Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:5]([CH:18]([OH:47])[CH2:19][C:20]([CH2:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([O:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:29][CH:28]=1)[CH2:21][CH2:22][CH3:23])[CH:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)[CH2:7][CH3:8])([O:3][CH3:4])=[O:2].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.C([O-])(=O)C.[Na+].[O-][Si]([O-])=O.[Mg+2]>C(Cl)Cl>[C:1]([CH:5]([C:18](=[O:47])[CH2:19][C:20]([CH2:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)([O:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[CH:29][CH:28]=1)[CH2:21][CH2:22][CH3:23])[CH:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)[CH2:7][CH3:8])([O:3][CH3:4])=[O:2]
Reactant: CCCC(CCc1ccccc1)(CC(O)C(C(=O)OC)C(CC)c1cccc([N+](=O)[O-])c1)OCOc1ccc(-c2ccccc2)cc1
Agent: O=[Cr](=O)([O-])Cl
Agent: CC(=O)[O-]
Agent: O=[Si]([O-])[O-]
Solvent: ClCCl
Product: CCCC(CCc1ccccc1)(CC(=O)C(C(=O)OC)C(CC)c1cccc([N+](=O)[O-])c1)OCOc1ccc(-c2ccccc2)cc1
Reaction time: 20 h

Procedure:
A solution of (3S),(7R) 4-carbomethoxy-3-(3-nitrophenyl)-7-(2-phenylethyl)-7-[(4-phenylphenoxy)methoxy]decan-5-ol (XIV, EXAMPLE 10, 11.12 g, 79.0 wt %, 13.73 mmol) in methylene chloride (530 ml) is added to a ground mixture of pyridinium chlorochromate (16.099 g, 74.685 mmol, 5.44 eq), sodium acetate (6.984 g, 85.14 mmol, 6.20 eq) and florisil (5.181 g) while maintaining less than 11°. The mixture is warmed to 21° and stirred at 20-25° for 20 hrs. The resultant slurry is filtered through magnesol (47.7 g) and rinsed with methylene chloride (375 ml). The filtrate is concentrated to an oil. An analytical sample of the title compound is obtained by chromatography (ethyl acetate/hexanes): TLC Rf =0.34 (ethyl acetate/hexanes, 10/90); HPLC rt=13.02, 13.23 min; NMR (CDCl3) 8.05-8.01, 7.60-7.00, 5.37, 5.21, 4.03, 3.94, 3.75, 3.58-3.43, 3.39, 2.96, 2.78-1.37, 1.20, 0.91, 0.71-0.61 δ; CMR (CDCl3) 200.89, 200.60, 168.29, 167.81, 157.10, 157.05, 148.38, 148.30, 143.58, 143.32, 141.99, 141.93, 140.73, 140.69, 135.29, 135.01, 134.78, 129.38, 129.23, 128.75, 128.45, 128.36, 128.23, 126.77, 125.91, 125.80, 122.96, 122.80, 122.04, 122.00, 116.16, 87.14, 86.92, 80.93, 80.44, 66.34, 65.92, 52.79, 52.35, 49.02, 48.62, 46.28, 46.20, 38.70, 38.51, 38.43, 37.99, 30.10, 29.52, 26.92, 26.71, 16.64, 16.39, 14.39, 14.16, 11.81, 11.58; MS (CI, ammonia) m/z (relative intensity) 656 (2.8), 655 (6.1), 136 (100).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:23]1[S:24][C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[N:27]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:23]2[S:24][C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=3[N:27]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Clc1nc2ccccc2s1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1COc1ccc(O)cc1
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1COc1ccc(Oc2nc3ccccc3s2)cc1
Yield: 71.5 %

