Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1]Br.[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[NH:9][C:10]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:12]=1[C:13]#[N:14].C([O-])(=O)C.[Na+].S(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:1][C:7]1[O:3][C:4]([C:8]2[NH:9][C:10]([C:15]([F:18])([F:16])[F:17])=[CH:11][C:12]=2[C:13]#[N:14])=[CH:5][CH:6]=1
Reactant: BrBr
Reactant: N#Cc1cc(C(F)(F)F)[nH]c1-c1ccco1
Agent: CC(=O)[O-]
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: N#Cc1cc(C(F)(F)F)[nH]c1-c1ccc(Br)o1
Reaction time: 0.25 h

Procedure:
Bromine (0.71 g, 4.42 mmol) is added to a solution of 2-(2-furyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile (1.00 g, 4.42 mmol) and sodium acetate (0.36 g, 4.42 mmol) in acetic acid. The reation mixture is stirred for 15 minutes and poured into a 1% sodium bisulfite solution. The solids are filtered from the aqueous mixture, dried overnight under high vacuum and recrystallized from ethyl acetate and hexane to obtain the title product as red crystals (1.21 g, 90%, mp 224°-226° C.
Reaction SMILES: [CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]([CH:16]=O)=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2].[C:18](#[N:22])[CH2:19][C:20]#[N:21].C(O)(=O)C.C([O-])(=O)C.[NH4+]>C1C=CC=CC=1>[CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]([CH:16]=[C:19]([C:18]#[N:22])[C:20]#[N:21])=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2]
Reactant: CCn1c2ccccc2c2cc(C=O)ccc21
Reactant: N#CCC#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: CCn1c2ccccc2c2cc(C=C(C#N)C#N)ccc21
Reaction time: 0.5 h

Procedure:
About 11.1 grams (0.05 moles) N-ethyl carbazole-3-carboxaldehyde, about 3.1 grams (0.05 moles) malononitrile, about 1 milliliter glacial acetic acid, about 0.35 grams ammonium acetate and about 40 milliliters benzene are heated to boiling under reflux conditions for about 30 minutes. The liquid portion of this mixture is separated from the brown colored solution by rotary evaporation, the solid residues twice recrystallized with glacial acetic acid washed with ethanol and dried in a vacuum oven. Yield: 7.0 grams of bright yellow needle like crystals m.p. 164°-165° C.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]1(=[O:30])[NH:24][C:23](=[O:25])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12.[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1[C:39]#[C:40][C:41]1[CH:42]=[C:43]([CH:47](O)[CH2:48][CH3:49])[CH:44]=[CH:45][CH:46]=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1[C:39]#[C:40][C:41]1[CH:42]=[C:43]([CH2:47][CH2:48][CH2:49][N:24]2[C:20](=[O:30])[C:21]3[C:22](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:23]2=[O:25])[CH:44]=[CH:45][CH:46]=1
Reactant: CCC(O)c1cccc(C#Cc2c(C)cccc2C)c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1cccc(C)c1C#Cc1cccc(CCCN2C(=O)c3ccccc3C2=O)c1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
Triphenylphosphine (0.087 g, 0.33 mmol), phthalimide (0.0.49 g, 0.33 mmol) and (3-((2,6-dimethylphenyl)ethynyl)phenyl)propan-1-ol (12) (0.085 g, 0.32 mmol) were dissolved in anhydrous THF (3 mL) under argon, and the solution was cooled over an ice bath. Diethyl azodicarboxylate (0.052 mL, 0.33 mmol) was added dropwise with rapid stirring, and the resulting mixture was stirred at room temperature for 2.5 h. The reaction mixture was concentrated under reduced pressure and purified by flash chromatography (6 to 60% EtOAc-hexanes gradient) to yield 2-(3-(3-((2,6-dimethylphenyl)ethynyl)phenyl)propyl)isoindoline-1,3-dione (13) as a white solid. Yield (0.095 g, 75%): 1H NMR (400 MHz, DMSO-d6) δ 7.82-7.89 (m, 4H), 7.42 (s, 1H), 7.13-7.35 (m, 6H), 3.63 (t, J=7.2 Hz, 2H), 2.67 (t, J=7.6 Hz, 2H), 2.51 (s, 6H), 1.90-1.97 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([CH:8]=1)[NH2:7].[F:9][C:10]([F:15])([F:14])[C:11](O)=O>>[CH2:6]([N:7]1[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:8][C:6]=2[N:7]=[C:11]1[C:10]([F:15])([F:14])[F:9])[C:5]#[CH:4]
Reactant: Nc1cccc(F)c1
Reactant: O=C(O)C(F)(F)F
Product: C#CCn1c(C(F)(F)F)nc2cc(F)ccc21
Temperature: 25 °C

