Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:13]3[CH:14]=[C:15]([CH2:17][O:18][C:19]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[N:20]=4)[N:16]=[C:12]3[C:11]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[N:10][CH:9]=2)=[CH:4][CH:3]=1.[C:35]([N:42]1[CH2:47][CH:46]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH2:44][CH2:43]1)([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>>[O:32]1[CH2:33][CH2:34][N:29]([C:11]2[C:12]3[N:13]([CH:14]=[C:15]([CH2:17][O:18][C:19]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[N:20]=4)[N:16]=3)[C:8]([C:5]3[CH:4]=[CH:3][C:2]([C:45]4[CH2:46][CH2:47][N:42]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:43][CH:44]=4)=[N:7][CH:6]=3)=[CH:9][N:10]=2)[CH2:30][CH2:31]1
Reactant: Clc1ccc(-c2cnc(N3CCOCC3)c3nc(COc4ccc5ccccc5n4)cn23)cn1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Product: CC(C)(C)OC(=O)N1CC=C(c2ccc(-c3cnc(N4CCOCC4)c4nc(COc5ccc6ccccc6n5)cn34)cn2)CC1

Procedure:
Compound 49b was prepared from compound 49a and N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester using the methods described in Example 1, Step G. Mass Spectrum (LCMS, ESI pos.) Calcd. For C35H37N7O4: 620.4 [M+H]. found 620.3.
Reaction SMILES: [NH2:1][CH:2]1[CH2:6][CH2:5][NH:4][CH2:3]1.[N+:7]([C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=1)[CH:13]=O)([O-:9])=[O:8].C1N2CCN(CC2)C1.[CH:26]1([N:29]2[C:38]3[C:33](=[C:34]([CH:42]=[CH2:43])[C:35]([F:41])=[C:36](F)[C:37]=3[F:39])[C:32](=[O:44])[C:31]([C:45]([OH:47])=[O:46])=[CH:30]2)[CH2:28][CH2:27]1>C(#N)C.CN(C)C=O>[CH:26]1([N:29]2[C:38]3[C:33](=[C:34]([CH:42]=[CH2:43])[C:35]([F:41])=[C:36]([N:4]4[CH2:5][CH2:6][CH:2]([N:1]=[CH:13][C:12]5[CH:15]=[CH:16][CH:17]=[C:10]([N+:7]([O-:9])=[O:8])[CH:11]=5)[CH2:3]4)[C:37]=3[F:39])[C:32](=[O:44])[C:31]([C:45]([OH:47])=[O:46])=[CH:30]2)[CH2:28][CH2:27]1
Reactant: C=Cc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: NC1CCNC1
Agent: C1CN2CCN1CC2
Solvent: CN(C)C=O
Solvent: CC#N
Product: C=Cc1c(F)c(N2CCC(N=Cc3cccc([N+](=O)[O-])c3)C2)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 87 %

Procedure:
A solution of 0.39 g of 3-amino-pyrrolidine in 4 ml of acetonitrile is treated with a solution of 0.75 g of 3-nitrobenzaldehyde in 4 ml of acetonitrile. After 1 hour at room temperature, the reaction mixture is treated with a solution of 1 g of DABCO and 0.93 g of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-5-vinyl-3-quinolinecarboxylic acid in 4 ml of dimethylformamide. After 1 hour under reflux, the reaction mixture is cooled to 0° C. and the product is filtered off with suction and dried. 1.33 g of 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(3-(3-nitro-benzylideneamino)-pyrrolidin-1-yl)-4-oxo-5-vinyl-3-quinolinecarboxylic acid are obtained.
Reaction SMILES: [C:1]1([C:7]#[C:8][CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:13]([O:15]CC)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+]>CO.O>[C:1]1([C:7]#[C:8][CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)/C=C/CCC#Cc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)/C=C/CCC#Cc1ccccc1
Temperature: 50 °C
Reaction time: 0.67 h
Yield: 91.2 %

