Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:23])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:12][CH:11]=2)=[CH:4][C:3]=1[NH:24][C:25]1[N:30]=[C:29]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[CH:28]=[CH:27][N:26]=1.[CH2:37]([O:39][C:40](=[O:56])[CH:41]([O:43][P:44]([CH2:53][CH:54]=O)([O:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:45])[CH3:42])[CH3:38].[BH3-]C#N.[Na+]>C(O)(=O)C.CN(C=O)C>[CH2:37]([O:39][C:40](=[O:56])[CH:41]([O:43][P:44]([CH2:53][CH2:54][N:20]1[CH2:19][CH2:18][N:17]([CH2:16][C:13]2[CH:12]=[CH:11][C:10]([C:9](=[O:23])[NH:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:24][C:25]4[N:30]=[C:29]([C:31]5[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=5)[CH:28]=[CH:27][N:26]=4)[CH:4]=3)=[CH:15][CH:14]=2)[CH2:22][CH2:21]1)([O:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:45])[CH3:42])[CH3:38]
Reactant: CCOC(=O)C(C)OP(=O)(CC=O)Oc1ccccc1
Reactant: Cc1ccc(NC(=O)c2ccc(CN3CCNCC3)cc2)cc1Nc1nccc(-c2cccnc2)n1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)OP(=O)(CCN1CCN(Cc2ccc(C(=O)Nc3ccc(C)c(Nc4nccc(-c5cccnc5)n4)c3)cc2)CC1)Oc1ccccc1
Reaction time: 0.5 h
Yield: 26.2 %

Procedure:
A solution of N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-piperazin-1-ylmethyl-benzamide (20 mg, 0.04 mmol) and 2-[(2-oxo-ethyl)-phenoxy-phosphinoyloxy]-propionic acid ethyl ester (60 mg, 0.2 mmol) in 1% Acetic Acid/DMF (1.5 mL) solution was stirred at room temperature for 7 hours followed by an addition of NaCNBH3 (30 mg, 0.24 mmol). The resulting mixture was stirred for additional 30 min when completion of the reaction was observed by LCMS. After evaporation of solvent, the residue was taken up in CH2Cl2 and then extracted with saturated aqueous NaHCO3 The organic extracts were dried in vacuo and the residue was purified by silica gel chromatography using MeOH—CH2Cl2 (7%) to afford 8 mg (26%) of the product. 31P NMR (121.4 MHz, CDCl3) δ 27.2, 28.6; MS (m/z) 764 [M+H]+.
Reaction SMILES: C([N:8]1[C:17]2[C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[N:14]([C:22]([C:24]3[CH:45]=[CH:44][C:27]([CH2:28][NH:29][C:30]([CH:32]4[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:34][CH2:33]4)=[O:31])=[C:26]([CH3:46])[CH:25]=3)=[O:23])[CH2:13][CH2:12][C:11]=2[N:10]=[C:9]1[CH3:47])C1C=CC=CC=1.C1CCCCC=1>C(O)C.[Pd]>[CH3:46][C:26]1[CH:25]=[C:24]([C:22]([N:14]2[CH2:13][CH2:12][C:11]3[N:10]=[C:9]([CH3:47])[NH:8][C:17]=3[C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]2=3)=[O:23])[CH:45]=[CH:44][C:27]=1[CH2:28][NH:29][C:30]([CH:32]1[CH2:33][CH2:34][N:35]([CH2:38][CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:36][CH2:37]1)=[O:31]
Reactant: Cc1cc(C(=O)N2CCc3nc(C)n(Cc4ccccc4)c3-c3ccccc32)ccc1CNC(=O)C1CCN(CCC(C)(C)C)CC1
Agent: [Pd]
Solvent: C1=CCCCC1
Solvent: CCO
Product: Cc1nc2c([nH]1)-c1ccccc1N(C(=O)c1ccc(CNC(=O)C3CCN(CCC(C)(C)C)CC3)c(C)c1)CC2
Temperature: 60 °C
Yield: 48 %

