Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=1.[H-].[Na+].F[C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([N+:31]([O-:33])=[O:32])=[CH:23][CH:22]=1.O>C1COCC1.CCOC(C)=O>[N+:31]([C:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21]([O:1][CH2:2][CH2:3][C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH:5]=2)=[CH:22][CH:23]=1)([O-:33])=[O:32]
Reactant: O=[N+]([O-])c1ccc(F)c2ccccc12
Reactant: CC(C)(C)OC(=O)Nc1cc(CCO)ccn1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1cc(CCOc2ccc([N+](=O)[O-])c3ccccc23)ccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 106.6 %

Procedure:
To a solution of tert-butyl 4-(2-hydroxyethyl)pyridin-2-ylcarbamate (11) (6.00 g, 25.2 mmol) in THF (70 mL) was added sodium hydride (2.52 g, 63.0 mmol, 60 wt %) at 0° C. The bright yellow suspension was stirred for 20 min at 0° C. before the addition of 1-fluoro-4-nitronaphthalene (4.81 g, 25.2 mmol) in a single portion. After stirring at RT for 2 hr, water (100 mL) was added followed by EtOAc (100 mL). The solid formed between the layers was collected by filtration and the organic phase was washed with saturated aq NaHCO3 (100 mL), brine (100 mL) and dried. The volatiles were removed to give an orange solid. The solids were combined and triturated from MeOH (50 mL) to give tert-butyl 4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate (12) as a yellow solid (11.0 g, 98%): m/z 410 (M+H)+ (ES+).
Reaction SMILES: [C:1]1([CH:7]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][Cl:18])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:20]=O>C1C=CC=CC=1>[C:1]1([CH:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:14]2[CH2:15][CH:16]([CH2:17][Cl:18])[O:19][CH2:20]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OC(CCl)CNC(c1ccccc1)c1ccccc1
Reactant: C=O
Solvent: c1ccccc1
Product: ClCC1CN(C(c2ccccc2)c2ccccc2)CO1

Procedure:
A mixture of 27.6 g of 1-diphenylmethylamino-2-hydroxy-3-chloropropane, 10 ml of a 37% strength solution of formaldehyde and 200 ml of benzene is heated to the reflux temperature, while continuously separating off water. The mixture is then evaporated in vacuo and 3-diphenylmethyl-5-chloromethyloxazolidine is obtained as a yellowish oil which, without purification, is heated together with the reacton solution obtained according to Example 43 from 2.3 g of sodium, 100 ml of ethanol and 17.8 g of 4-trans-propenylguaethol, to 100° in an autoclave for 12 hours. After cooling, the sodium chloride which has precipitated is filtered off. 50 ml of 4 N hydrochloric acid are added to the resulting alcoholic solution of 3-diphenylmethyl-5-(2-ethoxy-5-trans-propenyl-phenoxymethyl)-oxazolidine and the mixture is left to stand for 4 hours at room temperature.
Reaction SMILES: [C:1]([C:9]1[N:10]([CH2:24][CH2:25][O:26]CC2C=CC=CC=2)[CH:11]=[CH:12][C:13](=[O:23])[C:14]=1[O:15]CC1C=CC=CC=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CO>[C:1]([C:9]1[N:10]([CH2:24][CH2:25][OH:26])[CH:11]=[CH:12][C:13](=[O:23])[C:14]=1[OH:15])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1ccccc1)c1c(OCc2ccccc2)c(=O)ccn1CCOCc1ccccc1
Solvent: CO
Product: O=C(c1ccccc1)c1c(O)c(=O)ccn1CCO

