Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:8][N:7]=1.[C:17](Cl)(=[O:19])[CH3:18].C(N(CC)CC)C>O1CCCC1>[C:17]([NH:2][CH2:3][CH2:4][O:5][C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:8][N:7]=1)(=[O:19])[CH3:18]
Reactant: CC(=O)Cl
Reactant: NCCOc1cc(-c2ccccc2)on1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)NCCOc1cc(-c2ccccc2)on1
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 91.6 %

Procedure:
3-(2-Aminoethoxy)-5-phenylisoxazole hydrochloride (240 mg) was suspended in anhydrous tetrahydrofuran (5 ml), and the suspension was cooled to 5° C. Acetyl chloride (94 mg) and triethylamine (243 mg) were added thereto, and the resulting mixture was stirred at the same temperature for 30 minutes. At the end of this time, the reaction mixture was added to ice-cold water (40 ml) and extracted with ethyl acetate (40 ml×2). Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure. The crystals thus obtained were recrystallized from ethyl acetate to obtain the title compound (225 mg, 91%) as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9](Cl)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[CH2:13]([CH2:15][NH2:16])[OH:14]>>[OH:14][CH2:13][CH2:15][NH:16][S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10]
Reactant: NCCO
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Product: COc1ccc(S(=O)(=O)NCCO)cc1

Procedure:
The preparation is carried out as in Example 1(a) from 413.3 g (2 mol) of p-methoxybenzenesulphonyl chloride and 128.3 g (2.1 mol) of ethanolamine. Yield: 439.3 g, i.e. 95%.
Reaction SMILES: FC(F)(F)C(O)=O.[NH2:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C@H:18]1[C@@H:22]2[O:23]C(C)(C)[O:25][C@@H:21]2[C@H:20]([CH2:28][N:29]([CH3:47])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]([CH3:46])([CH3:45])[CH3:44])=[CH:39][CH:38]=2)=[O:35])[CH2:19]1.[ClH:48].CC#N>CO.O>[ClH:48].[NH2:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C@@H:18]1[CH2:19][C@@H:20]([CH2:28][N:29]([CH3:47])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([NH:36][C:37]2[CH:38]=[CH:39][C:40]([C:43]([CH3:45])([CH3:46])[CH3:44])=[CH:41][CH:42]=2)=[O:35])[C@@H:21]([OH:25])[C@H:22]1[OH:23]
Reactant: CN(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)C[C@@H]1C[C@@H](n2cnc3c(N)ncnc32)[C@@H]2OC(C)(C)O[C@H]12
Agent: Cl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: CN(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)C[C@@H]1C[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
Reaction time: 0.08 h
Yield: 43 %

