Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:24]2[CH:25]=[C:26]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]4)=[CH:36][N:35]=3)[C:27]3[N:28]([CH:30]=[CH:31][N:32]=3)[N:29]=2)[C:5]([CH2:22][OH:23])=[C:6]([N:8]2[CH2:20][CH2:19][N:11]3[C:12]4[CH2:13][CH2:14][CH2:15][CH2:16][C:17]=4[CH:18]=[C:10]3[C:9]2=[O:21])[CH:7]=1.ClC1C=C(NC2C=CC(N3CCN(C4[CH2:73][O:72][CH2:71]4)CC3)=CN=2)C2N(C=CN=2)N=1.C(OCC1C(B2OC(C)(C)C(C)(C)O2)=CC(F)=CC=1N1CCN2C3CCCCC=3C=C2C1=O)(=O)C>>[F:1][C:2]1[CH:3]=[C:4]([C:24]2[CH:25]=[C:26]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH2:45][CH2:44][N:43]([CH:46]5[CH2:73][O:72][CH2:71]5)[CH2:42][CH2:41]4)=[CH:36][N:35]=3)[C:27]3[N:28]([CH:30]=[CH:31][N:32]=3)[N:29]=2)[C:5]([CH2:22][OH:23])=[C:6]([N:8]2[CH2:20][CH2:19][N:11]3[C:12]4[CH2:13][CH2:14][CH2:15][CH2:16][C:17]=4[CH:18]=[C:10]3[C:9]2=[O:21])[CH:7]=1
Reactant: Clc1cc(Nc2ccc(N3CCN(C4COC4)CC3)cn2)c2nccn2n1
Reactant: CN1CCN(c2ccc(Nc3cc(-c4cc(F)cc(N5CCn6c(cc7c6CCCC7)C5=O)c4CO)nn4ccnc34)nc2)CC1
Agent: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
Product: O=C1c2cc3c(n2CCN1c1cc(F)cc(-c2cc(Nc4ccc(N5CCN(C6COC6)CC5)cn4)c4nccn4n2)c1CO)CCCC3
Yield: 9 %

Procedure:
Following the procedures as described for compound 104, Suzuki reaction of 105a (385 mg, 1.0 mmol) and 4-Fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 101l gave 105 as a yellow solid (60 mg, 9%). LCMS: [M+H]+ 664. 1H NMR (500 MHz, DMSO) δ 10.04 (d, J=4.0, 1H), 8.26 (s, 1H), 8.18 (s, 1H), 8.10-8.13 (m, 1H), 7.70 (s, 1H), 7.44-7.55 (m, 3H), 7.34-7.36 (m, 1H), 6.52 (s, 1H), 4.84 (s, 1H), 4.66-4.72 (m, 3H), 4.33-4.43 (m, 2H), 4.11-4.19 (m, 3H), 3.86-3.89 (m, 2H), 3.49-3.51 (m, 2H), 3.03-3.14 (m, 4H), 2.57-2.63 (m, 3H), 2.45-2.47 (m, 4H), 1.77-1.80 (m, 2H), 1.68-1.69 (m, 2H)
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@H:14]2[NH:15][C:16](=[O:18])[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20]CC2C=CC=CC=2)[C@H:10]1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+]>C(OC(=O)C)(=O)C.C(O)(=O)C.CO.[Cl-].[Cl-].[Zn+2]>[CH2:1]([O:8][CH:9]1[CH:14]2[NH:15][C:16](=[O:18])[O:17][CH:13]2[CH2:12][CH:11]([CH2:19][OH:20])[CH:10]1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1N[C@@H]2[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@@H](COCc3ccccc3)C[C@@H]2O1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Solvent: CO
Product: O=C1NC2C(CC(CO)C(OCc3ccccc3)C2OCc2ccccc2)O1
Temperature: 25 °C
Reaction time: 3 h
Yield: 76.5 %