Procedure:
1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(1-benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzylamide from Example E121 (110 mg, 0.17 mmol) was dissolved in absolute ethanol (5 ml) and placed under an inert atmosphere. 10% Palladium on carbon (110 mg) and cyclo-hexene (0.176 ml, 1.7 mmol) were added and the mixture was heated at 60° C. for 3 h. The catalyst was filtered off through Celite® filter agent and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane) to give a white powder identified as the title compound (45 mg, 48%).
Reaction SMILES: [C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:21]=[CH:22][CH:23]=2)[C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([OH:20])[CH:13]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2].C(=O)([O-])[O-].[K+].[K+].F[C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=1.O>CN(C)C=O>[C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:21]=[CH:22][CH:23]=2)[C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][C:31]3[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=3)[CH:13]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: COc1ccc(NC(=O)c2cccc(C3(C#N)CC3)c2)cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(NC(=O)c2cccc(C3(C#N)CC3)c2)cc1Oc1ccc([N+](=O)[O-])cc1
Temperature: 60 °C
Reaction time: 18 h
Yield: 88.5 %

Procedure:
To a suspension of 3-(1-cyanocyclopropyl)-N-(3-hydroxy-4-methoxyphenyl)-benzamide (1.54 mg, 5.00 mmol) and potassium carbonate (0.69 g, 5.00 mmol) in N,N-dimethylformamide (5 mL) was added 1-fluoro-4-nitrobenzene (0.78 g, 5.50 mmol), and the mixture was stirred at 60° C. for 18 hr. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane/ethyl acetate=1:1), and triturated with diethyl ether to give the title compound (1.90 g, 89%) as a white solid.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C:18]3[CH:23]=[CH:22][C:21]([O:24][Si](C(C)C)(C(C)C)C(C)C)=[CH:20][CH:19]=3)[C:13](=[O:17])[N:14]([CH2:15][CH3:16])[C:7]=12)(=[O:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[C:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C:18]3[CH:19]=[CH:20][C:21]([OH:24])=[CH:22][CH:23]=3)[C:13](=[O:17])[N:14]([CH2:15][CH3:16])[C:7]=12)(=[O:3])[CH3:2]
Reactant: CCn1c(=O)n(-c2ccc(O[Si](C(C)C)(C(C)C)C(C)C)cc2)c2nccc(COC(C)=O)c21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CCn1c(=O)n(-c2ccc(O)cc2)c2nccc(COC(C)=O)c21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 85 %

Procedure:
To a stirred solution of [1-ethyl-2-oxo-3-(4-{[tris(1-methylethyl)silyl]oxy}phenyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl]methyl acetate (480 mg) in THF (5 mL) was added a solution of tetrabutylammonium fluoride (778 mg) in THF (2 mL) at 0° C. The mixture was stirred at 0° C. for 30 min, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (AcOEt/Hexane=1/1) to give the title compound (276 mg).
Reaction SMILES: Br[C:2]1[C:3](=[O:14])[N:4]([CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[CH:5]=[C:6]([Br:8])[N:7]=1.Cl.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:24](=[C:25]([CH3:27])[CH:26]=1)[NH:23][CH2:22][CH2:21]2>>[Br:8][C:6]1[N:7]=[C:2]([N:23]2[C:24]3[C:20](=[CH:19][C:18]([O:17][CH3:16])=[CH:26][C:25]=3[CH3:27])[CH2:21][CH2:22]2)[C:3](=[O:14])[N:4]([CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[CH:5]=1
Reactant: COc1cc(C)c2c(c1)CCN2
Reactant: CCC(CC)n1cc(Br)nc(Br)c1=O
Agent: Cl
Product: CCC(CC)n1cc(Br)nc(N2CCc3cc(OC)cc(C)c32)c1=O