Procedure:
To a solution of ethyl 7-phenylhept-2E-en-6-ynoate (2.5 g) in methanol was added KOH (2.6 g) in water (6 ml). The mixture was stirred at 50° C. under a nitrogen atmosphere for 40 minutes, cooled, diluted with water (20 ml) and washed with ether (15 ml). The aqueous layer was acidified with 10% HCl and extracted with ether. The ether extracts were combined and dried over MgSO4, and the solvent was distilled off (adding dry benzene (4 ml) to form azeotrope with traces of water) to give 7-phenylhept-2E-en-6-ynoic acid (2 g) as a colourless oily solid.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[C:13]([C:26]([F:29])([F:28])[F:27])[CH:12]=3)[N:7]=[C:6]([C:30]#[N:31])[C:5]=2[N:4]=[N:3]1.C(N(CC)CC)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>ClCCl.CO>[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH:20]4[CH2:21][CH2:22][N:23]([S:40]([CH3:39])(=[O:42])=[O:41])[CH2:24][CH2:25]4)=[C:13]([C:26]([F:29])([F:28])[F:27])[CH:12]=3)[N:7]=[C:6]([C:30]#[N:31])[C:5]=2[N:4]=[N:3]1
Reactant: CS(=O)(=O)Cl
Reactant: Cn1nnc2c(C#N)nc(-c3ccc(OCCC4CCNCC4)c(C(F)(F)F)c3)cc21
Solvent: CCN(CC)CC
Solvent: CO
Solvent: ClCCl
Product: Cn1nnc2c(C#N)nc(-c3ccc(OCCC4CCN(S(C)(=O)=O)CC4)c(C(F)(F)F)c3)cc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1-Methyl-6-(4-(2-(piperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]-triazolo[4,5-c]pyridine-4-carbonitrile (50 mg), triethylamine (0.019 ml), and methanesulfonyl chloride (8.99 μl) were combined in dichloromethane (1 ml) and the reaction mixture stirred at room temperature for 3 hours. Washed with water, the organic layer was separated, dried, and blown down to afford crude product. Solid was suspended in methanol and filtered off to afford the title compound (32.5 mg).
Reaction SMILES: [C:1](Cl)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(N(CC)CC)C.[CH3:22][N:23]([CH2:25][CH:26]([OH:28])[CH3:27])[CH3:24]>C(Cl)(Cl)Cl>[C:1]([O:28][CH:26]([CH3:27])[CH2:25][N:23]([CH3:24])[CH3:22])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CC(O)CN(C)C
Reactant: CCCCCCCCCCCC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCC(=O)OC(C)CN(C)C

Procedure:
The (N,N-disubstituted amino)-alkanol alkanoates are readily prepared by reacting the corresponding aminoalkinol with lauroyl chloride in the presence of triethylamine. A solvent such as chloroform is optional but preferred. For example, 1-(N,N-dimethylamino)-2-propanol can be reacted with lauroyl chloride in chloroform and in the presence of triethylamine to form 1-(N,N-dimethylamino)-2-propanol dodecanoate (DAIPD).
Reaction SMILES: [CH:1]1([C:7]([OH:38])([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:8]([O:10][CH2:11][CH:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH:27]3OCC[O:28]3)[CH2:14][CH2:13]2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl>C1COCC1.C(OCC)(=O)C>[CH:32]1([C:7]([OH:38])([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]([O:10][CH2:11][CH:12]2[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH:27]=[O:28])[CH2:16][CH2:17]2)=[O:9])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1
Reactant: O=C(OCC1CCN(CCCCCCCCCC2OCCO2)CC1)C(O)(c1ccccc1)C1CCCCC1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=CCCCCCCCCCN1CCC(COC(=O)C(O)(c2ccccc2)C2CCCCC2)CC1
Reaction time: 3 h

Procedure:
(1-(9-(1,3-Dioxolan-2-yl)nonyl)piperidin-4-yl)methyl 2-cyclohexyl-2-hydroxy-2-phenylacetate (200 mg, 0.39 mmol) was dissolved in THF (2 mL) and hydrochloric acid (4 mL, 2 M aqueous solution) with stirring at RT. After 3 hours, the reaction mixture was diluted with ethyl acetate and washed with 10% aqueous potassium carbonate solution. The layers were separated and the organic extracts run through a hydrophobic fit. The solvents were removed in vacuo. The title compound was isolated (190 mg, >100%) and it was used without further purification in the next step.
Reaction SMILES: Cl.[C:2]1([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2([OH:20])[CH2:19][CH2:18][NH:17][CH2:16]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:21].[Na+]>CO.O.CCOCC>[C:8]([N:17]1[CH2:18][CH2:19][C:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH2:8][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)([OH:20])[CH2:16]1)(=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OC1(c2ccccc2Cc2ccccc2)CCNC1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: CCOCC
Product: O=C(c1ccccc1)N1CCC(O)(c2ccccc2Cc2ccccc2)C1
Reaction time: 2 h

