Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[N:25]1([CH:32]=[O:33])[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>CN(C=O)C.CS(C)=O.CO>[CH:32]([N:25]1[CH2:31][CH2:30][CH2:29][N:28]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:27][CH2:26]1)=[O:33]
Reactant: Cc1cc2nc(NC(=O)c3ccc(C(C)(C)O)cc3)cc(Cl)n2n1
Reactant: O=CN1CCCNCC1
Solvent: CO
Solvent: CN(C)C=O
Solvent: CS(C)=O
Product: Cc1cc2nc(NC(=O)c3ccc(C(C)(C)O)cc3)cc(N3CCCN(C=O)CC3)n2n1
Temperature: 25 °C
Yield: 77.3 %

Procedure:
A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 86 mg, 0.25 mmol) and 1,4-diazepane-1-carbaldehyde (97 mg, 0.75 mmol) in DMF (1.0 mL) was stirred at 100° C. for 2 h. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC (25-35% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (84.4 mg, 77%). 1H NMR (DMSO-d6) δ: 10.86 (s, 1H), [1:1 ratio of rotamers: 8.09 (s, 1H); 7.93 (s, 1H)], 7.98 (d, J=8.3 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.14 (d, J=2.8 Hz, 1H), 6.16 (s, 1H), 4.25-4.39 (m, 3H), 3.55-3.71 (m, 4H), 3.46-3.54 (m, 1H), 2.37 (s, 3H), 1.97-2.09 (m, 1H), 1.86-1.97 (m, 1H), 1.45 (s, 6H); ESI-MS: m/z 437.3 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:25]([C:27]5[N:28]([CH3:32])[CH:29]=[CH:30][N:31]=5)=[O:26])[C:19]=4[CH3:33])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[N:34]([CH:37]([CH3:39])[CH3:38])=[C:35]=[O:36]>ClCCCl>[CH:37]([NH:34][C:35](=[O:36])[NH:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:25]([C:27]5[N:28]([CH3:32])[CH:29]=[CH:30][N:31]=5)=[O:26])[C:19]=4[CH3:33])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1)([CH3:39])[CH3:38]
Reactant: Cc1c(NC(=O)c2nccn2C)cccc1-c1ccc(C(N)=O)c2[nH]c3cc(N)ccc3c12
Reactant: CC(C)N=C=O
Solvent: ClCCCl
Product: Cc1c(NC(=O)c2nccn2C)cccc1-c1ccc(C(N)=O)c2[nH]c3cc(NC(=O)NC(C)C)ccc3c12
Temperature: 40 °C
Reaction time: 2 h
Yield: 43.4 %

Procedure:
A solution of 7-amino-4-(2-methyl-3-(1-methyl-1H-imidazole-2-carboxamido)phenyl)-9H-carbazole-1-carboxamide (Example 54-15, 29 mg, 0.066 mmol) and 2-isocyanatopropane (0.019 mL, 0.198 mmol) in 1,2-dichloroethane (3 mL) was stirred at rt for 2.5 h, then at 50° C. for 2 h. Additional 2-isocyanatopropane was added and the mixture was stirred at 40° C. for 16 h. The mixture was concentrated and purified by HPLC. The appropriate effluent fractions were partially concentrated, treated with NaHCO3 (aq) and extracted with EtOAc. The organic phase was dried and concentrated to provide 7-(3-isopropylureido)-4-(2-methyl-3-(1-methyl-1H-imidazole-2-carboxamido)phenyl)-9H-carbazole-1-carboxamide as a pale pink solid (15 mg, 43%). 1H NMR (400 MHz, DMSO-d6) δ 11.32 (1H, s), 9.97 (1H, s), 8.37 (1H, s), 8.13 (1H, br. s.), 7.88 (1H, d, J=7.9 Hz), 7.81 (1H, d, J=1.8 Hz), 7.76 (1H, d, J=7.9 Hz), 7.40-7.48 (2H, m), 7.38 (1H, t, J=7.7 Hz), 7.13 (1H, d, J=7.5 Hz), 7.06 (1H, s), 6.82-6.92 (2H, m), 6.73 (1H, d, J=8.3 Hz), 5.98 (1H, d, J=7.5 Hz), 4.01 (3H, s), 3.68-3.81 (1H, m), 1.89-1.95 (3H, m), 1.07 (6H, d). Mass spectrum m/z 524.3 (M+H)+.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[C:6]([OH:10])(=[O:9])C=C.B.O1CC[CH2:14][CH2:13]1>C(OC(C)C)(C)C.O1CCCC1>[CH:5]12[O:1][CH:2]([CH:13]=[CH:14]1)[CH2:3][CH:4]2[C:6]([OH:10])=[O:9]
Reactant: C=CC(=O)O
Reactant: C1CCOC1
Reactant: c1ccoc1
Agent: B
Solvent: CC(C)OC(C)C
Product: O=C(O)C1CC2C=CC1O2
Temperature: 2 °C
Reaction time: 4 h
Yield: 58 %

