Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]([CH2:19][CH2:20][CH:21]([C:25]2[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[C:27]([O:35][CH3:36])[CH:26]=2)[C:22](O)=[O:23])C(O)=O)[CH:6]=[C:7]([S:13]C)[C:8]=1[O:9][CH2:10][CH2:11][CH3:12].BrC1C=C(C2CCC(C3C=C(OC)C(OC)=C(OC)C=3)C2=O)C=C(OC)[C:43]=1[O:44]CCC>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]2[CH2:19][CH2:20][CH:21]([C:25]3[CH:26]=[C:27]([O:35][CH3:36])[C:28]([O:33][CH3:34])=[C:29]([O:31][CH3:32])[CH:30]=3)[C:22]2=[O:23])[CH:6]=[C:7]([S:13][O:44][CH3:43])[C:8]=1[O:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCOc1c(OC)cc(C(CCC(C(=O)O)c2cc(OC)c(OC)c(OC)c2)C(=O)O)cc1SC
Reactant: CCCOc1c(Br)cc(C2CCC(c3cc(OC)c(OC)c(OC)c3)C2=O)cc1OC
Product: CCCOc1c(OC)cc(C2CCC(c3cc(OC)c(OC)c(OC)c3)C2=O)cc1SOC

Procedure:
Following substantially the same procedure of Step I but substituting 2-(3-bromo-5-methoxy-6-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,6-hexanedioic acid for 2-(3-methoxy-5-(methylthio)-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,6-hexanedioic acid there was prepared a 1:4 cis:trans mixture of 2-(3-bromo-5-methoxy-4-propoxyphenyl-5-(3,4,5-trimethoxyphenyl)cyclopentanone as an oil in a 15% yield,
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:17](=[O:19])[NH:16][CH:15]=[CH:14][C:13]=3[NH:12][C:11]([CH3:20])=[C:10]2[C:21]#[N:22])=[C:5]([O:23][CH3:24])[CH:4]=1)#[N:2].FC(F)(F)S(O[CH2:31][CH3:32])(=O)=O.CO>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[N:16][C:17]=3[O:19][CH2:31][CH3:32])[NH:12][C:11]([CH3:20])=[C:10]2[C:21]#[N:22])=[C:5]([O:23][CH3:24])[CH:4]=1)#[N:2]
Reactant: COc1cc(C#N)ccc1C1C(C#N)=C(C)Nc2cc[nH]c(=O)c21
Reactant: CCOS(=O)(=O)C(F)(F)F
Solvent: CO
Solvent: C1CCOC1
Product: CCOc1nccc2c1C(c1ccc(C#N)cc1OC)C(C#N)=C(C)N2
Reaction time: 0.17 h

Procedure:
505 mg (1.58 mmol) of 4-(4-cyano-2-methoxyphenyl)-2-methyl-5-oxo-1,4,5,6-tetrahydro-1,6-naphthyridine-3-carbonitrile are suspended in THF (20 ml), and 1.9 ml (1.9 mmol) of N′″-(tert-butyl)-N,N′,N″-tris[tris(dimethylamino)phosphoranylidene]phosphorimide triamide (phosphazene base P4-t-Bu; 1 M in hexane) are added. Then 240 μl (1.9 mmol) of ethyl trifluoromethanesulfonate are added to the dark red solution. The decolorized solution is stirred for a further 10 min and then mixed with methanol and concentrated. The residue is purified by preparative HPLC to result in 124 mg (21% of theory) of the title compound as a white solid.
Reaction SMILES: Cl.[Br:2][C:3]1[C:4]([NH:10][CH2:11][CH2:12][CH2:13][NH2:14])=[N:5][C:6]([Cl:9])=[N:7][CH:8]=1.[N+:15]([C:18]1[CH:19]=[C:20]([S:24](Cl)(=[O:26])=[O:25])[CH:21]=[CH:22][CH:23]=1)([O-:17])=[O:16].O.C(N(CC)CC)C>CC(C)=O>[Br:2][C:3]1[C:4]([NH:10][CH2:11][CH2:12][CH2:13][NH:14][S:24]([C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([N+:15]([O-:17])=[O:16])[CH:19]=2)(=[O:25])=[O:26])=[N:5][C:6]([Cl:9])=[N:7][CH:8]=1
Reactant: NCCCNc1nc(Cl)ncc1Br
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CC(C)=O
Product: O=[N+]([O-])c1cccc(S(=O)(=O)NCCCNc2nc(Cl)ncc2Br)c1
Reaction time: 2.5 h

