Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[C:5]2I.[N:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[C:21](B(O)O)[CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[C:5]2[C:21]1[CH:20]=[N:19][C:28]2[C:23]([CH:22]=1)=[CH:24][CH:25]=[CH:26][CH:27]=2
Reactant: CC(C)(C)OC(=O)n1cc(I)c2cc(Br)ccc21
Reactant: OB(O)c1cnc2ccccc2c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)OC(=O)n1cc(-c2cnc3ccccc3c2)c2cc(Br)ccc21
Temperature: 60 °C
Yield: 36.6 %

Procedure:
To a mixture of tert-butyl 5-bromo-3-iodo-1H-indole-1-carboxylate (1.750 g, 4.146 mmol, synchem), 3-quinolineboronic acid (1.076 g, 6.22 mmol), Pd(PPh3)4 (0.240 g, 0.207 mmol) and potassium carbonate ((1.719 g, 12.439 mmol) in dioxane (3.0 mL) was added H2O (1.0 mL) and the reaction was heated at 60° C. for 42 h. Saturated NaHCO3 solution (5.0 mL) was added to the mixture. The resulting mixture was extracted with EtOAc. The organic phases were combined, dried with sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography to give tert-butyl 5-bromo-3-(quinolin-3-yl)-1H-indole-1-carboxylate (642 mg, 36.6%) as a white foam. MS (ESI, pos. ion) m/z: 423 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.68 (s, 9H), 7.62 (dd, J=8.8, 1.8 Hz, 1H), 7.67 (t, J=7.8 Hz, 1H), 7.79 (t, J=7.3 Hz, 1H), 8.07 (d, J=8.5 Hz, 1H), 8.13-8.20 (m, 3H), 8.30 (s, 1H), 8.74 (d, J=1.5 Hz, 1H), 9.26 (d, J=2.0 Hz, 1H)
Reaction SMILES: [CH2:1]([C@H:3]([NH:10][C:11]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:14]=1[O:29][CH2:30][CH2:31][NH2:32])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].C1C2C(COC([NH:50][CH2:51][C:52](Cl)=[O:53])=O)C3C(=CC=CC=3)C=2C=CC=1>C(Cl)Cl>[CH2:1]([C@H:3]([NH:10][C:11]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:14]=1[O:29][CH2:30][CH2:31][NH:32][C:52](=[O:53])[CH2:51][NH2:50])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]
Reactant: O=C(Cl)CNC(=O)OCC1c2ccccc2-c2ccccc21
Reactant: CC[C@H](NC(=O)c1c(OCCN)c(-c2ccccc2)nc2ccccc12)c1ccccc1
Solvent: ClCCl
Product: CC[C@H](NC(=O)c1c(OCCNC(=O)CN)c(-c2ccccc2)nc2ccccc12)c1ccccc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 17.5 %

Procedure:
3.0 g (7.1 mmol) of (S)-N-(α-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide (compound of Description 4) were dissolved, under nitrogen atmosphere, in 60 ml of CH2Cl2 and 1.2 ml (8.5 mmol) of TEA were added; the solution was cooled to 0° C. and 2.7 g (8.5 mmol) of (9-fluorenylmethoxy carbonyl)glycinyl chloride (FMOC-glycinyl chloride), dissolved in 60 ml of CH2Cl2, were added dropwise. The reaction mixture was stirred at room temperature for 3 hours and then washed with sat. sol. NaCl, 20% citric acid, sat. sol. NaHCO3, sat. sol. NaCl, dried over Na2SO4 and evaporated in vacuo to dryness. The crude product was purified by gradient flash column chromatography on 230-400 mesh silica gel, utilising a mixture of hexane/EtOAc 1:1 as starting eluent and a mixture of EtOAc/MeOH 9:1 as final eluent. The product (5.0 g) was dissolved in 100 ml of a 10% solution of diethylamine in DMF and stirred at room temperature for 30 minutes. The reaction mixture was then evaporated in vacuo and purified by gradient flash column chromatography on 230-400 mesh silica gel, utilising a mixture of EtOAc/MeOH 9:1 as starting eluent and a mixture of EtOAc/MeOH 7:3 as final eluent, to yield 0.6 g of the title compound.
Reaction SMILES: C([O:3][C:4](=[O:42])[CH:5]([OH:41])[CH2:6][NH:7][C:8](=[O:40])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:28][C:29]([NH:31][C:32]2[CH:37]=[C:36]([Cl:38])[CH:35]=[C:34]([Cl:39])[CH:33]=2)=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]=3)=[CH:18][CH:17]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+].Cl>C(O)C.C1COCC1>[C:22]1([C:19]2[CH:18]=[CH:17][C:16]([CH:15]([NH:28][C:29]([NH:31][C:32]3[CH:33]=[C:34]([Cl:39])[CH:35]=[C:36]([Cl:38])[CH:37]=3)=[O:30])[C:12]3[CH:13]=[CH:14][C:9]([C:8]([NH:7][CH2:6][CH:5]([OH:41])[C:4]([OH:42])=[O:3])=[O:40])=[CH:10][CH:11]=3)=[CH:21][CH:20]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]=1
Reactant: CCOC(=O)C(O)CNC(=O)c1ccc(C(NC(=O)Nc2cc(Cl)cc(Cl)c2)c2ccc(C3=CCCCC3)cc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(Nc1cc(Cl)cc(Cl)c1)NC(c1ccc(C(=O)NCC(O)C(=O)O)cc1)c1ccc(C2=CCCCC2)cc1
Temperature: 40 °C
Reaction time: 4 h
Yield: 78.9 %