Procedure:
Prepared in a similar fashion as described for Example 413 using 3,5-dibromo-1-(1-ethylpropyl)-2(1H)-pyrazinone and 5-methoxy-7-methylindoline hydrochloride as the starting materials. mp 152-154° C.; 1H NMR (300 MHz, CDCl3): δ 6.73 (s, 1 H), 6.67 (s, 1 H), 6.59 (d, J=1.9 Hz, 1 H), 4.84-4.76 (m, 1 H), 4.38 (t, J=7.7 Hz, 2 H), 3.78 (s, 3 H), 3.05 (t, J=7.7 Hz, 2 H), 2.06 (s, 3 H), 1.87-1.73 (m, 2 H), 1.70-1.59 (m, 2 H), 0.89 (t, J=7.3 Hz, 6H); HRMS (ESI) calcd for C19H25N3O2Br (M+H)+: 406.1130; found m/z 406.1125.
Reaction SMILES: [CH3:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[H-].[Na+].[C:9]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[C:26]3[C:25](=[O:27])[CH2:24][CH2:23][CH2:22][C:21]=3[N:20]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=3)[C:19](=[O:38])[N:18]2[C:39](OC2C=CC([N+]([O-])=O)=CC=2)=[O:40])=[CH:13][CH:12]=1)#[N:10].O>O1CCCC1>[C:9]([C:11]1[CH:12]=[CH:13][C:14]([CH:17]2[C:26]3[C:25](=[O:27])[CH2:24][CH2:23][CH2:22][C:21]=3[N:20]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:35])([F:36])[F:37])[CH:29]=3)[C:19](=[O:38])[N:18]2[C:39]([O:4][CH2:3][C:2]([CH3:6])([CH3:5])[CH3:1])=[O:40])=[CH:15][CH:16]=1)#[N:10]
Reactant: N#Cc1ccc(C2C3=C(CCCC3=O)N(c3cccc(C(F)(F)F)c3)C(=O)N2C(=O)Oc2ccc([N+](=O)[O-])cc2)cc1
Reactant: CC(C)(C)CO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)COC(=O)N1C(=O)N(c2cccc(C(F)(F)F)c2)C2=C(C(=O)CCC2)C1c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A solution of 2,2-dimethyl-1-propanol (9 mg, 0.10 mmol) in dry tetrahydrofuran (1 mL) is cooled at −78° C. and treated with sodium hydride (60% in mineral oil, 5 mg, 0.11 mmol). After 20 min, a solution of 4-nitrophenyl 4-(4-cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazoline-3(4H)-carboxylate (intermediate 37, 60 mg, 0.10 mmol) in tetrahydrofuran (1 mL) is added and the mixture is stirred for 5 h at room temperature. Another portion of 2,2-dimethyl-1-propanol (9 mg, 0.10 mmol) is added and the mixture is stirred over night. Another portion of 2,2-dimethyl-1-propanol (18 mg, 0.20 mmol) is added and the mixture is heated at 50° C. for 2 h. Water is added and the mixture is extracted with dichlormethane. The organic layer is concentrated under reduced it) pressure and the residue is purified by flash chromatography on silica (gradient cyclohexane to cyclohexane/ethyl acetate 1:1). Yield: 12 mg; ESI mass spectrum [M+H]+=526; Retention time HPLC: 0.76 min (X012_S01).
Reaction SMILES: [F:1][C:2]1[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].I[CH2:25][CH3:26]>C(#N)C>[CH2:25]([N:15]1[CH2:16][CH2:17][CH:12]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])[C:2]=2[F:1])[CH2:13][CH2:14]1)[CH3:26]
Reactant: CS(=O)(=O)c1cccc(C2CCNCC2)c1F
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCN1CCC(c2cccc(S(C)(=O)=O)c2F)CC1

Procedure:
Preparation according to Example 1: 4-[2-fluoro-3-(methylsulfonyl)phenyl]-piperidine (0.185 g, 0.72 mmol), acetonitrile (10 ml), potassium carbonate (0.2 g, 1.44 mmol), 1-iodoethane (0.06 ml, 0.75 mmol). Yield: 0.15 g (73%). The amine was converted to several different salts and recrystallized from ethanol/diethyl ether. Hydrochloric acid salt m.p. 273-275° C., hydrobromic acid salt m.p. 267-268° C., fumaric acid salt m.p. 204-206° C., oxalic acid salt m.p. 163-165° C., sulfate salt m.p. 263-265° C., maleic acid salt m.p. 112-113° C. MS m/z (relative intensity, 70 eV) 285 (M+, 12), 271 (15), 270 (bp), 147 (7) 133 (8).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH2:13])[CH2:7]1.[S:18]1[CH:22]=[CH:21][C:20]([CH2:23][C:24](O)=[O:25])=[CH:19]1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH:13][C:24](=[O:25])[CH2:23][C:20]2[CH:21]=[CH:22][S:18][CH:19]=2)[CH2:7]1
Reactant: NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Reactant: O=C(O)Cc1ccsc1
Product: O=C(Cc1ccsc1)NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Yield: 20.3 %

