Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[F:14])[C:5](N(OC)C)=[O:6].[CH3:15][Mg]Cl>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:5](=[O:6])[CH3:15])[CH:11]=[CH:12][C:13]=1[F:14]
Reactant: C[Mg]Cl
Reactant: CON(C)C(=O)c1ccc(F)c(Br)c1
Solvent: C1CCOC1
Product: CC(=O)c1ccc(F)c(Br)c1
Reaction time: 1 h

Procedure:
A solution of 3-bromo-4-fluoro-N-methoxy-N-methylbenzamide (50 g, 0.19 mol) in 500 mL of THF was cooled to 0° C. in ice bath, and then the mixture was added MeMgCl (27.3 g, 0.21 mol) dropwise. The reaction mixture was stirred under N2 for 1 h. The reaction mixture was quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified with silica gel column chromatography to give 1-(3-bromo-4-fluorophenyl)ethanone.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[F:12])=O.[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][N:23]=1)[C:17]([O:19][CH3:20])=[O:18]>C(O)C>[F:12][C:6]1[CH:7]=[CH:8][C:9]([F:11])=[CH:10][C:5]=1[C:3]1[N:13]=[C:14]2[CH:15]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[CH:21]=[CH:22][N:23]2[CH:2]=1
Reactant: O=C(CBr)c1cc(F)ccc1F
Reactant: COC(=O)c1ccnc(N)c1
Solvent: CCO
Product: COC(=O)c1ccn2cc(-c3cc(F)ccc3F)nc2c1
Temperature: 60 °C
Reaction time: 18 h
Yield: 135.9 %

Procedure:
2-Bromo-1-(2,5-difluorophenyl)ethanone (1.5 g) was added to an ethanol (8.2 ml) solution of methyl 2-aminoisonicotinate (1.0 g), and the obtained mixture was then stirred in a nitrogen atmosphere at 60° C. for 18 hours. Thereafter, 2-bromo-1-(2,5-difluorophenyl)ethanone (0.77 g) was added to the reaction solution, and the obtained mixture was then stirred for 6 hours at the same temperature as described above. Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue. The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) and was then dried, so as to obtain the title compound (2.5 g) in the form of a pink solid.
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:12]=[C:13]=[S:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH2:15]([NH2:18])[CH2:16][NH2:17]>C(Cl)Cl.ClCl>[CH3:1][C:2]1[C:3]([NH:12][C:13]([NH:17][CH2:16][CH2:15][NH2:18])=[S:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2
Reactant: NCCN
Reactant: Cc1c(N=C=S)ccc2cccnc12
Agent: ClCl
Solvent: ClCCl
Product: Cc1c(NC(=S)NCCN)ccc2cccnc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 8-methyl-7-quinolinylisothiocyanate (1.36 g) in CH2Cl2 (50 mL) is added dropwise to ethylene diamine (2.26 mL) in solution in CH2 Cl2 (50 mL). The mixture is stirred for 30 minutes at room temperature then rotary evaporated. The residue is suspended in CH2 Cl2 (50 mL) and ether (50 mL) and filtered. The precipitate is dried in vacuo to afford N-(8-methyl-7-quinolinyl)-N'-2-aminoethylthiourea as a white powder.
Reaction SMILES: [Br:1][C:2]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].[CH2:15]1COCC1>C(OCC)C>[Br:1][C:2]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:3]=1[C:4](=[O:5])[CH3:15]
Reactant: CON(C)C(=O)c1cc(F)ccc1Br
Reactant: C1CCOC1
Solvent: CCOCC
Product: CC(=O)c1cc(F)ccc1Br
Temperature: 25 °C
Reaction time: 15 h
Yield: 81 %