Procedure:
A cooled (ice bath) solution of trifluoroacetic acid (2.9 mL, 38 mmol) in water (0.34 mL, 19 mmol) was added to a flask of 1-(3-((((3aR,4S,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)prop yl)-3-(4-(tert-butyl)phenyl)urea (0.056 g, 0.10 mmol). The reaction mixture was stirred for 5 min and the reaction mixture was then stirred at room temperature for 1.5 hours. The reaction mixture was concentrated in vacuo and taken up in CH2Cl2 (60 mL) and washed with 10% aqueous NH4OH (1×18 mL). The separated aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×18 mL) and the cloudy combined organics (pH>7) were diluted with MeOH (5 mL) to afford a clear solution, which was dried with MgSO4 and concentrated to afford a light tan semi-solid residue. This residue was taken up in 1 ml MeOH and 1N HCl (aq) added (0.1 ml, 0.1 mmol). All volatiles removed in vacuo to yield a tan resin. All efforts to form a solid via lyophilization were unsuccessful so the residue was taken up in 3 mls H2O and 20 mls MeCN added. The resulting cloudy suspension was concentrated to a tan solid which was taken up in MeOH (0.5 ml) and transferred to a vial. N2 passed over the methanolic solution until dryness. The resulting solid was further placed on the lyophilizer at room temperature overnight to obtain 1-(3-((((1S,2R,3S,4R)-4-(6-amino-9H-purin-9-yl)-2,3-dihydroxycyclopentyl)methyl)(methyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea hydrochloride (0.024 g; Yield=43%). MS (ESI+) for C26H38N8O3 m/z 511.5 [M+H]+; MS (ESI−) for C26H38N8O3 m/z 509.6 [M−H]−; HPLC purity>97% (ret. time, 2.936 min). 1H NMR (400 MHz, d4-MeOH) δ 8.44-8.39 (m, 2H), 7.29-7.26 (m, 4H), 5.06-4.99 (m, 1H), 4.64-4.58 (m, 1H), 4.31-4.26 (m, 1H), 3.70-3.63 (m, 1H), 3.53-3.47 (m, 1H), 3.28-3.22 (m, 1H), 3.15-3.10 (m, 2H), 2.99-2.98 (m, 3H), 2.51-2.26 (m, 2H), 2.11-1.99 (m, 2H), 1.30-1.27 (m, 11H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31][CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37]>>[F:1][C:2]1[CH:7]=[C:6]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[S:31][CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1
Reactant: C[Si](C)(C)CCOCSc1ccccc1Br
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)cn3)c(F)c2)OC1(C)C
Product: C[Si](C)(C)CCOCSc1ccccc1-c1ccc(-c2cnc(N)cn2)c(F)c1

Procedure:
The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amine and (2-(((2-bromophenyl)thio)methoxy)ethyl)trimethylsilane. MS (ESI): mass calcd. for C22H26FN3OSSi, 427.16; m/z found, 428.1 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.43-8.36 (m, 1H), 8.07 (d, J=1.5, 1H), 7.89 (m, 1H), 7.73 (dd, J=6.7, 1.4, 1H), 7.40-7.17 (m, 5H), 4.90 (s, 2H), 3.64-3.50 (m, 2H), 0.91-0.78 (m, 2H), 0.04 (s, 9H).
Reaction SMILES: [CH2:1]([C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].OO.[I:18]I>CO>[I:18][C:14]1[CH:15]=[C:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH:10]=[CH:11][C:12]=1[NH2:13]
Reactant: II
Reactant: CCCCCCCCc1ccc(N)cc1
Agent: OO
Solvent: CO
Product: CCCCCCCCc1ccc(N)c(I)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 173.6 %

Procedure:
To a stirred mixture of 4-octyl aniline (0.33 g, 1.6 mmol) and H2O2 (30%, 0.5 ml) in CH3OH (1.5 ml) was added I2 (0.2 g, 0.8 mmol) and the mixture was stirred overnight at room temperature. The solvent was distilled off and the residue was diluted to 10 ml with CH2Cl2, washed with H2O, dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give the title compound (0.46 g, 86%) as yellow paste. 1H NMR (CDCl3) 7.44 (d, 1H, J=1.83 Hz); 6.93 (dd, 1H, J=8.07, 1.86 Hz); 6.65 (d, 1H, J=8.1 Hz); 4.1 (b, 2H); 2.43 (t, 2H, J=7.5 Hz); 1.54-1.49 (m, 2H); 1.26 (b, 10H); 0.87 (t, 3H, J=6.39 Hz).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C=O>[CH2:17]([O:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][CH:3]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: OCCc1ccc(O)cc1
Reactant: BrCc1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OCCc1ccc(OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of 4-hydroxyphenethyl alcohol (33 g, 0.24 mol) in dry dimethylformamide (200 ml), cooled to 0° C., was added potassium tert-butoxide (29 g, 0.26 mol) by portions. After 10 minutes, benzyl bromide (41 g, 0.28 mol) was added slowly. The reaction mixture was stirred for 15 minutes at 0° C., then for 3 hours at room temperature and was quenched with water (200 ml). The precipitate was collected, dried and recrystallized from isopropyl ether/hexanes (34 g).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]2=[N:6][C:7](=[O:9])[N:8]=[C:4]2[CH:3]=1.[OH:12][C:13]1[C:14]([C:23](O)=[O:24])=[CH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2>>[OH:12][C:13]1[C:14]([C:23]([NH:1][C:2]2[CH:11]=[CH:10][C:5]3=[N:6][C:7](=[O:9])[N:8]=[C:4]3[CH:3]=2)=[O:24])=[CH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2
Reactant: O=C(O)c1cc2ccccc2cc1O
Reactant: Nc1ccc2c(c1)=NC(=O)N=2
Product: O=C1N=c2ccc(NC(=O)c3cc4ccccc4cc3O)cc2=N1

