Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[N:7]([C:17]1[CH:22]=[CH:21][C:20]([CH:23]([OH:33])[C:24]2[C:32]3[CH:31]=[N:30][CH:29]=[N:28][C:27]=3[NH:26][CH:25]=2)=[CH:19][N:18]=1)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[C:1]([O:5][C:6](=[O:34])[N:7]([CH2:8][C:9]1[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)[C:17]1[CH:22]=[CH:21][C:20]([C:23]([C:24]2[C:32]3[CH:31]=[N:30][CH:29]=[N:28][C:27]=3[NH:26][CH:25]=2)=[O:33])=[CH:19][N:18]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc(C(O)c3c[nH]c4ncncc34)cn2)cn1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc(C(=O)c3c[nH]c4ncncc34)cn2)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 35 %

Procedure:
To {5-[hydroxy-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (72, 0.189 g, 0.409 mmol) in 4.0 mL of dichloromethane, Dess-Martin periodinane (0.208 g, 0.490 mmol) was added. The reaction was stirred at room temperature for 1 hour, then poured into aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with methanol and dichloromethane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (73, 66 mg). 1H NMR was consistent with the compound structure.
Reaction SMILES: [F:1][C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[CH:3]=1.[C:17](Cl)([Cl:19])=[O:18]>C1(C)C=CC=CC=1>[F:1][C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:17]([Cl:19])=[O:18])[C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[CH:3]=1
Reactant: O=C(Cl)Cl
Reactant: FC1=Cc2ccccc2Nc2ccccc21
Solvent: Cc1ccccc1
Product: O=C(Cl)N1c2ccccc2C=C(F)c2ccccc21
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 2.3 g of 10-fluoro-5H-dibenz[b,f]azepine and 30 ml of toluene saturated with phosgene is stirred for 2 days at 25° C. Excess phosgene is then expelled with nitrogen and the reaction mixture is concentrated by rotary evaporation to yield crude 10-fluoro-5H-dibenz[b,f]azepine-5-carbonyl chloride as residue.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([NH:23][CH:24]2[CH2:26][CH2:25]2)[C:5]2[C:10]([C:11]#[N:12])=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:6]=2[N:7]=1.[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][N:37]([C:40](=[O:42])[CH3:41])[CH2:36][CH2:35]2)=[CH:30][CH:29]=1.C[Si](Cl)(C)C>C(O)CCC>[C:40]([N:37]1[CH2:36][CH2:35][N:34]([C:31]2[CH:32]=[CH:33][C:28]([NH:27][C:2]3[N:3]=[C:4]([NH:23][CH:24]4[CH2:25][CH2:26]4)[C:5]4[C:10]([C:11]#[N:12])=[CH:9][NH:8][C:6]=4[N:7]=3)=[CH:29][CH:30]=2)[CH2:39][CH2:38]1)(=[O:42])[CH3:41]
Reactant: CC(=O)N1CCN(c2ccc(N)cc2)CC1
Reactant: Cc1ccc(S(=O)(=O)n2cc(C#N)c3c(NC4CC4)nc(Cl)nc32)cc1
Agent: C[Si](C)(C)Cl
Solvent: CCCCO
Product: CC(=O)N1CCN(c2ccc(Nc3nc(NC4CC4)c4c(C#N)c[nH]c4n3)cc2)CC1
Temperature: 135 °C
Reaction time: 20 h
Yield: 15.5 %

Procedure:
A mixture of 2-chloro-4-(cyclopropylamino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (150 mg, 0.387 mmol), 1-(4-(4-aminophenyl)piperazin-1-yl)ethanone (132 mg, 0.602 mmol) and trimethylsilyl chloride (0.200 mL, 1.58 mmol) in nBuOH (4 mL) was stirred at 135° C. for 20 h. It was concentrated in vacuo. The residue was purified by HPLC to give the titled compound (25 mg). MS 417.4 (M+H); UV 203.4, 254.0, 291.5 nm.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[CH:13]=2)[CH:8]=1)(=O)=O.C([Sn](CCCC)(CCCC)[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=1[N+:34]([O-:36])=[O:35])CCC>>[CH3:18][O:17][C:12]1[CH:13]=[C:14]2[C:9]([CH:8]=[C:7]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=3[N+:34]([O-:36])=[O:35])[CH2:16][CH2:15]2)=[CH:10][CH:11]=1
Reactant: COc1ccc2c(c1)CCC(OS(=O)(=O)C(F)(F)F)=C2
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(OC)cc1[N+](=O)[O-]
Product: COc1ccc2c(c1)CCC(c1ccc(OC)cc1[N+](=O)[O-])=C2
Yield: 73.2 %

