Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[S:3][C:4]2[CH2:5][C:6]3[C:12]([C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=4)=[N:11][N:10]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:7]=3[C:8]=2[CH:9]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[C:39]([NH2:43])[CH:40]=[N:41][CH:42]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[CH3:20][O:19][C:16]1[CH:15]=[CH:14][C:13]([C:12]2[C:6]3[CH2:5][C:4]4[S:3][C:2]([C:37]5[CH:38]=[C:39]([NH2:43])[CH:40]=[N:41][CH:42]=5)=[CH:9][C:8]=4[C:7]=3[N:10]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[N:11]=2)=[CH:18][CH:17]=1
Reactant: CC1(C)OB(c2cncc(N)c2)OC1(C)C
Reactant: COc1ccc(-c2nn(COCC[Si](C)(C)C)c3c2Cc2sc(Br)cc2-3)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1ccc(-c2nn(COCC[Si](C)(C)C)c3c2Cc2sc(-c4cncc(N)c4)cc2-3)cc1
Temperature: 100 °C
Yield: 68 %

Procedure:
A mixture of the corresponding 2-Bromo-6-(4-methoxy-phenyl)-4-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalene (1.1 g, 2.3 mmol), 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-ylamine (0.75 g, 3.4 mmol), Na2CO3 (2 M, 5.4 mL), and Pd(PPh3)2Cl2 (260 mg, 0.23 mmol) in toluene/ethanol (1:1, 15 mL) was heated at 100° C. for 8 hr. The solution was cooled to room temperature and extracted with ethyl acetate. The target product was purified by gravity column chromatography (30% EtOAc in hexane) to give 5-[6-(4-Methoxy-phenyl)-4-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-2-yl]-pyridin-3-ylamine as brown solid in 68% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[O:18][C:17](=[O:19])[NH:16][N:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[N+:20]([C:23]1[O:27][C:26]([CH:28]=O)=[CH:25][CH:24]=1)([O-:22])=[O:21]>CC(O)=O.CO>[N+:20]([C:23]1[O:27][C:26](/[CH:28]=[N:1]/[C:2]2[CH:3]=[CH:4][C:5]([N:8]3[CH2:9][CH2:10][CH:11]([C:14]4[O:18][C:17](=[O:19])[NH:16][N:15]=4)[CH2:12][CH2:13]3)=[CH:6][CH:7]=2)=[CH:25][CH:24]=1)([O-:22])=[O:21]
Reactant: Nc1ccc(N2CCC(c3n[nH]c(=O)o3)CC2)cc1
Reactant: O=Cc1ccc([N+](=O)[O-])o1
Solvent: CC(=O)O
Solvent: CO
Product: O=c1[nH]nc(C2CCN(c3ccc(/N=C/c4ccc([N+](=O)[O-])o4)cc3)CC2)o1
Yield: 80 %