Procedure:
To a solution of 2-bromo-5-fluoro-N-methoxy-N-methylbenzamide (1.54 g, 5.88 mmol) in THF (60 mL) at 0° C. was added McMgI (3.0 M in diethyl ether, 1.998 mL, 5.99 mmol) dropwise over 5 min, the reaction immediately turned bright yellow after a few drops and then after continued addition the reaction lost the yellow color and a significant amount of white precipitate crashed out. After 15 min the reaction was warmed to room temperature and stirred for 15 h after which an additional 3×0.5 equiv. McMgI (1.0 mL) was added every 3 h until after 23 h the reaction was quenched by addition of sat. aq. NH4Cl solution and extracted with diethy ether (3×). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo and the resulting crude material was purified by column chromatography (SiO2, 0-20% EtOAc/Hexanes) to afford 1-(2-bromo-5-fluorophenyl)ethanone (1.038 g, 4.78 mmol, 81% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.57 (dd, J=8.8, 4.9 Hz, 1H), 7.18 (dd, J=8.4, 3.1 Hz, 1H), 7.07-6.99 (m, 1H), 2.63 (s, 3H).
Reaction SMILES: NC1C([N+]([O-])=O)=CC=C2C=1C=CC=N2.NC1C(N)=CC=C2C=1C=CC=N2.[Sn](Cl)Cl.[NH2:30][C:31]1[C:40]([NH:41][C:42]([CH3:44])=[O:43])=[CH:39][CH:38]=[C:37]2[C:32]=1[CH:33]=[CH:34][CH:35]=[N:36]2.C(OC(=O)C)(=O)C.[CH2:52]([S:58][CH:59]([CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH3:70])[C:60](O)=[O:61])[CH2:53][CH2:54][CH2:55][CH2:56][CH3:57]>N1C=CC=CC=1>[NH:41]([C:40]1[C:31]([NH:30][C:60](=[O:61])[CH:59]([S:58][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH3:70])=[C:32]2[C:37](=[CH:38][CH:39]=1)[N:36]=[CH:35][CH:34]=[CH:33]2)[C:42]([CH3:44])=[O:43]
Reactant: CC(=O)Nc1ccc2ncccc2c1N
Reactant: CCCCCCCCC(SCCCCCC)C(=O)O
Agent: Cl[Sn]Cl
Agent: Nc1c([N+](=O)[O-])ccc2ncccc12
Agent: Nc1ccc2ncccc2c1N
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CCCCCCCCC(SCCCCCC)C(=O)Nc1c(NC(C)=O)ccc2ncccc12

Procedure:
Commercially available 5-amino-6-nitroquinoline was reduced to 5,6-diaminoquinoline using a procedure analogous to that described in Example 34, except tin (II) chloride was used in place of iron. 5,6-Diaminoquinoline was converted to 5-amino-6-acetaminoquinoline by reaction with acetic anhydride and pyridine. Using the procedure outlined in Example 25, 5-amino-6-acetaminoquinoline and 2-(hexylthio)decanoic acid were coupled to give the title compound. Mass spectrum m/e: 471.3 (M+).
Reaction SMILES: I(Cl)(=O)=O.I(Cl)(=O)=O.C([N+](C)(C)C)C1C=CC=CC=1.[C:20]([C:24]1[C:29]2[O:30][CH2:31][C:32]([CH3:34])([CH3:33])[C:28]=2[CH:27]=[C:26]([C:35](=[O:37])[CH3:36])[CH:25]=1)([CH3:23])([CH3:22])[CH3:21].[Cl:38]CCCl>CO>[C:20]([C:24]1[C:29]2[O:30][CH2:31][C:32]([CH3:34])([CH3:33])[C:28]=2[CH:27]=[C:26]([C:35](=[O:37])[CH2:36][Cl:38])[CH:25]=1)([CH3:23])([CH3:21])[CH3:22]
Reactant: ClCCCl
Reactant: CC(=O)c1cc(C(C)(C)C)c2c(c1)C(C)(C)CO2
Agent: C[N+](C)(C)Cc1ccccc1
Agent: O=I(=O)Cl
Solvent: CO
Product: CC(C)(C)c1cc(C(=O)CCl)cc2c1OCC2(C)C
Temperature: 25 °C

