Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.Cl.[CH3:9][C@@:10]12[C:17]([CH3:19])([CH3:18])[CH:14]([CH2:15][CH2:16]1)[CH2:13][NH:12][CH2:11]2.Cl.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][C:28](O)=[O:29])[CH:22]=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][C:28]([N:12]2[CH2:13][CH:14]3[C:17]([CH3:19])([CH3:18])[C@:10]([CH3:9])([CH2:16][CH2:15]3)[CH2:11]2)=[O:29])[CH:22]=1
Reactant: CC1(C)C2CC[C@]1(C)CNC2
Reactant: O=C(O)Cc1cccnc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(C)C2CC[C@]1(C)CN(C(=O)Cc1cccnc1)C2
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Triethylamine 3.20 ml (23.0 mill) was added to a methylene chloride 40 ml solution of (IS)-1,8,8-trimethyl-3-azabicyclo[3.2.1]octane hydrochloride 1.74 g (9.18 mill) and 3-pyridylacetic acid hydrochloride 1.76 g (10.1 mill) and stirred at 0° C. for 30 min. WSC 2.47 g (12.9 mill) was added therein, then temperature of the reaction mixture was gradually changed to room temperature and stirred for 46 hours. The reaction mixture was washed with saturated aqueous sodium chloride solution and dried by anhydrous sodium sulfate. After the drying agent was removed by filtration, the filtrate was concentrated in vacuo to obtain crude (IS)-3-(3-pyridylacetyl)-1,8,8-trimethyl-3-azabicyclo[3.2.1]octane. The concentrate was added to THF 60 ml solution of lithium aluminum hydride 0.77 g (20.3 mill) and refluxed under heating for 3 hours. The reaction mixture was cooled, then water was added thereto and the insoluble material was removed by filtration. The filtrate was concentrate in vacuo. The thus obtained residue was purified by means of silica gel column chromatography (Wako gel, C200, chloroform:acetone=10:1-5:1) to obtain the product as yellowish oily material.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([C:14](=[CH:20][N:21](C)[CH3:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([F:25])=[C:7]([F:24])[CH:8]=2)[N:3]=1.[CH:26]1(N)C[CH2:27]1>ClC(Cl)Cl>[CH:22]1([N:21]2[C:2]3[N:3]=[C:4]4[CH:5]=[C:6]([F:25])[C:7]([F:24])=[CH:8][C:9]4=[CH:10][C:11]=3[C:12](=[O:13])[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:20]2)[CH2:27][CH2:26]1
Reactant: NC1CC1
Reactant: CCOC(=O)C(=CN(C)C)C(=O)c1cc2cc(F)c(F)cc2nc1Cl
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1cn(C2CC2)c2nc3cc(F)c(F)cc3cc2c1=O
Temperature: 75 °C
Reaction time: 0.5 h
Yield: 59.4 %

Procedure:
A solution of ethyl 2-(2-chloro-6,7-difluoro-3-quinolinecarbonyl)-3-(dimethylamino)acrylate (20 g) and cyclopropylamine (9.25 g) in trichloromethane (80 cc) is stirred at a temperature in the region of 20° C. for 5 hours. The solution is concentrated under reduced pressure (20 kPa) at approximately 40° C. The residue is taken up in ethanol (300 cc), treated with DBU (8.2 g) and heated with stirring to approximately 75° C. for 30 minutes. After cooling to approximately 20° C., the insoluble matter is drained and washed with ethanol (2×30 cc). 1-Cyclopropyl-3-ethoxycarbonyl-7,8-difluoro-4-oxo-1,4-dihydrobenzo[b][1,8]naphthyridine (11.1 g) is obtained in the form of a yellow solid, m.p. 230° C.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:28][OH:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30](Cl)(=[O:32])[CH3:31]>>[C:30]([O:29][CH2:28][C:9]1[N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:16]2[C:11]([CH:10]=1)=[CH:12][C:13]([C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:25])[F:26])=[CH:19][CH:18]=1)=[CH:14][CH:15]=2)(=[O:32])[CH3:31]
Reactant: OCc1cc2cc(-c3ccc(OC(F)(F)F)cc3)ccc2n1Cc1ccccc1
Reactant: CC(=O)Cl
Product: CC(=O)OCc1cc2cc(-c3ccc(OC(F)(F)F)cc3)ccc2n1Cc1ccccc1