Procedure:
A suspension of 5.0 g of 3-(α-phenyl-2-tolyl)-3-pyrrolidinol hydrochloride, Example 14, in 40 ml of methanol is diluted with water until a solution forms. The solution is treated with an excess of a 5% sodium hydroxide solution and then the methanol removed on a rotary evaporator leaving a suspension. The suspension is diluted with 50 ml of water and extracted successively with a 100 ml and a 20 ml portion of chloroform. The combined chloroform extracts are washed once with 50 ml of a 5% sodium hydroxide solution and twice with 50 ml portions of water and dried and the chloroform removed. The residue is subjected to azeotropic distillation with benzene and then dried in vacuo at 40° C. for 2 hours before being suspended in 30 ml of warmed chloroform containing 2.2 g of triethylamine. To this suspension is added dropwise 2.60 g of benzoyl chloride. After total addition, the resulting solution is stirred for 2 hours and then permitted to stand for 48 hours. The solution is diluted with 30 ml of chloroform, washed successively with a 50 ml portion of water and similar amount of a 5% sodium hydroxide and dried and the solvent removed leaving a tacky foam. The foam is dissolved in 60 ml of ether (warming may be required), and the solution filtered through glass wool. A precipitate forms which is collected by suction filtration and dried in vacuo at ambient temperature leaving a colorless solid, mp 113°-116° C. of 1-benzoyl-3-(α-phenyl-2-tolyl)-3-pyrrolidinol.
Reaction SMILES: [NH2:1][C:2]([C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11])=[CH:3][C:4](OCC)=[O:5].ClC1C(OC(C)C)=CC([N:27]=[C:28]=[O:29])=C(F)C=1>>[F:15][C:9]([F:14])([C:2]1[NH:1][C:28](=[O:29])[NH:27][C:4](=[O:5])[CH:3]=1)[C:10]([F:11])([F:12])[F:13]
Reactant: CCOC(=O)C=C(N)C(F)(F)C(F)(F)F
Reactant: CC(C)Oc1cc(N=C=O)c(F)cc1Cl
Product: O=c1cc(C(F)(F)C(F)(F)F)[nH]c(=O)[nH]1

Procedure:
using ethyl 3-amino-4,4,5,5,5-pentafluoro-2-pentenoate and 4-chloro-2-fluoro-5-isopropoxyphenyl isocyanate there is obtained 3- 4-chloro-2-fluoro-5-isopropoxyphenyl)-6-pentafluoroethyl-2,4(1H,3H)-pyrimidinedione, m.p. 141°-143° C.;
Reaction SMILES: [C:1]1([CH2:11][N:12]2[C:24]3[CH:23]=[CH:22][CH:21]=[C:20]([OH:25])[C:19]=3[C:18]3[C:13]2=[CH:14][CH:15]=[CH:16][C:17]=3[C:26]([O:28]C)=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[OH-].[NH4+:32]>C1COCC1.C(OCC)(=O)C>[C:1]1([CH2:11][N:12]2[C:24]3[CH:23]=[CH:22][CH:21]=[C:20]([OH:25])[C:19]=3[C:18]3[C:13]2=[CH:14][CH:15]=[CH:16][C:17]=3[C:26](=[O:28])[NH2:32])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: [NH4+]
Reactant: COC(=O)c1cccc2c1c1c(O)cccc1n2Cc1cccc2ccccc12
Agent: Cl
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: NC(=O)c1cccc2c1c1c(O)cccc1n2Cc1cccc2ccccc12
Yield: 40 %

