CH3:10])=[CH:4][C:3]=1[CH3:18].Cl>CO>[Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C@H:9]([NH2:11])[CH3:10])=[CH:4][C:3]=1[CH3:18]
Reactant: Cc1cc([C@@H](C)N[S@@](=O)C(C)(C)C)cc(C)c1Cl
Agent: Cl
Solvent: CO
Product: Cc1cc([C@@H](C)N)cc(C)c1Cl
Reaction time: 8 h

Procedure:
A solution of intermediate INT 40 (2.3 g, 8 mmol) in MeOH (50 mL) was treated with HCl (4 M in dioxane, 4 mL, 16 mmol) and stirred overnight. After evaporation of the solvents, a solid was obtained which was washed with Et2O. The solid was then dissolved in water, slightly acidified with 2 M HCl and washed with EtOAc. The aqueous layer was separated and the pH adjusted to about 11 using 2 M NaOH followed by extraction with Et2O (3×). The Et2O layers were combined, dried over sodium sulfate, filtered and concentrated.
Reaction SMILES: [F:1][C:2]1[C:10]2[O:9][C:8]([C:11]3([OH:24])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[CH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1>CCO.[Pd]>[F:1][C:2]1[C:10]2[O:9][CH:8]([C:11]3([OH:24])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:13][CH2:12]3)[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(c2cc3cccc(F)c3o2)CC1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC(O)(C2Cc3cccc(F)c3O2)CC1
Yield: 77.3 %

Procedure:
To a degassed solution of tert-butyl 4-(7-fluorobenzofuran-2-yl)-4-hydroxypiperidine-1-carboxylate (0.52 g, 1.55 mmol) in EtOH (9.62 mL) was added 10% Pd—C (0.495 g, 0.465 mmol). Upon completion of addition, the reaction mixture was charged with 55 psi of H2 overnight. After the conclusion of this period, the Pd—C was filtered off through a pad of CELITE®, and the filter cake was rinsed with EtOH. The solvent was removed under reduced pressure to afford Compound 1E as a light yellow solid (0.404 g, 77% yield).
Reaction SMILES: C(N(CC1C=CC=CC=1)[C:9]1([CH2:14][NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([CH3:26])[CH:24]=3)[N:19]=[C:18]([N:27]3[CH2:33][C:32]4[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=4[S:30](=[O:39])(=[O:38])[CH2:29][CH2:28]3)[CH:17]=2)CC[O:11][CH2:10]1)C1C=CC=CC=1.O1C=CC(N)=[N:48]1>>[O:39]=[S:30]1(=[O:38])[C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[CH2:33][N:27]([C:18]2[CH:17]=[C:16]([NH:15][C:14]3[CH:9]=[CH:10][O:11][N:48]=3)[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([CH3:26])[CH:24]=3)[N:19]=2)[CH2:28][CH2:29]1
Reactant: Nc1ccon1
Reactant: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(NCC3(N(Cc4ccccc4)Cc4ccccc4)CCOC3)c2c1
Product: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(Nc3ccon3)c2c1

Procedure:
The title compound was prepared in analogy to Example 3-1 in Scheme 5 by using 4-(4-bromo-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (prepared in analogy to 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 2-1 by using 4,6-dibromoquinoline and 2,3,4,5-tetrahydro-1,4-benzothiazepine) and 1,2-oxazol-3-amine. MS obsd. (ESI+) [(M+H)+] 421, 1H NMR (400 MHz, CD3OD) δ ppm 8.72 (s, 1 H), 8.20 (s, 2 H), 8.14 (d, J=7.2 Hz, 1 H), 8.07 (d, J=7.6 Hz, 1 H), 7.83 (d, J=8.8 Hz, 1 H), 7.63-7.68 (m, 2 H), 7.56 (t, J=7.6 Hz, 1 H), 6.65 (s, 1 H), 5.29 (s, 2 H), 4.61 (s, 2 H), 3.79 (s, 2 H), 2.54 (s, 3 H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[F:16])[N:12]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[CH:11]=[CH:10]2.[CH3:24][NH:25][CH2:26][CH2:27][OH:28]>>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([N:12]2[C:13]3[C:9](=[CH:8][C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:25]([CH3:24])[CH2:26][CH2:27][OH:28])=[C:15]([F:16])[CH:14]=3)[CH:10]=[CH:11]2)=[CH:18][CH:19]=1
Reactant: CNCCO
Reactant: Fc1cc2c(ccn2-c2ccc(Cl)cc2)cc1OCCCCBr
Product: CN(CCO)CCCCOc1cc2ccn(-c3ccc(Cl)cc3)c2cc1F