Procedure:
The product thus obtained is fit for the preparation of azo pigments of high fastness and according to HPLC contains <0.1% of 5-aminobenzimidazolone and <0.1% of 3-hydroxy-2-naphthoic acid.
Reaction SMILES: [OH-].[Na+:2].[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[C:10]([NH:17][C:18]([C:20]2[CH:21]=[N:22][CH:23]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:25]=2)=[O:19])[CH:9]=1>C(O)C>[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([O-:14])=[O:13])=[C:10]([NH:17][C:18]([C:20]2[CH:21]=[N:22][CH:23]=[C:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:25]=2)=[O:19])[CH:9]=1.[Na+:2]
Reactant: O=C(Nc1cc(-c2ccco2)ccc1C(=O)O)c1cncc(-c2ccccc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(Nc1cc(-c2ccco2)ccc1C(=O)[O-])c1cncc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Ethanol (4.5 mL) and a 2 mol/L aqueous solution of sodium hydroxide (0.085 mL) were added to the obtained 4-(furan-2-yl)-2-(5-phenylpyridine-3-carboxamido)benzoic acid (69 mg), followed by stirring at room temperature for 1 hour and 20 minutes. The solid substance was collected by filtration to obtain 31 mg of sodium 4-(furan-2-yl)-2-(5-phenylpyridine-3-carboxamido)benzoate as a white solid.
Reaction SMILES: [CH3:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][C:20]([F:23])([F:22])[F:21])[CH:10]=[CH:11][CH:12]=2)[N:5]=[C:4]([CH2:24][OH:25])[CH:3]=1.[C:26](N1C=CN=C1)([N:28]1C=CN=[CH:29]1)=[O:27].CN>ClCCl>[CH3:29][NH:28][C:26](=[O:27])[O:25][CH2:24][C:4]1[CH:3]=[C:2]([CH3:1])[N:6]([C:7]2[CH:8]=[C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][C:20]([F:22])([F:23])[F:21])[CH:10]=[CH:11][CH:12]=2)[N:5]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1cc(CO)nn1-c1cccc(-c2ccccc2OC(F)(F)F)c1
Agent: CN
Solvent: ClCCl
Product: CNC(=O)OCc1cc(C)n(-c2cccc(-c3ccccc3OC(F)(F)F)c2)n1
Reaction time: 8 h
Yield: 97 %

