Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:16]=2[CH2:24][NH:25][CH2:26][CH3:27])[CH:7]=1)[CH3:2].C(N(CC)CC)C.Cl[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:16]=2[CH2:24][N:25]([C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[CH2:26][CH3:27])[CH:7]=1)[CH3:2]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CCNCc1cc([N+](=O)[O-])ccc1Oc1cc(CC(=O)OCC)ccc1OC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)Cc1ccc(OC)c(Oc2ccc([N+](=O)[O-])cc2CN(CC)C(=O)OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To [3-(2-ethylaminomethyl-4-nitro-phenoxy)-4-methoxy-phenyl]-acetic acid ethyl ester (0.5 g, 1.29 mmol) in CH2Cl2 (20 mL) was added triethylamine (1 mL, 7.17 mmol), followed by benzyl chloroformate (0.25 g, 1.5 mmol), and the reaction was stirred at room temperature for 30 minutes. After work-up, the crude material was purified by silica gel chromatography (0-40% EtOAc in hexanes) to give the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:8]3[S:16][CH:15]=[CH:14][C:9]=3[C:10](=[O:13])[NH:11][N:12]=2)=[CH:3][CH:2]=1.[N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[CH2:27][CH2:28]O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C(Cl)Cl>[N:1]1[CH:2]=[CH:3][C:4]([C:7]2[C:8]3[S:16][CH:15]=[CH:14][C:9]=3[C:10](=[O:13])[N:11]([CH2:28][CH2:27][C:18]3[CH:19]=[CH:20][C:21]4[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=4)[N:17]=3)[N:12]=2)=[CH:5][CH:6]=1
Reactant: OCCc1ccc2ccccc2n1
Reactant: O=c1[nH]nc(-c2ccncc2)c2sccc12
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: O=c1c2ccsc2c(-c2ccncc2)nn1CCc1ccc2ccccc2n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 11.8 %

Procedure:
To a solution of 7-(pyridin-4-yl)thieno[3,2-d]pyridazin-4(5H)-one (100 mg, 0.44 mmol) from example 2.3, 2-quinolin-2-yl-ethanol from example a1 (83 mg, 0.48 mmol) and PPh3 (343 mg, 1.31 mmol) in DCM (10 mL), DEAD (228 mg, 1.31 mmol) was added dropwise. The mixture stirred at room temperature for 3 h, concentrated and the purified by Prep-HPLC to give the title compound as a white solid (20 mg, 11.8% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([SH:21])=[C:6]([NH:8][S:9]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[CH:16]=2)(=[O:11])=[O:10])[CH:7]=1.CC1(C)C2C=CC=CC=2I([C:32]([F:35])([F:34])[F:33])O1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:21][C:32]([F:35])([F:34])[F:33])=[C:6]([NH:8][S:9]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[CH:16]=2)(=[O:11])=[O:10])[CH:7]=1
Reactant: O=S(=O)(Nc1cc(Cl)ccc1S)c1cc2ccccc2o1
Reactant: CC1(C)OI(C(F)(F)F)c2ccccc21
Solvent: ClCCl
Product: O=S(=O)(Nc1cc(Cl)ccc1SC(F)(F)F)c1cc2ccccc2o1
Reaction time: 1 h
Yield: 93.8 %