Procedure:
The inside of a three-neck flask (inside volume 500 ml) equipped with a thermometer and a mechanical stirrer was substituted with nitrogen, and distilled furan (136 g, 2.0 mol), acrylic acid (72 g, 1.0 mol) and diisopropyl ether (70 ml) as a solvent were charged therein. The mixture was cooled to an inner temperature of 2° C. To this mixed solution was added dropwise a solution (11 ml, 0.01 mol) of a borane-tetrahydrofuran complex (BH3.THF) in 0.93 M tetrahydrofuran over 10 min., while maintaining the inner temperature at not more than 2° C. After the completion of the dropwise addition, the mixture was stirred at the same temperature for 4 hr. The resulting crystals were collected by filtration through a glass filter, washed with diisopropyl ether (100 ml) cooled to not more than 5° C. and dried under reduced pressure for 2 hr. to give 7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid as colorless crystals (81 g, endo form:exo form=95:5, purity >99%, yield 58% based on acrylic acid).
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.C1OC1C.N1C2C(=CC=CC=2)C=CC=1.[Cl:26]Cl>C(Cl)Cl>[Cl:26][N:5]1[C:1](=[O:11])[C:2]2=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]2[C:4]1=[O:6]
Reactant: ClCl
Reactant: O=C1NC(=O)c2ccccc21
Agent: CC1CO1
Solvent: ClCCl
Solvent: c1ccc2ncccc2c1
Product: O=C1c2ccccc2C(=O)N1Cl
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To 150 ml. of methylene chloride were added 7.35 g. (0.05 mole) of phthalimide and 17.5 ml. (5 equiv.) of propylene oxide. The resulting mixture was cooled to 0° C., 0.13 g. (0.001 mole; 0.02 equiv.) of quinoline was added, and the mixture was saturated with chlorine. The phthalimide began to dissolve within 30 minutes, and after one hour it was nearly all dissolved. Analysis of the sample by TLC at 1.25 hours showed only a trace of starting material. The mixture was subjected to partial vacuum to remove excess chlorine, and a small amount of amylene was added. The resulting mixture then was evaporated to obtain crystalline N-chlorophthalimide. The product was filtered and vacuum dried overnight to give 8.2 g. (90.4%) of product. Analysis: (1) Percent Cl+ : Theory: 19.6; Found: 19.3. (2) Percent total chlorine: 19.1.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[CH:6][CH:5]=1)([O-])=O.Cl>O.C(O)C.[Pd]>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[CH:6][CH:5]=1
Reactant: CS(=O)(=O)NCc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CCO
Product: CS(=O)(=O)NCc1ccc(N)cc1
Yield: 79.5 %