Procedure:
Followed the same procedure as that of step 1 in Example 99 with the use of (R)-2-(4-hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (293 mg, 1 mmol) and 2-chloro-benzothiazole (169 mg, 1 mmol) to afford the title product (305 mg, 75% yield); LCMS, 100% APCI+, Calcd: 426.50. Found m/z: 427.26 (M+1). 1H NMR (400 MHz, DMSO-d6); δ 1.41 (s, 9H), 1.78-2.13 (m, 4H), 3.24-3.36 (m, 2H), 3.89-4.12 (m, 3H), 7.08 (d, J=9.2 Hz, 2H), 7.31 (t, J=8.4 Hz, 1H), 7.37 (d, J=9.2 Hz, 2H), 7.42 (t, J=8.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.91 (d, J=8.0 Hz, 1H).
Reaction SMILES: [CH2:1]([N:5]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1)(=[O:17])=[O:16])[C@H:6]([C:12]([OH:14])=[O:13])[CH2:7][CH2:8][CH2:9][CH2:10][NH2:11])[CH:2]([CH3:4])[CH3:3].[CH2:27]1[O:40][C:39]2[CH:38]=[CH:37][C:31]([CH:32]=[CH:33][C:34](O)=[O:35])=[CH:30][C:29]=2[O:28]1>>[CH2:1]([N:5]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1)(=[O:17])=[O:16])[C@H:6]([C:12]([OH:14])=[O:13])[CH2:7][CH2:8][CH2:9][CH2:10][NH:11][C:34](=[O:35])[CH:33]=[CH:32][C:31]1[CH:37]=[CH:38][C:39]2[O:40][CH2:27][O:28][C:29]=2[CH:30]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)CN([C@@H](CCCCN)C(=O)O)S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Reactant: O=C(O)C=Cc1ccc2c(c1)OCO2
Product: CC(C)CN([C@@H](CCCCNC(=O)C=Cc1ccc2c(c1)OCO2)C(=O)O)S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Yield: 76 %

Procedure:
Nα-isobutyl-Nα-(4-nitrobenzenesulfonyl)-L-lysine was reacted with 3,4-methylenedioxycinnamic acid under the conditions described in example 86 to yield 76% of the desired product.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[N:2]1.[I:10]N1C(=O)CCC1=O>C(#N)C.O>[I:10][C:3]1[C:4]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[NH:1][N:2]=1
Reactant: c1cnc2[nH]ncc2c1
Reactant: O=C1CCC(=O)N1I
Solvent: O
Solvent: CC#N
Product: Ic1n[nH]c2ncccc12
Temperature: 75 °C
Reaction time: 17 h

Procedure:
A solution of the intermediate from Step A above (14.3 g, 120 mmol) and N-iodosuccinimide (28.4 g, 126 mmol) in acetonitrile (210 mL) was heated at 75° C. After 17 hours, N-iodosuccinimide (5.4 g, 24 mmol) was added and the reaction solution stirred at 75° C. for an additional 1.5 hours. The reaction solution was cooled to room temperature and diluted with water. The slurry was concentrated in vacuo to remove most of the acetonitrile. The solid was collected, washed with water, and dried under a vacuum with a nitrogen sweep for 17 hours to give the title compound. 1H NMR (400 MHz, CH3CN-d3): δ 11.85 (s, 1H); 8.55 (dd, J=4.53, 1.53 Hz, 1H); 7.87 (dd, J=8.11, 1.53 Hz, 1H); 7.24 (dd, J=8.11, 4.51 Hz, 1H). m/z=246.1 (M+H).
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([CH3:3])[CH3:2].[CH2:11]1[O:15][CH:12]1[CH2:13][CH3:14]>CO>[OH:15][CH:12]([CH2:13][CH3:14])[CH2:11][NH:7][C:6]1[CH:8]=[CH:9][CH:10]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=1
Reactant: CC(C)c1cccc(N)c1
Reactant: CCC1CO1
Solvent: CO
Product: CCC(O)CNc1cccc(C(C)C)c1
Temperature: 50 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
10 g (74 mmol) of m-isopropylaniline were dissolved in 100 ml of methanol, and 6.4 g (88.8 mmol) of 1,2-butylene oxide were added thereto. Next, the solution was heated up to 50° C., and then stirred for 1 hour. The solvent was distilled off under reduced pressure, and the solution was then purified through silica gel column chromatography [an eluting solvent: hexane/ethyl acetate=7/3 (v/v)] to obtain 13.2 g of the desired product in an oily state (yield: 86.2%).
Reaction SMILES: N1C=CC=CC=1.[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][CH2:14][NH2:15].[Cl:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]2[CH:23]=[C:24]([C:26]([O-])=[O:27])[S:25][C:18]=12.[Li+]>>[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][CH2:14][NH:15][C:26]([C:24]1[S:25][C:18]2[C:19](=[N:20][CH:21]=[CH:22][C:17]=2[Cl:16])[CH:23]=1)=[O:27]
Reactant: NCCc1ccccn1
Reactant: O=C([O-])c1cc2nccc(Cl)c2s1
Agent: [Li+]
Solvent: c1ccncc1
Product: O=C(NCCc1ccccn1)c1cc2nccc(Cl)c2s1