Procedure:
The title compound was prepared from {1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-2-yl}methanol and acetyl chloride in substantially the same manner, as described in step 4 of Example 1. The product was obtained as an oil. Mass spectrum (ESI, [M+H]+) m/z 440. 1H NMR (300 MHz, DMSO-d6) δ 7.88 (s, 1H), 7.77 (d, 2H, J=8.87 Hz), 7.48–7.40 (m, 4H), 7.29–7.22 (m, 3H), 7.00 (d, 2H, J=7.01 Hz), 6.72 (s, 1H), 5.50 (s, 2H), 5.24 (s, 2H), and 1.80 ppm (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]2[N:17]=[C:16]([NH2:18])[S:15][C:5]=2[C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1.Cl[CH2:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][N:29]=1)[C:24](Cl)=[O:25].C(N(C(C)C)C(C)C)C.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1>ClCCCl.C1COCC1>[CH3:1][O:2][C:3]1[C:4]2[N:17]=[C:16]([NH:18][C:24](=[O:25])[C:23]3[CH:27]=[CH:28][N:29]=[C:21]([CH2:20][N:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[CH:22]=3)[S:15][C:5]=2[C:6]([N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)=[N:7][CH:8]=1
Reactant: O=C(Cl)c1ccnc(CCl)c1
Reactant: COc1cnc(N2CCOCC2)c2sc(N)nc12
Reactant: C1COCCN1
Solvent: C1CCOC1
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1cnc(N2CCOCC2)c2sc(NC(=O)c3ccnc(CN4CCOCC4)c3)nc12

Procedure:
From 7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine with 2-chloromethyl-isonicotinoyl chloride and N-ethyldiisopropylamine in 1,2-dichloroethane and THF; then subsequent treatment with morpholine. ES-MS m/e (%): 471 (M+H+, 100).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:9])[CH:8]=1)[NH2:5].Br.Br[CH:12]([C:14]1[CH:15]=[C:16]([C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH:17]=[C:18]2[C:23]=1[O:22][C:21]([N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)=[CH:20][C:19]2=[O:30])[CH3:13]>>[F:1][C:2]1[CH:3]=[C:4]([NH:5][CH:12]([C:14]2[CH:15]=[C:16]([C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH:17]=[C:18]3[C:23]=2[O:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:20][C:19]3=[O:30])[CH3:13])[CH:6]=[C:7]([CH3:9])[CH:8]=1
Reactant: Cc1cc(N)cc(F)c1
Reactant: CC(Br)c1cc(C(=O)N(C)C)cc2c(=O)cc(N3CCOCC3)oc12
Agent: Br
Product: Cc1cc(F)cc(NC(C)c2cc(C(=O)N(C)C)cc3c(=O)cc(N4CCOCC4)oc23)c1
Yield: 58.4 %

Procedure:
3-fluoro-5-methylaniline (0.091 mL, 0.82 mmol) was reacted with 8-(1-bromoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (0.1 g, 0.20 mmol) using an analogous procedure to the one described in Example 3.03 to give 8-(1-(3-fluoro-5-methylphenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (0.053 g, 57%) as a white solid. Mass Spectrum: M+H+ 454.
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)Cl.[CH:7]1([CH2:10][N:11]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:14][CH2:13][C:12]2=[O:24])[CH2:9][CH2:8]1.II.[Br:27]Br>ClCCl>[Br:27][CH:13]1[CH2:14][CH:15]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:16][CH2:17][N:11]([CH2:10][CH:7]2[CH2:8][CH2:9]2)[C:12]1=[O:24]
Reactant: BrBr
Reactant: O=C1CCC(c2ccccc2)CCN1CC1CC1
Agent: ClP(Cl)(Cl)(Cl)Cl
Agent: II
Solvent: ClCCl
Product: O=C1C(Br)CC(c2ccccc2)CCN1CC1CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Phosphorus pentachloride (0.3 g, 1.44 mmol) was added slowly to a solution of 1-(cyclopropylmethyl)-5-phenylazepan-2-one (0.35 g, 1.44 mmol) in dichloromethane (8 mL) at 0° C. After 1 h, iodine (3.6 mg, 0.01 mmol) and bromine (0.07 mL, 1.44 mmol) were added, and the mixture was allowed to warm to ambient temperature. After 1 h, another 0.3 g of phosphorus pentachloride was added. After an additional 18 h, the reaction was quenched with saturated sodium bicarbonate. The mixture was extracted with dichloromethane (3×), and the combined organic extracts were washed with water (3×), saturated brine, dried over sodium sulfate, filtered and concentrated.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[CH2:12](Br)/[CH:13]=[C:14](/[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])\[CH3:15]>>[CH2:12]([O:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5])/[CH:13]=[C:14](/[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])\[CH3:15]
Reactant: COC(=O)c1ccccc1O
Reactant: CC(C)=CCC/C(C)=C/CBr
Product: CC(C)=CCC/C(C)=C/COc1ccccc1C(=O)O
Yield: 74.3 %