Procedure:
A solution of 530 mg (1.76 mmol) of N-(5-bromo-2-chloro-pyrimidin-4-yl)-propane-1,3-diamine hydrochloride and 352 mg (1.60 mmol) of 3-nitrobenzenesulfonyl chloride in 20 ml of acetone/6 ml of water is mixed at room temperature with 1 ml of triethylamine. After 2.5 hours, the organic solvent is drawn off in a rotary evaporator. After water (20 ml) is added, it is extracted with ethyl acetate. The combined organic phases are washed with citric acid (10%), saturated NaHCO3 solution as well as saturated NaCl solution, dried (Na2SO4), filtered and concentrated by evaporation. 633 mg (1.41 mmol, corresponding to 87% of theory) of the product is obtained.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][NH2:6].[CH3:8][O:9][C:10]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:11]=1[CH:12]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:8][O:9][C:10]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:11]=1[CH2:12][NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1]
Reactant: CN(C)CCCN
Reactant: COc1ccc(C=O)c(OC)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CO
Product: COc1ccc(CNCCCN(C)C)c(OC)c1
Temperature: 25 °C
Reaction time: 10 h
Yield: 95.3 %

Procedure:
A mixture of 3-dimethylaminopropylamine (3.06 g), 2,4-dimethoxybenzaldehyde (6.0 g) and sodium triacetoxyborohydride (9.54 g) in methanol (20 mL) was stirred at room temperature for 10 hours. The mixture was concentrated under vacuum and the residue was dissolved in ethyl acetate and washed with water and brine, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness to give N-(2,4-dimethoxybenzyl)-N-(3-dimethylaminopropyl)amine (7.2 g) as a brown oil which was used directly without further characterisation.
Reaction SMILES: [C:1]([C:4]1[CH:14]=[C:13]([NH:15][C:16](=[O:25])[C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])[C:7]2[O:8][C:9]([CH3:12])=[C:10]([CH3:11])[C:6]=2[CH:5]=1)(O)=[O:2].C([N:28](CC)CC)C.ClC(OCC(C)C)=O.N>ClCCl.CO>[C:1]([C:4]1[CH:14]=[C:13]([NH:15][C:16](=[O:25])[C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])[C:7]2[O:8][C:9]([CH3:12])=[C:10]([CH3:11])[C:6]=2[CH:5]=1)(=[O:2])[NH2:28]
Reactant: Cc1oc2c(NC(=O)c3c(Cl)cccc3Cl)cc(C(=O)O)cc2c1C
Reactant: CCN(CC)CC
Agent: CC(C)COC(=O)Cl
Agent: N
Solvent: CO
Solvent: ClCCl
Product: Cc1oc2c(NC(=O)c3c(Cl)cccc3Cl)cc(C(N)=O)cc2c1C
Temperature: -20 °C
Reaction time: 3 h
Yield: 46.2 %

Procedure:
A solution of 5-carboxy-7-(2,6-dichlorobenzoylamino)-2,3-dimethylbenzo[b]furan (152 mg) and triethylamine (61 mg) in dichloromethane (3 ml) was stirred at -20° C. and to the solution was added isobutyl chloroformate (66 mg). The mixture was stirred at -20° C. for 3 hours and added to cold (-20° C.) solution of 10% ammonia in methanol (3 ml). The reaction mixture was stirred at ambient temperature for 10 minutes and partitioned between dichloromethane and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel and the obtained oil was crystallized from ethyl acetate to give 5-carbamoyl-7-(2,6-dichlorobenzoylamino)-2,3-dimethylbenzo[b]furan (70 mg).
Reaction SMILES: [OH:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:3][C:4]#[N:5].[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1>CCOCC>[NH2:5][CH2:4][CH2:3][CH:2]([O:1][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][O:11]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCC(O)CC#N
Reactant: C1=COCCC1
Solvent: CCOCC
Product: CCCCCC(CCN)OC1CCCCO1
Temperature: 25 °C
Reaction time: 16 h
Yield: 93.6 %