Procedure:
A mixture of benzyltrimethylammonium dichloroiodate (18.18 g, 52.2 mmol), 1-(7-tert-butyl-3,3-dimethyl-2,3-dihydrobenzo[b]furan-5-yl)-ethan-1-one (6.65 g, 27.0 mmol), 325 mL of 1,2-dichloroethane, and 130 mL of methanol is heated at reflux for 1.5 h. The reaction mixture is cooled to room temperature and concentrated in vacuo; 5% aqueous sodium bisulfite solution (126 mL) is added to the residue obtained. This mixture is extracted with ether and the extract is dried over anhydrous magnesium sulfate and concentrated to afford 8.38 g of the title compound as a reddish solid.
Reaction SMILES: Cl.[OH:2][CH:3]1[CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.Cl[C:15]1[N:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18]>O1CCCC1.CO>[Cl:25][C:22]1[CH:23]=[N:24][C:15]([N:5]2[CH2:6][CH:3]([OH:2])[CH2:4]2)=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]
Reactant: COC(=O)c1cc(Cl)cnc1Cl
Reactant: OC1CNC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)c1cc(Cl)cnc1N1CC(O)C1
Temperature: 75 °C
Yield: 76.6 %

Procedure:
To a mixture of 3-Hydroxyazetidine hydrochloride (37.17 g, 0.339 mol) and triethylamine (70.93 ml, 0.508 mol) in tetrahydrofuran/methanol (840/280 ml) Methyl 2,5-dichloronicotinate (70 g, 0.339 mol) was added and the resulting mixture was heated at 75° C. for 4 hours then at 62° C. overnight. 3-Hydroxyazetidine hydrochloride (3.7 g, 0.03 mol) and triethylamine (23.60 ml, 0.16 mol) were added and the reaction mixture was further heated at 80° C. for 28 h. Solvents were evaporated in vacuo. The residue was taken in dichloromethane (400 ml) and water (500 ml). The formed solid was filtered, washed with water (500 ml) and dried in vacuum to afford a first batch of the title compound (D62) (63 g).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6](/[C:10](/[C:20]3[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([O:30]CC)=[O:29])=[CH:22][CH:21]=3)=[C:11](/[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)\[CH2:12][CH3:13])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[H][H]>[Pd].CCO.CCOC(C)=O>[NH:1]1[C:9]2[C:4](=[CH:5][C:6](/[C:10](/[C:20]3[CH:21]=[CH:22][C:23]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:24][CH:25]=3)=[C:11](/[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)\[CH2:12][CH3:13])=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: [H][H]
Reactant: CCOC(=O)/C=C/c1ccc(/C(=C(/CC)c2ccccc2)c2ccc3[nH]ncc3c2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC/C(=C(/c1ccc(CCC(=O)O)cc1)c1ccc2[nH]ncc2c1)c1ccccc1
Temperature: 25 °C
Reaction time: 36 h
Yield: 48 %