Procedure:
To a solution of benzofuran-2-sulfonic acid (5-chloro-2-mercapto-phenyl)-amide (332 mg, 0.98 mmol) in CH2Cl2 (10 ml) at −78° C. was added 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole (CAS #: 887144-97-0, 354 mg, 1.07 mmol) and the reaction was stirred for 1 h, and was concentrated in vacuo. The crude product was purified by column chromatography on silica gel (CH2Cl2) to give the title compound (375 mg, 94%).
Reaction SMILES: Br[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)=[O:5].O1CCOCCOCCOCCOCCOCC1.[OH-].[K+].[Cl-].[NH4+]>ClCCl>[F:13][C:10]1[CH:11]=[CH:12][C:7]([N:6]2[CH2:2][CH2:3][C:4]2=[O:5])=[CH:8][CH:9]=1
Reactant: O=C(CCBr)Nc1ccc(F)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [Cl-]
Agent: [K+]
Solvent: ClCCl
Product: O=C1CCN1c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
12.60 g of 3-bromo-N-(4-fluorophenyl)propanamide (Example 152A, 39.94 mmol, 1 equivalent) were initially charged in 97.1 ml of dichloromethane, 11.19 g of 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6, 42.33 mmol, 1.06 equivalents) and 2.33 g of potassium hydroxide (41.54 mmol, 1.04 equivalents) were added and the mixture was stirred at RT overnight. 0.35 equivalents of 1,4,7,10,13,16-hexaoxacyclooctadecane and 0.35 equivalents of potassium hydroxide were then added and the mixture was stirred at RT overnight. Saturated aqueous ammonium chloride solution was then added and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and filtered, and the filtrate was concentrated and purified [column: Reprosil C18, 10 μm, Spring Column 470×50 mm; acetonitrile/water gradient; flow rate: 200 ml/min; 22° C.; wavelength: 210 nM]. This gave 3.46 g (38% of theory) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][C@@:16]([CH3:24])([S:20]([CH3:23])(=[O:22])=[O:21])[C:17](O)=[O:18])[C:10](=[O:25])[CH:9]=2)=[C:4]([F:26])[C:3]=1[F:27].CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.[O:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH:47]1[O:52][NH2:53]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][C@@:16]([CH3:24])([S:20]([CH3:23])(=[O:21])=[O:22])[C:17]([NH:53][O:52][CH:47]3[CH2:48][CH2:49][CH2:50][CH2:51][O:46]3)=[O:18])[C:10](=[O:25])[CH:9]=2)=[C:4]([F:26])[C:3]=1[F:27]
Reactant: C[C@@](CCn1ccc(-c2ccc(Cl)c(F)c2F)cc1=O)(C(=O)O)S(C)(=O)=O
Reactant: NOC1CCCCO1
Agent: COc1nc(Cl)nc(OC)n1
Solvent: CN1CCOCC1
Product: C[C@@](CCn1ccc(-c2ccc(Cl)c(F)c2F)cc1=O)(C(=O)NOC1CCCCO1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (4500 mg, 10.7 mmol) in Me-THF (450 mL) was added N-methyl morpholine (1.80 mL, 16.1 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (2520 mg, 13.9 mmol). The reaction mixture was stirred at room temperature for 1 h. To the mixture was added O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (1630 mg, 13.9 mmol) and the resulting mixture was stirred at room temperature for 1 h. The reaction mixture was washed with water and passed through pad of sodium sulfate, celite and silica gel. The pad was washed with ethyl acetate. The combined organic solution was concentrated under reduced pressure to give the title compound as a solid in quantitative yield. LCMS m/z 519.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48-1.57 (m, 3H) 1.59 (d, J=3.90 Hz, 3H) 1.64-1.74 (m, 3H) 2.15-2.26 (m, 1H) 2.39-2.49 (m, 1H) 3.10 (d, J=6.44 Hz, 3H) 3.46-3.58 (m, 1H) 3.70-3.83 (m, 1H) 4.03 (d, J=7.02 Hz, 1H) 4.07-4.21 (m, 1H) 4.95-5.01 (m, 1H) 6.48-6.53 (m, 1H) 6.61-6.64 (m, 1H) 7.42-7.49 (m, 1H) 7.51-7.59 (m, 1H) 7.79 (dd, J=10.83, 7.12 Hz, 1H), H—N wasn't observed. 19F NMR (376 MHz, DMSO-d6) ppm −138.09 (dd, J=22.56, 7.52 Hz) −139.10 (dd, J=22.56, 7.52 Hz)
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][N:35]([CH2:39][CH3:40])[CH2:34]1.O>CN(C)C=O>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH:33]2[CH2:38][CH2:37][CH2:36][N:35]([CH2:39][CH3:40])[CH2:34]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]
Reactant: CCN1CCCC(CBr)C1
Reactant: CCCCOc1nc(N)c2nc(OC)[nH]c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCCCOc1nc(N)c2nc(OC)n(CC3CCCN(CC)C3)c2n1
Temperature: 60 °C
Reaction time: 1 h
Yield: 48 %