Procedure:
Synthesized from 6-methoxy-3,4-dihydronaphthalen-2-yl trifluoromethanesulfonate (2.3 g) and tributyl(4-methoxy-2-nitrophenyl)tin (3.9 g) according to an analogous synthetic method to Preparation Example 77, the title compound (1.7 g) was obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][C:7](=[O:11])[C:6]=2[CH:12]=1.CO[CH:15](OC)[N:16]([CH3:18])[CH3:17].C(N(CC)CC)C>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C:8](=[CH:15][N:16]([CH3:18])[CH3:17])[C:7](=[O:11])[C:6]=2[CH:12]=1
Reactant: O=C1CCOc2ccc(Cl)cc21
Reactant: COC(OC)N(C)C
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CN(C)C=C1COc2ccc(Cl)cc2C1=O
Reaction time: 1 h
Yield: 63.8 %

Procedure:
A solution of 6-chloro-3,4-dihydro-4-oxo-2H-1-benzopyran (3.285 g), N,N-dimethylformamide dimethyl acetal (8.568 g), and triethylamine (2.727 g) in benzene (36 ml) was refluxed with stirring for 1 hour and then about three-fourths of the solvent was distilled slowly at atmospheric pressure over a period of approximately 1 hour. To the residue was added benzene (36 ml) and the solvent was distilled again. The residue was dissolved in a mixture of chloroform and ethyl acetate, treated with activated charcoal, and evaporated in vacuo. The residual solid was washed with a mixture of diethyl ether and ethyl acetate to give 6-chloro-3,4-dihydro-3-dimethylaminomethylene-4-oxo-2H-1-benzopyran (2.73 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[C:11]2[N:12]([N:16]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[N:18]=2)[CH:13]=[CH:14][CH:15]=1.Cl[CH2:33][C:34]([N:36]([CH3:38])[CH3:37])=[O:35]>>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[C:11]2[N:12]([N:16]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([CH:26]4[CH2:27][CH2:28][N:29]([CH2:33][C:34]([N:36]([CH3:38])[CH3:37])=[O:35])[CH2:30][CH2:31]4)=[CH:22][CH:21]=3)[N:18]=2)[CH:13]=[CH:14][CH:15]=1
Reactant: COc1ccc(-c2cccn3nc(Nc4ccc(C5CCNCC5)cc4)nc23)c(F)c1
Reactant: CN(C)C(=O)CCl
Product: COc1ccc(-c2cccn3nc(Nc4ccc(C5CCN(CC(=O)N(C)C)CC5)cc4)nc23)c(F)c1

Procedure:
2-(4-{4-[8-(2-Fluoro-4-methoxy-phenyl)-[1,2,4]-triazolo[1,5-a]pyridin-2-ylamino]-phenyl}-piperidin-1-yl)-N,N-dimethyl-acetamide was prepared from [8-(2-fluoro-4-methoxy-phenyl)-[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-(4-piperidin-4-yl-phenyl)-amine (0.179 g, 0.429 mmol) and 2-chloro-N,N-dimethyl-acetamide (0.066 mL, 0.643 mmol) in a manner analogous to Example 313 to give product (0.105 g, 49%). MP=192-195° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.61 (s, 1H), 8.79 (d, 1H), 7.80 (m, 1H), 7.58 (m, 3H), 7.15 (m, 3H), 6.98 (m, 2H), 3.85 (s, 3H), 3.15 (s, 2H), 3.05 (s, 3H), 2.92 (m, 2H), 2.85 (s, 3H), 2.40 (m, 1H), 2.10 (m, 2H), 1.65 (m, 4H). MS=503 (MH)+.
Reaction SMILES: S(Cl)(Cl)=O.[F:5][C:6]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:7]=1[C:8]([NH:10][CH:11]([CH2:15][CH:16]=[CH2:17])[C:12]([OH:14])=[O:13])=[O:9].[CH3:23]O>>[CH3:23][O:13][C:12](=[O:14])[CH:11]([NH:10][C:8](=[O:9])[C:7]1[C:6]([F:5])=[CH:21][CH:20]=[CH:19][C:18]=1[F:22])[CH2:15][CH:16]=[CH2:17]
Reactant: C=CCC(NC(=O)c1c(F)cccc1F)C(=O)O
Reactant: CO
Solvent: O=S(Cl)Cl
Product: C=CCC(NC(=O)c1c(F)cccc1F)C(=O)OC