Procedure:
A solution of the 9-[(1-naphthyl)methyl]-4-hydroxy-5-carbomethoxy carbazole (210 mg, 0.55 mM) in 10 mL THF and 30 mL concentrated aqueous ammonium hydroxide was sonicated for 20 hours at 40-50° C. The mixture was diluted with ethyl acetate and acidified to pH 1 with 5 N HCl. The aqueous layer was extracted three times with ethyl acetate. The combined organic extracts were washed with saturated brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with gradient hexanes/ethyl acetate) to afford 80 mg (40%) of the 9-[(1-naphthyl)methyl]-4-hydroxy-5-carbamoyl carbazole as a white solid. 1H NMR (DMSO-d6) δ10.55 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 8.35 (d, 1H, J=8 Hz), 7.95 (d, 1H, J=8 Hz), 7.8 (d, 1H, J=8 Hz), 7.65 (m, 4H), 7.45 (m, 2H), 7.25 (t, 1H, J=8 Hz), 7.15 (t, 1H, J=8 Hz), 6.9 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), and 6.2 (s, 2H). MS (ES) m/e 365, 367.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.[C:11]([N:14]1[C:23]2[C:18](=[CH:19][C:20]([C:24](O)=[O:25])=[CH:21][CH:22]=2)[C:17]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([CH3:27])[CH2:16][C:15]1([CH3:35])[CH3:34])(=[O:13])[CH3:12].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[C:11]([N:14]1[C:23]2[C:18](=[CH:19][C:20]([C:24]([O:8][CH2:7][C:6]3[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[O:25])=[CH:21][CH:22]=2)[C:17]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([CH3:27])[CH2:16][C:15]1([CH3:35])[CH3:34])(=[O:13])[CH3:12]
Reactant: COc1ccc(CO)cc1
Reactant: CC(=O)N1c2ccc(C(=O)O)cc2C(C)(c2ccccc2)CC1(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1ccc(COC(=O)c2ccc3c(c2)C(C)(c2ccccc2)CC(C)(C)N3C(C)=O)cc1

Procedure:
Condensation of 4-methoxybenzylalcohol (6.2 mg) with 1-acetyl-4-phenyl-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline-6-carboxylic acid (10 mg), under the agency of HATU (23 mg) and N,N-diisopropylethylamine (19 μl) in dichloromethane (2 ml) was performed according to the method described in example 11.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:18])[CH3:17])=[CH:12][C:11]=1[F:19])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH3:21][Mg+].[Br-]>C(Cl)Cl.C(OCC)C>[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([OH:18])([CH3:21])[CH3:17])=[CH:12][C:11]=1[F:19])[CH3:9])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[Mg+]
Reactant: CC(=O)c1ccc([C@H](C)NC(=O)OC(C)(C)C)c(F)c1
Agent: [Br-]
Solvent: ClCCl
Solvent: CCOCC
Product: C[C@H](NC(=O)OC(C)(C)C)c1ccc(C(C)(C)O)cc1F
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 87.3 %

Procedure:
To a solution of (S)-tert-butyl(1-(4-acetyl-2-fluorophenyl)ethyl)carbamate (200 mg, 0.71 mmol) in DCM (7.1 mL), cooled to 0° C. (water/ice bath) under N2, was added 3M MeMgBr (10.95 mL, 2.84 mmol) in diethyl ether. Reaction mixture allowed to stir for 5 min at 0° C. Then gradually allowed to warm to room temperature and stirred for 30 min at room temperature. Reaction mixture was cooled to 0° C. then quenched with the slow addition of a saturated solution of NH4Cl and diluted with DCM. Phases partitioned, aqueous phase extracted with DCM and the organic layers combined washed with water, brine, dried (Na2SO4), filtered and concentrated to (S)-tert-butyl(1-(2-fluoro-4-(2-hydroxypropan-2-yl)phenyl)ethyl)carbamate (184 mg, 0.62 mmol, 87% yield) afford as a colorless oil which slowly crystallizes upon standing. 1H NMR (400 MHz, CDCl3) δ 1.39-1.48 (m, 12H) 1.57 (s, 6H) 7.15-7.25 (m, 2H) 7.31-7.36 (m, 1H).
Reaction SMILES: C(OC(=O)[N:7]([CH2:14][CH2:15][O:16][C:17]1[CH:22]=[C:21]([C:23](=[O:29])[N:24]([CH:26]([CH3:28])[CH3:27])[CH3:25])[CH:20]=[C:19]([Cl:30])[CH:18]=1)[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)(C)(C)C.[F:32][C:33]([F:38])([F:37])[C:34]([OH:36])=[O:35]>ClCCl>[F:32][C:33]([F:38])([F:37])[C:34]([OH:36])=[O:35].[Cl:30][C:19]1[CH:20]=[C:21]([CH:22]=[C:17]([O:16][CH2:15][CH2:14][NH:7][C:8]2[CH:9]=[CH:10][N:11]=[CH:12][CH:13]=2)[CH:18]=1)[C:23]([N:24]([CH:26]([CH3:28])[CH3:27])[CH3:25])=[O:29]
Reactant: CC(C)N(C)C(=O)c1cc(Cl)cc(OCCN(C(=O)OC(C)(C)C)c2ccncc2)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)N(C)C(=O)c1cc(Cl)cc(OCCNc2ccncc2)c1