Procedure:
A stirring mixture of 2-butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (200 mg) and potassium carbonate (236 mg) in dry N,N-dimethylformamide (2 ml) was heated with stirring at 60° C. for 1 hour. 3-(Bromomethyl)-1-ethylpiperidine (141 mg) was added and the stirring mixture heated at 50° C. for 3 hours. After 16 hours at ambient temperature, heating at 50° C. was continued for a further 3 hours to complete the reaction. Water was added and the mixture extracted three times with ethyl acetate. The combined extracts were washed with water then brine, dried by passing through a phase separation cartridge and stripped to give a brown oil. This was purified by C18 reverse phase chromatography using water (containing 0.1% formic acid)-acetonitrile (containing 0.05% formic acid) as eluent (10-45%) and the appropriate fractions combined and evaporated to remove acetonitrile. The remaining aqueous mixture was made basic with saturated sodium hydrogen carbonate, extracted three times with dichloromethane and the combined extracts dried by passing through a phase separation cartridge then evaporated to afford the title compound as a white solid (99 mg).
Reaction SMILES: [N:1]1([C:7](=[O:12])[CH2:8][C:9](=O)[CH3:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[CH2:21][C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26]C=1)=O.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>C(O)C>[Cl:20][C:17]1[CH:16]=[C:15]2[C:14](=[CH:19][CH:18]=1)[N:13]=[C:9]([CH3:10])[C:8]([C:7]([N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:12])=[C:21]2[C:22]1[CH:24]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: Nc1ccc(Cl)cc1CC(=O)c1ccccc1
Reactant: CC(=O)CC(=O)N1CCCCC1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CCO
Product: Cc1nc2ccc(Cl)cc2c(-c2ccccc2)c1C(=O)N1CCCCC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 47.9 %

Procedure:
To a solution of 1-(piperidin-1-yl)butane-1,3-dione (1.08 g, 6.5 mmol) in ethanol (20 ml) at room temperature was added 2-amino-5-chlorophenylacetophenone (1.16 g 5.0 mmol) followed by ytterbium triflate (294 mg, 0.5 mmol). The reaction mixture was stirred at room temperature for 12 hours. The white powdery precipitate that was formed in the reaction mixture was filtered off, washed with ethanol, and dried under reduced pressure to provide (6-chloro-2-methyl-4-phenylquinolin-3-yl)(piperidin-1-yl)methanone (874 mg, 48%) as a white powder. 1H NMR (CDCl3, 400 MHz) δ 8.1 (d, 1H, J=8.6 Hz); 7.67 (dd, 1H, J=8.6, 2.3 Hz); 7.63 (d, 1H, J=2.3 Hz); 7.6-7.5 (m, 4H); 7.33-7.28 (m, 1H); 3.55 (ddd, 1H, J=13.3, 7.4, 3.1 Hz); 3.37 (ddd, 1H, J=13.3, 7.4, 3.1 Hz); 3.05 (ddd, 1H, J=13.3, 7.4, 3.1 Hz); 2.80 (ddd, 1H, J=13.3, 7.4, 3.1 Hz); 2.77 (s, 3H); 1.60-1.2 (m, 5H); 1.0 (m, 1H). LC MS (CI) shows M+H 365.
Reaction SMILES: O[CH:2]([C:8]1[N:15]2[C:11]([N:12]([CH3:21])[C:13]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:14]=32)=[N:10][C:9]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:3]([N:5]([CH3:7])[CH3:6])=[O:4].S(Cl)(Cl)=O>ClCCl>[CH3:7][N:5]([CH3:6])[C:3](=[O:4])[CH2:2][C:8]1[N:15]2[C:11]([N:12]([CH3:21])[C:13]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:14]=32)=[N:10][C:9]=1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: Cc1ccc2c(c1)n1c(C(O)C(=O)N(C)C)c(-c3ccccc3)nc1n2C
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: Cc1ccc2c(c1)n1c(CC(=O)N(C)C)c(-c3ccccc3)nc1n2C
Reaction time: 48 h
Yield: 85.4 %