Procedure:
To the solution of the alcohol from EXAMPLE 123 (0.050 g, 0.14 mmol) in dry dichloromethane (3 mL) was added 1,1′-carbonyldiimidazole (0.023 g, 0.14 mmol). The reaction solution was stirred at room temperature for one hour before the methylamine was added. The reaction was then stirred at the same temperature for overnight. The reaction was quenched with 10% HCl aqueous, and extracted with dichloromethane (3 times). The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The product was purified via a column chromatography on silica gel. The carbamate was obtained as a white solid, 0.0565 g, 97% yield.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([CH:6](P(OCC)(OCC)=O)[F:7])=[O:5].[Cl:16][C:17]1[C:18]([O:36][CH2:37][CH3:38])=[C:19]([C:32](=O)[CH2:33][CH3:34])[CH:20]=[C:21]2[C:26]=1[O:25][C:24]([CH3:28])([CH3:27])[CH:23]=[C:22]2[CH:29]([CH3:31])[CH3:30]>>[Cl:16][C:17]1[C:18]([O:36][CH2:37][CH3:38])=[C:19](/[C:32](/[CH2:33][CH3:34])=[C:6](/[F:7])\[C:4]([O:3][CH2:2][CH3:1])=[O:5])[CH:20]=[C:21]2[C:26]=1[O:25][C:24]([CH3:28])([CH3:27])[CH:23]=[C:22]2[CH:29]([CH3:30])[CH3:31]
Reactant: CCOc1c(C(=O)CC)cc2c(c1Cl)OC(C)(C)C=C2C(C)C
Reactant: CCOC(=O)C(F)P(=O)(OCC)OCC
Product: CCOC(=O)/C(F)=C(/CC)c1cc2c(c(Cl)c1OCC)OC(C)(C)C=C2C(C)C

Procedure:
Following General Procedure K, triethyl-2-fluoro-2-phosphonoacetate (0.14 mL, 0.67 mmol) and 1-(8-chloro-4-isopropyl-7-ethoxy-2,2-dimethyl-2H-chromen-6-yl)-propan-1-one (Compound 141, 75 mg, 0.23 mmol) were reacted to give the title compound as a yellow oil after purification by flash chromatography (silica gel, 1:9 ethyl acetate/hexane).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[O:17][CH2:16][CH2:15][CH2:14]2)=O.C([SiH](CC)CC)C>C(#N)C.ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[CH2:9][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[O:17][CH2:16][CH2:15][CH2:14]2
Reactant: O=C(c1ccc2c(c1)CCCO2)c1cc(I)ccc1Br
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: CC#N
Product: Brc1ccc(I)cc1Cc1ccc2c(c1)CCCO2
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.5 %

Procedure:
To a stirred solution of (2-bromo-5-iodo-phenyl)-chroman-6-yl-methanone (2.0 g, 4.51 mmol) in acetonitrile:dichloromethane (2:1 mixture, 9 mL) was added triethylsilane (2.52 mL, 15.78 mmol) and boron trifluoride diethyl etherate complex (1.11 mL, 9.02 mmol) at 0° C. After stirring overnight at room temperature, reaction was quenched by the addition of saturated aqueous sodium bicarbonate solution. Volatiles were evaporated under reduced pressure. The aqueous layer was extracted with ethyl acetate (2×20 mL). Ethyl acetate layer was washed with water, brine, dried over sodium sulfate, concentrated and purified by silica gel column chromatography to furnish 6-(2-bromo-5-iodo-benzyl)-chroman (1.5 g).
Reaction SMILES: [C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].O[N:10]1[C:14](=[O:15])[CH2:13][CH2:12][C:11]1=[O:16].C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[C:1]([O:8][N:10]1[C:14](=[O:15])[CH2:13][CH2:12][C:11]1=[O:16])(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=C1CCC(=O)N1O
Reactant: CCCCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: C1CCOC1
Product: CCCCCC(=O)ON1C(=O)CCC1=O
Reaction time: 5 h
Yield: 87.1 %