Procedure:
A mixture of 3-hydroxycaprylonitrile (5.2 g., 36.8 millimole), dihydropyran (3.8 g., 45 millimole), and p-toluenesulfonic acid·hydrate (catalytic amount) is stirred at 25° C. for 16 hours, then diluted with ether (100 ml.). The resulting solution is washed with 5% aqueous sodium hydroxide (25 ml.) and water (2×25 ml.), dried over magnesium sulfate, and filtered. Evaporation of the filtrate in vacuo affords the title compound as a pale yellow oil (7.9 g., 95%), pmr (CDCl3) δ 0.93 (3H, t), 2.54 (2H, q) and 4.68 (H, m).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8](=O)[C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.CO.[NH2:15][OH:16]>C1C=CC=CC=1>[OH:16][N:15]=[C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=1)[C:9]([OH:11])=[O:10]
Reactant: NO
Reactant: O=C(O)C(=O)c1cccc(O)c1
Solvent: CO
Solvent: c1ccccc1
Product: O=C(O)C(=NO)c1cccc(O)c1
Reaction time: 0.42 h

Procedure:
A mixture of 3-hydroxyphenylglyoxylic acid (3.32 g.) and 1N-methanol solution of hydroxylamine (45 ml.) was refluxed with stirring, for 25 minutes. The reaction mixture was concentrated to dryness. The residue was dissolved in 1N-sodium hydroxide aqueous solution (50 ml.) and the solution was washed with ether, acidified with hydrochloric acid under cooling and extracted with ethyl acetate. The extract was washed with a saturated sodium chloride aqueous solution, dried and concentrated to give yellow oil. To the oil was added benzene and benzene was distilled off. The residue was crystallized with petroleum ether and the crystals were collected by filtration, washed with petroleum ether and dried to give 2-hydroxyimino-2-(3-hydroxyphenyl)acetic acid (a mixture of syn and anti isomers) (2.9 g.).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([OH:10])=[O:9])[N:3]=1.[ClH:11]>CO.O=[Pt]=O>[ClH:11].[NH2:1][C:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]([OH:10])=[O:9])[N:3]=1
Reactant: Nc1cccc(C(=O)O)n1
Agent: O=[Pt]=O
Agent: Cl
Solvent: CO
Product: NC1=NC(C(=O)O)CCC1
Reaction time: 2 h
Yield: 80.3 %

Procedure:
2-Aminopyridine-6-carboxylic acid (Farinaco. Ed. Sci. 1959, 14, 594; 2.01 g, 14.5 mmol) was dissolved in 90% methanol (200 ml) and conc. HCl (7.2 ml, 87.4 mmol) was added. The solution was hydrogenated over PtO2 (340 mg) in a Parr shaker apparatus at room temperature and 29 psig for 2 hours. Filtration and evaporation gave 2.08 g (80%) crude white crystals identified as the product by 300 MHz nmr and ir 1724 cm-1.
Reaction SMILES: Cl[C:2]1C=C(SC2C3C(=CC(C)=CC=3)NC=2CCC(N)=O)C=C(Cl)[CH:7]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32][C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][C:40]=3[CH3:42])[NH:35][C:34]=2[C:43]([OH:45])=[O:44])=[CH:28][CH:27]=1.C(Cl)(=O)C(Cl)=O.CCO>C1COCC1>[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([S:32][C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][C:40]=3[CH3:42])[NH:35][C:34]=2[C:43]([O:45][CH2:2][CH3:7])=[O:44])=[CH:30][CH:31]=1
Reactant: Cc1ccc2c(Sc3cc(Cl)cc(Cl)c3)c(CCC(N)=O)[nH]c2c1
Reactant: Cc1cccc2[nH]c(C(=O)O)c(Sc3ccc(Cl)cc3)c12
Agent: O=C(Cl)C(=O)Cl
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)c1[nH]c2cccc(C)c2c1Sc1ccc(Cl)cc1
Yield: 62 %