Procedure:
Example 32 was prepared in an analogous manner to Example 1 using a mixture of Intermediate 1 (0.056 g) and thien-3-ylacetic acid (0.028 g) to give the title compound (0.016 g).
Reaction SMILES: [OH:1][CH:2]([C:5]1[N:6]=[CH:7][N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12](=[O:19])[N:11]([CH3:20])[CH2:10][C:9]=12)[CH2:3][CH3:4]>[O-2].[O-2].[Mn+4].C(Cl)Cl>[CH3:20][N:11]1[C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:8]2[CH:7]=[N:6][C:5]([C:2](=[O:1])[CH2:3][CH3:4])=[C:9]2[CH2:10]1
Reactant: CCC(O)c1ncn2c1CN(C)C(=O)c1ccccc1-2
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: CCC(=O)c1ncn2c1CN(C)C(=O)c1ccccc1-2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 1.84 g (6.8 mmol) of 4,5-dihydro-3-(1-hydroxypropyl)-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one, 16 g of manganese dioxide and 150 ml of methylene chloride is stirred at room temperature under an argon atmosphere for 2 hours. The manganese dioxide is filtered off under suction over a glass filter and the filtrate is evaporated in vacuo. After recrystallisation of the residue from 100 ml of ethyl acetate, there is obtained 4,5-dihydro-5-methyl-3-propionyl-6H-imidazo[1,5-a][1,4]-benzodiazepin-6-one of melting point 215°-216° C.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:7]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=1)=[O:4].[C:35]([O:38][C@@H:39]1[C@@H:45]([O:46][C:47](=[O:49])[CH3:48])[C@H:44]([O:50][C:51](=[O:53])[CH3:52])[C@@H:43]([CH2:54][O:55][C:56](=[O:58])[CH3:57])[O:42][C@H:40]1[OH:41])(=[O:37])[CH3:36].[H-].[Na+].O>COCCOC>[C:35]([O:38][C@@H:39]1[C@@H:45]([O:46][C:47](=[O:49])[CH3:48])[C@H:44]([O:50][C:51](=[O:53])[CH3:52])[C@@H:43]([CH2:54][O:55][C:56](=[O:58])[CH3:57])[O:42][C@H:40]1[O:41][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:7]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=1)=[O:4])(=[O:37])[CH3:36]
Reactant: O=C(CBr)c1cc(OCc2ccccc2)c(OCc2ccccc2)c(OCc2ccccc2)c1
Reactant: CC(=O)OC[C@H]1O[C@@H](O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CC(=O)OC[C@H]1O[C@@H](OCC(=O)c2cc(OCc3ccccc3)c(OCc3ccccc3)c(OCc3ccccc3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Bromo-3′,4′,5′-tribenzyloxyacetophenone (11) (2.59 g, 5 mmol) and β-D-glucose-2,3,4,6-tetraacetate (8) (1.74 g, 5 mmol) were dissolved in dry DME (50 mL) and sodium hydride (0.18 g, 7.5 mmol) (0.3 g 60% NaH suspension in oil) was added in small portions. The reaction mixture was allowed to be stirred at room temperature overnight. Water (50 mL) was added and the water phase extracted with DCM (3×25 mL). The organic layers were combined and washed with water (2×50 mL), dried (MgSO4) and evaporated to give a dark viscous oil. The product was isolated by dry flash chromatography (PE/EtOAc 6:4) (PE=petroleum ether). Recrystallisation from a mixture of methylcyclohexane and ethyl acetate afforded the desired compound as white crystals, m.p. 156-158° C. Yield 0.51 g (13%). 1H NMR (300 MHz, CDCl3): δ=1.98 (3H, s), 2.00 (3H, s), 2.02 (3H, s), 2.06 (3H, s), 3.63-3.73 (2H, m), 4.08-4.30 (5H, m), 4.62-4.94 (1H, m), 5.02-5.34 (7H, m), 7.20-7.56 (17H, m); 13C NMR (75 MHz): δ=20.5, 20.6, 61.6, 68.2, 70.5, 70.8, 71.2, 71.8, 72.4, 75.0, 100.1, 107.9, 127.4, 127.9, 128.0, 128.1, 128.4, 128.5, 129.6, 136.4, 137.1, 143.2, 152.6, 169.3, 169.5, 170.0, 170.5, 193.4.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([C:8]1[CH:20]=[CH:19][C:18]2[C:17]3[C:12](=[CH:13][C:14]([C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25]Cl)=[CH:15][CH:16]=3)[CH2:11][C:10]=2[CH:9]=1)=[O:7].[NH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>>[N:28]1([CH2:2][CH2:3][CH2:4][CH2:5][C:6]([C:8]2[CH:20]=[CH:19][C:18]3[C:17]4[C:12](=[CH:13][C:14]([C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25][N:28]5[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]5)=[CH:15][CH:16]=4)[CH2:11][C:10]=3[CH:9]=2)=[O:7])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1
Reactant: C1CCNCC1
Reactant: O=C(CCCCCl)c1ccc2c(c1)Cc1cc(C(=O)CCCCCl)ccc1-2
Product: O=C(CCCCN1CCCCC1)c1ccc2c(c1)Cc1cc(C(=O)CCCCN3CCCCC3)ccc1-2