Procedure:
To a solution of (3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)hexahydrobenzo[d]oxazol-2(3H)-one (3.00 g, 6.34 mmol) in acetic anhydride (60 mL) and acetic acid (10 mL) was added anhydrous ZnCl2 (8.62 g, 63.4 mmol). The mixture was stirred at room temperature for 3 h. Most of the solvents were removed by evaporation under high vacuum. The residue was diluted with aqueous saturated NaHCO3 (200 mL) and extracted with EtOAc (2×50 mL). The extracts were washed with brine, dried with MgSO4. The solvent was evaporated to give white foam. This was dissolved in MeOH (50 mL) and K2CO3 (1.75 g, 12.7 mmol) was added. The mixture was stirred at room temperature for 2 h. Solvent was evaporated. The residue was diluted with water (50 mL) and extracted with DCM (2×30 mL). The extracts were washed with brine, dried with MgSO4. The solvent was evaporated to give white foam which was purified by a silica gel column, eluting with 5% MeOH in DCM to give 3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-(hydroxymethyl)hexahydrobenzo[d]oxazol-2(3H)-one as a white solid (1.86 g, 77%). 1H NMR (400 MHz, CDCl3) δ 7.33-7.42 (m, 10H), 4.95 (d, J=11.8 Hz, 1H), 4.89 (d, J=10.9 Hz, 1H), 4.82 (s, 1H), 4.69 (d, J=11.3 Hz, 1H), 4.64-4.69 (m, 1H), 4.60 (d, J=11.8 Hz, 1H), 3.72-3.77 (m, 1H), 3.50-3.56 (m, 3H), 3.40 (t, J=9.1 Hz, 1H), 2.12 (dt, J=15.3 Hz, 3.1 Hz, 1H), 1.91-1.98 (m, 1H), 1.69-1.77 (m, 1H), 1.55 (t, J=4.9 Hz, 1H).
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([O:17][CH:18]([F:20])[F:19])[C:11]([CH2:21][C:22]1[CH:23]=[N:24][CH:25]=[N:26][CH:27]=1)=[C:10]2[O:28][CH:29]([F:31])[F:30].[F:32][C:33]1[CH:49]=[CH:48][C:36]([C:37]([CH:39]2[CH2:44][CH2:43][N:42]([C:45](=[O:47])[CH3:46])[CH2:41][CH2:40]2)=[O:38])=[CH:35][CH:34]=1>C1COCC1>[F:19][CH:18]([F:20])[O:17][C:12]1[C:11]([CH2:21][C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)=[C:10]([O:28][CH:29]([F:31])[F:30])[C:9]2[C:14](=[CH:15][CH:16]=[C:7]([C:37]([C:36]3[CH:35]=[CH:34][C:33]([F:32])=[CH:49][CH:48]=3)([OH:38])[CH:39]3[CH2:40][CH2:41][N:42]([C:45](=[O:47])[CH3:46])[CH2:43][CH2:44]3)[CH:8]=2)[N:13]=1
Reactant: CC(=O)N1CCC(C(=O)c2ccc(F)cc2)CC1
Reactant: FC(F)Oc1nc2ccc(Br)cc2c(OC(F)F)c1Cc1cncnc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(=O)N1CCC(C(O)(c2ccc(F)cc2)c2ccc3nc(OC(F)F)c(Cc4cncnc4)c(OC(F)F)c3c2)CC1
Reaction time: 0.17 h