Procedure:
To a suspension of 25.9 g (113 mmol, 1.0 equiv.) of N-[(4-nitrophenyl)methyl]methanesulfonamide in 113 mL of 1N HCl (113 mmol, 1.0 equiv.), 113 mL of water and 225 mL of ethanol was added 5.18 g of 10% palladium on carbon. This mixture was hydrogenated in a Parr apparatus at 60 psi for sixteen hours. The mixture was filtered through Celite. The ethanol was removed in vacuo and the pH adjusted to 9, at which point the product had precipitated. The precipitate was isolated by filtration and dried in vacuo to yield 18.0 g (80%) of N-[(4-aminophenyl)methyl]-methanesulfonamide.
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]([CH2:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-])=O>C(O)C.C(OCC)(=O)C.[Pd]>[CH3:18][C:15]1[CH:14]=[CH:13][C:12]([S:9]([CH2:8][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:20][CH:19]=2)(=[O:11])=[O:10])=[CH:17][CH:16]=1
Reactant: Cc1ccc(S(=O)(=O)Cc2ccc([N+](=O)[O-])cc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)Cc2ccc(N)cc2)cc1
Yield: 89.2 %

Procedure:
In ethanol (10 ml) and ethyl acetate (60 ml) was dissolved 4-methylphenyl 4-nitrobenzyl sulfone (0.5 g; G. Bram et al., Synthesis, 1987, 56-59). To the mixture was added 10% palladium on carbon (0.05 g) and catalytic hydrogenation was carried out at room temperature over night. The catalyst was filtered off, and the solvent was evaporated to give 4-aminobenzyl 4-methylphenyl sulfone (0.4 g) as colorless crystals.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([C:15]3[O:16][C:17]([CH2:20]Cl)=[N:18][N:19]=3)=[CH:13][N:12]3[CH:22]=[CH:23][N:24]=[C:11]3[C:10]=2[Cl:25])=[C:4]([F:26])[CH:3]=1.[I-].[K+].[NH3:29]>O1CCCC1>[NH2:29][CH2:20][C:17]1[O:16][C:15]([C:14]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[F:26])=[C:10]([Cl:25])[C:11]3[N:12]([CH:22]=[CH:23][N:24]=3)[CH:13]=2)=[N:19][N:18]=1
Reactant: N
Reactant: Fc1cc(Br)ccc1Nc1c(-c2nnc(CCl)o2)cn2ccnc2c1Cl
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: NCc1nnc(-c2cn3ccnc3c(Cl)c2Nc2ccc(Br)cc2F)o1
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.6 %

Procedure:
(4-Bromo-2-fluoro-phenyl)-[8-chloro-6-(5-chloromethyl-[1,3,4]oxadiazol-2-yl)-imidazo[1,2-a]pyridin-7-yl]-amine (38 mg, 0.083 mmol) was dissolved in tetrahydrofuran (1 mL). Potassium iodide (14 mg, 0.083 mmol) was added and then ammonia (7 M solution in methanol, 0.30 mL, 2.08 mmol). The reaction mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography (gradient of 20:1 dichloromethane/methanol to 5:1) to yield the desired product (26 mg, 71%) as a yellow solid. MS ESI (+) m/z 437, 439 (M+, Cl, Br pattern) detected. 1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.33 (s, 1H), 8.17 (d, 1H), 7.70 (d, 1H), 7.51 (dd, 1H), 7.16 (d, 1H), 6.65 (t, 1H), 3.94 (s, 2H). 19F (376 MHz, DMSO-d6) −128.3 (t).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH:5]([O:18][CH2:19][CH3:20])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=1[O:14][CH:15]([CH3:17])[CH3:16])[CH3:2].[C:22]([C:26]1[CH:31]=[CH:30][C:29]([C:32]2[O:33][C:34]([CH3:39])=[C:35]([CH2:37]Cl)[N:36]=2)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23].C(C1C=CC(C=O)=CC=1)(C)(C)C.O=P(Cl)(Cl)Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:21])[CH:5]([O:18][CH2:19][CH3:20])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:37][C:35]2[N:36]=[C:32]([C:29]3[CH:28]=[CH:27][C:26]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:31][CH:30]=3)[O:33][C:34]=2[CH3:39])=[CH:9][C:8]=1[O:14][CH:15]([CH3:16])[CH3:17])[CH3:2]
Reactant: CCOC(=O)C(Cc1ccc(O)cc1OC(C)C)OCC
Reactant: Cc1oc(-c2ccc(C(C)(C)C)cc2)nc1CCl
Agent: CC(C)(C)c1ccc(C=O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Product: CCOC(=O)C(Cc1ccc(OCc2nc(-c3ccc(C(C)(C)C)cc3)oc2C)cc1OC(C)C)OCC