Procedure:
A 10-mL recovery flask equipped with a magnetic stir bar and a rubber septum was charged with Compound 1 (50 mg, 0.126 mmol) and EtOH-EtOAc (1:1, 2.5 mL). To this solution, palladium on carbon (13 mg, 10% Pd/C) was added in one portion. The flask was equipped with a hydrogen balloon, and the resulting mixture was stirred at room temperature 36 h. This mixture was filtered through Celite, concentrated, and purified on a RP-C18 column using 30-100% acetonitrile in water in the presence of 0.1% TFA to afford the title compound (24 mg). 1H NMR (300 MHz, Acetone-d6): 6; 7.94 (s, 1H), 7.58 (br, 1H), 7.44 (d, 1H), 7.17-6.97 (m, 6H), 6.8-6.73 (m, 4H), 2.64 (t, 2H), 2.39-2.32 (m, 4H), 0.80 (t, 3H), (NH and CO2H protons not observed). LCMS: 397 (M+H)+.
Reaction SMILES: CN(C)[CH:3]=[CH:4][C:5](=O)[C:6]([CH3:14])([C:8]1[O:12][N:11]=[C:10]([CH3:13])[N:9]=1)C.[N+]([O-])(O)=[O:18].[N+]([O-])(O)=O.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([NH:39][C:40]([NH2:42])=[NH:41])[CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1>>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([NH:39][C:40]2[N:42]=[C:5]([C:6]([C:8]3[O:12][N:11]=[C:10]([CH3:13])[N:9]=3)([OH:18])[CH3:14])[CH:4]=[CH:3][N:41]=2)[CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1
Reactant: COc1cc(NC(=N)N)ccc1-n1cnc(C)c1
Reactant: Cc1noc(C(C)(C)C(=O)C=CN(C)C)n1
Reactant: O=[N+]([O-])O
Product: COc1cc(Nc2nccc(C(C)(O)c3nc(C)no3)n2)ccc1-n1cnc(C)c1

Procedure:
The title compound was prepared from crude 1-dimethylamino-4-methyl-4-(3-methyl-[1,2,4]oxadiazol-5-yl)-pent-1-en-3-one (138 mg, 0.6 mmol) and N-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-guanidine dinitrate (185 mg, 0.5 mmol) using in analogous manner the procedure described in example 39b). Obtained as a pale-yellow solid (32 mg, 16%);
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:21])[N:10]([CH2:12][CH:13]([NH2:20])[CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN([C:27]([N:29]2[CH:33]=N[CH:31]=[CH:30]2)=[O:28])C=1.CCN(C(C)C)C(C)C.[O:43]1[C:47]2[C:48]([C@:52]([C@@H:60]3CCCN[CH2:61]3)([OH:59])[CH2:53][CH2:54][CH2:55][CH2:56][O:57][CH3:58])=[CH:49][CH:50]=[CH:51][C:46]=2[CH:45]=[CH:44]1>C(Cl)Cl>[O:43]1[C:47]2[C:48]([C@:52]([C@@H:60]3[CH2:61][CH2:31][CH2:30][N:29]([C:27]([NH:20][C@@H:13]([CH2:14][CH:15]4[CH2:16][CH2:17][CH2:18][CH2:19]4)[CH2:12][N:10]([CH3:11])[C:9](=[O:21])[O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:28])[CH2:33]3)([OH:59])[CH2:53][CH2:54][CH2:55][CH2:56][O:57][CH3:58])=[CH:49][CH:50]=[CH:51][C:46]=2[CH:45]=[CH:44]1
Reactant: CN(CC(N)CC1CCCC1)C(=O)OCc1ccccc1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: COCCCC[C@@](O)(c1cccc2ccoc12)[C@@H]1CCCNC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COCCCC[C@@](O)(c1cccc2ccoc12)[C@@H]1CCCN(C(=O)N[C@@H](CC2CCCC2)CN(C)C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.8 %