Procedure:
In the same manner as in Reference Example 35-(1), allylglycine (285 mg) was reacted with 2,6-difluorobenzoyl chloride (0.374 ml) to obtain 2-(2,6-difluorobenzamido)pent-4-enoic acid (471 mg). (2) In the same manner as in Reference Example 35-(2), thionyl chloride (0.242 ml) was reacted with a solution of 2-(2,6-difluorobenzamido)pent-4-enoic acid (471 mg) in methanol (20 ml) to obtain 2-(2,6-difluorobenzamido)pent-4-enoic acid methyl ester (430 mg).
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:13]([OH:15])=O)[C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[C:16]([O:20][CH2:21][O:22][C:23]([C:25]1[N:26]2[CH:29]([S:30][CH2:31][C:32]=1[CH2:33][O:34][C:35](=[O:37])[CH3:36])[CH:28]([NH2:38])[C:27]2=[O:39])=[O:24])(=[O:19])[CH2:17][CH3:18]>C(Cl)Cl.C(O)CC>[C:16]([O:20][CH2:21][O:22][C:23]([C:25]1[N:26]2[CH:29]([S:30][CH2:31][C:32]=1[CH2:33][O:34][C:35](=[O:37])[CH3:36])[CH:28]([NH:38][C:13](=[O:15])[CH:9]([C:6]1[CH:5]=[CH:4][C:3]([CH2:2][Cl:1])=[CH:8][CH:7]=1)[C:10]([OH:12])=[O:11])[C:27]2=[O:39])=[O:24])(=[O:19])[CH2:17][CH3:18]
Reactant: CCC(=O)OCOC(=O)C1=C(COC(C)=O)CSC2C(N)C(=O)N12
Reactant: O=C(O)C(C(=O)O)c1ccc(CCl)cc1
Solvent: ClCCl
Solvent: CCCO
Product: CCC(=O)OCOC(=O)C1=C(COC(C)=O)CSC2C(NC(=O)C(C(=O)O)c3ccc(CCl)cc3)C(=O)N12

Procedure:
α-Carboxy-p-chloromethylphenylacetylnitrophenyl polymer prepared as in the procedure of Example 22, carrying four m. mole of p-chloromethylphenylmalonic acid was suspended for about 8 hours in 20 ml of dry methylene chloride solution containing 1 millimole of 3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid propionyloxymethyl ester. After only traces of the 7-amino-cephalosporanic acid ester derivative remain in solution, which is determined by thin layer chromatography on cellulose in 70% aqueous propanol, the polymer is filtered off and washed with portions of 50 ml each of methylene chloride. The combined filtrates are evaporated and the residue is dissolved in 20 ml of distilled water. The solution is acidified to a pH of 2 by adding 0.2 normal hydrochloric acid and extracted twice with ethylacetate. The organic solution is dried over sodium sulfate and evaporated at room temperature. The remaining solid is dried overnight over phosphorus pentoxide under vacuum to give 3-[(acetyloxy)-methyl]-7-[[2-[4-(chloromethyl)phenyl]-2-carboxyacetyl]-amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid propionyloxymethyl ester.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[CH:12]=[C:11]([CH3:13])[S:10][C:9]=2[CH:14]=1)=[O:4].[OH-].[Na+].Cl>O>[CH3:13][C:11]1[S:10][C:9]2[CH:14]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=[CH:7][C:8]=2[CH:12]=1
Reactant: COC(=O)c1ccc2cc(C)sc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cc1cc2ccc(C(=O)O)cc2s1
Temperature: 0 °C
Yield: 100 %