Procedure:
n-BuLi (1.6 M in THF, 0.26 mL, 0.41 mmol) was added dropwise over a 1 minute period to a mixture of 6-bromo-2,4-bis(difluoromethoxy)-3-(pyrimidin-5-ylmethyl)quinoline (0.16 g, 0.37 mmol, Intermediate 50) and 1-(4-(4-fluorobenzoyl)piperidin-1-yl)ethanone (0.10 g, 0.41 mmol, Intermediate 44) in dry THF (3.8 mL) at −78° C. Stirring was continued at −78° C. for 10 minutes. The reaction mixture was then placed in an ice bath and stirred at 0° C. for 1 hour. The reaction was then quenched with aqueous NH4Cl, diluted with water and extracted with EtOAc (2×). The EtOAc extracts were dried over Na2SO4, filtered, evaporated in vacuo and purified by FCC (0-10% MeOH in DCM, gradient) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 9.00-9.19 (m, 1H), 8.61-8.79 (m, 2H), 8.05-8.22 (m, 1H), 7.69-7.93 (m, 3H), 7.37-7.56 (m, 2H), 6.93-7.13 (m, 2H), 6.36-6.89 (m, 1H), 4.59-4.83 (m, 1H), 4.20 (s, 2H), 3.67-3.97 (m, 1H), 2.95-3.23 (m, 1H), 2.43-2.83 (m, 2H), 2.04 (s, 3H), 1.61-1.79 (m, 1H), 1.30-1.51 (m, 3H); MS (ESI) 603 [M+H]+.
Reaction SMILES: [CH:1]1([CH:7]([C:9]2[C:10]([O:25][CH:26]([CH3:28])[CH3:27])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH:13]=2)O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([N:38]([CH3:46])[CH2:39][CH2:40][C:41]([O:43]CC)=[O:42])=[O:37])=[CH:32][CH:31]=1>>[CH:1]1([CH:7]([NH:29][C:30]2[CH:31]=[CH:32][C:33]([C:36]([N:38]([CH3:46])[CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[O:37])=[CH:34][CH:35]=2)[C:9]2[C:10]([O:25][CH:26]([CH3:27])[CH3:28])=[N:11][N:12]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:18][CH:19]=3)[CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CC(C)Oc1nn(-c2ccc(OC(F)(F)F)cc2)cc1C(O)C1CCCCC1
Reactant: CCOC(=O)CCN(C)C(=O)c1ccc(N)cc1
Product: CC(C)Oc1nn(-c2ccc(OC(F)(F)F)cc2)cc1C(Nc1ccc(C(=O)N(C)CCC(=O)O)cc1)C1CCCCC1
Yield: 36.4 %

Procedure:
Using cyclohexyl{3-(1-methylethoxy)-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}methanol (0.20 g) synthesized in Example 64(2) and ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (0.13 g) synthesized in Example 2(2) and in the same manner as in Example 1(7), the title object compound (0.11 g, 36%) was obtained as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([CH:22]([NH2:24])[CH3:23])[C:16]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)=[C:15]2[C:31]1[O:32][C:33]([CH3:36])=[N:34][N:35]=1.C(N(CC)C(C)C)(C)C>C(O)CCC>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:24][CH:22]([C:17]2[C:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)=[C:15]([C:31]3[O:32][C:33]([CH3:36])=[N:34][N:35]=3)[C:14]3[C:19](=[CH:20][CH:21]=[C:12]([F:11])[CH:13]=3)[N:18]=2)[CH3:23])[N:5]=[CH:4][N:3]=1
Reactant: Cc1nnc(-c2c(-c3ccccn3)c(C(C)N)nc3ccc(F)cc23)o1
Reactant: N#Cc1c(N)ncnc1Cl
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nnc(-c2c(-c3ccccn3)c(C(C)Nc3ncnc(N)c3C#N)nc3ccc(F)cc23)o1
Temperature: 120 °C
Reaction time: 20 h

Procedure:
A mixture of 4-amino-6-chloropyrimidine-5-carbonitrile (0.030 g, 0.192 mmol), 1-(6-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)-3-(pyridin-2-yl)quinolin-2-yl)-ethanamine (0.067 g, 0.192 mmol), and N,N-diisopropylethylamine (0.167 mL, 0.959 mmol) in 1-butanol (1.918 mL) was stirred at 120° C. After 20 h, the mixture was removed from heat and to the cooled mixture was added water (50 mL) and DCM (50 mL). The organic layer was concentrated in vacuo to give the crude material as a light yellow solid. The light yellow solid was absorbed onto a plug of silica gel and purified by silica gel column chromatography eluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM, to provide 4-amino-6-((1-(6-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)-3-(2-pyridinyl)-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.56-8.62 (1H, m), 8.22-8.29 (1H, m), 7.85-7.93 (3H, m), 7.82 (1H, td, J=7.7, 1.8 Hz), 7.58 (1H, d, J=7.2 Hz), 7.42-7.47 (1H, m), 7.38 (1H, ddd, J=7.6, 4.9, 1.2 Hz), 7.24 (2H, br. s.), 5.54 (1H, quin, J=6.7 Hz), 2.34 (3H, s), 1.39 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 468.1 [M+H]+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]([C:13]([O:15][CH3:16])=[O:14])[CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.C1COCC1.Cl.CO>C1COCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][CH:11]([C:13]([O:15][CH3:16])=[O:14])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)C1CC(=O)N(Cc2ccccc2)C1
Agent: B
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)C1CCN(Cc2ccccc2)C1
Temperature: 25 °C
Yield: 50.2 %