Procedure:
By the procedure of Example 7, 20.2g (0.05 mole) of 2,7-bis(5-chlorovaleryl)fluorene, prepared in Example 2, and 34.0g (0.4mole) of piperidine were reacted. The solid precipitate was recrystallized twice from methanol and chromatographed on alumina. Evaporation of solvent from the fraction collected gave the desired product. M.P. 124°-127° C, λmaxCHCl3 328, Elcm1% 731.
Reaction SMILES: [CH2:1]([OH:7])[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.[C:8]([N:11]1[C:20]2[C:15](=[CH:16][C:17]([NH:21][C:22]([CH2:24][C:25](O)=[O:26])=[O:23])=[CH:18][CH:19]=2)[C:14]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([CH3:28])[CH2:13][C:12]1([CH3:36])[CH3:35])(=[O:10])[CH3:9].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O1CCCC1>[C:8]([N:11]1[C:20]2[C:15](=[CH:16][C:17]([NH:21][C:22]([CH2:24][C:25]([O:7][CH2:1][C:2]3[O:6][CH:5]=[CH:4][CH:3]=3)=[O:26])=[O:23])=[CH:18][CH:19]=2)[C:14]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)([CH3:28])[CH2:13][C:12]1([CH3:36])[CH3:35])(=[O:10])[CH3:9]
Reactant: OCc1ccco1
Reactant: CC(=O)N1c2ccc(NC(=O)CC(=O)O)cc2C(C)(c2ccccc2)CC1(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(=O)N1c2ccc(NC(=O)CC(=O)OCc3ccco3)cc2C(C)(c2ccccc2)CC1(C)C

Procedure:
Condensation of furfuryl alcohol (17 μl) and 1-acetyl-6-(hydroxycarbonylmethylcarbonyl)amino-4-phenyl-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline (15 mg) under the agency of HATU (29 mg) and N,N-diisopropylethylamine (33 μl) in tetrahydrofuran (2 ml) was performed according to the method described in example 11.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12](=[O:14])[NH:11][CH:10]([C:15]3[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[C:18]([OH:24])=[C:17]([O:25][CH2:26][CH3:27])[CH:16]=3)[C:9]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.[CH3:34][C:35](OC(C)=O)=[O:36]>C(Cl)Cl>[CH2:26]([O:25][C:17]1[CH:16]=[C:15]([CH:10]2[NH:11][C:12](=[O:14])[NH:13][C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:35](=[O:36])[CH3:34])=[CH:3][CH:4]=3)=[C:9]2[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[C:18]=1[OH:24])[CH3:27]
Reactant: CC(=O)OC(C)=O
Reactant: CCOc1cc(C2NC(=O)NC(c3ccc(N)cc3)=C2c2ccccc2)cc([N+](=O)[O-])c1O
Solvent: ClCCl
Product: CCOc1cc(C2NC(=O)NC(c3ccc(NC(C)=O)cc3)=C2c2ccccc2)cc([N+](=O)[O-])c1O
Temperature: 25 °C
Reaction time: 4 h
Yield: 29.8 %

