Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH2:2]([N:4]([CH2:38][CH3:39])[CH2:5][CH2:6][O:7][CH:8]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[O:23][CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[C:11](=[O:31])[C:10]=2[C:9]1([N+]([O-])=O)[N+:32]([O-])=O)[CH3:3].O.O.[Cl:42][Sn]Cl>>[ClH:42].[NH2:32][C:9]1[C:10]2[C:11](=[O:31])[C:12]3[C:17](=[C:16]([O:23][CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[CH:15]=[CH:14][CH:13]=3)[C:18]=2[C:19]([O:21][CH3:22])=[CH:20][C:8]=1[O:7][CH2:6][CH2:5][N:4]([CH2:38][CH3:39])[CH2:2][CH3:3]
Reactant: CCN(CC)CCOc1cccc2c1C1=C(C2=O)C([N+](=O)[O-])([N+](=O)[O-])C(OCCN(CC)CC)C=C1OC
Reactant: Cl[Sn]Cl
Agent: Cl
Solvent: O
Product: CCN(CC)CCOc1cc(OC)c2c(c1N)C(=O)c1cccc(OCCN(CC)CC)c1-2

Procedure:
2,5-Bis-(2-diethylamino-ethoxy)-1-nitro-4-methoxy-1-nitro-fluoren-9-one hydrochloride (0.37 g, 0.70 mmol) and stannous chloride dihydrate (SnCl2.2H2O; 1.0 g, 0.7 mmol) are reacted as described in Example 9A to give the title compound which has the following structural formula: ##STR52##
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[N:11]=[C:12]=[S:13])[CH3:2].[CH:14]([NH2:17])([CH3:16])[CH3:15]>>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[NH:11][C:12]([NH:17][CH:14]([CH3:16])[CH3:15])=[S:13])[CH3:2]
Reactant: CCc1cccc(CC)c1N=C=S
Reactant: CC(C)N
Product: CCc1cccc(CC)c1NC(=S)NC(C)C

Procedure:
Reaction of 2,6-diethyl-phenyl isothiocyanate with isopropylamine in accordance with the process described above gives N-(2,6-diethyl-phenyl)-N'-isopropyl-thiourea of melting point: 108° to 110°.
Reaction SMILES: C([O:4][C:5]1[C:6]([CH3:39])=[C:7]([CH3:38])[C:8]2[O:12][C:11]([CH3:35])([C:13]([NH:15][C:16]3[CH:17]=[N:18][C:19]4[C:24]([C:25]=3[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:32])=[CH:23][C:22]([CH3:33])=[CH:21][C:20]=4[CH3:34])=[O:14])[CH2:10][C:9]=2[C:36]=1[CH3:37])(=O)C.Cl.CO>O>[Cl:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:25]1[C:24]2[C:19](=[C:20]([CH3:34])[CH:21]=[C:22]([CH3:33])[CH:23]=2)[N:18]=[CH:17][C:16]=1[NH:15][C:13]([C:11]1([CH3:35])[CH2:10][C:9]2[C:36]([CH3:37])=[C:5]([OH:4])[C:6]([CH3:39])=[C:7]([CH3:38])[C:8]=2[O:12]1)=[O:14]
Reactant: CC(=O)Oc1c(C)c(C)c2c(c1C)CC(C)(C(=O)Nc1cnc3c(C)cc(C)cc3c1-c1ccccc1Cl)O2
Agent: Cl
Solvent: CO
Solvent: O
Product: Cc1cc(C)c2ncc(NC(=O)C3(C)Cc4c(C)c(O)c(C)c(C)c4O3)c(-c3ccccc3Cl)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.2 %

Procedure:
A mixture of 3-(5-acetoxy-2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-ylcarbonyl)amino-4-(2-chlorophenyl) -6,8-dimethylquinoline (400 ml) and 6.92N-hydrochloric acid-methanol solution (10 ml) was stirred at room temperature for eight hours. After addition of water, the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), then concentrated. The residue was purified by a silica gel column chromatography with hexane-ethyl acetate (3:1,V/V), and then crystallized from isopropyl ether to give 4-(2-chlorophenyl)-3-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethylbenzofuran-2-ylcarbonyl) amino-6,8-dimethylquinoline (104 mg, 28.2%) as colorless prisms.
Reaction SMILES: F[C:2]1[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([CH:11]=1)[C:7]([NH:9][CH3:10])=[O:8].[F:15]C1C=CC(C(O)=O)=C([N+]([O-])=O)C=1>>[F:15][C:3]1[CH:2]=[CH:11][C:6]([C:7]([NH:9][CH3:10])=[O:8])=[C:5]([N+:12]([O-:14])=[O:13])[CH:4]=1
Reactant: CNC(=O)c1cc(F)ccc1[N+](=O)[O-]
Reactant: O=C(O)c1ccc(F)cc1[N+](=O)[O-]
Product: CNC(=O)c1ccc(F)cc1[N+](=O)[O-]