Procedure:
A solution of (RS)-3-{4-[1-(4-cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester (0.99 g, 1.61 mmol) in ethanol (15 mL) and THF (15 mL) was stirred and 1 M sodium hydroxide (6 mL) was added. The mixture was stirred at 40° C. for 4 hours and acidified with 1 N hydrochloric acid. After evaporation in vacuo the residue was purified on semipreperative HPLC (Gilson system). The pure fractions were combined and evaporated in vacuo to afford 0.74 g (79%) of the title compound as a solid.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:10]([N+:11]([O-])=O)=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[N+:14]([O-])=O.[OH-].[Na+]>>[Cl:2][C:3]1[C:10]([NH2:11])=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[NH2:14]
Reactant: N#Cc1cc([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: N#Cc1cc(N)c(Cl)c(N)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 352.5 grams (1.56 mole) of stannous chloride dihydrate in 860 ml. of concentrated hydrochloric acid is added 50 gm. (0.2195 mole) of 4-chloro-3,5-dinitrobenzonitrile. The mixture is stirred at room temperature for two hours and cooled to 0° in an ice-salt bath. A cold solution of 50% sodium hydroxide is added to the mixture until strongly basic. During the addition the temperature is kept below 30°.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:21]2[CH2:25][C@H:24]([CH2:26][N:27]3[CH:31]=[CH:30][N:29]=[N:28]3)[O:23][C:22]2=[O:32])[CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][C:11]([C:14]2[CH2:18][C@@H:17]([CH2:19][OH:20])[O:16][N:15]=2)=[CH:12][CH:13]=1.Cl[C:34]([O:36][CH2:37][CH2:38][O:39][CH3:40])=[O:35]>CN(C=O)C.N1C=CC=CC=1.O>[C:34](=[O:35])([O:36][CH2:37][CH2:38][O:39][CH3:40])[O:20][CH2:19][C@H:17]1[O:16][N:15]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:7]3[CH:6]=[CH:5][C:4]([N:21]4[CH2:25][C@H:24]([CH2:26][N:27]5[CH:31]=[CH:30][N:29]=[N:28]5)[O:23][C:22]4=[O:32])=[CH:3][C:2]=3[F:1])=[CH:9][N:10]=2)[CH2:18]1
Reactant: O=C1O[C@@H](Cn2ccnn2)CN1c1ccc(-c2ccc(C3=NO[C@H](CO)C3)nc2)c(F)c1
Reactant: COCCOC(=O)Cl
Solvent: CN(C)C=O
Solvent: c1ccncc1
Solvent: O
Product: COCCOC(=O)OC[C@@H]1CC(c2ccc(-c3ccc(N4C[C@H](Cn5ccnn5)OC4=O)cc3F)cn2)=NO1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 80.4 %