Procedure:
A solution of methyl 1-benzyl-2-oxo-4-pyrrolidylcarboxylate (D10, 35.4 g, 0.18 mole) in dry THF (135 ml) was added dropwise over 30 mins to 1M borane-THF solution (228 ml, 0.23 mole) at 0° C. under nitrogen, and when addition was complete the solution was heated under reflux for 1h. The solution was cooled to room temperature, then treated dropwise with 8% hydrogen chloride/methanol (114 ml, 0.25 mole HCl) and stirred for 18h, followed by 3h at reflux. The mixture was then concentrated in vacuo and the residue treated with water (40 ml), washed with ether (2×50 ml), basified with 40% sodium hydroxide solution, saturated with potassium carbonate and extracted with ether (3×70 ml). The combined extracts were dried (Na2SO4) and concentrated in vacuo to leave a yellow oil, which was purified by distillation (b.p. 146° C.0.7mm) to give the title compound (D11) as a colourless oil (19.8 g, 50%).
Reaction SMILES: C([CH:3]([CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH2:4][CH2:5][C:6]([O:8][CH3:9])=[O:7])=O.[BH4-].[Na+].[OH-].[Na+]>C(O)C>[CH2:10]([CH:3]1[CH2:9][O:8][C:6](=[O:7])[CH2:5][CH2:4]1)[CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCC(C=O)CCC(=O)OC
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCC1CCC(=O)OC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 100.3 %

Procedure:
1560.0 g of ethanol and 663.0 g (max. 2.74 mol) of 82.7% methyl 4-formylnonanoate obtained in Example 1 are placed in a four-liter round-bottomed flask with a mechanical stirrer and a thermometer, and the mixture is cooled to 0° C. 41.6 g (1.10 mol) of sodium borohydride are then added dropwise over four hours, without exceeding 5° C. in the bulk. Stirring is continued after the end of the addition for a further 24 hours at 0° C. 1900.0 g of aqueous 10% sodium hydroxide solution are added dropwise over two hours, without exceeding 10° C. in the bulk. A white precipitate forms. Stirring is continued until the dissolution of the precipitate is complete (about two hours). The flask is placed under a vacuum of about 3990 Pa and the ethanol is distilled off. The aqueous phase obtained is extracted twice with 200 ml of a mixture of toluene and hexane (50/50) to remove the neutral products. The aqueous phase is then cooled to 0° C. The resulting phase is acidified with 1900.0 g of 10% hydrochloric acid for three hours, without exceeding 10° C. in the bulk. After the end of the addition, stirring is continued for four hours, while allowing the temperature of the reaction medium to rise to room temperature (20° C.). The phases are allowed to separate by settling and the organic phase is recovered. The aqueous phase is extracted twice with 200 ml of toluene. The organic phases are combined and are washed twice with 100 ml of water and once with 200 ml of brine, and then concentrated under reduced pressure (3990 Pa). 696.0 g of a crude product are obtained, and are then blanched at 133 Pa to give 468.0 g of 86.1% 5-pentyltetrahydropyran-2-one. After distillation on a Vigreux column, a core fraction of 289.0 g (1.70 mol) of 98.3% 5-pentyltetrahydropyran-2-one is obtained (90-2° C./27 Pa) in a yield of 61%.
Reaction SMILES: Cl[C:2]([O:4][CH3:5])=[O:3].[CH2:6]([S:13][C:14]1[C:23]([NH:24][CH3:25])=[CH:22][CH:21]=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(=O)([O-])O.[Na+]>>[CH2:6]([S:13][C:14]1[C:23]([NH:24][CH2:25][C:2]([O:4][CH3:5])=[O:3])=[CH:22][CH:21]=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CNc1cccc(C(=O)OC)c1SCc1ccccc1
Reactant: COC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: COC(=O)CNc1cccc(C(=O)OC)c1SCc1ccccc1