Procedure:
Under a nitrogen atmosphere, a stirred solution of 5.0 grams (0.030 mole) of 2-propyn-1-ylamino)-5-fluoroaniline in 70 mL of trifluoroacetic acid was heated at reflux for 1.5 hours. The reaction mixture was then cooled to ambient temperature and poured into ice water. The mixture was extracted thoroughly with portions of diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium bicarbonate and then dried with magnesium sulfate. The mixture was filtered, and the filtrate concentrated under reduced pressure to a residual oil. The oil was triturated with cold water, and the resultant solid was collected by filtration. The solid was dried, yielding 5.0 grams of 1-(2-propyn-1-yl)-2-trifluoromethyl-5-fluorobenzimidazole. The NMR spectrum was consistent with the proposed structure. The reaction was repeated.
Reaction SMILES: [CH:1]1([C:6]2[C:7]3[C:14]([I:15])=[CH:13][NH:12][C:8]=3[N:9]=[CH:10][N:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[C:18]1([S:24](Cl)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCCC1>[C:18]1([S:24]([N:12]2[C:8]3[N:9]=[CH:10][N:11]=[C:6]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[C:7]=3[C:14]([I:15])=[CH:13]2)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Ic1c[nH]c2ncnc(C3CCCC3)c12
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=S(=O)(c1ccccc1)n1cc(I)c2c(C3CCCC3)ncnc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.9 %

Procedure:
To 4-cyclopentyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (49, 0.161 g, 0.514 mmol) in tetrahydrofuran, sodium hydride (0.0308 g, 0.771 mmol) was added under an atmosphere of nitrogen. Benzenesulfonyl chloride (40, 0.0984 mL, 0.771 mmol) in 1 mL of tetrahydrofuran was added dropwise at room temperature under nitrogen. The reaction was stirred overnight at room temperature. The aqueous layer was separated and washed with ethyl acetate. The organic layers were combined and washed with 1 M aqueous sodium bicarbonate, water, then brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with ethyl acetate and hexane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (50, 0.121 g). MS (ESI) [M+H+]+=454.3.
Reaction SMILES: [BrH:1].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10]O)=[CH:5][CH:4]=1>>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][Br:1])=[CH:5][CH:4]=1
Reactant: OCCc1ccc(Cl)cc1
Reactant: Br
Product: Clc1ccc(CCBr)cc1

Procedure:
reacting hydrogen bromide with 2-(4-chlorophenyl)ethanol to form 2-(4-chlorophenyl)ethyl bromide;
Reaction SMILES: C[O:2][C:3](=[O:22])[CH2:4][C:5]1[CH:14]=[C:13]([S:15]C(=O)N(C)C)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:21])[CH:11]=2)[CH:6]=1.[OH-].[K+].Cl>CO.O>[F:21][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:22])=[O:2])[CH:14]=[C:13]2[SH:15]
Reactant: COC(=O)Cc1cc(SC(=O)N(C)C)c2cc(F)ccc2c1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)Cc1cc(S)c2cc(F)ccc2c1
Temperature: 25 °C
Yield: 97.7 %