Procedure:
5-[1-(4-Aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 0.26 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0° C. for 10 h and the obtained solid is filtered, washed with water and recrystallized in ethanol to obtain product 5-[1-(4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9a, 306 mg, 80%).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([O-:18])=[O:17])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[OH-].[K+].Cl>C1COCC1.O.CCOC(C)=O>[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=C([O-])Cc1ccc(OCCn2ccnc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(O)Cc1ccc(OCCn2ccnc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirring mixture of 2-(4-(2-(1H-imidazol-1-yl)ethoxy)phenyl)acetate (240 mg) in THF/water (3.3 mL, 10:1) was added fine powder KOH (77 mg). The reaction mixture was stirred at rt overnight. The crude product mixture was acidified with 1.0 N HCl and diluted with EtOAc. A normal aqueous workup with EtOAc was followed. The organic layers were dried over MgSO4, filtered, and concentrated under reduce pressure. The crude acid was taken directly to the next reaction without further purification. Method[1], MS(ESI) 247.1, Retention time=0.323 min.
Reaction SMILES: C([Li])CCC.[C:6]1([CH2:12][C:13]([OH:15])=[O:14])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Br[CH2:17][CH2:18][Cl:19].Cl>CCCCCC.C1COCC1.C(OCC)(=O)C>[Cl:19][CH2:18][CH2:17][CH:12]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:13]([OH:15])=[O:14]
Reactant: ClCCBr
Reactant: O=C(O)Cc1ccccc1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=C(O)C(CCCl)c1ccccc1
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
A 2.64 M solution of butyl lithium in hexane (28 mL) was added to a solution of phenylacetic acid (5.07 g) in THF (150 mL) in a nitrogen atmosphere at −78° C., and the reaction solution was stirred at −78° C. for 20 minutes. The reaction solution was further stirred at 0° C. for one hour. Then, 1-bromo-2-chloroethane (3.1 mL) was added at 0° C., and the reaction solution was stirred at room temperature for 14 hours. Ethyl acetate and 1 N hydrochloric acid were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 5.54 g of the title compound. The property values of the compound are as follows.
Reaction SMILES: [CH:1]([CH:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:2].ClCC=CC1C=CC=CC=1.C(N(CC)CC)C.[F:28][C:29]([F:48])([C:33]([F:47])([F:46])[C:34]([F:45])([F:44])[C:35]([F:43])([F:42])[C:36]([F:41])([F:40])[CH:37]([F:39])[F:38])[C:30](Cl)=[O:31]>C(OCC)C>[CH:1]([CH:3]([O:10][C:30](=[O:31])[C:29]([F:28])([F:48])[C:33]([F:46])([F:47])[C:34]([F:44])([F:45])[C:35]([F:42])([F:43])[C:36]([F:40])([F:41])[CH:37]([F:38])[F:39])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:2]
Reactant: C=CC(O)c1ccccc1
Reactant: O=C(Cl)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)F
Agent: ClCC=Cc1ccccc1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: C=CC(OC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)F)c1ccccc1
Temperature: 0 °C
Yield: 44 %

Procedure:
100 ml of diethyl ether, 40.2 g (0.3 mol) of vinylbenzylalcohol (synthesized by the method described in "Polymer", 14 330 (1973) from chloromethylstyrene (meta: para=about 6: about 4); b.p.=69° to 73° C./0.4 mm Hg), 30.3 g (0.3 mol) of triethylamine, and 0.5 g of 2,6-di-tbutylphenol were charged into a 300-ml three-necked flask equipped with a stirrer, a reflux condenser, and a calcium chloride tube, and the mixture was then cooled with ice-water. 109.4 g (0.3 mol) of the 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-n-heptanoic acid chloride synthesized above was cooled with ice and was added to the mixture dropwise, with stirring. Next the mixture was stirred for 2 hours at room temperature, after which it was stirred for 1 hour under reflux. Then, after cooling, the deposited triethylamine hydrochloride was filtered off, the filtrate was washed twice with water, then with an aqueous sodium carbonate solution, and then it was dried over anhydrous sodium carbonate. Distillation was carried out twice to purify the dried filtrate, thus giving 61.0 g (yield: 44.0%; b.p.: 106 to 116° C./0.9 mm Hg; d: 1.47) of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-n-heptanoic acid vinylbenzyl ester.
Reaction SMILES: Br[CH:2]([CH3:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)=[O:4].[OH:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([CH3:24])=[O:23])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C>[Br:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:3](=[O:4])[CH:2]([O:14][C:15]2[CH:16]=[CH:17][C:18]([CH2:21][C:22](=[O:23])[CH3:24])=[CH:19][CH:20]=2)[CH3:13])=[CH:7][CH:8]=1
Reactant: CC(Br)C(=O)Nc1ccc(Br)cc1
Reactant: CC(=O)Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(=O)Cc1ccc(OC(C)C(=O)Nc2ccc(Br)cc2)cc1
Yield: 71.7 %