Procedure:
4.6 ml of methyl chloroformate are added dropwise to a suspension of 15.0 g (0.052 mol) of methyl 2-benzylmercapto-3-methylaminobenzoate and 5.88 g (0.07 mol) of sodium hydrogen carbonate in 100 ml of CH2CN. After 5 h volatile components are removed by distillation (15 torr, 40° C.). The residue is taken up in ethyl acetate and washed in succession with 1 N hydrochloric acid and water. The organic phase is dried over MgSO4 and then the solvent is removed by distillation. Methyl 2-benzylmercapto-3-(N-methoxycarbonylmethylamino)benzoate is obtained in the form of a yellowish oil )14.8 g); 1H NMR (CDCl3, 80 MHz): δ=3.0 (s, 3H, N-CH3), 3.6 (s, 3H, O-CH3), 3.9 (s, 5H, OCH3 and SCH2Ph), 7.1-7.6 (m, 8H, Harom.).
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Cl.Cl[CH2:25][C:26]1[CH:31]=[CH:30][N:29]=[C:28]([C:32]#[N:33])[CH:27]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([C:32]#[N:33])[CH:27]=4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1
Reactant: N#Cc1cc(CCl)ccn1
Reactant: COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2c(Nc3ccc(Cl)cc3F)ncnc2cc1OCc1ccnc(C#N)c1
Temperature: 80 °C
Yield: 4 %

Procedure:
A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (600 mg, 2 mmol), (prepared as described for the starting material in Example 24), 4-chloromethyl-2-cyanopyridine hydrochloride (620 mg, 3 mmol) and potassium carbonate (1.0 g 7 mmol) in DMF (8 ml) was heated at 80° C. for 30 minutes. The mixture was allowed to cool, poured into water and extracted with ethyl acetate. The combined extracts were dried (MgSO4) and the solvent removed by evaporation and azeotroped with toluene. The residue was triturated with ethyl acetate/hexane, the solid product collected by filtration and purified by column chromatography eluting with ethyl acetate and further chromatography eluting with methylene chloride/methanol (99/1). The purified product was recrystallised from ethyl acetate/hexane to give 4-(4-chloro-2-fluoroanilino)-7-((2-cyano-4-pyridyl)methoxy)-6-methoxyquinazoline (35 mg, 4%). m.p. 209-213° C. 1H NMR Spectrum: (DMSOd6) 3.98(s, 3H); 5.44(s, 2H); 7.26(s, 1H); 7.34(dd, 1H); 7.53(dd, 1H); 7.58(d, 1H); 7.80(d, 1H); 7.85(s, 1H); 8.27(s, 1H); 8.35(s, 1H); 8.80(d, 1H); 9.60(s, 1H) MS-ESI: 436 [MH]+
Reaction SMILES: [C:1]1([CH3:14])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2([C:10]([F:13])([F:12])[F:11])[N:9]=[N:8]2)[CH:2]=1.[Br:15]N1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[Br:15][CH2:14][C:1]1[CH:2]=[C:3]([C:7]2([C:10]([F:12])([F:11])[F:13])[N:9]=[N:8]2)[CH:4]=[CH:5][CH:6]=1
Reactant: Cc1cccc(C2(C(F)(F)F)N=N2)c1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: FC(F)(F)C1(c2cccc(CBr)c2)N=N1
Temperature: 85 °C
Yield: 53.8 %