Procedure:
A solution of (4-dimethylcarbamoylsulfanyl-6-fluoro-naphthalen-2-yl)-acetic acid methyl ester (40 mg, 0.13 mmol) and potassium hydroxide (72 mg, 1.3 mmol) in methanol (10 mL) was heated at reflux for 3 hours. The resulting mixture was cooled to room temperature, diluted with water (10 mL), acidified with 2 N hydrochloric acid, and extracted with ethyl acetate (10 mL×2). The combined organic layers were washed with water and brine, then dried over sodium sulfate and concentrated in vacuo to afford crude (6-fluoro-4-mercapto-naphthalen-2-yl)-acetic acid (30 mg) as a yellow solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7](F)=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12])([O-:3])=[O:2].[CH3:14][O:15][C:16]([C:18]1[N:19]=[CH:20][NH:21][CH:22]=1)=[O:17].[H-].[Na+].Cl>C1COCC1.C1(C)C=CC=CC=1>[CH3:14][O:15][C:16]([C:18]1[N:19]=[CH:20][N:21]([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([N+:11]([O-:13])=[O:12])[CH:6]=2)[CH:22]=1)=[O:17]
Reactant: O=[N+]([O-])c1ccc(F)cc1[N+](=O)[O-]
Reactant: COC(=O)c1c[nH]cn1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COC(=O)c1cn(-c2ccc([N+](=O)[O-])c([N+](=O)[O-])c2)cn1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a stirred, 0° C. solution of 1,2-dinitro-4-fluorobenzene (325 mg, 1.74 mmole) and methyl-4-imidazolecarboxylate (200 mg, 1.59 mmole) in THF (5 mL) was added NaH (70 mg, 1.74 mmole) in one portion. The resulting mixture was stirred at 0° C. for 3 hours, then diluted with toluene and acidified with 6N HCl. The phases were separated and the aqueous phase washed with toluene, cooled to 0° C., and basified with conc. NH4OH. Ethyl acetate was added and the resulting mixture stirred until all solids dissolved. Phases separated, organic phase washed with brine, dried over Na2SO4, filtered, concentrated in vacuo. The mixture of regioisomers were separated and purified via flash chromatography (silica gel, 5%-->20% ethanol/ethyl acetate gradient) to fford the desired adduct 19 (225 mg, 48%) as an off-white solid. 1H NMR (500 MHz, dmso d6): 8.41 (1H, d); 8.13 (1H, d); 7.5(1H, broad s); 7.28 (1H, s); 7.02 (1H, d); 3.80 (3H, s)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:19])=[N:13][C:14]([C:15]([O:17]C)=O)=[C:10]3[CH2:9][C:8](=[O:20])[N:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:6]=2[CH:27]=1.[Cl-].[Li+].[CH3:30][N:31]([CH3:40])P(=O)(N(C)C)N(C)C>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:19])=[N:13][C:14]([C:15]([N:31]([CH3:40])[CH3:30])=[O:17])=[C:10]3[CH2:9][C:8](=[O:20])[N:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:6]=2[CH:27]=1
Reactant: COC(=O)c1nc(C)n2c1CC(=O)N(c1ccccc1)c1cc(Cl)ccc1-2
Reactant: CN(C)P(=O)(N(C)C)N(C)C
Agent: [Cl-]
Agent: [Li+]
Product: Cc1nc(C(=O)N(C)C)c2n1-c1ccc(Cl)cc1N(c1ccccc1)C(=O)C2