Procedure:
A solution of 2-bromo-N-(4-bromophenyl)propanamide (3.00 g, 10.2 mmol), 1-(4-hydroxyphenyl)acetone (1.54 g, 10.2 mmol) and potassium carbonate (2.83 g, 20.5 mmol) in DMF (20 ml) was stirred at room temperature for 4 hrs. Ethyl acetate was added to the reaction mixture, and the mixture was washed with 1N aqueous sodium hydroxide solution and brine. The solvent was evaporated under reduced pressure, and the obtained crude crystals were recrystallized from isopropyl ether-ethyl acetate to give the title compound (2.75 g).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][C:5]1[C:6]([N+:25]([O-])=O)=[C:7]([CH2:11][S:12]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH:8]=[CH:9][CH:10]=1.C(O)=O>C1COCC1.CO.[Pd]>[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][S:12]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[C:6]=1[NH2:25]
Reactant: O=[N+]([O-])c1c(CS(=O)(=O)c2cccc3ccccc23)cccc1OCCCl
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Solvent: O=CO
Product: Nc1c(CS(=O)(=O)c2cccc3ccccc23)cccc1OCCCl
Reaction time: 20 h
Yield: 88.6 %

Procedure:
A mixture of 1-[3-(2-chloro-ethoxy)-2-nitro-phenyl-methanesulfonyl]-naphthalene (1.24 g, 3.5 mmoles) and 10% Pd/C in THF (20 mL), methanol (5 mL), and formic acid (5 mL) was hydrogenated in a Parr hydrogenation bottle (250 mL) at 40 lb/in2 for 20 hours. The mixture was filtered through Celite, and the filtrate was diluted with EtOAc, washed with water, dried over Na2SO4, and concentrated under vacuum. The crude product was purified by flash chromatography using as eluent 5% EtOAc/CH2Cl2 to afford the title compound as an off-white solid (1.0 g, 3.1 mmoles).
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][O:16][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([O:27][C:28]1[CH:35]=[C:34]([CH3:36])[C:31]([CH:32]=[O:33])=[C:30]([CH3:37])[CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC>C(N(CC)CC)C>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@@H:15]([O:16][CH2:17][CH3:18])[C@@H:32]([C:31]1[C:30]([CH3:37])=[CH:29][C:28]([O:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:35][C:34]=1[CH3:36])[OH:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOCC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Reactant: Cc1cc(OCc2ccccc2)cc(C)c1C=O
Agent: CCCC[B+]CCCC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCN(CC)CC
Product: CCO[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)[C@H](O)c1c(C)cc(OCc2ccccc2)cc1C

Procedure:
In analogy to the procedure described in example 17 a], (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one (for the preparation of (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one see: D. Haigh, H. C. Birrell, B. C. C. Cantello, D. S. Eggleston, R. C. Haltiwanger, R. M. Hindley, A. Ramaswamy, N. C. Stevens, Tetrahedron: Asymmetry 1999, 10, 1353-1367) was reacted with 4-benzyloxy-2,6-dimethyl-benzaldehyde in the presence of triethylamine and di-n-butylboron triflate to give (S)-4-benzyl-3-[(2S,3R)-3-(4-benzyloxy-2,6-dimethyl-phenyl)-2-ethoxy-3-hydroxy-propionyl]-oxazolidin-2-one as colorless liquid. According to 1H-NMR spectroscopy, one of the four isomers is strongly predominating. The configuration was tentatively assigned as 2S,3R according to D. Haigh et al., Tetrahedron: Asymmetry 1999, 10, 1353-1367.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:9]=2[CH:20]=1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:22][CH2:23][CH2:24][CH2:25][N:26]1[C:30](=[O:31])[C:29]2[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=2[S:27]1(=[O:37])=[O:36]>>[O:36]=[S:27]1(=[O:37])[C:28]2[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=2[C:30](=[O:31])[N:26]1[CH2:25][CH2:24][CH2:23][CH2:22][N:17]1[CH2:18][CH2:19][CH:14]([N:10]2[C:9]3[CH:20]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=[CH:7][C:8]=3[O:12][C:11]2=[O:13])[CH2:15][CH2:16]1
Reactant: O=C1c2ccccc2S(=O)(=O)N1CCCCBr
Reactant: CC(C)(C)c1ccc2oc(=O)n(C3CCNCC3)c2c1
Product: CC(C)(C)c1ccc2oc(=O)n(C3CCN(CCCCN4C(=O)c5ccccc5S4(=O)=O)CC3)c2c1