Procedure:
In analogy to example 23.7, 5-(4-Bromo-butoxy)-1-(4-chloro-phenyl)-6-fluoro-1H-indole and 2-(methylamino)ethanol were converted to yield 2-({4-[1-(4-Chloro-phenyl)-6-fluoro-1H-indol-5-yloxy]-butyl}-methyl-amino)-ethanol as a colorless oil, MS: 391 (MH+,1Cl).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9]([OH:13])=[CH:10]2)=[CH:5][CH:4]=1.[N:14]([O-])=[O:15].[Na+]>C(O)(=O)C.O>[N:14]([C:10]1[C:11]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=2)[CH:7]=[CH:8][C:9]=1[OH:13])=[O:15]
Reactant: O=N[O-]
Reactant: COc1ccc2ccc(O)cc2c1
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: COc1ccc2ccc(O)c(N=O)c2c1
Reaction time: 2 h
Yield: 93.5 %

Procedure:
110.2 g (0.633 mol) of 7-methoxy-β-naphthol were nitrosated in a mixture of 650 ml of glacial acetic acid and 65 ml of water at 0° C. in the course of two hours using a solution of 45.0 g (0.65 mol) of sodium nitrite in 340 ml of water. Stirring was continued for a further two hours and in this time the temperature of the reaction mixture was allowed to rise to 22° C. Then the volume was made up to 1.6 l with water and the precipitated product was filtered off by suction. After drying, 120.3 g (93.5%) of 1-nitroso-7-methoxy-β-naphthol were obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]([C:21]([F:24])([F:23])[F:22])=[N:11][N:12]([C:15]3[N:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:13]=2[NH2:14])[CH:5]=[C:6]([Cl:8])[CH:7]=1.CO[CH:27](OC)[N:28]([CH3:30])[CH3:29]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]([C:21]([F:22])([F:24])[F:23])=[N:11][N:12]([C:15]3[N:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:13]=2[N:14]=[CH:27][N:28]([CH3:30])[CH3:29])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: Nc1c(-c2cc(Cl)cc(Br)c2)c(C(F)(F)F)nn1-c1ncccn1
Reactant: COC(OC)N(C)C
Solvent: Cc1ccccc1
Product: CN(C)C=Nc1c(-c2cc(Cl)cc(Br)c2)c(C(F)(F)F)nn1-c1ncccn1

Procedure:
1.19 g (2.84 mmol) of 4-(3-bromo-5-chlorophenyl)-1-(pyrimidin-2-yl)-3-(trifluoromethyl)-1H-pyrazol-5-amine (known from WO 2008/077843 A) and 0.51 g (4.26 mmol) of dimethylformamide dimethyl acetal are dissolved in 20 ml of toluene and stirred under reflux for 18 hours. After cooling, the toluene solution is washed with water, the organic phase is separated off, dried with magnesium sulphate and filtered and the filtrate is concentrated under reduced pressure using a rotary evaporator. The residue is stirred with a solvent mixture of cyclohexane and ethyl acetate (vol. 1:1) and the precipiated solid is filtered off and air-dried. This gives 0.99 g (67% of theory) of the compound N′-[4-(3-bromo-5-chlorophenyl)-1-(pyrimidin-2-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N,N-dimethylimidoformamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]#[CH:10]>S(=O)(=O)(O)O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]#[C:10][CH2:7][CH2:8][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: C#Cc1ccccc1OC
Agent: O=S(=O)(O)O
Product: CCCCCCC#Cc1ccccc1OC
Temperature: -70 °C
Yield: 170.8 %

Procedure:
2-Methoxyphenyl acetylene (9.00 g, 0.068M, Literature reference J. Villieras et al, Synthesis 459, 1975), was dissolved in dry, deaerated tetrahydrofuran/diethyl ether 1:1 (200 ml) and the solution stirred at -70° C. n-Butyl lithium 1.565M in hexane (43.5 ml, 0.068M) was added dropwise and the pale red mixture warmed to room temperature and stirred at that temperature for 15 min. The mixture was cooled to -70° C. and dry iodohexane (14.42 g, 0.068M) added dropwise. The white mixture was warmed to room temperature and stirred for 1 h, then refluxed for 4 h during which time a yellow solution formed. The reaction was cooled, poured into 1M sulphuric acid, (200 ml), and the product extracted with diethyl ether, (three times). The combined organic phases were washed with water, brine and dried, (MgSO4). Evaporation in vacuo yielded the crude produce as a pale yellow oil. Purification with column chromatography using silica gel and eluting with dichloromethane/n-hexane (1:3) gave 12.58 g (86%) of the title compound as a colourless oil.
Reaction SMILES: [F:1][C:2]([F:11])([C:7]([F:10])([F:9])[F:8])[CH2:3][CH2:4][CH2:5][NH2:6].[CH3:12][S:13][C:14](SC)=[N:15][C:16]#[N:17]>C(O)C>[C:16]([NH:15][C:14](=[N:6][CH2:5][CH2:4][CH2:3][C:2]([F:11])([F:1])[C:7]([F:8])([F:9])[F:10])[S:13][CH3:12])#[N:17]
Reactant: CSC(=NC#N)SC
Reactant: NCCCC(F)(F)C(F)(F)F
Solvent: CCO
Product: CSC(=NCCCC(F)(F)C(F)(F)F)NC#N
Yield: 69.3 %