Procedure:
A solution of {2-[3-chloro-5-(isopropyl-methyl-carbamoyl)-phenoxy]-ethyl}-pyridin-4-yl-carbamic acid tert-butyl ester (0.060 g) in dichloromethane (4 ml) and trifluoroacetic acid (4 ml) was stored at room temperature for 2 h and then concentrated under reduced pressure. The residue was subjected to preparative hplc to give the title compound as a yellow gum (0.061 g).
Reaction SMILES: Cl.[NH2:2][CH:3]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=1)[CH2:4][C:5]([O:7][CH3:8])=[O:6].C(N(CC)CC)C.[N+:26]([C:29]1[CH:37]=[CH:36][C:32]([C:33](Cl)=[O:34])=[CH:31][CH:30]=1)([O-:28])=[O:27]>O1CCCC1>[N+:26]([C:29]1[CH:30]=[CH:31][C:32]([C:33]([NH:2][CH:3]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=2)[CH2:4][C:5]([O:7][CH3:8])=[O:6])=[O:34])=[CH:36][CH:37]=1)([O-:28])=[O:27]
Reactant: COC(=O)CC(N)c1ccc(OC)c(OC)c1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)CC(NC(=O)c1ccc([N+](=O)[O-])cc1)c1ccc(OC)c(OC)c1
Reaction time: 0.25 h
Yield: 95.8 %

Procedure:
To an ice bath cooled stirred suspension of methyl 3-amino-3-(3,4-dimethoxyphenyl)propionate hydrochloride(1.38 grams, 5.00 mmol) and triethylamine (1.5 milliliters, 10.8 mmol) in 25 milliliters of tetrahydrofuran was added 4-nitrobenzoyl chloride (0.928 grams, 5.00 mmol) in a single portion. After 15 minutes, the cooling bath was removed and the reaction mixture stirred for 45 minutes. The reaction mixture was then diluted with 50 milliliters of water. The reaction slurry was filtered and the solid washed with water, air-dried, and then dried in vacuo (60 C, <1 mm) to afford 1.86 grams (94%) of the product as a yellow powder: 1H NMR (CDCl3 /TMS, 250 MHz) δ 8.27 (d, J=8.8 Hz, 2 H), 7.98 (d, J=8.8 Hz, 2 H), 7.77 (d, J=8.1 Hz, 1 H, NH), 6.95-6.75 (m, 3 H, Ar), 5.55 (m, 1 H, CH), 3.86 & 3.85 (2 s, 6 H, 2 OCH3), 3.68 (s, 3 H, CO2 CH3), 3.00 (m, 2 H, CH2); 13C NMR (CDCl3 /TMS) δ 172.2, 164.4, 149.6, 1491, 148.7, 139.7, 132.6, 128.2, 123.8, 118.1, 111.2, 109.9, 55.9, 55.8, 52.0, 50.0, 39.3.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].Cl.N1C=CC=CC=1.[C:25]([NH2:34])(=[O:33])[C:26]1[C:27](=[CH:29][CH:30]=[CH:31][CH:32]=1)[NH2:28]>C(OCCO)C>[C:16]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:28][C:27]1[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=1[C:25]([NH2:34])=[O:33])=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH3:15])[CH:7]=2)#[N:17]
Reactant: NC(=O)c1ccccc1N
Reactant: COc1cc2ncc(C#N)c(Cl)c2cc1OC
Agent: Cl
Solvent: CCOCCO
Solvent: c1ccncc1
Product: COc1cc2ncc(C#N)c(Nc3ccccc3C(N)=O)c2cc1OC
Yield: 83.9 %