Procedure:
In a manner similar to Reference Example 1, methyl 2-hydroxybenzoate (7.61 g) was reacted with geranyl bromide (10.9 g) and then hydrolyzed to yield 10.2 g (75%) of 2- geranyloxybenzoic acid.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([N:15]3[CH2:19][CH2:18][CH2:17][C:16]3=[O:20])[C:7]=2[CH:21]=1.C(N(CC)CC)C.[C:29](Cl)(=[O:31])[CH3:30]>ClCCl>[C:29]([NH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:12])([CH3:13])[C@@H:9]([OH:14])[C@H:8]([N:15]3[CH2:19][CH2:18][CH2:17][C:16]3=[O:20])[C:7]=2[CH:21]=1)(=[O:31])[CH3:30]
Reactant: CC(=O)Cl
Reactant: CC1(C)Oc2ccc(CN)cc2[C@@H](N2CCCC2=O)[C@@H]1O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCc1ccc2c(c1)[C@@H](N1CCCC1=O)[C@H](O)C(C)(C)O2
Reaction time: 2 h

Procedure:
To the compound of example 10 (0.57 g) and triethylamine (0.55 ml) stirred in dichloromethane (50 ml) was added acetyl chloride (0.154 ml) dropwise, at 0° C. After 2 h at 0° C., more acetyl chloride (0.154 ml) was added and the reaction mixture stirred for a further 16 h and allowed to attain room temperature. The organic phase was washed with water and brine and dried over anhydrous magnesium sulphate. Filtration and evaporation gave the crude product (0.33 g) which was recrystallised from ethyl acetate-dichloromethane to give the title compound (0.24 g) as colourless crystals of mp 206°-208° C.
Reaction SMILES: Cl.[CH3:2][C:3]1[C:11]2[CH2:10][O:9][C:8](=[O:12])[C:7]=2[CH:6]=[CH:5][C:4]=1[CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[CH3:21][O:22][C:23]1[CH:30]=[C:29]([CH2:31][CH:32]=O)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26]>>[CH3:21][O:22][C:23]1[CH:30]=[C:29]([CH2:31][CH2:32][N:18]2[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][C:4]3[C:3]([CH3:2])=[C:11]4[C:7](=[CH:6][CH:5]=3)[C:8](=[O:12])[O:9][CH2:10]4)[CH2:16][CH2:17]2)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26]
Reactant: COc1cc(CC=O)ccc1C#N
Reactant: Cc1c(CCN2CCNCC2)ccc2c1COC2=O
Agent: Cl
Product: COc1cc(CCN2CCN(CCc3ccc4c(c3C)COC4=O)CC2)ccc1C#N

Procedure:
2-Methoxy-4-[2-[4-[2-(4-methyl-1-oxo-3H-isobenzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]benzonitrile was prepared in a similar fashion to that described for the synthesis of Example 38 starting from 4-methyl-5-[2-(piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one hydrochloride and 2-methoxy-4-(2-oxoethyl)benzonitrile. LC-MS (IE, m/z): 420.2 [M+1]+. (0.035 μM)
Reaction SMILES: CN(C)C=O.[Br:6][C:7]1[N:24]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:10]2[CH:11]=[N:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:14](=[O:15])[C:9]=2[C:8]=1[CH2:33]Br.[CH3:35][C:36]([CH3:39])([O-:38])[CH3:37].[Na+]>O>[Br:6][C:7]1[N:24]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:31])([CH3:30])[CH3:32])[C:10]2[CH:11]=[N:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:23])[CH3:21])[C:14](=[O:15])[C:9]=2[C:8]=1[CH2:33][O:38][C:36]([CH3:39])([CH3:37])[CH3:35]
Reactant: C[Si](C)(C)CCOCn1ncc2c(c(CBr)c(Br)n2COCC[Si](C)(C)C)c1=O
Reactant: CC(C)(C)[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OCc1c(Br)n(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Reaction time: 3 h
Yield: 24.5 %