Procedure:
The title compound was prepared from 2-pyridine-2-yl-ethylamine pyridine and lithium 7-chloro-thieno[3,2-b]pyridine-2-carboxylate by a procedure analogous to Example 1B. MS: 318/320 (MH+); HPLC Rf: 4.33 min.; HPLC purity: 97%.
Reaction SMILES: CO[C:3]1[CH2:4][CH2:5][CH:6]([C:8]([O:10][CH3:11])=[O:9])[N:7]=1.[N-:12]=[N+:13]=[N-:14].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(O)(=O)C.C(OCC)C>[N:12]1[N:13]=[N:14][N:7]2[CH:6]([C:8]([O:10][CH3:11])=[O:9])[CH2:5][CH2:4][C:3]=12
Reactant: [N-]=[N+]=[N-]
Reactant: COC(=O)C1CCC(OC)=N1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CCOCC
Solvent: CC(=O)O
Product: COC(=O)C1CCc2nnnn21
Temperature: 60 °C
Reaction time: 48 h
Yield: 30.3 %

Procedure:
To a solution of starting methyl 5-methoxy-3,4-dihydro-2H-pyrrole-2-carboxylate (900 mg, 6.04 mmol) in 4 mL of acetic acid was added sodium azide (975 mg, 12.08 mmol) and the resulting suspension heat to 60° C. and stirred vigorously for 48 h. The solution was cooled to room temperature and diluted with 35 mL of ethyl ether. Solid potassium carbonate was added to the solution which was stirred at room temperature for 20 min. The solids were filtered off via fritted funnel, washed with cool ethyl ether and concentrated under vacuum. Solid precipitated during concentration and was filtered off after concentrating to one-fifth volume. The solids were washed once with cold ether (3 mL) and dried under high vacuum overnight to afford the title compound (308 mg, 31%). LC-MS: m/z (ES)=169 (MH)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]2[N:20]=[C:19]([NH:21][C:22]3[CH:27]=[N:26][CH:25]=[CH:24][N:23]=3)[CH:18]=[CH:17][C:12]=2[C:13]([O:15]C)=[O:14])[CH3:9])=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]2[N:20]=[C:19]([NH:21][C:22]3[CH:27]=[N:26][CH:25]=[CH:24][N:23]=3)[CH:18]=[CH:17][C:12]=2[C:13]([OH:15])=[O:14])[CH3:9])=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc(Nc2cnccn2)nc1N[C@@H](C)c1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C[C@H](Nc1nc(Nc2cnccn2)ccc1C(=O)O)c1ccc(F)cc1
Yield: 91.5 %