Procedure:
(5R)-3-(3-Fluoro-4-{6-[(5S)-5-hydroxymethyl)-4,5-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 1, 0.2 g, 0.46 mmol) was dissolved in DMF (4 ml) and pyridine (0.5 ml), then cooled to 0° C. 2-Methoxyethyl chloroformate (0.2 ml, 1.73 mmol) was added, the mixture was stirred at 0° C. for 45 minutes followed by addition of a second portion of 2-methoxyethyl chloroformate. The mixture was stirred for one additional hour at 0° C., then diluted with water, extracted twice with ethyl acetate and dried over sodium sulfate. The residue obtained upon filtration and evaporation was purified via chromatography (silica gel, 0 to 10% acetonitrile in ethyl acetate). Evaporation of the product containing fractions and trituration of the resulting solid with diethyl ether yielded the title compound as a white solid (0.20 g), melting point: 112° C.
Reaction SMILES: [F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]2[N:13]=[C:12]([C:14]3[CH:24]=[C:23]([CH3:25])[C:17]([O:18][CH2:19][C:20](Cl)=[O:21])=[C:16]([CH3:26])[CH:15]=3)[O:11][C:9]=2[N:10]=1.Cl.C([O:36][C:37](=[O:43])[C@@H:38]1[CH2:42][CH2:41][CH2:40][NH:39]1)(C)(C)C.C(N(CC)CC)C>ClCCl>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]2[N:13]=[C:12]([C:14]3[CH:24]=[C:23]([CH3:25])[C:17]([O:18][CH2:19][C:20]([N:39]4[CH2:40][CH2:41][CH2:42][C@H:38]4[C:37]([OH:43])=[O:36])=[O:21])=[C:16]([CH3:26])[CH:15]=3)[O:11][C:9]=2[N:10]=1
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCN1
Reactant: Cc1cc(-c2nc3cnc(Oc4ccccc4F)nc3o2)cc(C)c1OCC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(-c2nc3cnc(Oc4ccccc4F)nc3o2)cc(C)c1OCC(=O)N1CCC[C@H]1C(=O)O
Reaction time: 2 h

Procedure:
A solution of 175 mg of {4-[5-(2-fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethyl-phenoxy}-acetyl chloride in 2 ml of dichloromethane was added slowly to a suspension of 102 mg of proline tert-butyl ester hydrochloride and 170 μl of triethylamine in 5 ml of dichloromethane. After stirring for 2 h, the solvent was removed in vacuo. 1.6 ml of trifluoroacetic acid were added and the mixture was stirred for 2 h at room temperature. Then 10 ml water were added and the aqueous layer was extracted three times with 15 ml of a dichloromethane/isopropanol mixture (3:1). After drying with sodium sulfate and filtration, the solvents were removed in vacuo and the title compound was isolated via preparative HPLC. Yield: 56 mg of a white solid.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C:12]([O:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][O:25]1)([C:18]([O:20]CC)=[O:19])[C:13]([O:15]CC)=[O:14].[Li+].[OH-]>CO.CO.O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C:12]([O:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][O:25]1)([C:13]([OH:15])=[O:14])[C:18]([OH:20])=[O:19]
Reactant: CCOC(=O)C(Cc1ccc2ccccc2n1)(OC1CCCCO1)C(=O)OCC
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)C(Cc1ccc2ccccc2n1)(OC1CCCCO1)C(=O)O
Reaction time: 12 h
Yield: 90.7 %

Procedure:
A solution of ethyl 3-(quinolin-2-yl)-2-(2-tetrahydropyranyloxy)-2-ethoxycarbonyl-propanoate (0.5 g) in 5 ml of methanol is hydrolysed by treatment with a LiOH in MeOH-H2O solution. After 12 h at r.t., the solvent is evaporated off under vacuum and the residue is partitioned between AcOEt and an excess of a monobasic potassium phosphate saturated solution. The organic phase is separated, dried, evaporated to dryness to obtain 0.39 g of 3-(quinolin-2-yl)-2-(2-tetrahydropyranyloxy)-2-carboxy-propanoic acid.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:13]=[CH:12][C:6]([O:7][CH2:8][CH:9]([OH:11])[CH3:10])=[CH:5][CH:4]=1.[C:14]([N:18]1[C:23](=[O:24])[C:22]([Cl:25])=[C:21](O)[CH:20]=[N:19]1)([CH3:17])([CH3:16])[CH3:15].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.O>[C:14]([N:18]1[C:23](=[O:24])[C:22]([Cl:25])=[C:21]([O:1][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([O:7][CH2:8][CH:9]([OH:11])[CH3:10])=[CH:12][CH:13]=2)[CH:20]=[N:19]1)([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)n1ncc(O)c(Cl)c1=O
Reactant: CC(O)COc1ccc(CO)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: CC(O)COc1ccc(COc2cnn(C(C)(C)C)c(=O)c2Cl)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 51.5 %