Procedure:
At room temperature and under normal pressure, 0.95 g of 2-benzoyl-3-benzyloxy-1-(2-benzyloxy-ethyl)-1H-pyridin-4-one is hydrogenated in methanol until 2 mol of H2 per mol of starting material have been taken up. The catalyst is removed and the reaction mixture is concentrated by evaporation using a rotary evaporator. The residue is chromatographed on 20 g of silica gel. A mixture of ethyl acetate and ethanol in a ratio of 95:5 is used as eluant. With fraction sizes of 17 ml, the product in fractions 6-20 is eluted. Recrystallisation from ethanol yields 2-benzoyl-3-hydroxy-1-(2-hydroxy-ethyl)-1H-pyridin-4-one in the form of colourless crystals. M.p.: 195°-200° C.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2[Br:25])[C:21](=[O:26])[N:20](CC2C=CC(OC)=CC=2)[CH:19]=[CH:18]3)[CH2:10][CH2:9]1)=O)(C)(C)C>FC(F)(F)C(O)=O>[Br:25][C:24]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][NH:20][C:21]2=[O:26])=[CH:16][C:15]=1[O:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: COc1ccc(Cn2ccc3cc(OC4CCN(C(=O)OC(C)(C)C)CC4)c(Br)cc3c2=O)cc1
Solvent: O=C(O)C(F)(F)F
Product: O=c1[nH]ccc2cc(OC3CCNCC3)c(Br)cc12
Temperature: 140 °C
Reaction time: 2 h

Procedure:
182 mg 4-[7-bromo-2-(4-methoxy-benzyl)-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (314) were dissolved in 5 mL of trifluoroacetic acid. After 2 h at room temperature, the mixture was heated at 140° C. in a microwave for 2 h. The solvent was removed i. vac. and the residue was dissolved 2 N HCl. The aqueous solution was washed twice with dichloromethane and the organic layers were extracted with 2 N HCl. The combined aqueous solutions were evaporated i. vac. and the residue was dissolved in water. After lyophilization the title compound was isolated as HCl-salt. Rt=0.80 min (Method B). Detected mass: 323.1/325.1 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:12])[CH:5]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:7]=1.[Br:13][CH2:14][CH2:15]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:13][CH2:14][CH2:15][O:12][C:4]1[CH:5]=[C:6]([S:8]([CH3:11])(=[O:9])=[O:10])[CH:7]=[C:2]([Cl:1])[CH:3]=1
Reactant: CS(=O)(=O)c1cc(O)cc(Cl)c1
Reactant: BrCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CS(=O)(=O)c1cc(Cl)cc(OCCBr)c1

Procedure:
Preparation according to Preparation 2: 3-chloro-5-methylsulfonyl-phenol (2.8 g, 13.5 mmol), 1,2-dibromoethane (12 ml, 135 mmol), potassium carbonate (3.7 g, 27.1 mmol), acetonitrile (15 ml) Yield: 2.1 g, 50%). MS m/z (relative intensity, 70 eV 314 (M+, 35), 312 (M+, 25), 206 (7), 126 (9), 109 (98), 107 (bp).
Reaction SMILES: C(Cl)(=O)C(C)(C)C.[C:8]([OH:14])(=O)[CH2:9][CH2:10][CH:11]=[CH2:12].CN1CCOCC1.C([Li])CCC.CCCCCC.[CH3:33][CH:34]([C@H:36]1[CH2:40][O:39][C:38](=[O:41])[NH:37]1)[CH3:35].[NH4+].[Cl-]>C1COCC1.O>[CH3:33][CH:34]([C@H:36]1[CH2:40][O:39][C:38](=[O:41])[N:37]1[C:8](=[O:14])[CH2:9][CH2:10][CH:11]=[CH2:12])[CH3:35]
Reactant: C=CCCC(=O)O
Reactant: CC(C)[C@H]1COC(=O)N1
Agent: CC(C)(C)C(=O)Cl
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: C=CCCC(=O)N1C(=O)OC[C@@H]1C(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of mixed anhydride was prepared by adding under a N2 atmosphere pivaloyl chloride (14.8 mL, 120 mmol) over a period of 5 min to a cooled solution (0°) of 4-pentenoic acid (12.3 mL, 120 mmol) and N-methylmorpholine (15.4 mL, 140 mmol). The mixture was stirred at 0° for 30 min. Meanwhile, a second solution was prepared by adding dropwise under a N2 atmosphere a 1.4M solution of butyllithium in hexane (71 mL, 100 mmol) to a stirred cooled solution (-78°) of (S)-4-(1-methylethyl)-2-oxazolidinone [12.9 g, 100 mmol, described by L. N. Pridgen et al., J. Org. Chem., 54, 3231 (1989)] in dry THF (300 mL) over a period of 45 min. (Note: The agitation was done by an overhead stirrer.) After stirring for 15 min at -78°, the latter solution was added by cannulation to the stirred solution of the mixed anhydride at -78° over a period of 20 min. The mixture was stirred for an additional 30 min at the same temperature. A saturated aqueous solution of NH4Cl (50 mL) was added and the mixture was allowed to warm to room temperature. The mixture was diluted with H2O (300 mL). The organic layer was separated. The aqueous layer was extracted with EtOAc (3×). The combined organic phases were dried (Na2SO4) and evaporated to dryness under reduced pressure to give an oily residue [i.e. 4(S)-(1-methylethyl)-3-(1-oxo-4-pentenyl)-2-oxazolidinone].
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][C:2]1=2.[F:12][C:13]1[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:14]=1[NH2:15]>CC(C)=O>[F:12][C:13]1[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:14]=1[NH:15][C:4](=[O:5])[C:3]1[CH2:7][CH2:8][CH2:9][CH2:10][C:2]=1[C:1]([OH:6])=[O:11]
Reactant: O=C1OC(=O)C2=C1CCCC2
Reactant: Nc1ccc(Br)cc1F
Solvent: CC(C)=O
Product: O=C(O)C1=C(C(=O)Nc2ccc(Br)cc2F)CCCC1
Reaction time: 2 h