Procedure:
Using an analogous procedure to that described in Example 286, 248.7 mg (1 mmol) of 4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile in 12 mL of 2-ethoxyethanol and in the presence of 115.6 mg (1 mmol) of pyridine hydrochloride was reacted with 177.0 mg (1.3 mmol) of anthranilamide to give 292.4 mg (84.0%) of the product as a deep yellow solid, m.p. 238-240.5° C., mass (electrospray, m/e): M+H 348.9.
Reaction SMILES: [OH:1][C:2](C(O)(C)C)(C)[CH3:3].CC1(C)C(C)(C)OB([C:17]2[CH:22]=[CH:21][C:20]([C:23]3NC([C@@H]4CCCN4C(OC(C)(C)C)=O)=NC=3)=[CH:19][CH:18]=2)O1>>[CH2:2]([OH:1])[CH3:3].[CH3:21][CH2:22][CH2:17][CH2:18][CH2:19][CH2:20][CH3:23]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1c1ncc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)[nH]1
Reactant: CC(C)(O)C(C)(C)O
Product: CCCCCCC
Product: CCO

Procedure:
Pd(Ph3P)4 (469 mg, 0.406 mmol) was added to a pressure tube containing a mixture of bromide (28) (4.008 g, 10.22 mmol), bis(pinacolato)diboron (5.422 g, 21.35 mmol), potassium acetate (2.573 g, 26.21 mmol) and 1,4-dioxane (80 mL). The reaction flask was purged with nitrogen, capped and heated with an oil bath at 80° C. for 16.5 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The crude material was partitioned carefully between CH2Cl2 (150 mL) and an aqueous medium (50 mL water+10 mL saturated NaHCO3 solution). The aqueous layer was extracted with CH2Cl2, and the combined organic phase was dried (MgSO4), filtered, and concentrated in vacuo. The resulting material was purified with flash chromatography (sample was loaded with eluting solvent; 20-35% ethyl acetate/CH2Cl2) to provide boronate (17), contaminated with pinacol, as an off-white dense solid; the relative mole ratio of (17) to pinacol was about 10:1 (1H NMR). The sample weighed 3.925 g after ˜2.5 days exposure to high vacuum. 1H NMR (DMSO-d6, δ=2.5 ppm, 400 MHz): 12.22/11.94/11.87 (m, 1H), 7.79-7.50/7.34-7.27 (m, 5H), 4.86-4.70 (m, 1H), 3.52 (app br s, 1H), 3.36 (m, 1H), 2.27-1.77 (m, 4H), 1.45-1.10 (m, 21H). LC/MS: Anal. Calcd. for [M+H]+ C24H35BN3O4: 440.27. found 440.23.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)[N:3]=1.[CH:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20]>[Pd]>[F:16][C:15]([F:18])([F:17])[O:14][C:11]1[CH:12]=[CH:13][C:8]([C:4]2[N:3]=[C:2]([C:24]3[CH:25]=[CH:26][C:21]([CH:19]=[O:20])=[CH:22][CH:23]=3)[CH:7]=[CH:6][N:5]=2)=[CH:9][CH:10]=1
Reactant: O=Cc1ccc(B(O)O)cc1
Reactant: FC(F)(F)Oc1ccc(-c2nccc(Cl)n2)cc1
Agent: [Pd]
Product: O=Cc1ccc(-c2ccnc(-c3ccc(OC(F)(F)F)cc3)n2)cc1