Procedure:
Following the method used to prepare 24a, the use of 1a (0.19 mmol) and oxalyl chloride in THF followed by allowing the intermediate acid chloride to react with EtOH (3 mL) provided 41 mg (62%) of product 11 as a white solid, mp 186-188° C. 1H NMR (300 MHz, DMSO-d6) δ 1.25 (t, J=7 Hz, 3H), 2.59 (s, 3H), 4.31 (q, J=7 Hz, 2H), 6.88 (d, J=7 Hz, 1H), 6.94-6.98 (m, 2H), 7.23 (t, J=8 Hz, 1H), 7.25-7.30 (m, 2H), 7.42 (d, J=8 Hz, 1H), 12.48 (s, 1H). LC-MS (CI): m/z 346.1 [(M+H)+ C18H16ClNO2S requires 345.06]. Purity (100%). Calcd for C18H16ClNO2S: C, 62.51; H, 4.66; N, 4.05; S, 9.27; Cl, 10.25. Found: C, 62.53; H, 4.59; N, 4.08; S, 9.27; Cl, 10.35.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[C:12]([N:17]2[CH2:21][CH2:20][CH:19]([C:22](O)=[O:23])[CH2:18]2)[CH:13]=[CH:14][C:15]=1[Cl:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)=[O:64])([CH3:61])([CH3:60])[CH3:59]>>[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][N:68]([C:22]([CH:19]2[CH2:20][CH2:21][N:17]([C:12]3[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([C:2]4[NH:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)[CH:11]=3)[CH2:18]2)=[O:23])[CH2:67][CH2:66]1)=[O:64])([CH3:61])([CH3:59])[CH3:60]
Reactant: O=C(O)C1CCN(c2ccc(Cl)c(-c3nc4ccccc4[nH]3)c2)C1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCN(C(=O)C2CCN(c3ccc(Cl)c(-c4nc5ccccc5[nH]4)c3)C2)CC1
Temperature: 35 °C
Yield: 83 %

Procedure:
Method G—Step a To a mixture of 1-[3-(1H-Benzoimidazol-2-yl)-4-chloro-phenyl]-pyrrolidine-3-carboxylic acid (obtained as described in general method 2, step e) (0.01 g, 0.26 mmol) in dcm (4 mL), HATU (0.10 g, 0.29 mmol), diisopropylethylamine (DIPEA) (0.14 mL, 0.76 mmol) and tert-butyl-1-piperazine carboxylate (0.06 g, 0.32 mmol) were added. The reaction mixture was heated at 35° C. overnight, cooled to room temperature and washed with water (2×5 mL) and saturated Na2CO3 solution (2×5 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure to obtain a crude that was triturated with diethylether (3 mL), filtered and dried. The precipitate was then purified by flash chromatography (eluent gradient: EtOAc 100% to EtOAc:NH3 in MeOH (2M)/4:0.8), and then a filtration on an SCX cartridge was run (eluent gradient: DCM:MeOH/1:1 to NH3 in MeOH), to obtain 0.11 g of the title compound (67%).
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C@@H:4]([CH2:5][CH2:6][C@:7]3([CH3:38])[C@@H:16]2[CH2:15][CH2:14][C@H:13]2[C@@:8]3([CH3:37])[CH2:9][CH2:10][C@@:11]3([C:27]([O:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[O:28])[CH2:23][CH2:22][C@@H:21]([CH:24]([CH3:26])[CH3:25])[C@@H:12]32)[C:3]1([CH3:40])[CH3:39].C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[CH:24]([C@H:21]1[C@@H:12]2[C@@H:13]3[C@@:8]([CH3:37])([CH2:9][CH2:10][C@@:11]2([C:27]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[O:28])[CH2:23][CH2:22]1)[C@@:7]1([CH3:38])[C@@H:16]([C@:17]2([CH3:20])[C@@H:4]([CH2:5][CH2:6]1)[C:3]([CH3:39])([CH3:40])[C:2](=[O:1])[CH2:19][CH2:18]2)[CH2:15][CH2:14]3)([CH3:26])[CH3:25]
Reactant: CC(C)[C@@H]1CC[C@]2(C(=O)OCc3ccccc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)[C@@H]1CC[C@]2(C(=O)OCc3ccccc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CCC(=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reaction time: 4 h