Procedure:
12.73 g (0.035 mol) of α-Hydroxy-N,N,6,9-tetramethyl-2-phenyl-9H-imidazo[1,2-a]benzimidazole-3-acetamide are treated with 75 ml of thionyl chloride in 250 ml of dichloromethane for 24 h. The solvent is evaporated and the excess thionyl chloride is evaporated under reduced pressure. The residue is taken up in toluene and the mixture is again evaporated. The residue is taken up in 600 ml of dichloromethane, 22 g of Rongalite® are added and the mixture is stirred for 48 h. Insoluble matter is removed by filtration. The filtrate is washed with water, with an aqueous sodium bicarbonate solution and again with water. The organic phase is dried over sodium sulphate, and the solvent is evaporated under reduced pressure. 10.36 g of solid are isolated which are purified by silica gel column chromatography, eluting with a chloroform/methanol 90/10 mixture. 7.86 g of product are isolated of which 1.3 g are removed and dissolved in dichloromethane. The solution is filtered and the filtrate is evaporated under reduced pressure. The residue is treated with carbon black in methanol, the suspension is filtered, the methanol is evaporated under reduced pressure, and the residue is dried under vacuum. 0.9 g of white solid are obtained. Melting point: 222°-223° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH3:23])[CH2:18]1)[CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:24]([NH2:28])[CH2:25][CH2:26][CH3:27]>>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C@@H:17]([OH:21])[CH2:18][C@@H:19]([CH3:23])[C:20]([NH:28][CH2:24][CH2:25][CH2:26][CH3:27])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@@H]1C[C@@H]([C@H](CC2CCCCC2)NC(=O)OC(C)(C)C)OC1=O
Reactant: CCCCN
Product: CCCCNC(=O)[C@H](C)C[C@H](O)[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C

Procedure:
A mixture of 0.4 g (1.23 mmole) of (3R, 5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-methyldihydrofuran-2(3H)-one (prepared as described in Preparation 2) and 6 ml of butylamine was heated under reflux for 3.0 hours, whilst stirring. At the end of this time, the reaction mixture was concentrated by distillation under reduced pressure, after which the residue was purified by column chromatography through silica gel (using ethyl acetate as the eluent) to afford 0.48 g of the title compound as a white powder.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([CH:9]=1)[CH2:7][OH:8].[CH3:11][O:12][CH2:13][CH2:14][O:15][CH2:16]Cl.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([CH2:7][O:8][CH2:11][O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:9]=1
Reactant: COCCOCCl
Reactant: OCc1cc(Br)ccc1Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COCCOCOCc1cc(Br)ccc1Cl
Yield: 88.1 %

Procedure:
To a solution of 100 g (4.52 mmol) of 5-bromo-2-chlorobenzyl alcohol in dry dichloromethane (20 ml) were added 675 mg (5.42 mmol) of 2-methoxyethoxymethyl chloride and 1.20 ml (6.89 mmol) of N,N-diisopropylethylamine in an atmosphere of argon, and the mixture was allowed to react at room temperature for 18 hours. To the reaction solution at 0° C. was a added saturated aqueous solution of ammonium chloride followed by extraction with ethyl acetate. The organic layer was washed with water and then concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography for separation and purification. Elution with dichloromethane-hexane (1:5) yielded 1.23 g (3.98 mmol) of 4-bromo-1-chloro-2-(2-methoxyethoxymethoxymethyl)benzene.
Reaction SMILES: Br[CH:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[CH2:8][C:9]#[N:10].Cl.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[O:21])=[CH:16][CH:15]=1.C(N(CC)CC)C>C(#N)C>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([CH:22]2[CH2:27][CH2:26][N:25]([CH:5]3[CH2:6][CH2:2][N:3]([CH2:8][C:9]#[N:10])[C:4]3=[O:7])[CH2:24][CH2:23]2)=[O:21])=[CH:18][CH:19]=1
Reactant: N#CCN1C(=O)CCC1Br
Reactant: COc1ccc(C(=O)C2CCNCC2)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COc1ccc(C(=O)C2CCN(C3CCN(CC#N)C3=O)CC2)cc1
Yield: 77.3 %