Procedure:
To a solution of (2-amino-3-cyclopentyl-propyl)-methyl-carbamic acid benzyl ester (87 mg, 0.3 mmol) and CDI (48.6 mg, 0.3 mmol) in CH2Cl2 (5 mL) cooled to 0-5° C. was added DIEA (0.5 mL). After stirring for 30 minutes, a solution of (S)-1-(benzofuran-7-yl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (95.1 mg, 0.3 mmol) in CH2Cl2 (3 mL) was added dropwise. The reaction mixture was allowed to warm to rt and stirred overnight. The mixture was washed with water (10 mL). The aqueous layer was extracted with CH2Cl2 (2×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by prep HPLC to give benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamate (98.5 mg, 51.9%).
Reaction SMILES: [CH:1]1[C:22]2[C:5](=[CH:6][C:7]3[C:20]([CH:21]=2)=[CH:19][C:18]2[C:9](=[CH:10][C:11]4[C:16]([CH:17]=2)=[CH:15][CH:14]=[CH:13][CH:12]=4)[CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[C:23]1(=[O:29])[NH:27][C:26](=[O:28])[CH:25]=[CH:24]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60]O.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Br:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][C:24]1[C:23]([NH:27][C:26](=[O:28])[CH:25]=1)=[O:29].[CH:4]1[C:5]2[C:22](=[CH:21][C:20]3[C:7]([CH:6]=2)=[CH:8][C:9]2[C:18](=[CH:17][C:16]4[C:11]([CH:10]=2)=[CH:12][CH:13]=[CH:14][CH:15]=4)[CH:19]=3)[CH:1]=[CH:2][CH:3]=1.[Br:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][N:27]1[C:26](=[O:28])[CH:25]=[CH:24][C:23]1=[O:29].[CH:4]1[C:5]2[C:22](=[CH:21][C:20]3[C:7]([CH:6]=2)=[CH:8][C:9]2[C:18](=[CH:17][C:16]4[C:11]([CH:10]=2)=[CH:12][CH:13]=[CH:14][CH:15]=4)[CH:19]=3)[CH:1]=[CH:2][CH:3]=1
Reactant: OCCCCCCCCCCCBr
Reactant: O=C1C=CC(=O)N1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: c1ccc2cc3cc4cc5ccccc5cc4cc3cc2c1
Solvent: C1CCOC1
Product: O=C1C=C(CCCCCCCCCCCBr)C(=O)N1
Product: O=C1C=CC(=O)N1CCCCCCCCCCCBr
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Pentacene-maleimide adduct (5c) (375 mg, 1 mmole) are added to a solution of triphenyl phosphine (393 mg, 1.5 mmole) and 11-bromo-1-undecanol (375 mg, 1.5 mmole) in 40 mL of anhydrous tetrahydrofuran. To this mixture a solution of diisopropyl azodicarboxylate (300 mg, 1.5 mmole) in 10 mL of anhydrous THF is added dropwise under a stream of nitrogen. After completion of the addition, the solution is stirred at room temperature for 18 hours. The solvent is evaporated under reduced pressure and the residue is titrated with diethyl ether and the precipitate is filtered, washed with 1:1 ether-hexane and dried. Crystallization from benzene affords the pure sample of 11-bromoundecylmaleimide-pentacene adduct 5d.
Reaction SMILES: [NH2:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8]=2[CH3:22])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][C:33]=1[C:42](Cl)=[O:43]>ClCCl>[CH:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][C:33]=1[C:42]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8]=2[CH3:22])=[CH:23][CH:24]=1)=[O:43]
Reactant: CCOC(=O)Cn1c(C)c(Cc2ccc(N)cc2)c2ccccc21
Reactant: O=C(Cl)c1ccc2ccccc2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)Cn1c(C)c(Cc2ccc(NC(=O)c3ccc4ccccc4c3)cc2)c2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 21.8 %

Procedure:
In a dry reaction vessel, ethyl 2-[3-(4-aminobenzyl)-2-methyl-1H-indol-1-yl]acetate (1.644 g, 5.1 mmol) was added, and dissolved in 30 mL dichloromethane. Triethylamine (2.13 mL, 15.3 mmol) was added, and in an ice bath a dichloromethane solution dissolving 2-naphthoyl chloride (1.067 g, 5.6 mmol) was added slowly. After completion of dropwise addition, it was reacted in an ice bath for 1 h, and stirred at room temperature overnight. It was filtered. An aqueous solution of sodium bicarbonate was added, extracted with dichloromethane, rotate evaporated to dryness, chromatographed on a column to obtain a white solid 0.53 g, at a yield of 21.8%.
Reaction SMILES: [CH2:1]([C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20](O)=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:24]([O-:27])([O-])=O.[Cs+].[Cs+].CCO[CH2:33][CH3:34]>CN(C)C=O>[CH2:1]([C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([O:27][CH2:24][CH2:11][CH2:1][CH2:2][CH2:3][CH:33]=[CH2:34])=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCc1cnc(-c2ccc(O)cc2)nc1
Reactant: CCOCC
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: C=CCCCCCOc1ccc(-c2ncc(CCCCCCCCCC)cn2)cc1