Procedure:
To 50 ml of N,N-dimethylformamide solution containing 2.52 g (4.44 mmol) of 2-bromo-3-bromomethyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 25-(a) was added 0.43 g (4.44 mmol) of sodium tert-butoxide at −10° C., and the mixture was stirred at the same temperature for 3 hours. The mixture was further stirred at 0° C. for 10 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with toluene. The organic layer after separation was washed successively with water and then with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=98:2→65:35 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 0.61 g of the title compound as a pale yellowish solid. (Yield: 25%)
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[C:11](=[O:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N#N.[CH2:23]([Mg]Br)[CH3:24].COC(C)(C)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[C:11]([CH2:23][CH3:24])([OH:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc2c(c1)N(C(=O)OC(C)(C)C)CCC2=O
Reactant: CC[Mg]Br
Agent: N#N
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Product: CCC1(O)CCN(C(=O)OC(C)(C)C)c2cc(OC)ccc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 45 %

Procedure:
To a flame dried 250 mL round bottom flask equipped with a magnetic stir bar and a N2 gas inlet was added IV (2.23 mg, 8.05 mmol) in dry THF (100 mL). The solution was cooled to 0° C. under a blanket of N2 and a 1.0M solution of ethyl magnesium bromide (EtMgBr) in methyl-tert-butyl ether (16.1 mL, 16.1 mmol, 2 equiv) was added via syringe. The solution was stirred at 0° C. for 1 h. The reaction was quenched with NH4Cl (saturated aqueous solution) extracted with EtOAc, dried (MgSO4), and concentrated to give V as a colorless oil (1.11 g, 3.61 mmol, 45%). Spectral data matched that previously disclosed for this compound.
Reaction SMILES: C(Br)C.Cl[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[CH2:10])=[CH:7][CH:6]=1.CN([CH:16]=[O:17])C>C1COCC1>[CH:9]([C:8]1[CH:11]=[CH:12][C:5]([CH:16]=[O:17])=[CH:6][CH:7]=1)=[CH2:10]
Reactant: C=Cc1ccc(Cl)cc1
Reactant: CN(C)C=O
Solvent: C1CCOC1
Solvent: CCBr
Product: C=Cc1ccc(C=O)cc1
Reaction time: 2 h
Yield: 95 %

Procedure:
7.6 gms (0.312 moles) of Mg tunings were transferred to an RB flask containing 50 ml of dry THF under nitrogen atmosphere. 2 ml of ethyl bromide was then added to the Mg metal and the reaction mixture was warmed to 50°-55° C. The mixture reacted vigorously and activated Mg metal was formed. A solution of 20 ml (0.156 moles) of 4-chlorostyrene in 50 ml of THF was added dropwise at room temperature to the activated Mg. The reaction mixture was stirred for an additional two hours. A dark gray solution appeared and was allowed to settle down. In a separate 1L RB flask, a solution of 12 ml (0.15 moles) of anhydrous DMF was prepared in 300 ml of THF. The DMF solution was cooled in an icebath under dry nitrogen atmosphere for 15 mins. Grignard reagent was added dropwise to the DMF solution over a period of 1 hr with vigorous stirring. The reaction flask was then allowed to stir for three hrs. at 5° C. and RT overnight. The reaction was quenched by pouring the entire reaction mixture into 300 ml of dilute HCl in an icebath. The product was separated by solvent extraction with ether. The ether layer was dried over anhyd. MgSO4 and filtered. Finally, ether was evaporated under reduced pressure. A viscous yellow liquid was obtained and was dried under vacuum for 2 hrs and stored in a freezer at -10° C. containing a small amount of hydroquinone as an inhibitor. A yield of 65% high purity (above 95%) 4-vinyl benzaldehyde was obtained.
Reaction SMILES: [CH2:1]1[N:12]2[C:13]3[C:3](=[CH:4][CH:5]=[CH:6][C:7]=3[C:8](=S)[NH:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=32)[CH2:2]1.[CH2:19]([NH2:22])[C:20]#C.[C:23]1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)CCC>[CH3:23][C:15]1[CH:16]=[CH:17][C:10]2[N:9]3[CH:20]=[CH:19][N:22]=[C:8]3[C:7]3[CH2:6][CH2:5][CH:4]=[C:3]4[CH:2]=[CH:1][N:12]([C:13]=34)[C:11]=2[CH:14]=1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: C#CCN
Reactant: S=C1Nc2ccccc2N2CCc3cccc1c32
Solvent: CCCCO
Product: Cc1ccc2c(c1)-n1ccc3c1=C(CCC=3)c1nccn1-2
Yield: 71.4 %