Procedure:
1.0 g of methyl (S)-2-[1-(4-fluorophenyl)ethylamino]-6-(pyrazin-2-ylamino)nicotinate was dissolved in 60 ml of methanol, and 20 ml of 10% sodium hydroxide aqueous solution was added thereto, and the reaction solution was heated at reflux for 4 hour. The reaction solution was distilled off under reduced pressure to remove methanol. The obtained aqueous layer was washed with diethyl ether, and the pH of the mixture was adjusted to 3 by 10% hydrochloric acid. The precipitated solid was filtered, and washed with water. The obtained solid was dried under reduced pressure to obtain 880 mg of the objective compound as pale yellow powder.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[C:14]([C:26]3[N:27]([CH3:31])[N:28]=[CH:29][CH:30]=3)[CH:13]=2)=[O:10])=[CH:4][CH:3]=1.[Cl:32]N1C(=O)CCC1=O>CO>[Cl:32][C:30]1[CH:29]=[N:28][N:27]([CH3:31])[C:26]=1[C:14]1[CH:13]=[C:12]([NH:11][C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:10])[CH:17]=[CH:16][C:15]=1[O:18][CH2:19][CH2:20][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: Cn1nccc1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCN1CCCC1
Reactant: O=C1CCC(=O)N1Cl
Solvent: CO
Product: Cn1ncc(Cl)c1-c1cc(NC(=O)Nc2ccc(Cl)cc2)ccc1OCCN1CCCC1
Reaction time: 1 h
Yield: 38 %

Procedure:
To a solution 1-(4-chloro-phenyl)-3-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-urea in cold methanol was added a solution of N-chloro succinimide (0.044 g, 0.3215 mmol) in methanol. The reaction mixture was stirred for 60 minutes. Then the methanol was evaporated and the residue was purified using silica flash chromatography with 15% methanol in DCM as eluant. The fractions containing the product were evaporated and dried in vacuo to afford 1-[3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea (Compound 17) (0.05 g, 38%) as an off-white solid. LCMS m/z (%)=474 (M+H 35Cl 35Cl, 100), 476 (M+H 35Cl, 37Cl, 81.7), 478 (M+H 37Cl 37Cl, 11.2). 1H NMR (400 MHz, DMSO-d6) δ: 8.83 (bs, 1H), 8.73 (bs, 1H), 7.61 (s, 1H), 7.54 (dd, J=2.65, 2.69 Hz, 1H), 7.46 (dd, J=2.06, 2.11 Hz, 2H), 7.37 (d, J=2.7 Hz, 1H), 7.31 (dd, J=2.09, 2.04 Hz, 2H), 7.16 (d, J=9.03 Hz, 1H), 4.2-4.0 (bm, 2H), 3.65 (s, 3H), 2.7-2.5 (bm, 2H), 2.4-2.3 (bm, 4H), 1.7-1.5 (bm, 4H).
Reaction SMILES: [NH2:1][C:2]1[N:23]=[C:22](Cl)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5].C1C=CC(CC(NCN[C@H](C(O)=O)CC2[CH:44]=[CH:43][C:42]([N+:45]([O-])=O)=CC=2)=O)=CC=1.C1(N)CC1>CS(C)=O.C(N(CC)C(C)C)(C)C.[Cl-].[Na+].O>[NH2:1][C:2]1[N:23]=[C:22]([NH:45][CH:42]2[CH2:44][CH2:43]2)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5]
Reactant: O=C(Cc1ccccc1)NCN[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Reactant: Nc1nc(Cl)ccc1C(=O)NCc1ccc(Oc2ccccc2)s1
Agent: NC1CC1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: Nc1nc(NC2CC2)ccc1C(=O)NCc1ccc(Oc2ccccc2)s1
Temperature: 130 °C
Yield: 47.5 %