Procedure:
To a solution of 55.2 g (0.475 mol) of hexanoic acid and 60.161 g (0.523 mol) of N-hydroxy succinimide in 600 mL THF, 107.855 g (0.523 mol) of DCCI was added. The mixture was cooled with an ice-water bath and stirred for 5 h. The dicyclohexyl urea (DCU) precipitate was removed by filtration, and the THF solvent was removed by vacuum rotary evaporation. The yellow oil residue was dissolved again in 600 mL hexane followed by another vacuum filtration to remove the excess dicyclohexyl urea (DCU). The filtrate was then concentrated under vacuum evaporation yield a white solid, which was vacuum dried at ambient temperature to give 88.187 g (87.07%) of N-hexanoyloxy succinimide. IR (KBr): 1816 cm−1 (ν(C═O) of ester), 1745-1786 cm−1 (ν(C═O) of imide). 1H-NMR (DMSO-d6, ppm): 0.86 (3H, —CH3), 1.31 (4H, —(CH2)2CH3), 1.62 (2H, CH2CH2COO—), 2.64 (2H, —CH2COO—), 2.80 (4H, —COCH2CH2CO—).
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16](=[O:29])[C@H:17]([CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)[NH2:18])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:30]12([CH2:40][CH:41]=O)[CH2:39][CH:34]3[CH2:35][CH:36]([CH2:38][CH:32]([CH2:33]3)[CH2:31]1)[CH2:37]2.C(OCC)(=O)C.C(Cl)Cl>C(Cl)Cl>[C:30]12([CH2:40][C@@H:41]3[C:21]4[NH:22][C:23]5[C:28]([C:20]=4[CH2:19][C@@H:17]([C:16]([O:15][CH2:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)=[O:29])[NH:18]3)=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH2:31][CH:32]3[CH2:38][CH:36]([CH2:35][CH:34]([CH2:33]3)[CH2:39]1)[CH2:37]2
Reactant: N[C@@H](Cc1c[nH]c2ccccc12)C(=O)OCc1ccccc1
Reactant: O=CCC12CC3CC(CC(C3)C1)C2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(OCc1ccccc1)[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](CC23CC4CC(CC(C4)C2)C3)N1
Temperature: 25 °C
Reaction time: 7 h

Procedure:
Trifluoroacetic acid (270 μl, 3.5 mmol) was added to a solution of L-tryptophan benzyl ester (10.23 g, 34.8 mmol) and 1-adamantylacetaldehyde (6.2 g, 34.8 mmol) in dry DCM (300 ml) wth 3A molecular sieves (46.5 g) at -10° C. The reaction mixture was allowed to warm to room temperature and stirred for 7 hours. The mixture was cooled to 0° C. trifluoroacetic acid (5.6 ml, 72.7 mmol) added, and stirring continued at room temperature for 16 hours. The reaction mixture was filtered, washed successively with saturated NaHCO3 solution (200 ml), brine (2×200 ml) and dried (MgSO4). Filtration and evaporation of the solvent gave the crude product. The compound was obtained by isolation of the more polar component by flash chromatography on silica gel with ethyl acetate-DCM (1:40) as eluant. (6.2 g, 39%)
Reaction SMILES: [O:1]1[CH2:13][CH:2]1[CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]#[N:12].[NH2:14][CH2:15][CH2:16][NH:17][C:18]([NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[CH:22]=1)=[S:19]>C(O)(C)C>[C:11]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[O:4][CH2:3][CH:2]([OH:1])[CH2:13][NH:14][CH2:15][CH2:16][NH:17][C:18]([NH:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[CH:22]=1)=[S:19])#[N:12]
Reactant: COc1cc(NC(=S)NCCN)cc(OC)c1
Reactant: N#Cc1ccccc1OCC1CO1
Solvent: CC(C)O
Product: COc1cc(NC(=S)NCCNCC(O)COc2ccccc2C#N)cc(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 41.7 %