Procedure:
A solution of 4,4,5,5,5-pentafluoropentylamine (0.118M, 30 ml, 3.55 mmole) and of dimethyl N-cyanodithioiminocarbonate (700 mg, 4.26 mmole) in ethanol (30 ml) was heated under reflux for 18 hours. Concentration under reduced pressure, followed by crystallization from ethyl acetate and petroleum ether afforded 1-cyano-3-(4,4,5,5,5-pentafluoropentyl)-2-methylisothiourea (677 mg, 69%).
Reaction SMILES: [N:1]1([S:7]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1C(=O)N([Br:26])C(=O)C1>C(Cl)Cl>[Br:26][C:16]1[CH:17]=[C:12]([CH2:11][CH2:10][S:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)(=[O:9])=[O:8])[CH:13]=[CH:14][C:15]=1[NH2:18]
Reactant: O=C1CCC(=O)N1Br
Reactant: Nc1ccc(CCS(=O)(=O)N2CCOCC2)cc1
Solvent: ClCCl
Product: Nc1ccc(CCS(=O)(=O)N2CCOCC2)cc1Br
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 100 %

Procedure:
A solution of 103 mg (0.381 mmol) of 4-[2-(morpholine-4-sulfonyl)-ethyl]-phenylamine (as prepared in the previous step) in CH2Cl2 (15 mL) was cooled to 0° C. and treated portionwise with 67.8 mg (0.381 mmol) of solid NBS. The mixture was stirred at 0° C. for 15 min, diluted with CH2Cl2 (30 mL) and washed with saturated aqueous NaHCO3 (1×20 mL). The organic layers were dried (MgSO4) and concentrated in vacuo to afford 133 mg (100%) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C12H17N2O3SBr, 349.0/351.0 (M+H). found 348.7/350.8.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[S:11][CH3:12])[NH:7][C:6](=O)[C:5]2=O.ClC1C=C(F)C=C2C=1NC=C2>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[S:11][CH3:12])[NH:7][CH:6]=[CH:5]2
Reactant: CSc1cc2c(cc1F)C(=O)C(=O)N2
Agent: Fc1cc(Cl)c2[nH]ccc2c1
Product: CSc1cc2[nH]ccc2cc1F