Procedure:
To a solution of (1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-benzyl 9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysene-3a-carboxylate (3.3 g, 6.01 mmol) in DCM (50 mL) was added PCC (3.89 g, 18.04 mmol). The reaction mixture was stirred for 4 hours. TLC indicated sm was consumed and desired product was formed. The reaction mixture was concentrated under reduced pressure. The residue was purified by biotage with 0-10% ethyl acetate/hexane to provide the title compound as white solid (3.05, 93%). LCMS: m/e 547.25 (M+H)+, 2.77 min (method 1). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.41-7.28 (m, 5H), 5.10 (q, J=12.41 Hz, 2H), 2.57-2.34 (m, 2H), 2.31-2.16 (m, 3H), 1.98-1.86 (m, 1H), 1.85-1.73 (m, 2H), 1.73-1.61 (m, 1H), 1.54-1.07 (m, 17H), 1.06 (s, 3H), 1.01 (s, 3H), 0.92 (s, 3H), 0.90 (s, 3H), 0.84 (d, J=7.02 Hz, 3H), 0.76 (s, 3H), 0.73 (d, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[O:19][CH:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:17][S:16][C:15]=3[CH:26]=2)=[N:8][CH:9]=1)([O-:3])=[O:2].[OH2:27]>CO>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[O:19][CH:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:17][S:16](=[O:27])[C:15]=3[CH:26]=2)=[N:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O
Reactant: O=[N+]([O-])c1ccc(Oc2ccc3c(c2)SCC(c2ccccc2)O3)nc1
Solvent: CO
Product: O=[N+]([O-])c1ccc(Oc2ccc3c(c2)S(=O)CC(c2ccccc2)O3)nc1

Procedure:
To 5-nitro-2-(2-phenyl-2,3-dihydrobenzo[1,4]oxathiin-6-yloxy)pyridine (214 mg) in methanol (80 ml) at 60° C., NaIO4 (total 2.5 eq) was added in small portions until disappearance of the starting material. The mixture was poured into water and precipitate was filtered and washed with water. The crude product was purified by column chromatography using heptane-ethyl acetate (1:1) as an eluant. 1H NMR (400 MHz, CDCl3) δ: 9.02 (d, 1H, J 2.8 Hz), 8.51 (dd, 1H, J 9.1, 2.8 Hz), 7.45-7.56 (m, 6H), 7.32 (dd, 1H, J 9.0, 2.8 Hz), 7.21 (d, 1H, J 9.0 Hz), 7.10 (d, 1H, J 9.1 Hz), 5.77 (dd, 1H, J 12.0, 1.5 Hz), 3.34 (dd, 1H, 14.4, 1.5 Hz), 3.13 (dd, 1H, 14.4, 12.0 Hz).
Reaction SMILES: [Si]([O:8][CH2:9][C@@H:10]([N:20]1[C:32]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[N:25]=[CH:24][C:23]=2[N:22]=[C:21]1[CH2:33]Cl)[CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)(O)[O-].[Na+].CC(C)([O-])C.[K+]>O1CCCC1.C(Cl)(Cl)Cl.C(Cl)(Cl)Cl.CO.C(Cl)Cl>[CH:30]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:31]=1[C:32]1[N:20]3[C@@H:10]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])[CH2:9][O:8][CH2:33][C:21]3=[N:22][C:23]=1[CH:24]=[N:25]2
Reactant: CC(C)(C)OC(=O)NC[C@@H](CO[Si](C)(C)C(C)(C)C)n1c(CCl)nc2cnc3ccccc3c21
Agent: CC(C)(C)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC[C@H]1COCc2nc3cnc4ccccc4c3n21
Temperature: -78 °C
Yield: 74.2 %