Procedure:
To a solution of intermediate 63, 3-m-tolyl-3-trifluoromethyl-3H-diazirine, (200 mg, 1 mmol) in CCl4 (4 mL) was added N-bromosuccinimide (200 mg, 1.1 mmol, re-crystallized from water), and the stirred mixture heated at 85° C. To this was added AIBN (50 mg) and the mixture heated at reflux for an additional 2.5 hrs. After cooling, the mixture was purified by column chromatography (SiO2, pentane) to provide 150 mg (Yield 54%) of the title compound as a clear oil. 1H NMR (300 MHz, CDCl3) δ ppm: 4.42 (2H, s) 7.10–7.17 (2H, m) 7.31–7.45 (2H, m).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O-:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.F[C:13]1[CH:22]=[CH:21][C:20]2[N+:19]3[CH:23]=[C:24]4[CH:33]=[CH:32][C:31]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[N:25]4[C:18]=3[CH:17]=[CH:16][C:15]=2[CH:14]=1.[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>CN1CCCC1=O>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([S:7]([O-:10])(=[O:8])=[O:9])=[CH:5][CH:6]=1.[N:34]1([C:13]2[CH:22]=[CH:21][C:20]3[N+:19]4[CH:23]=[C:24]5[CH:33]=[CH:32][C:31]6[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=6[N:25]5[C:18]=4[CH:17]=[CH:16][C:15]=3[CH:14]=2)[CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: Fc1ccc2c(ccc3n4c(ccc5ccccc54)c[n+]23)c1
Reactant: C1CCNC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CN1CCCC1=O
Product: c1ccc2c(c1)ccc1c[n+]3c4ccc(N5CCCC5)cc4ccc3n12

Procedure:
A mixture of 202 g. of 3-fluoroimidazo[1,2-a:3,4-a']diquinolin-15-ium p-toluenesulfonate, 600 ml. of N-methyl-2-pyrrolidinone and 111 ml. of pyrrolidine is heated at reflux (158 C. ) for 45 minutes, then cooled to 0°-5° C. The resulting precipitate of 3-(1-pyrrolidinyl)-imidazo[1,2-a:3,4-a']diquinolin-15-ium p-toluenesulfonate is collected by filtration, washed with ethyl acetate, then with water, and dried; m.p. 228°-237° C.
Reaction SMILES: [CH3:1][C:2]1([S:12][CH3:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:11].Cl[CH2:15][CH2:16][O:17]C1CCCCO1>>[OH:17][CH2:16][CH2:15][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]([CH3:1])([S:12][CH3:13])[C:3]1=[O:11]
Reactant: CSC1(C)C(=O)Nc2ccccc21
Reactant: ClCCOC1CCCCO1
Product: CSC1(C)C(=O)N(CCO)c2ccccc21

Procedure:
Prepared from 3-methyl-3-methylthio-1,3-dihydro-2H-indol-2-one and 2-(2-chloroethoxy)tetrahydro-2H-pyran as described in Example 1.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([N:11]([S:18]([C:21]3[CH:22]=[CH:23][CH:24]=[C:25]4[C:30]=3[N:29]=[CH:28][CH:27]=[CH:26]4)(=[O:20])=[O:19])[CH2:12][C:13]([O:15]CC)=[O:14])=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:31][NH:32][C:33]1[CH:38]=[CH:37][C:36]([C:39](=[NH:41])[NH2:40])=[CH:35][CH:34]=1.[OH-].[Na+]>>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([N:11]([S:18]([C:21]3[CH:22]=[CH:23][CH:24]=[C:25]4[C:30]=3[N:29]=[CH:28][CH:27]=[CH:26]4)(=[O:20])=[O:19])[CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:31][NH:32][C:33]1[CH:34]=[CH:35][C:36]([C:39](=[NH:40])[NH2:41])=[CH:37][CH:38]=1
Reactant: CCOC(=O)CN(c1ccc2c(c1)cc(CNc1ccc(C(=N)N)cc1)n2C)S(=O)(=O)c1cccc2cccnc12
Agent: [Na+]
Agent: [OH-]
Product: Cn1c(CNc2ccc(C(=N)N)cc2)cc2cc(N(CC(=O)O)S(=O)(=O)c3cccc4cccnc34)ccc21

Procedure:
Prepared analogously to Example 3 from 1-methyl-2-[N-(4-amidinophenyl)-aminomethyl]-5-[N-(ethoxycarbonylmethyl)-quinoline-8-sulphonylamino]-indole and sodium hydroxide solution.
Reaction SMILES: [CH2:1]([N:8]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C@@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[C:12](Br)[CH:13]=[CH:14][CH:15]=2)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[B:32](OCC)([O:36]CC)[O:33]CC>O1CCCC1>[CH2:1]([N:8]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C@H:9]1[CH2:10][C:11]2[C:12]([B:32]([OH:36])[OH:33])=[CH:13][CH:14]=[CH:15][C:16]=2[CH2:17][CH2:18]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOB(OCC)OCC
Reactant: Brc1cccc2c1C[C@H](N(Cc1ccccc1)Cc1ccccc1)CC2
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1cccc2c1C[C@H](N(Cc1ccccc1)Cc1ccccc1)CC2
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 67 %