Procedure:
2-Methyl-benzo[b]thiophene-6-carboxylic acid methyl ester (0.83 g, 4.0 mmol) is reacted with NaOH (0.80 g, 20 mmol) in H2O (20 mL). at reflux for 2 h. The reaction is cooled to 0° C. and acidified with 1.0 M HCl to pH (3˜4). It is extracted with EtOAc (3×100 mL); dried with Na2SO4 filtered and concentrated gives the title compound (0.78 g, 4.0 mmol, quant.). 1H NMR (CDCl3): δ 2.64 (d, J=0.89 Hz, 3H), 7.06 (s, 1H), 7.71 (d, J=8.3 Hz, 1H), 8.03 (dd, J=8.3, 1.7 Hz, 1H), 8.54 (d, J=0.8 Hz, 1H) ppm. ES-MS (m/z): calcd for C10H8O2S (M−H)−: 191.2. found: 191.0.
Reaction SMILES: [CH2:1]([C:4]1[C:13]([O:14][CH3:15])=[C:12]([O:16][CH3:17])[CH:11]=[C:10]2[C:5]=1[C:6]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)=[N:7][CH:8]=[N:9]2)[CH:2]=[CH2:3].[I:26]I>ClCCl.C(Cl)(Cl)Cl>[Cl:25][C:22]1[CH:21]=[CH:20][C:19]([N:18]2[CH:2]([CH2:3][I:26])[CH2:1][C:4]3[C:5]4[C:6]2=[N:7][CH:8]=[N:9][C:10]=4[CH:11]=[C:12]([O:16][CH3:17])[C:13]=3[O:14][CH3:15])=[CH:24][CH:23]=1
Reactant: II
Reactant: C=CCc1c(OC)c(OC)cc2ncnc(Nc3ccc(Cl)cc3)c12
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: COc1cc2ncnc3c2c(c1OC)CC(CI)N3c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (5-allyl-6,7-dimethoxy-quinazolin-4-yl)-(4-chloro-phenyl)-amine (0.3 g, 0.85 mmol) (from Example 16, Step E, supra) in dichloromethane (50 mL) was added I2 (0.53 g, 4.2 mmol). The reaction mixture was stirred at room temperature for 3 hours. The mixture was diluted with chloroform (100 mL), and washed with a saturated aqueous Na2SO3 solution. The organic layer was separated, dried over Na2SO4, and concentrated. The residue was purified by chromatography using EtOAc/CH2Cl2/Et3N (2:1:0.01) as eluent to give the desired 4-(4-chloro-phenyl)-5-iodomethyl-7,8-dimethoxy-5,6-dihydro-4H-1,3,4-triaza-phenalene as a white solid. (Yield 0.15 g, 37%).
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:9]([C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=1)=[O:10]>>[OH:10][CH:9]([C:11]1[CH:12]=[CH:13][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:19][CH:20]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Br[Mg]c1ccccc1
Reactant: COC(=O)c1ccc(C=O)cc1
Product: COC(=O)c1ccc(C(O)c2ccccc2)cc1
Reaction time: 0.17 h

Procedure:
Under a nitrogen atmosphere phenyl magnesium bromide (39 mL of 3 M in ether) was added via a syringe over a period of 30 minutes to a solution of methyl 4-formylbenzoate (19.2 g, 117 mmol). The mixture was allowed to stir for an additional 10 minutes and then it was quenched by the addition of 1 M hydrochloric acid (125 mL). The reaction mixture was extracted with diethyl ether (2×200 mL). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and then concentrated under vacuum to provide a yellow oil. This material was purified by flash chromatography (silica gel eluting with 6:1 hexanes:ethyl acetate) to provide 6.9 g of methyl 4-(α-hydroxybenzyl)benzoate as a clear oil.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:22])=[CH:7][N:8]3[C:15](=[O:16])[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][N:12]=[C:9]32)=[CH:4][CH:3]=1.[C:23]1([N:29]=[C:30]=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>N1C=CC=CC=1>[C:23]1([NH:29][C:30](=[O:31])[NH:1][C:2]2[CH:11]=[C:10]3[C:5]([C:6]([CH3:22])=[CH:7][N:8]4[C:15](=[O:16])[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][N:12]=[C:9]43)=[CH:4][CH:3]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C=Nc1ccccc1
Reactant: CCOC(=O)c1cnc2c3cc(N)ccc3c(C)cn2c1=O
Solvent: c1ccncc1
Product: CCOC(=O)c1cnc2c3cc(NC(=O)Nc4ccccc4)ccc3c(C)cn2c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of ethyl 10-amino-7-methyl-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxylate (600 mg) in pyridine (60 ml) was added phenyl isocyanate (0.22 ml) at ice bath temperature. The reaction mixture was allowed to stir overnight at room temperature. The precipitate was collected, washed with methanol and dried. Recrystallization from dimethyl sulfoxide gave ethyl 10-(3-phenylureido)-7-methyl-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxylate (0.58 g).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8].[CH2:9]([O:11][SiH:12]([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[CH3:10].CS(O)(=O)=O.C([Si](C=C)(C)O[Si](C)(C)C)=C>[Pt].C1(C)C=CC=CC=1>[CH2:8]([Si:12]([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])[O:11][CH2:9][CH3:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]
Reactant: CCO[SiH](OCC)OCC
Reactant: C=CCCCCCC
Agent: [Pt]
Agent: C=C[Si](C)(C=C)O[Si](C)(C)C
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: CCCCCCCC[Si](OCC)(OCC)OCC
Yield: 88 %