Procedure:
The title compound was prepared using the procedure from 5-fluoro-N-methyl-2-nitrobenzamide (Compound 102B) with the commercially available 4-fluoro-2-nitrobenzoic acid. 1H NMR (CDCl3, 400 MHz): δ=3.04 (d, J=4.80 Hz, 3H), 5.88 (br. s., 1H), 7.39 (ddd, J=8.46, 7.45, 2.53 Hz, 1H), 7.55 (dd, J=8.59, 5.31 Hz, 1H), 7.78 (dd, J=8.34, 2.53 Hz, 1H). MS (ES+): m/z 199.05 [MH+] (TOF, polar).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][OH:12].O[C:14]1[CH:46]=[CH:45][C:17]([CH2:18][CH:19]2[S:23][C:22](=[O:24])[N:21]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]2=[O:44])=[CH:16][CH:15]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1C=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][O:12][C:14]1[CH:46]=[CH:45][C:17]([CH2:18][CH:19]2[S:23][C:22](=[O:24])[N:21]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]2=[O:44])=[CH:16][CH:15]=1
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cn1c(CO)cc2ccccc21
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: c1ccccc1
Product: Cn1c(COc2ccc(CC3SC(=O)N(C(c4ccccc4)(c4ccccc4)c4ccccc4)C3=O)cc2)cc2ccccc21
Yield: 46.6 %

Procedure:
A procedure similar to that described in Preparation 4 was repeated, except that 4.30 g of 1-methylindol-2-ylmethanol (prepared as described in Preparation 23), 10.3 g of 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione, 6.65 ml of tributylphosphine, 6.73 g of 1,1'-(azodicarbonyl)dipiperidine and 120 ml of benzene were used, to give 6.28 g of the title compound, melting at 134.3°-136.0° C.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([C:12]1[CH:13]=[C:14]([CH:26]=[CH:27][CH:28]=1)[C:15]([NH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=1)=[O:16])#[N:11].C(N(CC)CC)C>C(Cl)Cl>[C:10]([C:12]1[CH:13]=[C:14]([CH:26]=[CH:27][CH:28]=1)[C:15]([NH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:21][CH:20]=1)=[O:16])#[N:11]
Reactant: N#Cc1cccc(C(=O)NCc2ccc(N)cc2)c1
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N#Cc1cccc(C(=O)NCc2ccc(NC(=O)c3ccccc3)cc2)c1

Procedure:
A solution of 0.6 g (4.2 mmol) of benzoylchloride in 10 ml of methylene chloride is added dropwise to a solution of 1 g (4 mmol) of 3-cyano-N-(4-amino-benzyl)-benzamide and 0.6 g (6 mmol) of triethylamine in 30 ml of methylene chloride at ambient temperature. After 8 hours at ambient temperature the product which has crystallised out is dissolved in methylene chloride and methanol. After extraction with water the combined organic extracts are dried and evaporated down.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][C:9]2(O)[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[C:11]([O:19][CH2:20][CH3:21])[CH:10]2[CH3:22])=[C:6]([Cl:24])[CH:5]=[CH:4][N:3]=1.[OH2:25]>C1(C)C=CC=CC=1.[O-2].[O-2].[Mn+4]>[Cl:1][C:2]1[C:7]([C:8](=[O:25])[C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[C:11]([O:19][CH2:20][CH3:21])[C:10]=2[CH3:22])=[C:6]([Cl:24])[CH:5]=[CH:4][N:3]=1
Reactant: O
Reactant: CCOC1=C(S(C)(=O)=O)C=CC(O)(Cc2c(Cl)ccnc2Cl)C1C
Agent: [Mn+4]
Agent: [O-2]
Solvent: Cc1ccccc1
Product: CCOc1c(S(C)(=O)=O)ccc(C(=O)c2c(Cl)ccnc2Cl)c1C