Procedure:
To a solution of 2-(2-bromo-5-oxopyrrolidin-1-yl)acetonitrile (730 mg, 3.6 mmol) and (4-methoxyphenyl)(piperidin-4-yl)methanone hydrochloride (920 mg, 3.6 mmol) in acetonitrile (4 mL) was added triethylamine (1.5 mL, 11 mmol). The mixture was microwave at 130° C. for 12 minutes. The solvent was removed in vacuo and the residue was taken up in methylene chloride and water. The organic layer was purified via flash column chromatography (ethyl acetate:hexane, 10:90 to 100:0) to provide slightly yellow oil (950 mg, 74% yield). 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J=8.5 Hz, 2H), 6.96 (d, J=8.5 Hz, 2H), 4.22-4.39 (m, 2H), 3.90 (s, 3H), 3.57 (dt, J=22.6, 9.0 Hz, 2H), 3.40-3.51 (m, J=8.5 Hz, 1H), 3.23-3.39 (br s, 1H), 2.93-3.20 (m, 3H), 2.33-2.61 (m, 2H), 2.13-2.31 (m, 1H), 1.83-2.03 (m, 4H). HRMS calculated for C13H23N3O3 342.1818. found (ESI, [M+H]+), 342.1830.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([CH3:28])[CH:22]=4)=[CH:17][C:15]=3[N:16]=2)[C:5]([NH:8][CH2:9][CH2:10][CH3:11])=[CH:6][CH:7]=1.[CH:29]1[C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]2[C:38]([O:40][C:41](=O)[C:31]=2[CH:30]=1)=[O:39]>C(O)(=O)C>[CH2:9]([NH:8][C:5]1[C:4]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([CH3:28])[CH:22]=4)=[CH:17][C:15]=3[N:16]=2)=[CH:3][C:2]([N:1]2[C:38](=[O:39])[C:32]3[C:31](=[CH:30][CH:29]=[C:34]([C:35]([OH:37])=[O:36])[CH:33]=3)[C:41]2=[O:40])=[CH:7][CH:6]=1)[CH2:10][CH3:11]
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Reactant: CCCNc1ccc(N)cc1-c1nc2cc(-c3ccc(Cl)c(C)c3)ccc2o1
Solvent: CC(=O)O
Product: CCCNc1ccc(N2C(=O)c3ccc(C(=O)O)cc3C2=O)cc1-c1nc2cc(-c3ccc(Cl)c(C)c3)ccc2o1

Procedure:
Prepared by the method of Example 15f), from 2-(3-amino-6-propylaminophenyl)-5-(3-methyl-4-chlorophenyl)benzoxazole (94 mg, 0.24 mmol) and 1,2,4-benzenetricarboxylic anhydride (45.6 mg, 0.24 mmol) in acetic acid (10 ml) the title compound was obtained (109 mg, 81%). 1H NMR (DMSO) δ 13.79(s, 1H), 8.49(t, 1H), 8.42(dd, 1H), 8.31(s, 1H), 8.12(d, 1H), 8.07(m, 2H), 7.83(d, 1H), 7.80(d, 1H), 7.71(dd, 1H), 7.61(dd, 1H), 7.48(m, 2H), 7.03(d, 1H), 3.38(m, 2H), 2.42(s, 3H), 1.76(m, 2H), 1.08(t, 3H). MS 566.2 m/z (M+H)+.
Reaction SMILES: [C:1]([N:5]([CH2:10][CH:11]([OH:13])[CH3:12])[CH2:6][CH:7](O)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C1(/C=C/C(=O)C)C=CC=CC=1>>[C:1]([N:5]1[CH:6]=[C:7]([CH3:8])[O:13][CH:11]([CH3:12])[CH2:10]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(O)CN(CC(C)O)C(C)(C)C
Agent: CC(=O)/C=C/c1ccccc1
Product: CC1=CN(C(C)(C)C)CC(C)O1
Yield: 56 %

Procedure:
N-t-butyl-bis-(2-hydroxypropyl)amine (60g, 0.32 mol) and trans-4-phenyl-3-buten-2-one (85g 10.58 mole) were subjected to a reaction as described in Example 1 above, except that the reaction temperature wa 220° C. A 56% yield of 3,4-dihydro-4-t-butyl-2,6-dimethyl-2H-1,4-oxazine was obtained.
Reaction SMILES: [CH3:1][SiH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:11]=[CH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH3:1][Si:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCC[SiH2]C
Reactant: C=CCCCCCC
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCCCCCCC[Si](C)(CCCCCCCC)CCCCCCCC
Yield: 86 %