Procedure:
3,4,5,6-tetrahydrophthalic anhydride (16.0 g) and 2-fluoro-4-bromoaniline (20.0 g) were added to acetone (100 ml) and, after stirring at 40°-45° C. for 2 hours, the mixture was concentrated to dryness under reduced pressure. The resultant crystals were washed with n-hexane. Yield 30.3 g.; m.p. 98°-99° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)=[CH:4][CH:3]=1.Cl.[C:33]1([N:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)N)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:39]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:33]3[C:34]([C:9]=2[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=4)[CH2:15][CH2:14]2)=[CH:35][CH:36]=[CH:37][CH:38]=3)=[CH:4][CH:3]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccc(Br)cc3)CC2)c1
Reactant: NN(c1ccccc1)c1ccccc1
Agent: Cl
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4ccc(Br)cc4)n(-c4ccccc4)c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(4-bromophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 1,1-diphenylhydrazine hydrochloride: ESMS m/e: 634.0 (M+H)+.
Reaction SMILES: C1(N2C(=O)C3=CNC4C=[CH:15][C:16]([N:19]5[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]5)=NC=4C3=N2)C=CC=CC=1.F[C:28]1[CH:37]=[CH:36][C:35]2[NH:34][CH:33]=[C:32]3[C:38](=[O:47])[N:39]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=4)[N:40]=[C:31]3[C:30]=2[N:29]=1.CN1CCCNCC1.N1CCNCC1>>[CH3:24][N:19]1[CH2:16][CH2:15][CH2:23][N:22]([C:28]2[CH:37]=[CH:36][C:35]3[NH:34][CH:33]=[C:32]4[C:38](=[O:47])[N:39]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=5)[N:40]=[C:31]4[C:30]=3[N:29]=2)[CH2:21][CH2:20]1
Reactant: O=c1c2c[nH]c3ccc(F)nc3c-2nn1-c1ccccn1
Reactant: O=c1c2c[nH]c3ccc(N4CCNCC4)nc3c-2nn1-c1ccccc1
Agent: C1CNCCN1
Agent: CN1CCCNCC1
Product: CN1CCCN(c2ccc3[nH]cc4c(=O)n(-c5ccccn5)nc-4c3n2)CC1