Procedure:
To the product of step (a) in 30 ml of toluene was added 4 g manganese dioxide. The suspension was refluxed for 7 hours with mechanical stirring and with azeotropic removal of water. The mixture was filtered and the filter cake washed with ether. The solvent was evaporated in vacuo to yield 2.08 g of 2,4-dichloro-3-(3-ethoxy-2-methyl-4-methylsulfonylbenzoyl)pyridine as a brown semi-solid.
Reaction SMILES: O.O.[Sn](Cl)Cl.[F:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[CH:15]=[CH:16][C:17]3[C:23](=[O:24])[C:22]4[CH:25]=[CH:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][C:21]=4[CH2:20][O:19][C:18]=3[CH:32]=2)=[C:9]([N+:33]([O-])=O)[CH:8]=1>C(O)C>[NH2:33][C:9]1[CH:8]=[C:7]([F:6])[CH:12]=[CH:11][C:10]=1[NH:13][C:14]1[CH:15]=[CH:16][C:17]2[C:23](=[O:24])[C:22]3[CH:25]=[CH:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][C:21]=3[CH2:20][O:19][C:18]=2[CH:32]=1
Reactant: O=C1c2ccc([N+](=O)[O-])cc2COc2cc(Nc3ccc(F)cc3[N+](=O)[O-])ccc21
Agent: Cl[Sn]Cl
Solvent: CCO
Solvent: O
Product: Nc1cc(F)ccc1Nc1ccc2c(c1)OCc1cc([N+](=O)[O-])ccc1C2=O

Procedure:
In accordance with general method Y, 0.60 g (2.66 mmol) of tin(II) chloride dihydrate is dissolved in 10 ml of ethanol, and 0.10 g (0.89 mmol) of (11) is added. Yield: 0.01 g (11.9%);
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[CH3:12].[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[CH:20]([NH2:24])[CH2:19][CH2:18]2>>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:24][CH:20]2[C:21]3[C:17](=[CH:16][C:15]([O:14][CH3:13])=[CH:23][CH:22]=3)[CH2:18][CH2:19]2)=[O:9])=[CH:5][C:4]=1[CH3:12]
Reactant: COc1ccc(C(=O)O)cc1C
Reactant: COc1ccc2c(c1)CCC2N
Product: COc1ccc2c(c1)CCC2NC(=O)c1ccc(OC)c(C)c1

Procedure:
Prepared in a similar manner to example 4 using 4-methoxy-3-methylbenzoic acid and 5-methoxy-2,3-dihydro-1H-inden-1-amine (Example 121-2a) (47%). MS (M+Hs 312).
Reaction SMILES: C[O:2][C:3](=[O:21])[CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=2)[CH:8]=[N:7][CH:6]=1.[ClH:22]>>[ClH:22].[CH:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:19]=[CH:20][C:11]=1[CH2:10][N:9]1[C:5]([CH2:4][C:3]([OH:21])=[O:2])=[CH:6][N:7]=[CH:8]1
Reactant: COC(=O)Cc1cncn1Cc1ccc2ccccc2c1
Agent: Cl
Product: O=C(O)Cc1cncn1Cc1ccc2ccccc2c1
Temperature: 55 °C

Procedure:
2-[1-(Naphth-2-ylmethyl)-1H-imidazol-5-yl]acetic acid methyl ester (0.92 g, 3.28 mmol ) was dissolved in 2.5N hydrochloric acid (50 ml ) and heated to 55° C. for 3 hr. After this time, the solution was concentrated to dryness in vacuo to give the title compound as a white solid.
Reaction SMILES: S(Cl)(Cl)=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[N+:16]([O-:18])=[O:17])[C:10]([OH:12])=[O:11].[CH3:19]O>>[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[N+:16]([O-:18])=[O:17])[C:10]([O:12][CH3:19])=[O:11]
Reactant: CO
Reactant: COc1cc(C(=O)O)ccc1[N+](=O)[O-]
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc([N+](=O)[O-])c(OC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97 %