Procedure:
A mixture of 61 grams of methyloctylsilane and 186 grams of 1-octene was reacted in the presence of 0.0075 gram of chlorotris(triphenylphosphine)rhodium(I) for 2.5 hours at 85°-89° C. Analysis by GLC showed a total of 15 percent of unsaturated product. After removing unreacted octene by stripping, the residue was hydrogenated as in Example 1. Distillation revealed an 86 percent yield of methyltri(octyl)silane having a boiling point of 188°-189° C. (0.9 mm).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][NH:7][CH2:6][CH2:5]2.Br[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(=O)([O-])[O-].[Na+].[Na+].[Na+].[I-]>C(#N)C.O>[C:17]([O:16][C:14](=[O:15])[CH2:13][N:7]1[CH2:6][CH2:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=2)[CH2:8]1)([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: Brc1ccc2c(c1)CCNC2
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)CN1CCc2cc(Br)ccc2C1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 6-bromo-1,2,3,4-tetrahydro-isoquinoline (10.60 g, 50 mmol) and t-butyl bromoacetate (9.95 g, 51 mmol, 1.02 eq.) in acetonitrile (100 ml) are added sodium carbonate (10.6 g, 100 mmol, 2.0 eq.) and NaI (375 mg, 2.5 mmol, 0.05 eq.). The resulting mixture is stirred at rt for 16 hr. Water (100 ml) is added to quench the reaction, and the acetonitrile is evaporated. The residue is extracted with EtOAc (100 ml×3), and the combined organic phase is dried over sodium sulfate and concentrated. The residue is purified by silica gel flash chromatography (EtOAc/hexane, 1:4) to give the title compound. MS (+VE) m/z 326.10 (M++1).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[NH2:12][CH2:13][CH2:14][NH:15][C:16]1[N:25]=[C:24]([NH2:26])[C:23]2[C:18](=[CH:19][C:20]([O:29][CH3:30])=[C:21]([O:27][CH3:28])[CH:22]=2)[N:17]=1.CN(C)C=O>O>[O:5]([CH2:1][CH:2]([OH:4])[CH2:3][NH:12][CH2:13][CH2:14][NH:15][C:16]1[N:25]=[C:24]([NH2:26])[C:23]2[C:18](=[CH:19][C:20]([O:29][CH3:30])=[C:21]([O:27][CH3:28])[CH:22]=2)[N:17]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: c1ccc(OCC2CO2)cc1
Reactant: COc1cc2nc(NCCN)nc(N)c2cc1OC
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2nc(NCCNCC(O)COc3ccccc3)nc(N)c2cc1OC
Reaction time: 48 h

Procedure:
3.8 g. Phenyl glycidyl ether and 10 g. 2-(2-aminoethylamino)-4-amino-6,7-dimethoxyquinazoline are dissolved in 5 ml. dimethylformamide and left to stand for 48 hours at ambient temperature. The reaction mixture is then poured into water, filtered with suction and purified chromatographically on a silica gel column in the manner described in Example 24. There are obtained 2.5 g. (24% of theory) of the desired product in the form of colorless crystals; m.p. 122°-124° C., after recrystallization from isopropyl alcohol.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[O:5][C@@H:6]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[O:5][C@H:6]1[CH2:10][CH2:9][NH:8][CH2:7]1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](Oc2ccccc2C(F)(F)F)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: FC(F)(F)c1ccccc1O[C@H]1CCNC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl (3R)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine-1-carboxylate (8.4 g, 25.4 mmol) in CH2Cl2 (80 mL) at rt was added TFA (8 mL, 4.1 mmol). The mixture was stirred at rt overnight. Solvent was removed in vacuo. The residue was diluted with EtOAc, washed with 1N aqueous NaOH, brine; dried (Na2SO4) and concentrated to give the title compound as a light brown oil. 1H NMR (500 MHz, CDCl3): δ 7.58 (d, 1H), 7.49 (t, 1 H), 7.03-6.99 (m, 2 H), 4.97 (t, 1 H), 3.27-3.19 (m, 2 H), 3.02-2.92 (m, 2 H), 2.13-1.99 (m, 2 H).
Reaction SMILES: CO[C:3]1[CH:8]=[C:7](/[CH:9]=[CH:10]/[C:11]([CH2:13][C:14](/[CH:16]=[CH:17]/[C:18]2[CH:23]=[CH:22][C:21](O)=[C:20]([O:25]C)C=2)=O)=O)[CH:6]=[CH:5][C:4]=1O.[OH2:28]>>[C:20]([OH:25])(=[O:28])[CH2:21][CH2:22][CH2:23][CH2:18][CH2:17][CH2:16][CH2:14]/[CH:13]=[CH:11]\[CH2:10][CH2:9][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH3:8]
Reactant: COc1cc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)c(OC)c2)ccc1O
Reactant: O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)O

Procedure:
220 g HALAD™ 344 (water soluble polymer)