Procedure:
A mixture of 1.2 g of methyl 8-chloro-4,6-dihydro-1-methyl-6-phenyl-5-oxo-5H-imidazo[1,5-a][1,5]benzodiazepin-3-carboxylate, 2 g of lithium chloride and 12 ml of hexamethyl phosphoric triamide was stirred and heated up to 230°. As soon as this temperature was reached, the reaction mixture was cooled and partitioned between methylene chloride and water. The organic phase was washed with water, dried over sodium sulfate and evaporated. Crystallization of the residue from ether yielded the end product which was recrystallized from ethyl acetate/hexane for analysis, mp 213°-215°.
Reaction SMILES: [N:1]1([CH:7]2[CH2:10][N:9]([C:11]([C:13]3[S:17][C:16]4[CH:18]=[C:19]([C:22]([F:25])([F:24])[F:23])[CH:20]=[CH:21][C:15]=4[CH:14]=3)=[O:12])[CH2:8]2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:27]1[N:32]=[CH:31][CH:30]=[CH:29][N:28]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[N:28]1[CH:29]=[CH:30][CH:31]=[N:32][C:27]=1[N:4]1[CH2:5][CH2:6][N:1]([CH:7]2[CH2:10][N:9]([C:11]([C:13]3[S:17][C:16]4[CH:18]=[C:19]([C:22]([F:23])([F:25])[F:24])[CH:20]=[CH:21][C:15]=4[CH:14]=3)=[O:12])[CH2:8]2)[CH2:2][CH2:3]1
Reactant: Brc1ncccn1
Reactant: O=C(c1cc2ccc(C(F)(F)F)cc2s1)N1CC(N2CCNCC2)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: O=C(c1cc2ccc(C(F)(F)F)cc2s1)N1CC(N2CCN(c3ncccn3)CC2)C1

Procedure:
A mixture of (3-(piperazin-1-yl)azetidin-1-yl)(6-(trifluoromethyl)benzo[b]thiophen-2-yl)methanone (0.14 mmol, 50 mg), 2-bromopyrimidine (0.23 mmol, 37 mg), and K2CO3 (0.34 mmol, 47 mg) in THF (3 mL) and water (1.5 mL) was refluxed for 8 h. Following workup and extraction, the residue was purified by flash column chromatography (silica gel, 3% methanol/CH2Cl2) to yield (3-(4-(pyrimidin-2-yl)piperazin-1-yl)azetidin-1-yl)(6-(trifluoromethyl)benzo[b]thiophen-2-yl)methanone as a white solid.
Reaction SMILES: [OH-].[K+].C([O:6][C@H:7]1[CH2:26][CH2:25][C@@:24]2([CH3:27])[C:9](=[CH:10][CH2:11][C@@H:12]3[C@@H:23]2[CH2:22][CH2:21][C@@:17]2([CH:18]([F:20])[F:19])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[O:28]C(=O)C)[CH2:8]1)(=O)C>CO.C(OCC)(=O)C>[F:19][CH:18]([F:20])[C@:17]12[CH2:21][CH2:22][C@H:23]3[C@@H:12]([CH2:11][CH2:10][C:9]4[C@:24]3([CH3:27])[CH2:25][CH2:26][C:7](=[O:6])[CH:8]=4)[C@@H:13]1[CH2:14][CH2:15][C:16]2=[O:28]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C(F)F)CC[C@@H]32)C1
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Product: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C(F)F)C(=O)CC[C@@H]12

Procedure:
After adding 22 ml of a 10% strength potassium hydroxide solution, a solution of 2.3 g of 18,18-difluoro-androst-5-ene-3β,17β-diol diacetate (crude product) in 130 ml of methanol is stirred for 1 hour at room temperature, whilst passing nitrogen through the solution. The reaction mixture is then concentrated to about 60 ml in an aspirator vacuum and taken up in ethyl acetate and the mixture is washed with 1 N hydrochloric acid and with water until neutral, dried and evaporated in an aspirator vacuum. The crude 18,18-difluoro-androst-5-ene-3β,17β-diol is suspended, without purification, in 80 ml of toluene, the suspension is treated with 8 ml of cyclohexanone and 2.2 g of aluminium isopropylate and the mixture is refluxed for 45 minutes with stirring. The cooled reaction mixture is worked up by diluting it with ethyl acetate and washing it successively with saturated Seignette salt solution (potassium sodium tartrate solution) and with water. The washings are further extracted with ethyl acetate and the organic phases are dried and evaporated in an aspirator vacuum. The amorphous residue is then chromatographed over 100 times the amount by weight of silica gel. Elution with a mixture of hexane/ethyl acetate (3:1) gives successively, in approximately equal amounts by weight, 18,18-difluoro-androst-4-ene-3,17-dione, which after recrystallisation from acetone/hexane melts at 161°-163° C, and 18,18-difluoro-17β-hydroxy-androst-4-en-3-one of melting point 183°-184° C (recrystallised from acetone/hexane).
Reaction SMILES: [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=1.C([O-])([O-])=O.[K+].[K+].O>CN1C(=O)CCC1>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)=[N:8][CH:9]=1
Reactant: c1nc[nH]n1
Reactant: Brc1ccc(Br)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN1CCCC1=O
Product: Brc1ccc(-n2cncn2)nc1
Temperature: 100 °C
Reaction time: 5 h
Yield: 13.2 %