Procedure:
The title compound was prepared following the procedure described for 6a using 5b and 4-methyl-[1,4]-diazepane instead of 5a and piperazine respectively. 1H-NMR (DMSO-d6) δ (ppm): 2.04 (2H, m), 2.35 (3H, s), 2.60 (2H, m), 2.76 (2H, m), 3.76 (2H, d, J=6.32 Hz), 3.98 (2H, t, J=4.67 Hz), 6.96 (1H, d, J=9.36 Hz), 7.25 (1H, ddd, J=7.14, 4.55, 0.82 Hz), 7.82 (1H, d, J=9.34 Hz), 7.92 (1H, m), 8.30 (1H, dt, J=8.24, 0.82 Hz), 8.49 (1H, m), 8.52 (1H, s). m/z 376.4 (MH+).
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([S:18]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)(=[O:20])=[O:19])[CH2:14][C@@H:13]2[CH2:26][NH:27][CH:28]([CH3:30])[CH3:29])=[CH:8][CH:7]=1)([OH:5])[CH3:4].[C:33]1([S:39](Cl)(=[O:41])=[O:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:30][CH:28]([N:27]([CH2:26][C@H:13]1[CH2:14][N:15]([S:18]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)(=[O:20])=[O:19])[CH2:16][CH2:17][N:12]1[C:9]1[CH:8]=[CH:7][C:6]([C:3]([OH:5])([CH3:4])[C:2]([F:1])([F:31])[F:32])=[CH:11][CH:10]=1)[S:39]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=[O:41])=[O:40])[CH3:29]
Reactant: CC(C)NC[C@H]1CN(S(=O)(=O)c2cccs2)CCN1c1ccc(C(C)(O)C(F)(F)F)cc1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)N(C[C@H]1CN(S(=O)(=O)c2cccs2)CCN1c1ccc(C(C)(O)C(F)(F)F)cc1)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.3 %

Procedure:
To a solution of 1,1,1-trifluoro-2-(4-((2S)-2-(((1-methylethyl)amino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.150 g, 0.305 mmol, Example 195, Step 1) in CH2Cl2 (5.0 mL) was added 4-dimethylaminopyridine (0.0075 g, 0.061 mmol), benzenesulfonyl chloride (0.108 g, 0.610 mmol), and Hünig's base (0.159 mL, 0.915 mmol). The resulting mixture was stirred at room temperature. After 2 h, the mixture was concentrated and the crude product was purified by column chromatography (40 g of silica, 10 to 40% acetone in hexanes) to give N-(1-methylethyl)-N-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)benzenesulfonamide (0.176 g) as a mixture of two isomers.
Reaction SMILES: [F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([Sn](C)(C)C)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.Br[C:24]1[C:25]([N:44]2[CH2:48][CH2:47][CH2:46][C:45]2=[O:49])=[CH:26][C:27]2[O:31][C:30]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)=[C:29]([C:39]([NH:41][CH3:42])=[O:40])[C:28]=2[CH:43]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:24]5[C:25]([N:44]6[CH2:48][CH2:47][CH2:46][C:45]6=[O:49])=[CH:26][C:27]6[O:31][C:30]([C:32]7[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=7)=[C:29]([C:39]([NH:41][CH3:42])=[O:40])[C:28]=6[CH:43]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N3CCCC3=O)c(Br)cc12
Reactant: C[Sn](C)(C)c1ccc2c(n1)-c1cc3c(F)cccc3n1CO2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N3CCCC3=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CO4)cc12
Temperature: 100 °C
Reaction time: 8 h
Yield: 30.8 %