Procedure:
1,2-Dihyrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-thione (4 g), propargylamine (1.2 ml), n-butanol (100 ml) and a catalytic amount of p-toluenesulfonic acid were combined and refluxed overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified by high performance liquid chromatography (2% methanol/dichloromethane) to give 3.1 g (71.4%) of product. Recrystallization from ethanol gave the analytical sample, mp 175° C.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]([CH3:44])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:40]([CH3:43])[CH2:41][CH3:42])[C@H:33]([O:38][CH3:39])[CH2:34][C:35]([OH:37])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.FC(F)(F)C(O[C:56]1[C:61]([F:62])=[C:60]([F:63])[C:59]([F:64])=[C:58]([F:65])[C:57]=1[F:66])=O>ClCCl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]([CH3:44])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:40]([CH3:43])[CH2:41][CH3:42])[C@H:33]([O:38][CH3:39])[CH2:34][C:35](=[O:37])[O:36][C:56]3[C:57]([F:66])=[C:58]([F:65])[C:59]([F:64])=[C:60]([F:63])[C:61]=3[F:62])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C
Reactant: O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)Oc1c(F)c(F)c(F)c(F)c1F)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C
Reaction time: 0.25 h

Procedure:
To a second flask containing #32 (360 mg, 0.59 mmol) in dichloromethane (0.6 mL, 1 M) and pyridine (0.095 mL, 1.2 mmol, 2 eq.) was added drop-wise pentafluorophenyl trifluoroacetate (0.203 mL, 1.18 mmol). This reaction mixture was stirred for 15 minutes.
Reaction SMILES: O[CH2:2][CH2:3][O:4][C:5](=[O:17])CCCCCCCCC([O-])=O.CN1C(C)(C)C[CH:22]([OH:27])[CH2:21]C1(C)C.[C:30]1(C)C=CC=C[CH:31]=1>C1(C)C(S(O)(=O)=O)=CC=CC=1.O>[CH:5]([O:4][CH2:3][CH3:2])([O:17][CH2:30][CH3:31])[O:27][CH2:22][CH3:21]
Reactant: Cc1ccccc1
Reactant: CN1C(C)(C)CC(O)CC1(C)C
Reactant: O=C([O-])CCCCCCCCC(=O)OCCO
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: O
Product: CCOC(OCC)OCC

Procedure:
Mono(2-hydroxyethyl)sebacate and 23.6 g (0.1 mole) 1,2,2,6,6-pentamethylpiperidin-4-ol 17.1 g (0.1 mole) were esterified by heating with 0.4 g toluenesulfonic acid catalyst and 100 cc toluene in a reflux apparatus including a Dean-Stark trap to collect the reaction water as it evolved. When no more water obtained 22.2 g (0.15 mole) triethyl orthoformate was added and heating under reflux continued for 9 hours. Stripping under vacuum removed toluene and excess triethyl orthoformate, and left an oily liquid product represented by formula ##STR49##
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=2)[C:16]([O:18]C)=[O:17])=[N:6][C:7]=1[C:8]([NH:10][CH2:11][CH3:12])=[O:9].[OH-].[Na+]>CO>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=2)[C:16]([OH:18])=[O:17])=[N:6][C:7]=1[C:8]([NH:10][CH2:11][CH3:12])=[O:9]
Reactant: CCNC(=O)c1nc(-c2cccc(C(=O)OC)c2)cnc1N
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCNC(=O)c1nc(-c2cccc(C(=O)O)c2)cnc1N
Temperature: 92.5 °C
Yield: 97.1 %