Procedure:
A solution of 1.28 g (7.3 mmoles) of 2,3-epoxy-1-(2-cyanophenoxy)propane, 7, in 30 ml of isopropyl alcohol (warmed and sonicated) was treated with 1.86 g (7.3 mmoles) of 14 all at once. This was heated under reflux for 2 hours and stirred overnight at room temperature. After this, a small amount of solid (860 mg) was removed and the solution was concentrated to 2.3 g of semi-solid gum. This was chromatographed over 150 g of silica gel 60 using 10% (v/v) CH3OH/CHCl3 saturated with NH3. Three fractions of 150 ml each were taken after an 800-ml forerun. The third fraction provided 1.31 g of a white foam. This was chromatographed again, taking 10-ml fractions. Cuts 17, 18 and 19 provided 80 mg (2.5%) of 15, m.p., 45°-55° C. Mass spectrum, m/e 430 (M+), base peak, m/e 195. Liquid chromatography showed 93.6% purity.
Reaction SMILES: [C:1]1([OH:11])[C:10]2[CH2:9][CH:8]=[CH:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.ClC1C=CC=C(C(OO)=[O:20])C=1.C(OCC)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O1CCCC1>[O:20]1[CH:8]2[CH:7]1[CH2:6][C:5]1[CH:4]=[CH:3][CH:2]=[C:1]([OH:11])[C:10]=1[CH2:9]2
Reactant: Oc1cccc2c1CC=CC2
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Oc1cccc2c1CC1OC1C2

Procedure:
Alternatively, the 2,3-trans-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(alkylamino)propoxy]-2,3-naphthalenediol of formula II can be prepared from a 5,8-dihydro-1-naphthol of formula IX by mixing a cooled solution (temperature less than about 30° C.) of 5,8-dihydro-1-naphthol in ethyl acetate with m-chloroperbenzoic acid and mixing the resulting slurry with a mixture of ethyl ether and aqueous sodium bicarbonate, to form a 5,6,7,8-tetrahydro-6,7-epoxy-1-naphthol having the formula ##STR17## A 5,6,7,8-tetrahydro-6,7-epoxy-1-naphthol of formula XVI in tetrahydrofuran can be reacted with aqueous perchloric acid at a temperature within the range of from about 0° to about 60° C., to form a trans-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol or formula XI which can be converted to the corresponding 2,3-trans-1,2,3,4-tetrahydro-5-[2,3-(epoxy)propoxy]-2,3-naphthanediol of formula XII, which in turn can be converted to the corresponding 2,3-trans-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(alkylamino)propoxy]-2,3-naphthalenediol of formula II using the procedures described above.
Reaction SMILES: [CH3:1][CH2:2][CH:3](P(OCC)(OCC)=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:17][C:18]1[CH2:23][CH2:22][CH2:21][C:20]([CH3:25])([CH3:24])[C:19]=1/[CH:26]=[CH:27]/[C:28](/[CH3:37])=[CH:29]/[CH:30]=[CH:31]/[C:32](/[CH3:36])=[CH:33]/[CH:34]=O>>[CH3:36][C:32]([CH:31]=[CH:30][CH:29]=[C:28]([CH3:37])[CH:27]=[CH:26][C:19]1[C:20]([CH3:25])([CH3:24])[CH2:21][CH2:22][CH2:23][C:18]=1[CH3:17])=[CH:33][CH:34]=[C:3]([CH2:2][CH3:1])[C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)C(CC)P(=O)(OCC)OCC
Reactant: CC1=C(/C=C/C(C)=C/C=C/C(C)=C/C=O)C(C)(C)CCC1
Product: CCOC(=O)C(=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C)CC

Procedure:
In analogy to the procedure given in Example 1: Triethyl 2-phosphonobutyrate was reacted with retinal to give ethyl 5,9-dimethyl-2-ethyl-11-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8,10-undecapentaenoate, which was converted by the procedure of Example 2 to 5,9-dimethyl-2-ethyl-11(2,6,6-trimethyl -1-cyclohexen-1-yl)-2,4,6,8,10-undecapentaenoic acid, m.p.=164°-165° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH2:31][CH2:32][CH2:33][CH2:34][S:35]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)(=[O:37])=[O:36]>>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH2:31][CH2:32][CH2:33][CH2:34][S:35]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)(=[O:36])=[O:37])[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(=O)(CCCCI)Cc1ccccc1
Reactant: C[Si](C)(C)CCN1C(=O)CN(c2ccc(I)cc2OCc2ccccc2)S1(=O)=O
Product: C[Si](C)(C)CCN1C(=O)CN(c2ccc(CCCCS(=O)(=O)Cc3ccccc3)cc2OCc2ccccc2)S1(=O)=O