Procedure:
2-Amino-6-chloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide described in Example A-101 (30 mg, 0.083 mmol) was dissolved in a mixture solution of dimethylsulfoxide (1 mL) and N,N-diisopropylethylamine (0.5 mL), cyclopropylamine (0.058 mL, 0.84 mmol) was added thereto, followed by heating in a sealed tube for 15 hours 30 minutes (oil bath temperature: 130° C.). The reaction mixture was allowed to room temperature, poured into brine, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then concentrated, the obtained residue was purified by NH silica gel column chromatography (ethyl acetate:hexane=2:1), and the title compound (15 mg, 0.039 mmol, 47.5%) was obtained.
Reaction SMILES: COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[C:23]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1(C)C(C)=CC=CC=1>[S:10]=[C:29]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]1[C:23]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30]
Reactant: O=C(OCc1ccccc1)c1ccccc1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1C
Product: O=C(OCc1ccccc1)C1C=CC=CC1=S
Yield: 67 %

Procedure:
Hy method A [Lawesson's reagent]. Benzyl benzoate (2.1 g) was heated at 140° C. for 24 h with Lawesson's Reagent (4.9 g) in anhydrous xylene (10 ml). After removal of the solvent and subjection of the mixture to chromatography on silica gel and recrystallization from pentane at low temperature, benzyl thionobenzoate was obtained in 67% yield. 1H NMR (CDCl3): δ=5.64 (s, 2H), 7.3-8.2 (m, 10H).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:11][C:10]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[C:19]([C:21]1[CH:22]=[C:23]([C:27]2[O:31][CH:30]=[N:29][C:28]=2[C:32](O)=[O:33])[CH:24]=[CH:25][CH:26]=1)#[N:20]>>[C:2]([C:7]1[S:11][C:10]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:32]([C:28]3[N:29]=[CH:30][O:31][C:27]=3[C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([C:19]#[N:20])[CH:22]=3)=[O:33])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: N#Cc1cccc(-c2ocnc2C(=O)O)c1
Reactant: CC1(c2ccc(Cn3cc(N)cn3)s2)OCCO1
Product: CC(=O)c1ccc(Cn2cc(NC(=O)c3ncoc3-c3cccc(C#N)c3)cn2)s1

Procedure:
Following general procedure X followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-1H-pyrazol-4-ylamine and 5-(3-cyano-phenyl)-oxazole-4-carboxylic acid. LC-MS-conditions 05c: tR=0.69 min; [M+H]+=417.76.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([OH:24])[CH3:23])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[C:25](O)(=[O:29])[CH2:26][CH2:27][CH3:28]>>[C:25]([O:24][CH:22]([CH3:23])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])=[CH:10][CH:11]=2)=[CH:16][CH:17]=1)(=[O:29])[CH2:26][CH2:27][CH3:28]
Reactant: CCCC(=O)O
Reactant: CCCCCCCOc1ccc(-c2ccc(CC(C)O)cc2)cc1
Product: CCCCCCCOc1ccc(-c2ccc(CC(C)OC(=O)CCC)cc2)cc1

Procedure:
Esterification of optically active 1-(4'-heptyloxybiphenyl-4-yl)-propane-2-ol (prepared from R-propylenoxide and 4'-heptyloxybiphenyl-4-yl-magnesiumbomide) with butyric acid in a similar way as described in example 2 yields optically active 1-(4'-heptyloxybiphenyl-4-yl)-2-propyl butyrate. In a similar way the following 2-propanol derivatives yield the corresponding esters by sterification with aliphatic carboxylic acids: ##STR60##
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([OH:13])=O)=[CH:9][N:10]=2)[CH:7]=1.C(Cl)(=O)C(Cl)=O.[CH2:20]([N:27]1[C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([NH2:36])[C:30]=2[CH:29]=[N:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(NC(C)CC(C)C)C>ClCCl>[CH2:20]([N:27]1[C:35]2[C:30](=[C:31]([NH:36][C:11]([C:8]3[N:6]4[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]4=[N:10][CH:9]=3)=[O:13])[CH:32]=[CH:33][CH:34]=2)[CH:29]=[N:28]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: Nc1cccc2c1cnn2Cc1ccccc1
Reactant: O=C(O)c1cnc2ccc(F)cn12
Agent: CCNC(C)CC(C)C
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: O=C(Nc1cccc2c1cnn2Cc1ccccc1)c1cnc2ccc(F)cn12
Reaction time: 0.17 h