Procedure:
Thionyl chloride (3.7 g) was added dropwise under ice cooling to a solution of 4.7 g (24 mmol) of 3-methoxy-4-nitrobenzoic acid in 250 ml of methanol. The thus-obtained mixture was stirred at room temperature for 2 hours and then stirred under heating and reflux for 3 hours. After the solvent was distilled out under reduced pressure, the residue was neutralized with aqueous ammonia and then extracted with methylene chloride. The extract was dried over sodium sulfate and then dried up under reduced pressure, whereby 4.9 g of white powder were obtained (yield: 97%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]12[CH2:13][CH2:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[C:9]1=[N:8][N:7]([C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=1)=[O:19])[CH2:6]2)=[O:4].C(N(CC)CC)C.Cl[S:39][N:40]([CH:46]([CH3:48])[CH3:47])[C:41](=[O:45])[O:42][CH2:43][CH3:44]>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]12[CH2:13][CH2:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[C:9]1=[N:8][N:7]([C:18]([N:20]([C:21]1[CH:22]=[CH:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=1)[S:39][N:40]([CH:46]([CH3:48])[CH3:47])[C:41]([O:42][CH2:43][CH3:44])=[O:45])=[O:19])[CH2:6]2)=[O:4]
Reactant: COC(=O)C12CCc3ccccc3C1=NN(C(=O)Nc1ccc(C(F)(F)F)cc1)C2
Reactant: CCOC(=O)N(SCl)C(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)N(SN(C(=O)N1CC2(C(=O)OC)CCc3ccccc3C2=N1)c1ccc(C(F)(F)F)cc1)C(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.7 %

Procedure:
To a solution of the title compound of Step B (2.0 g, 4.8 mmol) in 50 ml methylene chloride cooled to 0° C. was added triethylamine (1.0 g, 0.01 mol) and ethyl (chlorosulfenyl) (1-methylethyl)carbamate from Step D (1.4 g, 7.7 mmol). The mixture was allowed to warm to room temperature and stirred for one hour. The crude mixture was purified by silica column chromatography using ether-hexane (1:2) as eluent. The title compound (2.38 g) was obtained in about 90% purity (mp: 130°-134°). Extraction of the product with ether-hexane (2:1) gave 1.8 g of highly pure material mp: 139°-140° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9]O)=[CH:4][CH:3]=1.S(Cl)([Cl:13])=O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][Cl:13])=[CH:4][CH:3]=1
Reactant: OCCc1ccc(Cl)cc1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: ClCCc1ccc(Cl)cc1
Temperature: 60 °C
Reaction time: 8 h
Yield: 100.7 %

Procedure:
A 10-liter jacketed reactor equipped with an overhead stirrer, a thermocouple, an addition funnel, and a dry ice/acetone condenser was charged with 2-(4-chlorophenyl)ethanol (2005 g, 12.8 mol) and swept with nitrogen. DMF (49.6 mL, 640 mmol) was charged to the reactor and the reactor contents were heated to 60° C. Thionyl chloride (1607.3 g) was added at a rate sufficient to maintain the temperature at >49° C. and <70° C. On completion of the addition, the reaction was held at 52.6° C. (jacket temperature). It was then cooled to 20° C. and allowed to stir at room temperature overnight. The reaction mixture was concentrated at 22 torr and 60° C. (water bath) for 1.5 h, to leave 1-chloro-4-(2-chloroethyl)benzene (2256 g).
Reaction SMILES: [C:1]1([C:7]#[C:8][CH2:9][CH2:10][CH2:11][OH:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl.CCOCC>[C:1]1([C:7]#[C:8][CH2:9][CH2:10][CH:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCCCC#Cc1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: O=CCCC#Cc1ccccc1
Reaction time: 2.5 h

Procedure:
A solution of 5-phenylpent-4-yn-1-ol (250 mg) in dry CH2Cl2 (2 ml) was added to a suspension of pyridinium chlorochromate (520 mg) in dry CH2Cl2 (3 ml). The mixture was stirred for 2.5 hours and diluted with ether, and the organic solution was decanted off. The oily residue was treated with ether (5×20 ml) and the extracts were washed successively with 5% NaHCO3, water and brine. After drying, the solvent was removed to yield 5-phenylpent-4-ynal.
Reaction SMILES: C(OC([C:6]([C:20]([O:22]CC)=[O:21])([CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])[CH2:7][C:8]([OH:10])=O)=O)C.C(Cl)(=O)C(Cl)=O.O.Cl>C(Cl)Cl>[CH3:19][C:14]1[C:13]2[CH2:12][CH2:11][CH:6]([C:20]([OH:22])=[O:21])[CH2:7][C:8](=[O:10])[C:18]=2[CH:17]=[CH:16][CH:15]=1
Reactant: CCOC(=O)C(CCc1ccccc1C)(CC(=O)O)C(=O)OCC
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: ClCCl
Product: Cc1cccc2c1CCC(C(=O)O)CC2=O
Temperature: 5 °C
Reaction time: 8 h
Yield: 54.2 %