Procedure:
Reaction between octene-1 and triethoxysilane with platinum catalyst in the presence of trimethylsilyl ester of methanesulfonic acid. 325 mg Octene-1 and 475 mg triethoxysilane were introduced into a glass tube filled with argon gas, and 20 mg of a trimethylsilyl ester of methanesulfonic acid and 0.002 ml (1.7 mg) of a toluene solution of a 0-valent platinum complex of divinyltetramethyldisiloxane (0.04 wt % platinum content) were added. The tube was sealed with Teflon tape and a rubber septum, degassed, and then filled again with argon gas. The tube was placed in a 75° C. oil bath where it was heated for 1 hour. After cooling, the tube contents were analyzed by gas chromatography revealing an octyltriethoxysilane yield of 88%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[NH:9][CH:10]=[C:11]([CH:12]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:13][C:14]([NH:16][CH3:17])=O)[C:4]=12.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[NH:9][CH:10]=[C:11]([CH:12]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:13][CH2:14][NH:16][CH3:17])[C:4]=12
Reactant: CNC(=O)CC(c1ccccc1)c1c[nH]c2nccc(OC)c12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CNCCC(c1ccccc1)c1c[nH]c2nccc(OC)c12
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 60.9 %

Procedure:
To a RT suspension of 3-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-methyl-3-phenyl-propionamide (155 mg, 0.50 mmol) in THF (5 mL) was slowly added LAH (1 M in THF, 1.5 mmol). The mixture was refluxed overnight, cooled to RT, and quenched by addition of freshly ground Na2SO4.10H2O. After stirring for 20 min, the solid was filtered off and washed with EtOAc (10 mL, 3 times) and DCM (10 mL, 2 times). The filtrate was concentrated, and the residue was purified via flash chromatography (DCM/MeOH/NH4OH) to afford [3-(4-Methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-phenyl-propyl]-methyl-amine as a white solid (90 mg, 61% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([O:13][CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].Br[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32].C(N(CC)CC)C>CC(C)=O>[CH3:14][O:13][C:4]1[CH:5]=[C:6]2[C:11](=[C:2]([NH:1][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]3[C:26](=[O:27])[C:25]4=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]4[C:23]3=[O:32])[CH:3]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12]
Reactant: O=C1c2ccccc2C(=O)N1CCCCCCBr
Reactant: COc1cc(N)c2nccc(C)c2c1
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Product: COc1cc(NCCCCCCN2C(=O)c3ccccc3C2=O)c2nccc(C)c2c1
Reaction time: 0.5 h