Procedure:
6-Fluoroimidazo[1,2-a]pyridine-3-carboxylic acid (0.083 g, 0.46 mmol) was added as a suspension to dichloromethane, and then oxalyl dichloride (0.28 mL, 0.55 mmol) was added slowly. The mixture was allowed to stir for 10 minutes, then a solution of 1-benzyl-1H-indazole-4-amine (0.10 g, 0.46 mmol, above, step D) and N-ethyl-isopropylpropan-2-amine (0.11 mL, 0.60 mmol) were added and the reaction stirred for 2 hours. The solvent was concentrated and the resulting crude material was purified on silica gel using ethyl acetate and methanol (Rf=0.18 in 5% MeOH in ethyl acetate) to provide 20 mg of the desired product. MS (ES+APCI) m/z=386.4 (M+H).
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][OH:18])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>ClCCl>[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][O:18][S:27]([CH3:26])(=[O:29])=[O:28])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(CCCO)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)Oc1ccc(CCCOS(C)(=O)=O)cc1
Temperature: 2.5 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
A solution of 3-(4-tert-butyldimethylsilyloxy-phenyl)-1-propanol (P. A. Grieco and C. J. Markworth, Tet. Lett., 1999, 40: 665) (2.86 g, 10.73 mmol) in dry dichloromethane (25 ml), was cooled to 0-5° C. and treated with triethylamine (2.4 ml, 17.0 mmol). Then methanesulfonyl chloride (1.08 ml, 14 mmol) was added dropwise over 10 minutes. The reaction mixture was stirred at 0-5° C. for 1 hour, then quenched with sat. sodium bicarbonate, diluted with ethyl acetate (300 mL), washed with water, brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was filtered aon a silica gel pad (toluene/ethyl acetate 95:5) to give the title material (3.68 g, 100%) as a clear oil.
Reaction SMILES: [Cl:1][C:2]([Cl:32])([Cl:31])[CH2:3][O:4][C:5](=[O:30])[CH:6]([S:18]([CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:20])=[O:19])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]([OH:17])=[O:16])=[CH:10][CH:9]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[F:62][C:63]([F:73])([F:72])[C:64]1[CH:71]=[CH:70][C:67]([CH2:68]O)=[CH:66][CH:65]=1>CN(C=O)C.CCOC(C)=O>[Cl:32][C:2]([Cl:31])([Cl:1])[CH2:3][O:4][C:5](=[O:30])[CH:6]([S:18]([CH2:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)(=[O:20])=[O:19])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][C:15]([O:17][CH2:68][C:67]2[CH:66]=[CH:65][C:64]([C:63]([F:62])([F:72])[F:73])=[CH:71][CH:70]=2)=[O:16])=[CH:12][CH:13]=1
Reactant: OCc1ccc(C(F)(F)F)cc1
Reactant: O=C(O)Cc1ccc(CC(C(=O)OCC(Cl)(Cl)Cl)S(=O)(=O)CCc2ccc(F)cc2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: O=C(Cc1ccc(CC(C(=O)OCC(Cl)(Cl)Cl)S(=O)(=O)CCc2ccc(F)cc2)cc1)OCc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 102.4 %