Procedure:
The title compound is prepared from 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one and (4-iodobutane-1-sulfonylmethyl)-benzene analogous to Example 571 step B.
Reaction SMILES: [Cl:1][C:2]1[N:6]([C@@H:7]2[O:27][C@H:26]([CH2:28][O:29]CC3C=CC=CC=3)[C@@H:17]([O:18]CC3C=CC=CC=3)[C@@H:8]2[O:9]CC2C=CC=CC=2)[C:5]2[CH:37]=[C:38]([Cl:42])[C:39]([Cl:41])=[CH:40][C:4]=2[N:3]=1.B(Cl)(Cl)Cl.CO.[NH4+].[OH-]>C(Cl)Cl>[Cl:1][C:2]1[N:6]([C@@H:7]2[O:27][C@H:26]([CH2:28][OH:29])[C@@H:17]([OH:18])[C@@H:8]2[OH:9])[C:5]2[CH:37]=[C:38]([Cl:42])[C:39]([Cl:41])=[CH:40][C:4]=2[N:3]=1
Reactant: Clc1cc2nc(Cl)n([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@@H]3OCc3ccccc3)c2cc1Cl
Agent: ClB(Cl)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: OC[C@H]1O[C@@H](n2c(Cl)nc3cc(Cl)c(Cl)cc32)[C@@H](O)[C@@H]1O
Reaction time: 4.5 h

Procedure:
Compound 133 (1.25 g 2 mmole) was dissolved in dry CH2Cl2 (20 ml) and this solution was cooled in an acetone-dry ice bath. A 1M solution of BCl3 in CH2Cl2 (10 ml) was added and the mixture was stirred at -70° for 4.5 hr. At this point TLC showed no starting material. CH3OH (10 ml) was added and the solution was made neutral with NH4OH. The solution was evaporated in vacuo to dryness. H2O (20 ml) was added and the solution was extracted with EtOAc. The EtOAc layer was washed with H2O, dried (Na2SO4) and evaporated in vacuo to obtain a syrup. This syrup was subjected to flash column chromatography on silica gel (Kieselgel 60, 230-400 mesh) with CH2 Cl-MeOH (20:1) as eluent solvent to give 134. Yield 0.551 g, 77.9%.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[CH:8]=[N:7]2.[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=2)[CH2:16][CH2:15]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:23]1[CH:22]=[CH:21][C:20]([N:17]3[CH2:18][CH2:19][N:14]([CH3:13])[CH2:15][CH2:16]3)=[CH:25][CH:24]=1)[CH:8]=[N:7]2
Reactant: CN1CCN(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: Clc1cnc2cccc(Br)c2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Product: CN1CCN(c2ccc(-c3cnc4cccc(Br)c4n3)cc2)CC1
Temperature: 105 °C

Procedure:
A microwave tube is charged with 8-Bromo-2-chloro-quinoxaline (Step 1.4, 2.5 g, 10.267 mmol), 1-Methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-piperazine (2.88 g, 9.24 mmol), K3PO4 (6.67 g, 30.8 mmol) and PdCl2(PPh3)2 (221 mg, 0.308 mmol). After several cycles of vacuum/purge with argon, a mixture of 21 ml of DMA and 560 μl deionized water is added. The reaction mixture is then heated to 105° C. for 4 h. After cooling, the suspension is poured onto de-ionized water and diluted with EtOAc. The phases are separated and the aqueous phase re-extracted twice with EtOAc. The combined organic phases are washed with saturated brine and dried over Na2SO4. After filtration, the mixture is concentrated in vacuo. The residue is purified by chromatography (silicagel, CH2Cl2:EtOH:NH3 95:4.5:0.5 from 1:0=>0:1) to afford the title compound as a yellow orange solid, Rt=0.930 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 383 (M+1, 79Br)+.