Procedure:
16.8 g (0.0499 mol) of 3,3-bis-ethoxycarbonyl-5-o-tolyl-pentanoic acid were dissolved in 120 mL of CH2Cl2 under a nitrogen atmosphere. The solution was cooled to 5° C. and 19 mL (0.1498 mol) of oxalyl chloride were added dropwise. After 3 h the volatiles were removed in vacuo, the resulting oil was dissolved in 200 mL of CH2Cl2 and this solution was added dropwise, at 0° C. and under inert atmosphere, to a suspension of 26.6 g (0.1996 mol) of AlC3 in 300 mL of CH2Cl2. The resulting suspension was vigorously stirred overnight, during which time it was allowed to warm to room temperature. Water was added, followed by 1N HCl up to pH 1. The layers were separated, the organic phase was dried and the solvent was removed in vacuo. The resulting crude product was taken up in dioxane (60 mL) and 6N HCl (200 mL) and heated to reflux for 6 h. After cooling, water was added and the reaction mixture was extracted with Et2O. The organic phase was dried, the solvent was removed in vacuo and the resulting crude product was purified by flash chromatography eluting with Et2O, yielding 5.9 g of compound which was triturated in (i-Pr)2O, filtered and dried, yielding 4.33 g of the title product.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[CH2:10]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: BrCc1ccccc1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: O=Cc1ccc(OCc2ccccc2)cc1
Reaction time: 8 h
Yield: 88.2 %

Procedure:
A mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mmol), benzyl bromide (25.66 g, 150 mmol), and cesium carbonate (97.8 g, 300 mmol) in DMSO (200 mL) under nitrogen at room temperature was stirred overnight. The reaction was filtered to remove the solids, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give an oil. The product was purified by FCC on silica gel eluting ethyl acetate:hexane (15:85, v:v) to give 4-benzyloxy-benzaldehyde (18.72 g, 80%) as a glass. MS found: (M+H)+=213.
Reaction SMILES: [NH2:1][N:2]1[CH:6]=[CH:5][CH:4]=[CH:3]1.C(O[CH:10]=[C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])C>>[N:2]1([NH:1][CH:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:6]=[CH:5][CH:4]=[CH:3]1
Reactant: Nn1cccc1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Product: CCOC(=O)C(=CNn1cccc1)C(=O)OCC
Temperature: 125 °C

Procedure:
A mixture of N-aminopyrrole (6.2 g, 75.5 mmol) and diethyl ethoxymethylenemalonate (18.2 mL, 90.6 mmol) was heated at 125° C. for 2 hours to give diethyl 2-((1H-pyrrol-1-ylamino)methylene)malonate as an intermediate and then diphenyl ether (22 mL) was added thereto. The resulting reaction mixture was heated under nitrogen atmosphere at 220° C. for 2 hours and ethanol produced during the reaction was removed by distillation. The reaction mixture with ethanol removed was cooled to room temperature and purified by silica gel chromatography. The target compound was yielded as a yellow solid (11.0 g, 53.3 mmol, 71% yield).
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[C:19]([C:26]2[CH:31]=[CH:30][C:29]([NH:32][S:33]([CH3:36])(=[O:35])=[O:34])=[CH:28][CH:27]=2)=[CH:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)(=O)=O)C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH:21]1([CH:20]=[C:19]([C:26]2[CH:27]=[CH:28][C:29]([NH:32][S:33]([CH3:36])(=[O:35])=[O:34])=[CH:30][CH:31]=2)[C:11]2[NH:10][C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=2)[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: CS(=O)(=O)Nc1ccc(C(=CC2CCCC2)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CS(=O)(=O)Nc1ccc(C(=CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Temperature: 45 °C
Reaction time: 96 h
Yield: 77.7 %

Procedure:
A mixture of N-{4-[1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-phenyl}-methanesulfonamide (150 mg, 0.28 mmol) and tetrabutylammonium fluoride solution in tetrahydrofuran (1 M, 3 ml) was stirred at 45° C. for 96 h. The reaction was quenched with a saturated aqueous ammonium chloride solution (20 mL). The mixture was extracted with ethyl acetate (2×50 mL), washed with a saturated aqueous ammonium chloride solution (3×50 mL), brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford N-{4-[2-cyclopentyl-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-vinyl]-phenyl}-methanesulfonamide (83 mg, 75%) as a white solid: LC/MS m/e calcd for C21H23N3O2S [M+H]+ 382.50, observed 382.0.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:11]([Sn](CCCC)(CCCC)C=C)[CH2:12]CC.[Cl-].[Li+]>CN(C)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>[CH:11]([C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1)=[CH2:12]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: O=[N+]([O-])c1cccnc1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: C=Cc1ncccc1[N+](=O)[O-]
Temperature: 90 °C
Yield: 39.6 %