Procedure:
5-Fluoro-6-methylthioindole was prepared from 5-fluoro-6-methylthioindole-2,3-dione according to the method described in the preparation of 7-chloro-5-fluoroindole as a white solid (1.21 g, 37%): mp 51° C.; C9H8FNS requires: C, 59.65; H, 4.45; N, 7.73; S, 17.69%. Found C, 59.75; H, 4.44; N, 7.72; S, 17.65%; IR δmax (Nujol)/cm−1 3461, 3408, 3361, 2925, 2855, 1455, 1304 and 1137; NMR δH (400 MHz, CDCl3) 2.49 (3H, s), 6.49-6.51 (1H, m), 7.22 (1H, t, J 3.0 Hz), 7.30 (1H, d, J 10.0 Hz), 7.36 (1H, d, J 6.5 Hz), 8.0-8.25 (1H, brm).
Reaction SMILES: [C:1]1([C:39]2[CH:44]=[CH:43][C:42]([C:45]3[CH:54]=[CH:53][C:48]([C:49]([O:51]C)=[O:50])=[CH:47][CH:46]=3)=[CH:41][CH:40]=2)[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:22]=[CH:21][C:16]([C:17]([O:19]C)=[O:18])=[CH:15][CH:14]=3)=[CH:9][CH:8]=2)[CH:4]=[C:3]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:38]=[CH:37][C:32]([C:33]([O:35]C)=[O:34])=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)[CH:2]=1.[OH-].[Na+].C1COCC1.O>CO>[C:1]1([C:39]2[CH:44]=[CH:43][C:42]([C:45]3[CH:46]=[CH:47][C:48]([C:49]([OH:51])=[O:50])=[CH:53][CH:54]=3)=[CH:41][CH:40]=2)[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[CH:14]=[CH:15][C:16]([C:17]([OH:19])=[O:18])=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[CH:4]=[C:3]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:38]=[CH:37][C:32]([C:33]([OH:35])=[O:34])=[CH:31][CH:30]=3)=[CH:27][CH:28]=2)[CH:2]=1
Reactant: COC(=O)c1ccc(-c2ccc(-c3cc(-c4ccc(-c5ccc(C(=O)OC)cc5)cc4)cc(-c4ccc(-c5ccc(C(=O)OC)cc5)cc4)c3)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1ccc(-c2ccc(-c3cc(-c4ccc(-c5ccc(C(=O)O)cc5)cc4)cc(-c4ccc(-c5ccc(C(=O)O)cc5)cc4)c3)cc2)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Trimethyl 4,4′,4″-(benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate (2.00 g, 2.82 mmol), 2.2 g of NaOH, THF, water, and methanol (200, 80, and 50 mL, respectively) were mixed in a 1 L round bottom flask equipped with a magnetic stirring bar, and the mixture was stirred for 2 days at room temperature. The solution was evaporated under vacuum. The residue was acidified with 3 M HCl. The white solid was collected by filtration, washed with methylene chloride and methanol and dried in vacuum overnight (1.80 g, 96%): mp 326° C.; 1H-NMR (DMSO-d6, 400 MHz) δ 13.07 (br, 3H) 8.07 (d, 6H, J=8.0 Hz), 8.06 (s, 3H), 8.05 (d, 6H, J=8.0 Hz), 7.91 (d, 6H, J=7.6 Hz), 7.89 (d, 6H, J=7.2 Hz); 13C-NMR (DMSO-d6, 100 MHz) δ 168.0, 144.6, 141.9, 140.7, 139.2, 130.9, 130.6, 128.8, 128.4, 127.6, 125.3; FT-IR (KBr, 4000-400 cm−1) 3448 (br), 3029 (br), 2661 (w), 2536 (w), 1925 (w), 1686 (s), 1606 (s), 1419 (m), 1276 (m), 1177 (m), 1118 (m), 1003 (m), 824 (s), 773 (s); MALDI-TOF MS (m/z) [M]+ 666.2976 (found), 666.2042 (calcd. for C45H30O6).
Reaction SMILES: [C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([CH3:6])=[O:5].C(O)=O.[C:12]1(C)[C:13](S(O)(=O)=O)=[CH:14][CH:15]=[CH:16][CH:17]=1.C=CCCCC>>[C:1]([O:8][CH2:14][CH2:13][CH2:12][CH2:17][CH2:16][CH3:15])(=[O:7])[CH2:2][CH2:3][C:4]([CH3:6])=[O:5]
Reactant: CC(=O)CCC(=O)O
Reactant: Cc1ccccc1S(=O)(=O)O
Solvent: C=CCCCC
Solvent: O=CO
Product: CCCCCCOC(=O)CCC(C)=O
Temperature: 100 °C

Procedure:
A 5 cc autoclave is charged with 2 cc of an aqueous solution containing 2 mmoles of levulinic acid and 0.2 mmoles of formic acid. 3 wt. % toluene sulfonic acid is added as a catalyst. The reactor is pressurized to 0.69 MPa with 1-hexene and heated to 100° C. for 2 hours while maintaining a constant pressure of 1-hexene. After cooling, the organic phase is separated. A mixture of hexyl formate and hexyl levulinate is formed as product.
Reaction SMILES: [CH2:1]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=[CH:15][C:16]2[N:21]=[C:20]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:19]=[CH:18][CH:17]=2)[N:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].II>C1COCC1.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].C1CCCCC1>[CH2:1]([O:7][C:8]1[CH:13]=[CH:12][C:11]2[C:17]3[C:16](=[N:21][C:20]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:19][CH:18]=3)[CH:15]=[CH:14][C:10]=2[N:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCOc1cccc(C=Cc2cccc(OCCCCCC)n2)n1
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: II
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: CCCCCCOc1ccc2c(ccc3nc(OCCCCCC)ccc32)n1