Procedure:
A stirred mixture of 20.9 g (0.111 mole) of 8-amino-6-methoxy-4-methylquinoline and 34.5 g (0.111 mole) of N-(6-bromohexyl)phthalimide was heated in an oil bath (130° ) while 11.2 g (15.4 ml; 0.111 mole) of triethylamine was added dropwise over a period of 45 minutes. The temperature of the bath was kept at 130° for 60 minutes, at 150° for 60 minutes, between 150° and 190° for 30 minutes, and at 190° for 30 minutes. The mixture was cooled then diluted with acetone (100 ml). The precipitate as collected on a filter, washed with acetone (2×50 ml), dried, then discarded. The filtrate was concentrated in vacuo to a dark oil; yield 53 g. The oil was dissolved in 100 ml of dischloromethane, and the solution was chromatographed on a column (40 cm× 8 cm dia) of silica gel (1000 g; activity III) using dichloromethane (1.5 l) as the eluent. Fractions containing the product were combined then concentrated in vacuo; yield 35.5 g (83.7%). That material was satisfactory for conversion to the target compound, however a 93% recovery of analytically pure material (mp 84°-85° ) could be obtained by crystallization from ethanol.
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4].C([BH3-])#N.[Na+]>C(O)(=O)C>[CH2:1]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH:12]=2)[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1ccc2ccc(C(=O)OC)cc21
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Product: CCCCN1CCc2ccc(C(=O)OC)cc21
Temperature: 40 °C
Yield: 77.4 %

Procedure:
To a mixture of methyl 1-butyl-1H-indole-6-carboxylate, (2.1 g) in glacial acetic acid (25 mL) was added sodium cyanoborohydride (2.28 g). The mixture was heated at 40° C. for 3 h then cooled to room temperature, partitioned between water and ethyl acetate and the layers were separated. The organic layer was washed three times with brine, dried over anhydrous sodium sulfate and concentrated to give 1.64 g of the title compound: 1H NMR (CDCl3) δ 0.969, 1.43, 1.59, 2.99, 3.1, 3.4, 3.88, 7.07, 7.34.
Reaction SMILES: [CH2:1]([C:3]1([CH3:10])[CH2:8][CH2:7][CH2:6][CH2:5][C:4]1=[O:9])[CH3:2].[Br:11]C1CC(C(C)C)CCC1=O>>[Br:11][CH:5]1[C:4](=[O:9])[C:3]([CH2:1][CH3:2])([CH3:10])[CH2:8][CH2:7][CH2:6]1
Reactant: CCC1(C)CCCCC1=O
Reactant: CC(C)C1CCC(=O)C(Br)C1
Product: CCC1(C)CCCC(Br)C1=O

Procedure:
The bromination of 2-ethyl-2-methyl-cyclohexanone takes place in a manner similar to that described above for the preparation of 2-bromo-4-isopropyl-cyclohexanone. The title compound is reacted as a crude product without further characterization.
Reaction SMILES: [CH3:1][O:2]C1C=CC2N=C(C3C=CC(N)=NC=3)SC=2C=1.[CH3:19][NH:20][C:21]1[N:26]=[CH:25][C:24]([C:27]2[S:28][C:29]3[CH:35]=[C:34](O)[CH:33]=[CH:32][C:30]=3[N:31]=2)=[CH:23][CH:22]=1>>[CH3:1][O:2][C:33]1[CH:34]=[CH:35][C:29]2[S:28][C:27]([C:24]3[CH:23]=[CH:22][C:21]([NH:20][CH3:19])=[N:26][CH:25]=3)=[N:31][C:30]=2[CH:32]=1
Reactant: COc1ccc2nc(-c3ccc(N)nc3)sc2c1
Reactant: CNc1ccc(-c2nc3ccc(O)cc3s2)cn1
Product: CNc1ccc(-c2nc3cc(OC)ccc3s2)cn1