Procedure:
From the hydrochloride salt of 4-(5-tert-butyl-2-oxo-3-benzoxazolinyl)-piperidine and 2-(4-bromobutyl)-1,1-dioxido-1,2-benzothiazol-3(2H)-one using the procedure described for Example 15, Step 5 there was obtained a white solid: 1H NMR (300 MHz, CDCl3) 8.07 (dd, J=6.6, 2.25 Hz, 1H), 7.88 (m, 3H), 7.19 (s, 1H), 7.11 (s, 2H), 4.17 (tt, J=12.21, 3.66 Hz, 1H), 3.85 (t, J=7.14 Hz, 2H), 3.09 (d, J=10.85 Hz, 2H), 2.46 (t, J=7.38 Hz, 2H), 2.36 (dt, J=12.15, 3.5 Hz, 2H), 2.13 (dt, J=10.89, 1.27 Hz, 2H), 1.91 (m, 4H), 1.66 (m, 2H), 1.342 (s, 9H).
Reaction SMILES: [F:1][CH:2]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([OH:5])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.C(N(CC)CC)C.FC(F)(F)C(O)=O.[NH:43]1[CH2:47][CH2:46][C@@H:45]([S:48][C:49]2[CH:54]=[CH:53][C:52]([OH:55])=[CH:51][CH:50]=2)[CH2:44]1>CN(C=O)C>[F:1][CH:2]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([N:43]1[CH2:47][CH2:46][C@@H:45]([S:48][C:49]2[CH:54]=[CH:53][C:52]([OH:55])=[CH:51][CH:50]=2)[CH2:44]1)=[O:5]
Reactant: Oc1ccc(S[C@@H]2CCNC2)cc1
Reactant: O=C(O)C(F)CCc1ccccc1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: O=C=O
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Product: O=C(C(F)CCc1ccccc1)N1CC[C@@H](Sc2ccc(O)cc2)C1
Temperature: 55 °C
Reaction time: 2 h
Yield: 94.4 %

Procedure:
(RS)-2-Fluoro-4-phenyl-butyric acid (0.66 g, 3.63 mmol) was dissolved in DMF (5 ml) and carbonyldiimidazole (0.64 g, 3.8 mmol) was added portionwise. After evolution of CO2 has ceased, the reaction mixture was warmed to 55° C. for 20 minutes and then cooled to room temperature. A mixture of triethylamine (0.46 ml, 3.3 mmol) and (3R)-4-(pyrrolidin-3-ylsulfanyl)-phenol trifluoroacetic acid (1.02 g, 3.3 mmol) in DMF (5 ml) was added. The mixture was stirred at room temperature for 2 hours. The solvent was removed in vacuo and the residue taken up in H2O (30 ml).The mixture was extracted with ethylacetate (3×20 ml). The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The residue was chromatographed over silica gel (CH2Cl2—MeOH, 99:1) to provide (2RS,3R)-2-fluoro-1-[3-(4-hydroxy-phenylsulfanyl)-pyrrolidin-1-yl]-4-phenyl-butan-1-one (1.12 g, 95%) as light yellow oil, MS: m/e=359.1(M+).
Reaction SMILES: [CH3:1][CH2:2]/[CH:3]=[CH:4]\[CH2:5]/[CH:6]=[CH:7]\[CH2:8]/[CH:9]=[CH:10]\[C:11]#[C:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C1(BC2CCCCC2)CCCCC1.[OH-].[Na+].OO>CCCCC.C1COCC1.C(O)(=O)C>[CH3:19][CH2:18]/[CH:17]=[CH:16]\[CH2:15]/[CH:14]=[CH:13]\[CH2:12]/[CH:11]=[CH:10]\[CH:9]=[CH:8]/[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]
Reactant: CC/C=C\C/C=C\C/C=C\C#CCCCCCCC
Agent: B(C1CCCCC1)C1CCCCC1
Agent: OO
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: CCCCC
Product: CC/C=C\C/C=C\C/C=C\C=C/CCCCCCC
Reaction time: 2 h