Procedure:
A mixture of 7.7 g of 2-bromo-6-hexyloxypyridine (prepared by reacting 2,6-dibromopyridine with sodium hexoxide in DMF), 3.9 g of trimethylsilylacetylene, 0.4 g of bis(triphenylphosphine)palladium(II) chloride and 0.05 g of copper (I) iodide in 100 ml of diethylamine is stirred at 20° C. for 12 hours. After the volatile constituents have been removed in a rotary evaporator, the mixture is filtered through SiO2 using dichloromethane; the crude 1-(2-bromopyridin-6-yl)-2-trimethylsilylethtne (7.5 g of melting point 24° to 27° C.) obtained is stirred for 1 hour at 20° C. in 100 ml of methanol with 25 ml of 1N aqueous NaOH solution. The solvent is evaporated, and the residue is chromatographed over SiO2 using dichloromethane/heptane 9:1, giving 4.3 g of 2-bromo-6-ethynylpyridine (brownish oil). A solution of 2 g of 2-bromo-6-ethynylpyridine in 50 ml of benzene to which 2.6 g of 2-bromo-6-hexyloxypyridine, 0.2 g of tetrakis(triphenylphisphine)palladium(0) and 30 ml of n-propylamine have been added is stirred at 20° C. for 10 hours. The volatile constituents are removed by distillation, and the residue is chromatographed over SiO2 using dichloromethane, giving 1.9 g of 1,2-bis(2-hexyloxypyridin-6-yl)ethyne. The latter is hydrogenated quantitatively in 50 ml of THF using Lindlar catalyst [Org. Synth. 46, 89 (1966)] to 1,2-bis(2-hexyloxypyridin-6-yl)ethene. The latter is dissolved in 500 ml of cyclohexane, 4 mol % of iodine are added, and the mixture is exposed to UV light for 10 hours at 25° C. in a quartz apparatus. Chromatography on SiO2 using dichloromethane and recrystallization from acetonitrile give 0.9 g of 2,7-bis(hexyloxy)-1,8-diazaphenanthrene as colorless crystals of melting point 91° C.
Reaction SMILES: C(OC([N:8]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH3:42])=[CH:36][CH:35]=1)[C:9]1[N:20]2[C:16](=[CH:17][CH:18]=[N:19]2)[N:15]=[C:14]2[C:10]=1[CH2:11][CH2:12][N:13]2[C@H:21]1[CH2:26][CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH2:41]([O:40][C:37]1[CH:36]=[CH:35][C:34]([NH:8][C:9]2[N:20]3[C:16](=[CH:17][CH:18]=[N:19]3)[N:15]=[C:14]3[C:10]=2[CH2:11][CH2:12][N:13]3[C@H:21]2[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]2)=[CH:39][CH:38]=1)[CH3:42]
Reactant: CCOc1ccc(N(C(=O)OC(C)(C)C)c2c3c(nc4ccnn24)N([C@H]2CCCN(C(=O)OC(C)(C)C)C2)CC3)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOc1ccc(Nc2c3c(nc4ccnn24)N([C@H]2CCCNC2)CC3)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 37 %

Procedure:
To a methylene chloride (4 mL) solution containing tert-butyl (S)-3-{8-[tert-butoxycarbonyl-(4-ethoxyphenyl)amino]-6,7-dihydro-1,4,5,8a-tetraaza-s-indacen-5-yl}piperidine-1-carboxylate (0.693 mmol), trifluoroacetic acid (2 mL) was added with ice-cooling, and the mixture was allowed to warm to room temperature and stirred for 16 hr. After the reaction, the reaction solution was poured into aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine and dried over sodium sulfate. After the sodium sulfate was filtered off, the solvent was distilled off and the residue was purified with PTLC {10% (2 mol/L ammonia/methanol)-methylene chloride} to obtain the title compound (97.0 mg).
Reaction SMILES: [CH:1]1[C:6]2[CH2:7][NH:8][CH2:9][CH2:10][S:11][C:5]=2[CH:4]=[CH:3][C:2]=1[NH2:12].[CH2:13](N(C(C)C)C(C)C)[CH3:14].BrCC>C(Cl)Cl>[CH2:13]([N:8]1[CH2:7][C:6]2[CH:1]=[C:2]([NH2:12])[CH:3]=[CH:4][C:5]=2[S:11][CH2:10][CH2:9]1)[CH3:14]
Reactant: Nc1ccc2c(c1)CNCCS2
Reactant: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CCBr
Product: CCN1CCSc2ccc(N)cc2C1
Reaction time: 20 h
Yield: 86.2 %

Procedure:
To a solution of 6,7,8,9-tetrahydro-5-thia-8-aza-benzocyclohepten-2-ylamine (0.07 g, 0.00039 mol) and N-ethyldiisopropylamine (0.066 g, 0.00047 mol) in DCM (4 mL) was added bromoethane (0.051 g, 0.00047 mol), stirred 20 h and evaporated to give 8-ethyl-6,7,8,9-tetrahydro-5-thia-8-aza-benzocyclohepten-2-ylamine (0.07 g) as an oil. MS (ESI+): 209 (M+H).