Procedure:
To solution of the product of Example 6B (269 mg, 1.48 mmol) and 2-tert-butyl-4-chloro-5-hydroxy-2H-pyridazin-3-one (250 mg, 1.23 mmol) dissolved in anhydrous THF (18.5 mL) was added solid PPh3 (485 mg, 1.85 mmol) and DIAD (0.358 mL, 1.85 mmol). After completion of addition the reaction mixture continued to stir at room temperature. After 20 hours, the reaction mixture was diluted with water. The aqueous layer was separated and extracted with ethyl acetate (3×). All combined organic layers were dried over Na2SO4, filtered, and concentrated to provide an oil. The crude material was purified using silica gel chromatography (1:1 pentane:ethyl acetate) to provide the desired product (234 mg, 0.634 mmol) in 51% yield. 1H (CDCl3 7.71 (1H, s), 7.33 (2H, d, 600 MHz): δ J=8.7 Hz), 6.94 (2H, d, J=8.7 Hz), 5.24 (2H, s), 4.19 (1H, m), 3.95 (1H, dd, J=9.2, 3.1 Hz), 3.81 (1H, dd, J=9.2, 7.7 Hz), 1.62 (9H, s) 1.29 (3H, d, J=6.4 Hz).
Reaction SMILES: [CH2:1]([C:3](=[CH2:6])[CH:4]=[O:5])[CH3:2].[CH:7]1([Mg]Cl)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.C(OCC)C>[NH4+].[Cl-]>[CH:7]1([CH:4]([OH:5])[C:3](=[CH2:6])[CH2:1][CH3:2])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: C=C(C=O)CC
Reactant: Cl[Mg]C1CCCCC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: C=C(CC)C(O)C1CCCCC1
Temperature: 25 °C
Yield: 60 %

Procedure:
2-Ethylacroleine (25 g, 267 mmol) was added drop-wise to a 2 molar solution of cyclohexylmagnesium chloride in diethyl ether (167 ml, 334 mmol), at 0° C. under nitrogen. The reaction was then warmed up slowly to room temperature overnight. After cooling to 0° C., saturated aqueous NH4Cl (500 ml) was added slowly. The reaction was warmed up to room temperature and phases separated. The aqueous phase was re-extracted with diethyl ether. Each organic phase was washed with brine. Combined extracts were dried over sodium sulfate. The product was purified by column chromatography on silica gel (eluent: heptanes/ethyl acetate 5:1) followed by bulb-to-bulb distillation (90-100° C./1 mbar). The product was obtained as colorless liquid (yield: 60%).
Reaction SMILES: [NH2:1][C:2]1[CH2:7][CH2:6][CH:5]([CH3:8])[CH2:4][C:3]=1[C:9]([O:11]CC)=O.[C:14](OCC)(=[O:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]>>[C:16]([C:15]1[C:14](=[O:21])[NH:1][C:2]2[CH2:7][CH2:6][CH:5]([CH3:8])[CH2:4][C:3]=2[C:9]=1[OH:11])([O:18][CH2:19][CH3:20])=[O:17]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CCOC(=O)C1=C(N)CCC(C)C1
Product: CCOC(=O)c1c(O)c2c([nH]c1=O)CCC(C)C2

Procedure:
Condensation of ethyl 2-amino-5-methyl-cyclohex-1-ene-1-carboxylate (37 g; 0.202 mole) with diethyl malonate (32.4 g; 0.202 mole) at 110° C as described in Example 1 gave the title compound; m.p. (EtOH) 214°-216° C.
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:22])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[O:4]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][OH:32]>C(#N)C>[CH3:9][C:7]1([CH3:8])[C:3]([CH3:22])([CH3:2])[O:4][B:5]([C:10]2[CH:11]=[CH:12][C:13]([N:16]3[CH2:17][CH2:18][N:19]([CH2:30][CH2:31][OH:32])[CH2:20][CH2:21]3)=[CH:14][CH:15]=2)[O:6]1
Reactant: CC1(C)OB(c2ccc(N3CCNCC3)cc2)OC1(C)C
Reactant: OCCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC1(C)OB(c2ccc(N3CCN(CCO)CC3)cc2)OC1(C)C
Temperature: 60 °C

Procedure:
To a solution of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine hydrochloride (500 mg, 1.54 mmol) and potassium carbonate (430 mg, 3.1 mmol) in acetonitrile (20 mL) was added 2-bromoethanol (388 mg, 3.1 mmol), then the mixture was heated at 60° C. overnight under an atmosphere of nitrogen. Then the mixture was filtered over celite and washed with DCM, concentrated to give product as a light brown solid. MS (m/z): 333 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([Sn:10]([CH3:13])([CH3:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1.[CH3:14][S:15](Cl)(=[O:17])=[O:16]>>[CH3:14][S:15]([NH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([Sn:10]([CH3:12])([CH3:11])[CH3:13])[CH:7]=[CH:8][CH:9]=1)(=[O:17])=[O:16]
Reactant: CS(=O)(=O)Cl
Reactant: C[Sn](C)(C)c1cccc(CCN)c1
Product: CS(=O)(=O)NCCc1cccc([Sn](C)(C)C)c1