Procedure:
In analogy to the procedure described in example 1 f], [rac]-2-ethoxy-3-(4-hydroxy-2-isopropoxy-phenyl)-propionic acid ethyl ester was reacted with 2-(4-tert-butyl-phenyl)-4-chloromethyl-5-methyl-oxazole (prepared from 4-tert-butyl-benzaldehyde and diacetyl monoxyme followed by treatment with POCl3 in analogy to the procedures described in examples 5 a] and 2 b]) in N,N-dimethylformamide in the presence of potassium carbonate to yield [rac]-3-{4-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-isopropoxy-phenyl}-2-ethoxy-propionic acid ethyl ester, which was further saponified in analogy to the procedure described in example 1 g], to yield [rac]-3-{4-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-isopropoxy-phenyl}-2-ethoxy-propionic acid as colorless viscous oil, which can be separated into its antipodes by methods known in the art, such as separation of the antipodes via diastereomeric salts by crystallization with optically pure amines such as e.g. (R) or (S)-1-phenyl-ethylamine, (R) or (S)-1-naphthalen-1-yl-ethylamine, brucine, quinine and quinidine or by separation of the antipodes by specific chromatographic methods using either a chiral adsorbens or a chiral eluent to give the title compound.
Reaction SMILES: C([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]([CH3:22])[CH2:17][C:18](=[O:21])[NH:19][N:20]=2)=[CH:11][C:10]=1[OH:23])C1C=CC=CC=1.[H][H]>[Pd].CO>[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]([CH3:22])[CH2:17][C:18](=[O:21])[NH:19][N:20]=2)=[CH:11][C:10]=1[OH:23]
Reactant: [H][H]
Reactant: CC1CC(=O)NN=C1c1ccc(NCc2ccccc2)c(O)c1
Agent: [Pd]
Solvent: CO
Product: CC1CC(=O)NN=C1c1ccc(N)c(O)c1

Procedure:
43.0 g (139 mmol) 6-(4-benzylamino-3-hydroxy-phenyl)-5-methyl-4,5-dihydro-2H-pyridazin-3-one, 2.2 g of 10% palladium/charcoal and 400 ml of methanol are hydrogenated together for 24 h at RT and 3.45 bar of hydrogen pressure. The catalyst is filtered off and the filtrate is concentrated by rotary evaporation i. V., the residue is triturated with ethyl acetate, suction filtered and then dried at 50° C. in the vacuum dryer.
Reaction SMILES: [NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[N:1]1([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1
Reactant: C1CNCCNC1
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(CN2CCCNCC2)cc1
Yield: 56.2 %