Procedure:
To a solution of 11-fluoro-2-(trimethylstannyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (60 mg, 0.14 mmol), 5-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide (50 mg, 0.11 mmol) in DMF (4 mL), Pd(PPh3)4 was added. The reaction mixture was stirred at 100° C. overnight. The reaction mixture was filtered through a Celit pad. The filtrate was concentrated in vacuo. The resulting residue was suspended in water, extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-HPLC to provide 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide (20 mg, yield: 29.2%). 1H-NMR (CDCl3, 400 MHz) δ 7.97 (s, 1H), 7.89˜7.93 (m, 2H), 7.44 (s, 1H), 7.40˜7.42 (m, 2H), 7.11˜7.19 (m, 4H), 7.05 (d, J=8.8 Hz, 1H), 6.77˜6.82 (m, 1H), 5.92 (s, 2H), 5.85 (br s, 1H), 3.83 (t, J=7.2 Hz, 2H), 2.95 (d, J=4.8 Hz, 3H), 2.26 (t, J=8.4 Hz, 2H), 2.00˜2.06 (m, 2H). MS (M+H)+: 591.
Reaction SMILES: [O:1]1CCO[CH:2]1[CH2:6][N:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:15]=2)[C:10]([CH3:23])=[CH:9][C:8]1=[O:24].FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[CH3:23][C:10]1[C:11]2[C:16](=[CH:15][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[N:7]([CH2:6][CH:2]=[O:1])[C:8](=[O:24])[CH:9]=1
Reactant: Cc1cc(=O)n(CC2OCCO2)c2cc(-c3ccccc3)ccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(=O)n(CC=O)c2cc(-c3ccccc3)ccc12
Temperature: 25 °C

Procedure:
, To 94 mg of 1-(1,3-dioxolan-2-ylmethyl)-4-methyl-7-phenylquinolin-2(1H)-one, 3 mL of 80% aqueous trifluoroacetic acid solution was added, and stirred at room temperature for 5 and half hours, thereafter ethyl acetate and aqueous saturated sodium hydrogen carbonate solution were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and extracts were combined, washed sequentially with water and aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give (4-methyl-2-oxo-7-phenyl-1,2-dihydroquinolin-1-yl)acetaldehyde as a pale brown oil.
Reaction SMILES: [C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH2:7][OH:8])=[CH:3][CH:2]=1.CN(CCN(C)C)C.C([Li])CCC.C([Cu])#N.[CH:31](N1CCCCC1)=[O:32]>CCOCC>[OH:8][CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][C:5]=1[CH:31]=[O:32]
Reactant: OCc1ccc(-c2ccccc2)cc1
Reactant: O=CN1CCCCC1
Agent: N#C[Cu]
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: CCOCC
Product: O=Cc1cc(-c2ccccc2)ccc1CO
Temperature: -60 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-biphenylmethanol (0.368 g, 2 mmol) in ether (25 mL) and TMEDA (1.21 mL, 8 mmol), at 0° C. was added n-butyllithium (2.5N hexanes; 3.2 mL, 8 mmol). The solution was then heated at reflux for 1 h, cooled to -60° C. and CuCN (0.2 g, 2.2 mmol) added. After 30 minutes, the solution was cooled to -78° C. and N-formylpiperidine (1.11 mL, 10 mmol) was then added dropwise and stirring was continued for 1 h. The mixture was then warmed to -10° C., quenched with saturated NH4Cl, extracted with ether washed with brine, dried and the solvent removed in vacuo. Chromatography of the residue (silica gel; hexane:EtOAc 4:1) afforded the title compound as a colorless oil.
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([NH2:50])[CH:46]([O:51]C)[CH2:45]2)[CH:7]([CH3:54])[CH2:6][CH2:5][C:4]1=[O:55])[CH3:2].[CH2:56]1[O:59][CH:57]1[CH3:58].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([NH:50][CH2:56][CH:57]([OH:59])[CH3:58])[CH:46]([OH:51])[CH2:45]2)[CH:7]([CH3:54])[CH2:6][CH2:5][C:4]1=[O:55])[CH3:2]
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(N)C(OC)C3)C(C)CCC1=O)C(C)CC2OC
Reactant: CC1CO1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(NCC(C)O)C(O)C3)C(C)CCC1=O)C(C)CC2OC
Reaction time: 20 h