Procedure:
To a solution of (Z,Z,Z)-3,6,9-nonadecatrien-11-yne (516 mg, 2 mmol) in 10 ml of dry pentane (0° C.) was added 4.2 ml of 0.5 M dicyclohexylborane in pentane. After 2 h at 0° C., the reaction mixture was diluted with 15 ml of THF and treated with 0.6 ml of glacial acetic acid for 3 h at 50° C. The mixture was then made basic with 4 ml of 5.0 N aqueous sodium hydroxide and treated with 0.86 ml of 30% hydrogen peroxide for 0.5 h. The hexane extract (3×30 ml) was washed with water (3×30 ml), dried over MgSO4 and evaporated to leave an oily residue. Elution of the residue through silica gel (hexane) gave 292 mg (56.2%) of the desired (Z,Z,Z,Z)3,6,9,11-19:H (89% isomeric purity). This material contained (Z,Z,Z,E)3,6,9,11-19:H (1.1%) and 3 major unknown impurities (8.3%). Purification by HPLC on the silver ion-loaded Partisil M9™ 10/50 SCX column (eluted with 0.1% dimethoxyethane in hexane) yielded material which was greater than 99.0% pure; PMR (360 MHz, C6D6) δ ##STR2## 0.88 (3H, t, J=7.0 Hz, CH3CH2CH2 --). IR 3020 cm-1 (m, C--H stretch of alkenes), 2980 cm-hu -1, 2950 cm-1, 2880 cm-1 (s, C--H stretch of alkanes). CMR (90 MHz, CDCl3) δ132.8, 132.1, 129.4, 128.8, 127.7, 127.1, 123.9, 123.3, 31.8, 29.65, 29.26, 29.17, 27.6, 25.90, 25.60, 22.6, 20.6, 14.21, 14.03. EIMS (% relative abundance) 260 (0.3), 231 (0.2), 217 (0.2), 206 (0.2), 191 (0.1), 180 (1.5), 178 (0.8), 161 (1.2), 147 (1.1), 133 (1.8), 119 (5.0), 108 (67.5), 93 (26.3), 91 (24.1), 79 (100), 67 (25.6), 55 (18.2). Analysis: Calc. for C 19 H32 : 260.46. C, 87.62; H, 12.38. Found: C, 87.66, H, 12.32.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[C:15]3[S:16][CH:17]=[CH:18][C:14]=3[O:13][N:12]=2)[CH:8]=[CH:9][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].[F:25][C:26]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:27]=1[CH2:28][NH2:29]>C(#N)C>[F:25][C:26]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:27]=1[CH2:28][NH:29][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[C:15]3[S:16][CH:17]=[CH:18][C:14]=3[O:13][N:12]=2)[CH:6]=1
Reactant: NCc1ccc(F)cc1F
Reactant: BrCCOc1cccc(-c2noc3ccsc23)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Fc1ccc(CNCCOc2cccc(-c3noc4ccsc34)c2)c(F)c1
Reaction time: 8 h

Procedure:
The title compound is prepared from 3-[3-(2-bromo-ethoxy)-phenyl]-thieno[2,3-d]isoxazole, potassium carbonate, 2,4-difluorobenzylamine and acetonitrile essentially as described above in example 18 except that the reaction is run overnight and the compound is purified by column chromatography using a graded solvent mixture of 5% ethyl acetate in dichloromethane to 10% methanol in ethyl acetate. Purity by LC/MS (APCI)=98%, [M+H]+=387.
Reaction SMILES: [CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[C:14](Cl)(=[O:19])[O:15][CH:16]([Cl:18])[CH3:17].O>C(Cl)(Cl)Cl>[C:14](=[O:19])([O:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[O:15][CH:16]([Cl:18])[CH3:17]
Reactant: CC(Cl)OC(=O)Cl
Reactant: OC1CCCCC1
Solvent: O
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: CC(Cl)OC(=O)OC1CCCCC1
Temperature: -78 °C
Reaction time: 24 h