Procedure:
A mixture of 1,2,4-triazole (1.17 g, 16.9 mmol), 2,5-dibromopyridine (2 g, 8.4 mmol) and K2CO3 (1.2 g, 8.7 mmol) in NMP (20 mL) was heated at 100° C. with stirring for 5 hours. After cooling, the reaction mixture was poured into water (100 mL) and solid was collected by filtration and further purified by column chromatography on silica gel. Elution with EtOAc/Hexanes (0-50%) provided the title compound (250 mg, 13%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7].[CH3:12][CH2:13][N:14](CC)CC.C(N)C>C(Cl)Cl>[CH2:13]([NH:14][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:12]
Reactant: COc1cccc(C(=O)Cl)c1
Reactant: CCN(CC)CC
Agent: CCN
Solvent: ClCCl
Product: CCNC(=O)c1cccc(OC)c1
Reaction time: 1 h

Procedure:
To a solution of 3-methoxybenzoyl chloride (commercially available from Aldrich, 5 mL, 35 mol) and Et3N (10 mL) in 100 mL of DCM was added and EtNH2 (2 M/THF, 30 mL, 60 mmol) dropwise for 30 min at 0° C. and the resulting solution was stirred for additional 1 h. The reaction mixture was washed with aq. NaHCO3 and brine, consecutively. The organic layer was dried over Na2SO4 and concentrated in vacuo, yielding oily residue, which was subjected to column chromatography to yield Example A175a (6.2 g, >95%) as a colorless oil.
Reaction SMILES: C([N:8]1[CH2:20][CH2:19][C:11]2[NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=3[C:10]=2[CH2:9]1)(OC(C)(C)C)=O.[H-].[Na+].[CH3:23][S:24](Cl)(=[O:26])=[O:25]>CN(C=O)C>[CH3:23][S:24]([N:12]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[C:10]2[CH2:9][NH:8][CH2:20][CH2:19][C:11]1=2)(=[O:26])=[O:25]
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]c3ccccc3c2C1
Reactant: CS(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)n1c2c(c3ccccc31)CNCC2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 18.3 %

Procedure:
N-Boc-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (800 mg, 2.94 mmol) was dissolved in DMF (20 mL) and stirred at room temperature. The vessel was flushed with argon and sodium hydride (235 mg, 5.87 mmol) was added. After 30 minutes, the reaction was cooled to 0° C. and methanesulphonyl chloride (0.46 mL, 5.87 mmol) was added dropwise over 5 minutes. The mixture was stirred and allowed to warm to room temperature overnight and the solvent removed in vacuo. TLC and LCMS showed that the BOC group was removed during this process. Therefore the residue was partitioned between 2M aqueous sodium hydroxide (30 mL) and dichloromethane (2×100 mL) and combined organics treated with brine (30 mL), dried (sodium sulphate), concentrated in vacuo. Flash column chromatography (silica, eluting with 100% dichloromethane/5% methanolic ammonia in 50% ethanol/dichloromethane) gave 5-methanesulphonyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as a pale yellow brittle solid (135 mg, 18%).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][S:14]([CH2:17][C:18](NC1N=NN(CCCCCCCCCCCC)N=1)=[O:19])(=[O:16])=[O:15])([CH3:3])[CH3:2].[CH2:38]([OH:50])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]>>[CH2:38]([O:50][C:18](=[O:19])[CH2:17][S:14](=[O:15])(=[O:16])[NH:13][C:5]1[C:6]([CH:10]([CH3:12])[CH3:11])=[CH:7][CH:8]=[CH:9][C:4]=1[CH:1]([CH3:2])[CH3:3])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]
Reactant: CCCCCCCCCCCCn1nnc(NC(=O)CS(=O)(=O)Nc2c(C(C)C)cccc2C(C)C)n1
Reactant: CCCCCCCCCCCCO
Product: CCCCCCCCCCCCOC(=O)CS(=O)(=O)Nc1c(C(C)C)cccc1C(C)C