Procedure:
tert-Butyl (2S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propylcarbamate (3.11 g, 6.16 mmol) was dissolved in 60 mL of tetrahydrofuran (THF) and the solution was cooled to −78° C. under N2. A 1.0 M solution of tetrabutylammonium fluoride in THF (6.8 mL) was added and the reaction mixture was allowed to warm to −10° C. over 2 hours. The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution and 200 mL of CH2Cl2. The layers were separated and the organic portion was washed with H2O (50 mL) and brine (4×25 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a golden syrup. The syrup was concentrated from toluene (3×) to give a pale yellow foam. This material was dissolved in 70 mL of anhydrous THF and the solution was stirred under N2. Solid potassium tert-butoxide (507 mg, 6.18 mmol) was then added and the reaction mixture was allowed to stir for 2.5 hours. A solution of 50 mL of saturated sodium bicarbonate was then added and the THF was then removed under reduced pressure. The resulting material was treated with 150 mL of CH2Cl2 and layers were separated. The organic portion was washed with H2O and brine. The organic portion was then dried over Na2SO4, filtered and concentrated under reduced to give brown foam. Chromatography (SiO2, 20% 80:18:2 CHCl3/methanol/concentrated NH4OH (CMA)/CHCl3) gave tert-butyl (11S)-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-11-ylmethylcarbamate (1.62 g) as a light yellow foam.
Reaction SMILES: [CH2:1]([O:19][CH2:20][C:21]([CH2:65][O:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])([CH2:45][O:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64])[CH2:22][O:23][C:24]1[CH:36]=[CH:35][C:34]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=3)(O)[C:26]=2[CH:25]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C([Br:88])(=O)C>C(Cl)(Cl)Cl>[CH2:1]([O:19][CH2:20][C:21]([CH2:65][O:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])([CH2:45][O:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64])[CH2:22][O:23][C:24]1[CH:36]=[CH:35][C:34]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=3)([Br:88])[C:26]=2[CH:25]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCCOCC(COCCCCCCCCCCCCCCCCCC)(COCCCCCCCCCCCCCCCCCC)COc1ccc2c(c1)C(O)(c1ccc(Cl)cc1)c1ccccc1-2
Reactant: CC(=O)Br
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCCOCC(COCCCCCCCCCCCCCCCCCC)(COCCCCCCCCCCCCCCCCCC)COc1ccc2c(c1)C(Br)(c1ccc(Cl)cc1)c1ccccc1-2
Reaction time: 2 h
Yield: 78571432 %

Procedure:
2-(3-Octadecyloxy-2,2-bis-octadecyloxymethyl-propoxy)-9-(4-chlorophenyl)-9-fluorenol (66 mg, 56 μmol) was dissolved in chloroform (1 ml), acetyl bromide (41 μl, 0.55 mmol) was added dropwise thereto and the mixture was stirred for 2 hours. After completion of the reaction, the solvent was evaporated, and the residue was crystallized from acetonitrile (1 ml) to give 2-(3-octadecyloxy-2,2-bis-octadecyloxymethyl-propoxy)-9-(4-chlorophenyl)-9-bromofluorene (55 mg, 44 mol, 79%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([CH2:14][CH2:15][CH3:16])[CH2:9]2)[CH:5]=[CH:4][C:3]=1[OH:17].C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CO>CN(C=O)C>[CH2:24]([O:17][C:3]1[CH:4]=[CH:5][C:6]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([CH2:14][CH2:15][CH3:16])[CH2:9]2)=[CH:7][C:2]=1[Br:1])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCc1ccccc1
Reactant: CCCN1CCOC(c2ccc(O)c(Br)c2)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CN(C)C=O
Product: CCCN1CCOC(c2ccc(OCc3ccccc3)c(Br)c2)C1
Temperature: 150 °C
Yield: 100 %