Procedure:
A vinyl-terminated phenyl pyrimidine side group was synthesized from 4-(5-decylpyrimidin-2-yl)phenol for siloxane coupling to 1,2 polybutadiene using standard ether chemistry as follows: 4-(5-decylpyrimidin-2-yl)phenol (1.93 grams, 6.15 mmols), a bromoalkene (7-bromohept-1-ene, 1.22 mL, 8 mmol) and oven-dried Cs2CO3 (2.56 grams, 8 mmol) were stirred at room temperature in 40 mL of dimethyl formamide overnight, resulting in near-quantitative conversion to the ether (Scheme 6), as monitored by thin layer chromatography. The reaction mixture was extracted three times with 50 mL of dichloromethane. The organic extracts were washed three times with water and dried with MgSO4. The crude product was recrystallized in hot 95% ethanol, resulting in analytically pure white crystals of 5-decyl-2-(4-(hept-6-enyloxy)phenyl)pyrimidine, enyloxy)phenyl)pyrimidine, or C7PPC10V, (1.69 g, 66.0% overall yield).
Reaction SMILES: [C:1]1([C@H:7]([OH:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10]=[C:11]1[O:14][C:13](=[O:15])[CH2:12]1>O1CCCC1.CN(C1C=CN=CC=1)C>[O:14]=[C:11]([CH3:10])[CH2:12][C:13]([O:9][C@@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:8])=[O:15]
Reactant: C=C1CC(=O)O1
Reactant: C[C@@H](O)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CC(=O)CC(=O)O[C@H](C)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 99.9 %

Procedure:
To a solution of (R)-1-phenylethanol (6.0 ml, 50 mmol) in dry tetrahydrofuran (75 ml) at room temperature was added 4-(N,N-dimethylamino)pyridine (610 mg, 5.0 mmol) followed by dropwise addition of 4-methyleneoxetan-2-one (3.83 ml, 50 mmol). The reaction was stirred for 12 hours at room temperature, then the solvent removed under reduced pressure. The residue was dissolved in ethyl acetate, poured into a separatory funnel, and washed with 1M aqueous hydrochloric acid, water, saturated aqueous sodium bicarbonate, then brine. The organic phase was separated and the solvent removed under rescued pressure to provide (R)-1-phenylethyl 3-oxobutanoate as a light reddish oil (10.3 g, 100%). 1H NMR (CDCl3, 400 MHz) δ 7.4-7.2 (m, 5H); 5.94 (q, 1H, J=6.6 Hz); 3.45 (s, 2H); 2.22 (s, 3H); 1.56 (d, 3H, J=6.6 Hz).
Reaction SMILES: [N:1]1([C:7]2[N:12]=[C:11]([N:13]3[CH:18]4[CH2:19][CH2:20][CH:14]3[CH2:15][O:16][CH2:17]4)[N:10]=[C:9]([C:21]3[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=3)[N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.ClC(Cl)(O[C:32](=[O:38])OC(Cl)(Cl)Cl)Cl.[NH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1>>[N:1]1([C:7]2[N:12]=[C:11]([N:13]3[CH:14]4[CH2:20][CH2:19][CH:18]3[CH2:17][O:16][CH2:15]4)[N:10]=[C:9]([C:21]3[CH:27]=[CH:26][C:24]([NH:25][C:32]([NH:40][C:41]4[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=4)=[O:38])=[CH:23][CH:22]=3)[N:8]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1ccc(-c2nc(N3CCOCC3)nc(N3C4CCC3COC4)n2)cc1
Reactant: Nc1cccnc1
Product: O=C(Nc1ccc(-c2nc(N3CCOCC3)nc(N3C4CCC3COC4)n2)cc1)Nc1cccnc1
Yield: 50.5 %