Procedure:
To a solution of (2R)-N,N-dibenzyl-8-bromo-1,2,3,4-tetrahydronaphthalen-2-amine (1000 mg, 2.46 mmol) in dry tetrahydrofuran (10 mL) under an atmosphere of nitrogen, n-butyllithium (1.6M, 2.3 mL, 3.69 mmol) was added over 5 min at −70° C. The reaction mixture was stirred at 0° C. for 10 min before triethyl borate (0.50 mL, 2.95 mmol) was added. The reaction mixture was stirred for additional 5 min at 0° C. and then allowed to reach ambient temperature and stirred for another 2 h. The reaction mixture was quenched with saturated ammonium chloride (aq) and a white precipitate was filtered off. The filtrate was extracted with ethyl acetate, the organic layer was dried over magnesium sulfate and concentrated in vacuo to yield 612 mg (67%) of the title compound as a solid: 1H NMR (400 MHz, CDCl3) δ ppm 8.31 (d, 1 H), 7.39-7.45 (m, 4 H), 7.28-7.37 (m, 2 H), 7.02-7.26 (m, 6 H), 3.65-3.92 (m, 4 H), 3.34-3.45 (m, 1 H), 2.70-3.19 (m, 4 H), 2.16 (br. s., 1 H), 1.66-1.79 (m, 1 H); MS (ESI) m/z 371, 372[M+H+].
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][O:4][CH:3]=1.[C:7]([C:10]1[O:14][C:13]([CH2:15][CH3:16])=[N:12][C:11]=1[CH3:17])(=[O:9])[CH3:8]>>[CH2:15]([C:13]1[O:14][C:10]([C:7]([C:2]2[CH:6]=[CH:5][O:4][CH:3]=2)([OH:9])[CH3:8])=[C:11]([CH3:17])[N:12]=1)[CH3:16]
Reactant: Brc1ccoc1
Reactant: CCc1nc(C)c(C(C)=O)o1
Product: CCc1nc(C)c(C(C)(O)c2ccoc2)o1

Procedure:
Starting with 3-bromofuran and 5-acetyl-2-ethyl-4methyloxazole and following the general method of Example 4 the title compound was prepared.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]([O:15]C)=[N:13][C:12]2[C:7]1=[N:8][C:9]([O:18][CH2:19][CH2:20][CH2:21][CH3:22])=[N:10][C:11]=2[NH2:17].Cl[S:24]([C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[CH:29][CH:28]=1)(=[O:26])=[O:25]>C(N(CC)CC)C>[NH2:17][C:11]1[N:10]=[C:9]([O:18][CH2:19][CH2:20][CH2:21][CH3:22])[N:8]=[C:7]2[C:12]=1[NH:13][C:14](=[O:15])[N:6]2[CH2:5][CH2:4][CH2:3][CH2:2][NH:1][S:24]([C:27]1[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[CH:31][CH:32]=1)(=[O:26])=[O:25]
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCCCN)c2n1
Reactant: COC(=O)CCc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CCCCNS(=O)(=O)c3ccc(CCC(=O)OC)cc3)c2n1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
The compound obtained in Example 2-8 step (ii) (308 mg), methyl 3-[4-(chlorosulfonyl)phenyl]propanoate (263 mg) and triethylamine (0.284 ml) were mixed under stirring at 60° C. for 1 hour, and then cooled. After concentration under reduced pressure, the residue was purified by RPHPLC. The resulting white substance was dissolved in methanol, and 4M hydrochloric acid-dioxane was added thereto. The mixture was stirred at room temperature overnight and then concentrated under reduced pressure to give the titled compound as a white solid. Yield: 124 mg (24%); mp 150-152° C., MS APCI+ve 521 (M+H).