Procedure:
Into a solution of the commercially available 2-chloro-3-nitropyridine (2 g, 12.6 mMol) in 5 mL of anhydrous N,N-dimethylformamide under inert atmosphere was added tributyl(vinyl)tin (4 mL, 13.87 mMol, 1.1 eq), lithium chloride (2.68 g, 50.46 mMol, 5 eq), and dichlorobis(triphenylphosphine)-palladium(II) (442 mg, 0.64 mMol, 5 Mol %). This was heated for 18 h at 90° C., concentrated in vacuo, and purified by flash silica gel chromatography using 10% ethyl acetate in hexanes as an eluent to afford the title compound as a brown oil (0.75 g).
Reaction SMILES: FC(F)(F)C(O)=O.C(OC(=O)[NH:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][S:23][C:24]2[CH:33]=[N:32][C:31]3[C:26](=[CH:27][C:28]([O:34][CH3:35])=[CH:29][CH:30]=3)[N:25]=2)[CH2:17][CH2:16]1)(C)(C)C>ClCCl>[CH3:35][O:34][C:28]1[CH:27]=[C:26]2[C:31]([N:32]=[CH:33][C:24]([S:23][CH2:22][CH2:21][N:18]3[CH2:17][CH2:16][CH:15]([NH2:14])[CH2:20][CH2:19]3)=[N:25]2)=[CH:30][CH:29]=1
Reactant: COc1ccc2ncc(SCCN3CCC(NC(=O)OC(C)(C)C)CC3)nc2c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1ccc2ncc(SCCN3CCC(N)CC3)nc2c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 93.9 %

Procedure:
Trifluoroacetic acid (5.41 mL, 70.2 mmol, 15.0 eq) is added at 0° C. to a stirred solution of {1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester (2.0 g, 4.68 mmol, 1.0 eq) in dichloromethane (200 mL). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×50 mL) and water (50 mL) and the pH value adjusted to 12 by the addition of a 1N sodium hydroxide aqueous solution. The combined organic layers are dried over sodium sulfate, filtered and concentrated to afford 1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-ylamine as an orange oil (1.40 g, 92% yield).
Reaction SMILES: C([N:8]1[CH2:13][CH:12]([CH3:14])[C:11](=[O:15])[C:10]([CH3:17])([CH3:16])[CH2:9]1)C1C=CC=CC=1>CO.[H][H].[OH-].[OH-].[Pd+2]>[CH3:16][C:10]1([CH3:17])[C:11](=[O:15])[CH:12]([CH3:14])[CH2:13][NH:8][CH2:9]1
Reactant: CC1CN(Cc2ccccc2)CC(C)(C)C1=O
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC1CNCC(C)(C)C1=O

Procedure:
A mixture of 20% Pd(OH)2 on carbon (0.3 g) and 1-benzyl-3,3,5-trimethyl-4-piperidone (1.5 g, 6.5 mmol) in methanol (20 ml) was stirred in hydrogen atmosphere (1 atm.) at 30° C. for 6 hr. The catalyst was filtered off, washed with methanol and filtrate was concentrated to dryness to afford 3,3,5-trimethyl-4-piperidinone. Yield 0.8 g (88%), C8H15NO, m/z 142 (M+1).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[OH:21])[C:14]([O:22]C)=[N:13][CH:12]=2)=[CH:7][CH:6]=1)[CH3:3].Br.O>C(O)(=O)C>[CH3:3][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[OH:21])[C:14](=[O:22])[NH:13][CH:12]=2)=[CH:9][CH:10]=1)[CH3:1]
Reactant: COc1ncc(-c2ccc(CN(C)C)cc2)c2c(O)cccc12
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: CN(C)Cc1ccc(-c2c[nH]c(=O)c3cccc(O)c23)cc1
Yield: 67.9 %

Procedure:
Process 2: To a solution of 4-[4-(dimethylaminomethyl)phenyl]-5-hydroxy-1-methoxyisoquinoline (102 mg, 331 μmol) in acetic acid (15 mL) were added 47% hydrobromic acid (1.5 mL) and water (1.5 mL), and the mixture was refluxed for 1 hour. Water was added to the residue obtained by concentrating the reaction mixture under reduced pressure, which was made basic with saturated aqueous solution of sodium hydrogen carbonate. The precipitated crystals were collected by filtration, washed with water, and then air-dried, thereby affording 66.2 mg of the title compound as brown powder. Yield 68%.