Procedure:
Following the procedure described in example 34, reaction of 4-[4-morpholin-4-yl-6-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1,3,5-triazin-2-yl]aniline (22 mg, 0.06 mmol) (22 mg, 0.06 mmol, triphosgene (18 mg, 0.06 mmol) and 3-aminopyridine (17 mg, 0.18 mmol) gave the title compound as off-white solid (1TFA salt, 14.8 mg, 41% yield). MS (ESI) m/z 489.5.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]2[NH:8][C:9]([S:11]([CH3:14])(=[O:13])=[O:12])=[N:10][C:4]=2[CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:24][Si:25]([CH3:32])([CH3:31])[CH2:26][CH2:27][O:28][CH2:29]Cl.CCOC(C)=O>CN(C=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[N:8]([CH2:29][O:28][CH2:27][CH2:26][Si:25]([CH3:32])([CH3:31])[CH3:24])[C:9]([S:11]([CH3:14])(=[O:13])=[O:12])=[N:10][C:4]=2[CH:3]=1
Reactant: CS(=O)(=O)c1nc2cc(Cl)ncc2[nH]1
Reactant: C[Si](C)(C)CCOCCl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: C[Si](C)(C)CCOCn1c(S(C)(=O)=O)nc2cc(Cl)ncc21
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirring solution of 6-chloro-2-(methylsulfonyl)-3H-imidazo[4,5-c]pyridine (847 mg, 3.66 mmol) and N,N-diisopropylethylamine (5.11 mL, 29.20 mmol) in anhydrous DMF (25.0 mL) was added 2-(trimethylsilyl)ethoxymethyl chloride (3.24 mL, 18.28 mmol). The reaction was stirred under N2 at RT for 18 h, then added to EtOAc (1.4 L) and washed with saturated NH4Cl (0.3 L). The aqueous layer was separated and back-extracted with EtOAc (0.3 L). The combined organic layers were evaporated under reduced pressure. Flash chromatography of the resulting residue utilizing a 40 g silica RediSep Rf® Gold column and employing a 0-30% EtOAc/hexane gradient afforded the title compound. LC-MS: calculated for C13H20ClN3O3SSi 361.07 observed m/e: 362.31 (M+H)+ (Rt 1.32/2.0 min)
Reaction SMILES: [C:1]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].C(O)(=O)C.[N:19]([O-])=[O:20].[Na+]>O>[N:19](=[CH:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:6])[OH:20]
Reactant: CC(=O)CC(=O)OCc1ccccc1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: O=C(C=NO)CC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In a three necked one liter flask fitted with a thermometer, a dropping funnel and a magnetic stirrer were placed 173 g. (0.9 mole) of benzyl acetoacetate [The benzyl acetoacetate was prepared as described by Baker et al., J. Org. Chem. 17, 91 (1952)] and 130 ml. of glacial acetic acid. The contents were cooled in an ice bath and a solution of 69 g. (1 mole) of sodium nitrite in 130 ml. of water was added over a period of half an hour; the temperature was kept at 0° to 10° C. After the reaction mixture was stirred for one hour at room temperature, 400 ml. of water was added and the stirring was continued for an additional two hours. The reaction mixture was extracted three times with 200 ml. portions of diethyl ether. The diethyl ether extracts were combined, washed once with water, three times with saturated sodium bicarbonate solution and once with brine. After drying over anhydrous sodium sulfate, the diethyl ether solution was evaporated leaving [1.1] as a clear oil which solidified upon trituration with petroleum ether (30° - 60°) to give 186.5 g. (93.2%) of white solid. Its NMR spectrum was consistent with the assigned structure. Generally the product was used as such in subsequent reaction but it can be recrystallized from toluene, m.p. 81° - 82° C.