Procedure:
Methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate (480 mg, 1.6 mmol) was suspended in a 20 mL of 1:1 MeOH-5% aqueous sodium hydroxide and heated at 90-95° C. for 4 hours. The homogeneous reaction mixture was cooled to room temperature, concentrated to half the initial volume, cooled in an ice-bath, and acidified to pH 4 with concentrated HCl. A white solid precipitated and was collected by filtration, washed with water and dried in vacuo to give 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoic acid (445 mg, 97% yield). The acid (40 mg, 0.14 mol) was dissolved in DMF (1 mL) and 1-hydroxybenzotriazole (30 mg, 0.22 mmol), 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (30 mg, 0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were added sequentially. After one hour, 2-chloro-6-fluorobenzylamine (30 mg, 0.19 mmol) was added to the reaction mixture and stirring was continued at room temperature for 18 hours. It was then diluted with ethyl acetate (10 mL), washed with water, saturated sodium bicarbonate solution, and brine, dried over sodium sulfate, filtered, and concentrated. The oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield) to give 3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-ethylpyrazine-2-carboxamide (a tan color solid, 31 mg, 51% yield): 1H NMR (400 MHz, DMSO-d6): 8.86 (s, 1H), 8.85-8.83 (b, 1H), 8.45 (s, 1H), 8.33-8.31 (d, 1H), 7.83-7.81 (d, 1H), 7.53-7.51 (t, 1H), 7.39-7.34 (m, 2H), 7.26-7.21 (t, 1H), 4.63-4.61 (d, 2H), 3.38-3.29 (m, 2H), 1.15-1.11 (t, 3H); MS (EI) for C21H19ClFN5O2: 428 (MH+).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([Cl:21])=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[N:7]=1.[CH3:22][P:23]([C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[C:28]([O:33][C:34]([F:37])([F:36])[F:35])[CH:27]=1)([CH3:25])=[O:24].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CC(O)C.ClCCl>[Cl:21][C:5]1[N:4]=[N:3][C:2]([NH:30][C:29]2[CH:31]=[CH:32][C:26]([P:23]([CH3:25])([CH3:22])=[O:24])=[CH:27][C:28]=2[O:33][C:34]([F:37])([F:35])[F:36])=[N:7][C:6]=1[NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16]
Reactant: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)nnc1Cl
Reactant: CP(C)(=O)c1ccc(N)c(OC(F)(F)F)c1
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: CC(C)O
Solvent: ClCCl
Product: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(P(C)(C)=O)cc2OC(F)(F)F)nnc1Cl
Temperature: 25 °C

Procedure:
A mixture of 3,6-dichloro-N-[2-(propan-2-ylsulfonyl)phenyl]-1,2,4-triazin-5-amine (prepared as in Example 106: 0.7 mmol), 4-(Dimethylphosphoryl)-2-(trifluoromethoxy)aniline (0.7 mmol) and camphorsulfonic acid (0.7 equiv.), is refluxed for 20-48 hours in 2-propanol. The reaction mixture is allowed to cool to room temperature, dissolved in dichloromethane and washed with an aqueous solution of Na2CO3. The dichloromethane extract is dried over MgSO4 and evaporated. The crude product is purified by Prep-HPLC.
Reaction SMILES: C(O)C=C.[C:5]([O:8]C(=O)C)(=[O:7])[CH3:6].C(O)(=O)C.[C:16]([O:35]C)(=[O:34])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>>[C:5]([O-:8])(=[O:7])[CH3:6].[C:16]([O-:35])(=[O:34])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CC(=O)OC(C)=O
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Solvent: CC(=O)O
Solvent: C=CCO
Product: CC(=O)[O-]
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]

Procedure:
Polyallyl acetate is prepared as described by Bartlett and Altschul, cited above. A 500-mL reaction flask equipped with a thermometer, stirrer, and reflux condenser is charged with 1.5 moles (102 mL) of allyl alcohol, 0.75 mole (71 mL) of acetic anhydride, and 1.5 moles (86 mL) acetic acid. Five mL concentrated sulfuric is added and the mixture heated under reflux for two hours. The mixture is poured slowly with stirring into ice water, and extracted with ice-cold sodium carbonate and cold saturated calcium chloride solutions. After drying with 12 g. of anhydrous potassium carbonate, the ester is distilled twice through an all-glass apparatus in a stream of nitrogen. The middle fractions only are collected to yield a product having a boiling point (124-126 mm) of 53.2° to 54° C. Using the method of Bartlett and Altschul, the polymer had an average of about 13 monomer units. The polymer is interesterified with methyl oleate as described in Example 1 above and purified to obtain polyallyl oleate.