Procedure:
This compound was prepared in the same manner as for the title compound of Example 2, except that 2-DAT was replaced with dodecanol, mp 58°-59° C.
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][NH:7][C:8](=[O:22])[O:9][CH2:10][CH2:11][NH:12][C:13](=[O:21])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20])=[N+]=[N-].[H][H]>CO.[Pd]>[NH2:1][CH2:4][CH2:5][CH2:6][NH:7][C:8](=[O:22])[O:9][CH2:10][CH2:11][NH:12][C:13](=[O:21])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20]
Reactant: [H][H]
Reactant: [N-]=[N+]=NCCCNC(=O)OCCNC(=O)c1ccccc1O
Agent: [Pd]
Solvent: CO
Product: NCCCNC(=O)OCCNC(=O)c1ccccc1O
Yield: 75.1 %

Procedure:
2-(2-Hydroxybenzoylamino)ethyl N-(3-azidopropyl)carbamate (128 mg) was dissolved in methanol (15 ml), 10% Pd/C (140 mg) was added and the reaction mixture was vigorously stirred while hydrogen was bubbled at r.t. for 3 hrs. The catalyst was filtered off and the methanol removed under vacuum to provide 2-(2-hydroxybenzoylamino)ethyl N-(3-aminopropyl)carbamate (88 mg) as a colorless oil.
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:23]C)[N:12]2[CH2:15][C:16]2[CH:17]=[N:18][C:19](Cl)=[CH:20][CH:21]=2)=[C:8]([NH2:25])[N:7]=1)[CH2:2][CH2:3][CH3:4].[CH2:26]([O:28][C:29]([CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30])[CH3:27]>C(O)C>[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([OH:23])[N:12]2[CH2:15][C:16]2[CH:17]=[N:18][C:19]([N:34]3[CH2:35][CH2:36][CH:31]([C:29]([O:28][CH2:26][CH3:27])=[O:30])[CH2:32][CH2:33]3)=[CH:20][CH:21]=2)=[C:8]([NH2:25])[N:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1nc(N)c2nc(OC)n(Cc3ccc(Cl)nc3)c2n1
Reactant: CCOC(=O)C1CCNCC1
Solvent: CCO
Product: CCCCOc1nc(N)c2nc(O)n(Cc3ccc(N4CCC(C(=O)OCC)CC4)nc3)c2n1
Reaction time: 8 h
Yield: 44 %

Procedure:
2-Butoxy-9-(6-chloro-3-pyridylmethyl)-8-methoxyadenine (0.28 mg, 0.77 mmol) was added to 4-ethoxycarbonylpiperidine (10 ml), and the mixture was refluxed under stirring for 8 hours. After the mixture was allowed to cool, ethanol was added thereto. The resulting solid was filtered and purified by column chromatography (SiO2 20 g, eluting solvent: CHCl3/MeOH=80/1˜20/1) to give the captioned compound (0.15 g, 1.41 mmol, yield: 44%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]3[N:17](C(OC(C)(C)C)=O)[CH2:16][C@H:15]([CH3:25])[N:14]3[C:10]=2[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl.CCO>C(Cl)(Cl)Cl>[CH3:25][C@@H:15]1[N:14]2[C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=[C:2]([NH2:1])[C:11]=3[N:12]=[C:13]2[NH:17][CH2:16]1
Reactant: C[C@H]1CN(C(=O)OC(C)(C)C)c2nc3c(N)nc4ccccc4c3n21
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: C[C@H]1CNc2nc3c(N)nc4ccccc4c3n21
Yield: 60 %