Procedure:
5-(6-Methoxy-1,3-benzothiazol-2-yl)pyridin-2-amine (190 mg, 0.74 mmol) was exposed to the procedure used for the preparation of 2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol. After neutralization, the precipitate was filtered off and washed with water. The crude solid was slurred in hot EtOAc/MeOH 95:5 and filtered. The filtrate was concentrated under reduced pressure and the residue was subjected to flash chromatography (EtOAc/MeOH 95:5) to give a product that was chromatographed once more (DCM/MeOH 95:5) to yield the title compound (65 mg). 1H NMR δ 9.74 (s, 1 H) 8.53 (d, 1 H) 7.93 (dd, 1 H) 7.73 (d, 1 H) 7.35 (d, 1 H) 6.93 (dd, 1 H) 6.61 (br s, 2 H) 6.55 (d, 1 H); MS ink (M+H) 244.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:22])=[C:4]([CH2:17][CH2:18][N+:19]([O-:21])=[O:20])[N:5]([S:7]([C:10]2[CH:16]=[CH:15][C:13]([CH3:14])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:6]=1.[CH3:23][O:24][CH:25]([O:32][CH3:33])[C:26](=[O:31])[CH:27]=[C:28]([CH3:30])[CH3:29].C1CCN2C(=NCCC2)CC1>[NH4+].[Cl-]>[Br:1][C:2]1[C:3]([CH3:22])=[C:4]([CH2:17][CH:18]([N+:19]([O-:21])=[O:20])[C:28]([CH3:30])([CH3:29])[CH2:27][C:26](=[O:31])[CH:25]([O:24][CH3:23])[O:32][CH3:33])[N:5]([S:7]([C:10]2[CH:11]=[CH:12][C:13]([CH3:14])=[CH:15][CH:16]=2)(=[O:8])=[O:9])[CH:6]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(Br)c(C)c2CC[N+](=O)[O-])cc1
Reactant: COC(OC)C(=O)C=C(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCC2=NCCCN2CC1
Product: COC(OC)C(=O)CC(C)(C)C(Cc1c(C)c(Br)cn1S(=O)(=O)c1ccc(C)cc1)[N+](=O)[O-]
Reaction time: 0.25 h
Yield: 86.6 %

Procedure:
Following a general procedure,50 a mixture of 4-Ts (9.00 g, 23.3 mmol) and 1,1-dimethoxy-4-methyl-3-penten-2-one (11.1 g, 69.9 mmol, 3 equiv) was treated with DBU (10.5 mL, 69.9 mmol). The reaction mixture was stirred for 15 min under argon. A saturated solution of cold aqueous NH4Cl (50 mL, 0° C.) was added. The mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with brine, dried (Na2SO4), concentrated and dried overnight under high vacuum. Addition of diethyl ether (50 mL) to the resulting solid, trituration, and filtration afforded a pale brown solid (11.0 g, 86%): mp 114-115° C.; 1H-NMR δ 1.22 (s, 3H), 1.27 (s, 3H), 1.85 (s, 3H), 2.42 (s, 3H), 2.64, 2.74 (AB, 2J=19.0 Hz, 2H), 3.15 (ABX, 2JAB=15.4 Hz, 3JBX=1.8 Hz, 1H), 3.32 (ABX, 2JAB=15.4 Hz, 3JAX=11.7 Hz, 1H), 3.41 (s, 3H), 3.43 (s, 3H), 4.37 (s, 1H), 5.19 (ABX, 3JAX=11.7 Hz, 3JBX=1.8 Hz, 1H), 7.28 (s, 1H), 7.31 (d, J=8.1 Hz, 2H), 7.59 (d, J=8.1 Hz, 2H); 13C NMR δ 0.7, 21.9, 23.8, 24.0, 25.9, 36.8, 44.2, 55.28, 55.29, 94.4, 104.9, 105.9, 122.6, 125.1, 125.9, 126.7, 130.5, 135.9, 145.6, 203.2; Anal. Calcd for C22H29BrN2O7S: C, 48.44; H, 5.36; N, 5.14. Found: C, 48.70; H, 5.30; N, 5.17.
Reaction SMILES: [CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[C:12]([CH3:14])[N:11]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22]O)=[CH:18][CH:17]=4)[C:8]=3[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.[NH:24]1[CH2:27][CH2:26][CH2:25]1>>[N:24]1([CH2:22][C:19]2[CH:20]=[CH:21][C:16]([CH2:15][N:11]3[C:8]4[CH:9]=[CH:10][C:5]5[N:6]([C:2]([CH3:1])=[N:3][N:4]=5)[C:7]=4[CH:13]=[C:12]3[CH3:14])=[CH:17][CH:18]=2)[CH2:27][CH2:26][CH2:25]1
Reactant: C1CNC1
Reactant: Cc1cc2c(ccc3nnc(C)n32)n1Cc1ccc(CO)cc1
Product: Cc1cc2c(ccc3nnc(C)n32)n1Cc1ccc(CN2CCC2)cc1
Reaction time: 8 h

Procedure:
The title compound was prepared according to the procedures of Example 45, using the alcohol of Example 49 as starting material and using azetidine (0.013 mL, 0.20 mmol, Aldrich) in the displacement, which was performed overnight (8.0 mg, 47%).