Procedure:
To a solution of 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (52 mg, Example 13) in dry methanol (1 ml) was added a large excess of propylene oxide (200 μl) followed by a catalytic amount of p-toluenesulfonic acid at room temperature. After stirring at this temperature for 20 h, the solution was concentrated and purified by preparative tlc on silica gel (1% NH4OH in 5% i-PrOH/CH2Cl2) to give 35 mg of the title compound.
Reaction SMILES: [C:1]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)(=[O:4])[CH:2]=[CH2:3].[C:20]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44](O)=[O:45])=[CH:40][CH:39]=2)=[CH:34][C:33]=1[O:47][CH3:48])(=[O:23])[CH:21]=[CH2:22].C(Cl)CCl>CN(C1C=CN=CC=1)C>[C:1]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:44]([C:41]2[CH:40]=[CH:39][C:38]([C:35]3[CH:36]=[CH:37][C:32]([O:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][O:24][C:20](=[O:23])[CH:21]=[CH2:22])=[C:33]([O:47][CH3:48])[CH:34]=3)=[CH:43][CH:42]=2)=[O:45])=[CH:14][CH:13]=1)=[O:19])(=[O:4])[CH:2]=[CH2:3]
Reactant: C=CC(=O)OCCCCCCOc1ccc(-c2ccc(C(=O)O)cc2)cc1OC
Reactant: C=CC(=O)OCCCCOC(=O)c1ccc(O)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Product: C=CC(=O)OCCCCCCOc1ccc(-c2ccc(C(=O)Oc3ccc(C(=O)OCCCCOC(=O)C=C)cc3)cc2)cc1OC

Procedure:
The preparation is analogous to Example 1 from 2.64 g (10 mmol) of 4-hydroxybenzoic acid 4-acryloyloxybutyl ester, 3.99 g (10 mmol) of 4′-(6-acryloyloxyhexyloxy)-3′-methoxybiphenyl-4-carboxylic acid, 0.12 g (1 mmol) of DMAP and 2.11 g (11 mmol) of EDC. Purification of the residue by chromatography on silica gel using cyclohexane/ethyl acetate (7:3) and recrystallisation once from ethanol yields 4′-(6-acryloyloxyhexyloxy)-3′-methoxybiphenyl-4-carboxylic acid 4-(4-acryloyloxybutoxycarbonyl)-phenyl ester.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:14])([CH3:13])[CH2:10][C:11]#[N:12])=[CH:5][CH:4]=1.C(C1(C2C=CC(OC)=C(C=2)[CH:25]=[O:26])CC1)#N>>[C:11]([CH2:10][C:9]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[C:8]([CH:7]=1)[CH:25]=[O:26])([CH3:14])[CH3:13])#[N:12]
Reactant: COc1ccc(C2(C#N)CC2)cc1C=O
Reactant: COc1ccc(C(C)(C)CC#N)cc1
Product: COc1ccc(C(C)(C)CC#N)cc1C=O

Procedure:
This compound was prepared from Compound 46 in the same manner of Compound 2.
Reaction SMILES: [CH2:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([CH2:16][CH2:17]OS(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[CH2:4][CH:3]=[CH:2]1.O.[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH2:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([CH2:16][CH2:17][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[C:5]=2[CH2:4][CH:3]=[CH:2]1
Reactant: C1CCNC1
Reactant: Cc1ccc(S(=O)(=O)OCCC2C3=C(CC=CC3)CCc3ccccc32)cc1
Solvent: O
Product: C1=CCC2=C(C1)CCc1ccccc1C2CCN1CCCC1
Temperature: 25 °C
Reaction time: 21 h

Procedure:
A suspension of 59.8 g of 2-(4,5,10,11-tetrahydro-1H-dibenzo[a,d]cyclohepten-5-yl)ethyl-p-toluenesulfonate in 180 ml of pyrrolidine is stirred under argon at room temperature for 21 hours, subsequently poured into a mixture of ice and 300 ml of water and extracted twice with 1.2 l of distilled ether each time. The organic extracts are washed twice with 400 ml of water each time and a small amount of ice, combined, dried over magnesium sulfate and evaporated. The residue is taken up twice in 100 ml of dry toluene each time and the solutions obtained are in each case evaporated to dryness. There is obtained 1-[2-(4,5,10,11-tetrahydro-1H-dibenzo[a,d]cyclohepten-5-yl)ethyl]pyrrolidine in the form of an oil which crystallizes upon standing; m.p. 56°-57°. By recrystallization from pentane there is obtained product of melting point 62°.