Procedure:
To a solution of compound 6-(4-aminophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one (Compound 84) (100 mg, 0.22 mmol) in DCM (2 mL) was added Ac2O (27 mg, 0.27 mmol) at room temperature, and the mixture was stirred at room temperature for 4 hours. The mixture was evaporated in vacuo and purified by column to give the Compound 73 (32.07 mg, yield 34%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (brs, 1H), 9.95 (s, 1H), 8.66 (s, 1H), 7.52 (s, 1H), 7.45-7.42 (m, 3H), 7.19 (d, J=1.8 Hz, 1H), 7.13-6.97 (m, 5H), 6.83 (d, J=6.6 Hz, 2H), 5.17 (d, J=2.7 Hz, 1H), 4.10-4.01 (m, 2H), 2.02 (s, 3H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 489.1 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]([NH:15][C:16]2[C:21]([C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:28])=O)=[CH:11][C:10]([C:29]([F:32])([F:31])[F:30])=[N:9]1.S(Cl)(Cl)=O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[O:23][C:22](=[N:24][CH:25]([CH3:26])[CH3:27])[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([CH3:28])[C:16]=3[N:15]=2)=[CH:11][C:10]([C:29]([F:32])([F:31])[F:30])=[N:9]1
Reactant: Cc1cccc(C(=O)NC(C)C)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ccccc1Cl
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: Cc1cccc2c(=NC(C)C)oc(-c3cc(C(F)(F)F)nn3-c3ccccc3Cl)nc12
Yield: 58 %

Procedure:
To the title compound of Step D (1.2 g, 2.7 mmol) dissolved in 8 mL of dichloromethane, 5 mL of thionyl chloride was added and the solution heated at reflux for 8 hours. The solvent was removed in vacuo and remaining residue partitioned between 70 mL of ethyl acetate and water. The organic layer was separated, washed with water, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo to give a crude oily solid residue. Purification by flash chromatography on silica gel (2:1 hexane/ethyl acetate) and filtering from hexane afforded 700 mg of the title compound, a compound of the invention, isolated as a white solid melting at 133-135° C.
Reaction SMILES: [NH2:1][CH:2]([C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[O:17][CH3:18])[CH2:3][CH2:4][C:5]([O:7]C)=O.[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[CH:29]=O>>[CH3:18][O:17][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[CH:2]1[N:1]([CH2:29][C:20]2[CH:21]=[CH:22][C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:19]=2)[C:5](=[O:7])[CH2:4][CH2:3]1
Reactant: O=Cc1ccc2ccccc2c1
Reactant: COC(=O)CCC(N)c1c(OC)cccc1OC
Product: COc1cccc(OC)c1C1CCC(=O)N1Cc1ccc2ccccc2c1

Procedure:
Prepared according to the described general procedure 1 (GP1) by reaction of methyl 4-amino-4-(2,6-dimethoxyphenyl)butanoate with commercially available 2-naphthaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.87 min.; [M+H]+: 362.35 g/mol.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:6]=1[CH2:18]Br)[CH3:2].[NH:21]([S:27]([C:30]1[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=1)(=[O:29])=[O:28])[CH2:22][C:23]([O:25][CH3:26])=[O:24].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:6]=1[CH2:18][N:21]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[S:27]([C:30]1[CH:31]=[CH:32][C:33]([CH3:34])=[CH:35][CH:36]=1)(=[O:29])=[O:28])[CH3:2]
Reactant: COC(=O)CNS(=O)(=O)c1ccc(C)cc1
Reactant: CCOC(=O)c1ccc(Oc2ccccn2)cc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(Oc2ccccn2)cc1CN(CC(=O)OC)S(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.4 %

Procedure:
A mixture of 2-bromomethyl-4-(pyridin-2-yloxy)-benzoic acid ethyl ester (855 mg, crude from previous step), Ts-Gly-OMe (502 mg), potassium carbonate (425 mg) and KI (32 mg) in DMF (10 mL) was stirred at rt overnight. Then the reaction mixture was diluted with EtOAc, washed with water, diluted NaCl sol and dried over anhydrous sodium sulfate, filtered, concentrated and the residue was column purified to give product (745 mg). LC MS ESI+: 499 (M+1)+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([NH2:19])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][C:21]=1[O:30][CH2:31][CH2:32][CH2:33][CH2:34]Cl>CS(C)=O.O>[CH2:7]([NH:19][CH2:34][CH2:33][CH2:32][CH2:31][O:30][C:21]1[CH:22]=[CH:23][C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:20]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: ClCCCCOc1ccc2ccccc2c1
Reactant: CCCCCCCCCCCCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CCCCCCCCCCCCNCCCCOc1ccc2ccccc2c1
Temperature: 150 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and n-dodecylamine (0.48 ml, 0.003 mole) was taken in dry DMSO (40 ml). Now 4-(2-naphthyloxy)-1-chlorobutane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 150° C. for 8 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(n-dodecyl)-(4-(naphthalen-2-yloxy)-butyl)amine, solid. m.p. 129° C., (yield 0.78 gm, 95.5%).