Procedure:
Cyclohexanol (4.58 g) was dissolved in chloroform (75 ml), pyridine (3.63 g) was added, and the mixture was cooled to −78° C. 1-Chloroethyl chlorocarbonate (5.0 ml) was added. The reaction mixture was gradually returned to room temperature and stirred for one day. Water was added to the reaction mixture to separate the organic layer. The organic layer was washed successively with water and brine, dried over sodium sulfate, and concentrated under reduced pressure to give the title compound (8.85 g).
Reaction SMILES: [C:1]1([C:7]2([CH2:13][CH2:14][CH2:15][OH:16])[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)=[O:19].OS(O)(=O)=O.O=[Cr](=O)=O.C(Cl)Cl>CC(C)=O>[C:1]1([C:7]2([CH2:13][CH2:14][C:15]([OH:19])=[O:16])[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)=O
Reactant: OCCCC1(c2ccccc2)CCCCO1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: O=C(O)CCC1(c2ccccc2)CCCCO1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 3-(2-phenyltetrahydro-2H-pyran-2-yl)propan-1-ol (640 mg, 2.91 mmol) in acetone (10 mL) at 0° C. was added 4.15 mL of 0.7 M Jones reagent, and the mixture was stirred for 30 mins at 0° C. and for 1 hr at room temperature. It was added to CH2Cl2 and washed with water twice. The extract was dried over Na2SO4 and evaporated to give an oily residue. The residue was purified by Combiflash (40 g silica gel) eluting with 4:6 EtOAc-hexane to 3-(2-phenyltetrahydro-2H-pyran-2-yl)propanoic acid (346 mg). LC/MS: m/e 235.21 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH2:21])=[CH:5][C:6]2[CH2:12][CH2:11][N:10]([CH:13]([CH2:17][O:18][CH3:19])[CH2:14][O:15][CH3:16])[CH2:9][CH2:8][C:7]=2[CH:20]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][CH2:32][C@H:31]2[NH:36][S:37]([CH3:40])(=[O:39])=[O:38])[C:26]([Cl:41])=[CH:25][N:24]=1>>[Cl:41][C:26]1[C:27]([NH:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][CH2:32][C@H:31]2[NH:36][S:37]([CH3:40])(=[O:39])=[O:38])=[N:28][C:23]([NH:21][C:4]2[C:3]([O:2][CH3:1])=[CH:20][C:7]3[CH2:8][CH2:9][N:10]([CH:13]([CH2:14][O:15][CH3:16])[CH2:17][O:18][CH3:19])[CH2:11][CH2:12][C:6]=3[CH:5]=2)=[N:24][CH:25]=1
Reactant: CS(=O)(=O)N[C@@H]1CCCC[C@H]1Nc1nc(Cl)ncc1Cl
Reactant: COCC(COC)N1CCc2cc(N)c(OC)cc2CC1
Product: COCC(COC)N1CCc2cc(Nc3ncc(Cl)c(N[C@@H]4CCCC[C@H]4NS(C)(=O)=O)n3)c(OC)cc2CC1

Procedure:
The title compound was prepared from 8-Methoxy-3-(2-methoxy-1-methoxymethyl-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine and N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide in an analogous manner to Example 61e. Product isolated as an off-white solid (0.044 g, 45%). MP: 167-172° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.96-7.92 (m, 2H), 7.30 (s, 1H), 6.65 (s, 1H), 5.37-5.30 (m, 2H), 3.98-3.87 (m, 1H), 3.86 (s, 3H), 3.57-3.51 (m, 2H), 3.47-3.41 (m, 2H), 3.32 (s, 6H), 3.30-3.19 (m, 1H), 3.06-2.98 (m, 1H), 2.90-2.75 (m, 11H), 2.25-2.15 (m, 2H), 1.86-1.75 (m, 2H), 1.42-1.30 (m, 4H). MS: 597.44 (MH)+.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.C(N(CC)CC)C.[C:19](Cl)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1(C)C=CC=CC=1>[C:19]([N:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CCOC(=O)C1CCNCC1
Reactant: O=C(Cl)c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)C1CCN(C(=O)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.6 %

Procedure:
18 ml (0.117 mol) of ethyl piperidine-4-carboxylate and 32.4 ml (0.2325 mol) of triethylamine were dissolved in 580 ml of toluene and treated with 18 ml (0.155 mol) of benzoyl chloride. The mixture was stirred at room temperature for 2 hrs., filtered and the solvent was evaporated. The residue was chromatographed on silica gel with ethyl acetate/hexane (1:3→1:1) as the eluent. 28.3 g (92%) of ethyl 1-benzoyl-4-piperidine-carboxylate were obtained as white crystal; m.p. 75°-78°.