Procedure:
Alternatively, a mixture of hexahydro-1H-1,4-diazepine (17.47 g, 174.4 mmol) and methyl 4-(bromomethyl)benzoate (5.0 g, 21.8 mmol) was heated with triethylamine (24 mL, 174.4 mmol) in tetrahydrofuran (872 mL) to reflux for three hours. After cooling, the mixture was treated with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Flash chromatography gave 3.04 g of methyl 4-[(hexahydro-1H-1,4-diazepin-1-yl)methyl]benzoate, 1H NMR (300 MHz, CDCl3) δ 7.98 (d, 2H), 7.42 (d, 2H), 3.90 (s, 3H), 3.70 (s, 2H), 2.97 (m, 2H), 2.91 (m, 2H), 2.67 (m, 2H), 2.66 (m, 2H), 1.77 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:32]C)=[C:6]([C:8]([CH3:31])([CH3:30])[CH2:9][C:10]([C:26]([F:29])([F:28])[F:27])([OH:25])[CH2:11][NH:12][C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][C:17]([CH2:23][OH:24])=[N:18]3)[CH:7]=1.B(Br)(Br)Br.CO>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:32])=[C:6]([C:8]([CH3:30])([CH3:31])[CH2:9][C:10]([C:26]([F:27])([F:28])[F:29])([OH:25])[CH2:11][NH:12][C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][C:17]([CH2:23][OH:24])=[N:18]3)[CH:7]=1
Reactant: COc1ccc(F)cc1C(C)(C)CC(O)(CNc1cccc2nc(CO)ccc12)C(F)(F)F
Agent: BrB(Br)Br
Solvent: CO
Solvent: ClCCl
Product: CC(C)(CC(O)(CNc1cccc2nc(CO)ccc12)C(F)(F)F)c1cc(F)ccc1O
Reaction time: 20 h

Procedure:
290 mg (0.62 mmol) of 4-(5-fluoro-2-methoxyphenyl)-1-(2-(hydroxymethyl)quinolin-5-ylamino)-4-methyl-2-(trifluoromethyl)pentan-2-ol in 7.0 ml of dichloromethane is mixed at room temperature with 12.5 ml (12.5 mmol) of a 1 M boron tribromide solution. After 20 hours at room temperature, the reaction is brought to a halt by adding methanol. The solvent is removed in a vacuum, the residue is taken up in saturated sodium bicarbonate solution and ethyl acetate, extracted with ethyl acetate, and the combined organic phases are dried on sodium sulfate. After the solvent is removed and after purification on silica gel with hexane-ethyl acetate (0-70%) as well as with ethyl acetate-methanol (0-10%), 160 mg (51% of theory) of the product is obtained.
Reaction SMILES: [Cl:1][C:2]1[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[C:4]#N.CC(C[AlH]CC(C)C)C.C(O)(=[O:25])C.O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:25]
Reactant: CC(=O)O
Reactant: N#Cc1ccc(C(F)(F)F)nc1Cl
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Solvent: O
Product: O=Cc1ccc(C(F)(F)F)nc1Cl
Temperature: -78 °C
Reaction time: 1 h
Yield: 33.3 %

Procedure:
2-Chloro-6-(trifluoromethyl)nicotinonitrile (340 mg, 1.65 mmol) was diluted with toluene (2.0 mL), placed under nitrogen and cooled to −78° C. DIBAL-H (3292 μl, 3.29 mmol) was added dropwise and the reaction was stirred for 1 hour. The reaction was warmed to 0° C. and acetic acid (1 mL) was added followed by 5 mL of water. After stirring for 2 hours, the reaction was extracted twice with ethyl acetate, washed with Rochelle's salt, dried over MgSO4, filtered and concentrated. The material was loaded onto silica gel and eluted with 5% ethyl acetate/hexanes to 30% ethyl acetate/hexanes to yield the desired compound (115 mg, 0.549 mmol, 33.3% yield) as a clear oil.
Reaction SMILES: [Cl:1][C:2]1[C:15]2[C:6](=[C:7]([CH:17]=O)[C:8]3[C:13]([CH:14]=2)=[C:12]([Cl:16])[CH:11]=[CH:10][CH:9]=3)[CH:5]=[CH:4][CH:3]=1.[CH3:19][C:20]([NH2:25])([CH2:23][OH:24])[CH2:21][OH:22]>>[ClH:1].[Cl:1][C:2]1[C:15]2[C:6](=[C:7]([CH2:17][NH:25][C:20]([CH3:19])([CH2:23][OH:24])[CH2:21][OH:22])[C:8]3[C:13]([CH:14]=2)=[C:12]([Cl:16])[CH:11]=[CH:10][CH:9]=3)[CH:5]=[CH:4][CH:3]=1
Reactant: CC(N)(CO)CO
Reactant: O=Cc1c2cccc(Cl)c2cc2c(Cl)cccc12
Product: CC(CO)(CO)NCc1c2cccc(Cl)c2cc2c(Cl)cccc12
Product: Cl