Procedure:
To the phenol from example 30 (117.5 mg 0.39 mmol) in dry DMF (10 ml) under an atmosphere of nitrogen, was added potassium carbonate (75 mg, 0.54 mmol) and benzyl bromide (0.07 ml, 0.54 mmol). The reaction mixture was heated to 150° C. for 48 hours. After cooling, the reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate (50 ml) and water (50 ml). The aqueous layer was then re-extracted with ethyl acetate (2×20 ml). The combined organic extracts were then dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give the crude product as a brown oil. This was purified by column chromatography on silica eluting with dichloromethane:methanol (9832) to give the title compound as a colourless oil (153 mg, 0.39 mmol, 100%). 1H NMR (CDCl3, 400 MHz) δ: 0.93 (t 3H), 1.56 (q, 2H), 2.05 (t, 1H), 2.25 (t, 1H), 2.37 (t, 2H), 2.82 (d, 1H), 2.92 (d, 1H), 3.85 (t, 1H), 4.02 (d, 1H), 4.52 (d, 1H), 5.15 (s, 2H), 6.87 (d, 1H), 7.20 (d, 1H), 7.30 (d, 1H), 7.37 (t, 2H), 7.45 (d, 2H), 7.58 (s, 1H). LRMS: m/z 392 (M-H+).
Reaction SMILES: C([O:4][C:5]1[C:6](=[O:16])[C:7]2[C:12]([C:13](=[O:15])[CH:14]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)(=O)C.[CH3:17][CH:18]([CH2:22][CH2:23][CH3:24])C(O)=O>>[OH:4][C:5]1[C:6](=[O:16])[C:7]2[C:12]([C:13](=[O:15])[C:14]=1[CH:18]([CH3:17])[CH2:22][CH2:23][CH3:24])=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: CC(=O)OC1=CC(=O)c2ccccc2C1=O
Reactant: CCCC(C)C(=O)O
Product: CCCC(C)C1=C(O)C(=O)c2ccccc2C1=O
Yield: 43.4 %

Procedure:
The method of Example 1 was followed using 2-acetyloxynaphthalene-1,4-dione (1.24 g, 5.74 mmol) and 2-methylpentanoic acid (1.00 g) yielded the title compound (608 mg) after hydrolysis in. 30 ml THF using potassium hydroxide (5×exess) in water (8 ml) (mp 82-83° C.). This compound is listed as compound 3 in the Tables below.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[C:10]1[CH:15]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:13]=[C:12]([C:25]([O:27]C)=[O:26])[CH:11]=1)#[N:2].Br[C:30]1[CH:37]=[N:36][CH:35]=[CH:34][C:31]=1[C:32]#[N:33].C(=O)([O-])[O-].[Cs+].[Cs+].O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[C:10]1[CH:15]=[C:14]([C:34]2[CH:35]=[N:36][CH:37]=[CH:30][C:31]=2[C:32]#[N:33])[CH:13]=[C:12]([C:25]([OH:27])=[O:26])[CH:11]=1)#[N:2]
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)cc(-c2ccc(C)cc2C#N)c1
Reactant: N#Cc1ccncc1Br
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(-c2cc(C(=O)O)cc(-c3cnccc3C#N)c2)c(C#N)c1

Procedure:
Into a 5 mL microwave vial were charged methyl 2′-cyano-4′-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-3-carboxylate (150 mg, 0.36 mmol), 3-bromoisonicotinonitrile (131 mg, 0.72 mmol), cesium carbonate (583 mg, 1.79 mmol), tetra-n-butylammonium iodide (132 mg, 0.36 mmol), POPd (18 mg, 0.036 mmol), water (0.3 mL) and N,N-dimethylformamide (1 mL). The reaction mixture was subjected to microwave irradiation at 150° C. for 10 mins. The reaction mixture was purified by HPLC to afford the title compound.