Procedure:
tert-Butyl (10S)-6-amino-10-methyl-9,10-dihydro-8H-imidazo[1′,2′:1,2]imidazo[4,5-c]quinoline-8-carboxylate (130 mg, 0.383 mmol) was treated with 10 mL of 3.0 M HCl/EtOH and heated up to reflux for about 20 minutes. The volatiles were then removed under reduced pressure, and the resulting residue was partitioned between CH2Cl2 and H2O. The layers were separated, and the aqueous one was extracted again with CH2Cl2, and the combined organic layers were discarded. The aqueous layer was then treated with concentrated ammonium hydroxide solution until the pH ˜11. The layer was extracted with CH2Cl2 (3×). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give a white solid. Chromatography (SiO2, 20-40% CMA/CHCl3) afforded (10S)-10-methyl-9,10-dihydro-8H-imidazo[1′,2′:1,2]imidazo[4,5-c]quinolin-6-amine (55 mg) as an off white solid, m.p. 265-273° C.
Reaction SMILES: [CH3:1][C:2]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[C:10]([OH:15])[CH:11]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1.Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1>>[CH3:1][C:2]1[C:14]2[N:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH2:17][C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[CH:11]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: Cc1nccc2c1[nH]c1cc(O)ccc12
Product: Cc1nccc2c3ccc(OCc4ccc(F)cc4)cc3n(Cc3ccc(F)cc3)c12
Yield: 62 %

Procedure:
The title compound was synthesized from 1-methyl-7-hydroxy-β-carboline (0.5 g, 1.587 mmol) in presence of 1-bromomethyl-4-fluorobenzene (0.6 g, 3.173 mmol) as described here above.
Reaction SMILES: [C:1](#[N:4])[CH:2]=[CH2:3].[CH2:5]([O:7][P:8]([CH:10]1[CH2:14][CH2:13][CH2:12][O:11]1)[OH:9])[CH3:6].[O-]CC.C(O)(=O)C>C(O)C>[C:1]([CH2:2][CH2:3][P:8]([CH:10]1[CH2:14][CH2:13][CH2:12][O:11]1)(=[O:9])[O:7][CH2:5][CH3:6])#[N:4]
Reactant: C=CC#N
Reactant: CCOP(O)C1CCCO1
Agent: CC[O-]
Solvent: CCO
Solvent: CC(=O)O
Product: CCOP(=O)(CCC#N)C1CCCO1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 0.68 g of acrylonitrile and 2.11 g of tetrahydrofuran-2-yl phosphonous acid ethyl ester in 5 ml of absolute ethanol is cooled to 0° under argon and treated, dropwise, with an ethanolic solution ofsodium ethoxide (from 0.15 g of sodium metal and 15 ml of absolute ethanol)at such a rate so that the temperature does not exceed 5° (extremelyexothermic). After the addition is completed the reaction mixture is stirred at room temperature for 30 minutes and 0.4 g of glacial acetic acid are added. The solvent is removed in vacuo and the residue partitioned between dichloromethane water. The organic layer is dried withanhydrous magnesium sulphate and removed in vacuo to afford ethyl 2-cyanoethyl(tetrahydrofuran-2-yl)-phosphinate; 1H-NMR (CDCl3): δ4.15 (3 H, m), 3.90 (2 H, m), 2.72 (2 H, m, CH2CN), 2.34-1.87(6 H, m), 1.32 (3 H, m, CH3).