Procedure:
The compound was prepared by palladium-catalyzed arylation of the product of step 1 with 4-formylphenyl boronic acid: 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 8.91 (d, J=4.8 Hz, 1H), 8.74 (d, J=8.5 Hz, 2H), 8.28 (d, J=8.4 Hz, 2H), 8.03 (d, J=8.4 Hz, 2H), 7.65 (d, J=5.3 Hz, 1H), 7.39 (d, J=8.6 Hz, 2H); EIMS m/z 344 (M+).
Reaction SMILES: [CH2:1](N)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH2:7].Cl[C:10]1[C:19]2[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=2)[N:13]=[CH:12][CH:11]=1.O>C(Cl)Cl>[NH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][C:10]1[C:19]2[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=2)[N:13]=[CH:12][CH:11]=1
Reactant: Clc1ccc2c(Cl)ccnc2c1
Reactant: NCCCCCCN
Solvent: ClCCl
Solvent: O
Product: NCCCCCCc1ccnc2cc(Cl)ccc12
Temperature: 150 °C

Procedure:
17.1 Grams of hexane-1,6-diamine and 4.3 g of 4,7-dichloroquinoline were mixed together and heated to 150° C. for four hours. The reaction was cooled and water and methylene chloride were then added. The organic phase was washed, dried with anhydrous magnesium sulfate and evaporated thereby affording 1-amino-6-(7-chloro-4-quinolinyl)hexane having a melting point of 133°-134°.
Reaction SMILES: CN(P(N(C)C)N(C)C)C.[Cl:11][C:12]1[C:22]2[CH2:21][CH2:20][N:19]([CH3:23])[CH2:18][CH2:17][C:16]=2[CH:15]=[CH:14][CH:13]=1.C[S-:25].[Na+].[CH2:27](Br)[CH:28]=[CH2:29]>[Cl-].[Na+].O>[ClH:11].[CH2:27]([S:25][C:12]1[C:22]2[CH2:21][CH2:20][N:19]([CH3:23])[CH2:18][CH2:17][C:16]=2[CH:15]=[CH:14][CH:13]=1)[CH:28]=[CH2:29]
Reactant: CN1CCc2cccc(Cl)c2CC1
Reactant: C[S-]
Reactant: C=CCBr
Agent: CN(C)P(N(C)C)N(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: C=CCSc1cccc2c1CCN(C)CC2
Product: Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Into 10 ml of hexamethylphosphorus triamide was dissolved 784 mg (4 mmol) of 6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine and 840 mg (12 mmol) of sodium thiomethoxide. The reaction was heated to 125° for 4 hours, cooled to ice-bath temperature and 968 mg (18 mmol) of allyl bromide was added in one portion. The mixture was warmed to room temperature and stirred overnight. It was poured into 75 ml of brine and extracted with three 75 ml portions of ether. The combined extracts were washed with three 50 ml portions of water, dried over magnesium sulfate and treated with excess ethereal hydrogen chloride. The solvent was reduced to 10 ml and decanted from an insoluble oil. The oil was triturated with 10 ml ether which was removed and discarded. The residue was taken up in hot ethanol, diluted with ether and allowed to crystallize. The precipitate was removed and recrystallized from acetonitrile to give 6-allylthio-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride, as white crystals, m.p. 158°-160°.
Reaction SMILES: [CH3:1][C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[O:4][C:3]=1[S:13][CH3:14].C1C=C(Cl)C=C(C(OO)=[O:23])C=1>ClCCl>[CH3:14][S:13]([C:3]1[O:4][C:5]2[C:10]([C:11](=[O:12])[C:2]=1[CH3:1])=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:23]
Reactant: CSc1oc2ccccc2c(=O)c1C
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Cc1c(S(C)=O)oc2ccccc2c1=O
Reaction time: 2 h
Yield: 82.8 %

Procedure:
To a solution containing 3-methyl-2-methylsulfanyl-chromen-4-one (1.95 g, 9.45 mmol) in dichloromethane (75 mL) at 0° C. was added mCPBA (2 g, 11.82 mmol). The reaction stirred for 2 hours. After consumption of the starting material, the reaction mixture was filtered and the resulting filtrate was washed with cold 5% sodium carbonate, water, and saturated sodium bisulfate. The organic layer was dried over sodium sulfate, filtered, and concentrated to obtain the desired product as a light yellow solid (1.74 g, 83% yield), which was taken on to the next step without further purification. 1H NMR (600 MHz, DMSO-d6): δ 8.08 (dd, 1H, J=7.8, 1.2 Hz), 7.88 (m, 1H), 7.76 (d, 1H, J=7.8 Hz), 7.55 (m, 1H), 3.01 (s, 3H), 2.12 (s, 3H).