Procedure:
Using the reductive amination procedure outlined in 1, 4,5-dichloro-9-anthracenecarbaldehyde and 2-methyl-2-amino-1,3-propanediol (Aldrich) gave 2-((4,5-dichloro-9-anthracenylmethyl)amino)-2-methyl-1,3-propanediol hydrochloride mp 239.5°-240.5° (dec), (EtOH/Et2O), (C,H,Cl,N).
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][C:8]2[NH:9][C:10](=[O:12])[NH:11][C:7]=2[CH:6]=1)=[O:4].[N-:15]=[N+:16]=[N-:17].[Na+]>>[N:15]([CH2:2][C:3]([C:5]1[CH:14]=[CH:13][C:8]2[NH:9][C:10](=[O:12])[NH:11][C:7]=2[CH:6]=1)=[O:4])=[N+:16]=[N-:17]
Reactant: O=C(CCl)c1ccc2[nH]c(=O)[nH]c2c1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Product: [N-]=[N+]=NCC(=O)c1ccc2[nH]c(=O)[nH]c2c1
Yield: 93 %

Procedure:
Treatment of give 5-(2-chloroethanoyl)-1,3-dihydrobenzimidazol-2-one with sodium azide, following the procedure described in Example 6. Step 4, gave 6-(2-azidoethanoyl)-1,3-dihydrobenzimidazol-2-one (5.75 g, 93%):
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[C:5]([NH:7][C:8]1[C:13]([Br:14])=[CH:12][C:11]([C:15]([C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)([OH:20])[C:16]([F:19])([F:18])[F:17])=[CH:10][C:9]=1[Br:29])=[O:6].N1C=CC=CC=1.[C:39]([C:41]1[CH:49]=[CH:48][C:44]([C:45](Cl)=[O:46])=[CH:43][CH:42]=1)#[N:40].C(=O)([O-])O.[Na+]>O1CCCC1>[C:39]([C:41]1[CH:49]=[CH:48][C:44]([C:45]([NH:1][C:2]2[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=2)[C:5]([NH:7][C:8]2[C:9]([Br:29])=[CH:10][C:11]([C:15]([C:21]3[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=3)([OH:20])[C:16]([F:19])([F:17])[F:18])=[CH:12][C:13]=2[Br:14])=[O:6])=[O:46])=[CH:43][CH:42]=1)#[N:40]
Reactant: Nc1cccc(C(=O)Nc2c(Br)cc(C(O)(c3cc(Cl)cc(Cl)c3)C(F)(F)F)cc2Br)c1
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: N#Cc1ccc(C(=O)Nc2cccc(C(=O)Nc3c(Br)cc(C(O)(c4cc(Cl)cc(Cl)c4)C(F)(F)F)cc3Br)c2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-amino-N-{2,6-dibromo-4-[1-(3,5-dichloro-phenyl)-2,2,2-trifluoro-1-hydroxy-ethyl]-phenyl}-benzamide (Example I8) (0.147 mg, 0.24 mmol) in tetrahydrofuran (5 ml) were added successively pyridine (0.058 ml, 0.72 mmol) and 4-cyano-benzoyl chloride (48 mg, 0.29 mmol). The reaction mixture was stirred at ambient temperature for 2 hours. Aqueous sodium hydrogen carbonate (saturated) was added and the phases were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:1) to give the title compound.