Procedure:
3-(4-Carboxymethyl-phenyl)-2-[2-(4-fluoro-phenyl)-ethanesulfonyl]-propionic acid 2,2,2-trichloro-ethyl ester (121 mg, 0.23 mmol) was dissolved in anhydrous DMF (2.0 mL) and TBTU (147 mg, 0.46 mmol), N-methyl morpholine (46.5 mg, 0.46 mmol) and 4-(trifluoromethyl)benzyl alcohol (81.06 mg, 0.46 mmol) were added under nitrogen atmosphere. The reaction was stirred at ambient temperature for 18 h. EtOAc was added and the mixture was extracted with water and brine. After drying the organic layer over Na2SO4 the solvent was evaporated under reduced pressure to afford the crude product as an oil (161 mg, 102.3%). No further purification was done. 1H NMR (400 MHz, CDCl3): δ 7.44-7.62 (m, 6H), 7.12-7.23 (m, 4H), 6.97-7.02 (t, 2H) 5.14 (s, 2H), 4.74 (s, 2H), 4.69 (d, 1H), 3.62 (s, 2H), 3.34-58 (m, 4H), 3.15-3.19 (t, 2H).
Reaction SMILES: [CH:1]1([NH:6][C:7]([NH:9][C:10]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([F:36])[CH:27]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24]C)[N:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Si](I)(C)(C)C.CO>C(Cl)(Cl)Cl>[CH:1]1([NH:6][C:7]([NH:9][C:10]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[C:28]([F:36])[CH:27]=2)([C:18]2[NH:19][C:20](=[O:24])[CH:21]=[CH:22][CH:23]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1cccc(C(Cc2ccccc2)(NC(=O)NC2CCCC2)c2cc(F)cc(C(F)(F)F)c2)n1
Agent: C[Si](C)(C)I
Solvent: CO
Solvent: ClC(Cl)Cl
Product: O=C(NC1CCCC1)NC(Cc1ccccc1)(c1cc(F)cc(C(F)(F)F)c1)c1cccc(=O)[nH]1
Temperature: 25 °C
Yield: 54.4 %

Procedure:
1-Cyclopentyl-3-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(6-methoxypyridin-2-yl)-2-phenylethyl)urea (25 mg, 0.049 mmol) was stirred in CHCl3 (1 mL) in a pyrex tube at room temperature. TMSI (0.04 mL) was added and the reaction mixture was refluxed for 3 h. Additional TMSI (0.04 mL) was added. The mixture was refluxed for an additional two hours. The mixture was cooled to room temperature and MeOH (1 mL) was added. The reaction mixture was concentrated. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc, came out 100% EtOAc) to give 1-cyclopentyl-3-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(6-oxo-1,6-dihydropyridin-2-yl)-2-phenylethyl)urea (13 mg, yield: 54%) as a white solid. LC-MS ESI (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=3.75 min, 488.12 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 12.06 (s, br, 1H), 7.52 (dd, J=8.8, 7.3 Hz, 1 H), 7.19 (t, J=7.0 Hz, 2 H), 7.12 (t, J=7.3 Hz, 2 H), 6.94 (s, br, 1 H), 6.83 (d, J=10 Hz, 1 H), 6.68 (d, J=7.3 Hz, 2 H), 6.61 (d, J=7.1 Hz, 1 H), 6.30 (d, J=8.8 Hz, 1 H), 6.15 (s, br, 1 H), 5.22 (s, br, 1 H), 4.32 (d, J=12.2 Hz, 1 H), 3.88-3.98 (m, 1 H), 3.19 (d, J=12.7 Hz, 1 H), 1.92-1.86 (m, 1 H), 1.83-1.74 (m, 1 H) 1.65-1.48 (m, 4 H), 1.43-1.35 (m, 1 H) 1.25-1.18 (m, 1 H).
Reaction SMILES: [Br:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8]([OH:10])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5](/[CH:6]=[CH:7]/[C:8]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:10])=[CH:11][CH:12]=1
Reactant: C1CCNC1
Reactant: O=C(O)C=Cc1ccc(Br)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(/C=C/c1ccc(Br)cc1)N1CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 5.0 g (22.0 mmol) of 4-bromocinnamic acid, 6 mL of oxalyl chloride and 3 drops of DMF in 40 mL of CH2Cl2 was heated to gentle reflux until gas evolution ceased. The volatiles were removed in vacuo and the residue was taken up in 50 mL of CH2Cl2. Pyrrolidine (10 mL; 120 mmol) was added and the mixture was stirred overnight at room temperature. The reaction mixture was evaporated in vacuo and chromatographed to afford 5.36 g (19.1 mmol; 87%) of the title compound.