Procedure:
The title compound was prepared by the method of example 17, part A, from 3(2′-aminoethyl)phenyl trimethylstannane and methanesulfonyl chloride.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([N+:38]([O-:40])=[O:39])=[C:34]([CH:37]=1)[CH:35]=O>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:35][C:34]3[CH:37]=[C:30]([Cl:29])[CH:31]=[CH:32][C:33]=3[N+:38]([O-:40])=[O:39])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: O=Cc1cc(Cl)ccc1[N+](=O)[O-]
Product: O=[N+]([O-])c1ccc(Cl)cc1CNc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1

Procedure:
The title compound was prepared from {3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amine and 5-chloro-2-nitro-benzaldehyde according to the procedure of step 1, Example 66. MS (ESI) m/z 548.
Reaction SMILES: [CH3:1][CH:2]([N:4]([CH2:8][CH2:9][S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=[O:12])=[O:11])[C:5](Cl)=[O:6])[CH3:3].[CH2:19]([N:21]([CH2:32][CH3:33])[CH2:22][CH2:23][NH:24][CH2:25][CH2:26][N:27]([CH2:30][CH3:31])[CH2:28][CH3:29])[CH3:20].C(N(CC)CC)C>O1CCCC1.CCOCC>[CH2:30]([N:27]([CH2:28][CH3:29])[CH2:26][CH2:25][N:24]([CH2:23][CH2:22][N:21]([CH2:32][CH3:33])[CH2:19][CH3:20])[C:5]([N:4]([CH:2]([CH3:3])[CH3:1])[CH2:8][CH2:9][S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=[O:12])=[O:11])=[O:6])[CH3:31]
Reactant: CCN(CC)CCNCCN(CC)CC
Reactant: CC(C)N(CCS(=O)(=O)c1ccccc1)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CCN(CC)CCN(CCN(CC)CC)C(=O)N(CCS(=O)(=O)c1ccccc1)C(C)C
Temperature: 25 °C
Reaction time: 7 h

Procedure:
A mixture of 7.67 g (0.0265 mole) of N-(1-methylethyl)-N-[2-(phenylsulfonyl)ethyl]carbamic chloride and 6.24 g (0.029 mole) of N'-[2-(diethylamino)ethyl]-N,N-diethyl-1,2-ethanediamine and 2.73 g (0.0270 mole) of triethylamine in 400 ml of tetrahydrofuran was refluxed for 6 hr and then was stirred at room temperature for 7 hr. The solvent was removed in vacuo and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over sodium sulfate, and the solvent was removed in vacuo to give an oil. This was dissolved in ether, and the solution was extracted with three portions of water. The ether solution was dried over sodium sulfate, and the solvent was removed in vacuo to give an oil. This was pumped under high vacuum at 56° C. for 20 hr to give the title compound as an oil.
Reaction SMILES: [CH3:1][N:2]1[C:6](=[O:7])[CH:5]=[C:4]([CH2:8][CH2:9][CH3:10])[NH:3]1.[OH-].[Ca+2].[OH-].[Cl:14][C:15]1[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=1[C:17](Cl)=[O:18].Cl>C1C=CC=CC=1.O1CCOCC1>[CH3:1][N:2]1[C:6]([OH:7])=[C:5]([C:17](=[O:18])[C:16]2[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=2[Cl:14])[C:4]([CH2:8][CH2:9][CH3:10])=[N:3]1
Reactant: CCCc1cc(=O)n(C)[nH]1
Reactant: O=C(Cl)c1ccccc1Cl
Agent: Cl
Agent: [Ca+2]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: c1ccccc1
Product: CCCc1nn(C)c(O)c1C(=O)c1ccccc1Cl
Temperature: 50 °C
Yield: 9.2 %

Procedure:
1.4 g. of 1-methyl-3-n-propyl-5-pyrazolone is dissolved in 10 ml. of dioxane with heating and then 1.5 g. of calcium hydroxide is added to the resulting solution. 1.75 g. of 2-chlorobenzoyl chloride is added dropwise with stirring at 50° C. After completion of the dropwise addition, the mixture is heated under reflux for 1 hour. After completion of the reaction, the reaction mixture is allowed to cool and 100 ml. of a 2 N hydrochloric acid solution is added thereto. The mixture is extracted with 70 ml. of chloroform and an organic layer is separated. The layer is washed with water, dried over anhydrous sodium sulfate and the solvent is distilled off from the layer to give 2 g. of brown oily residue. The residue thus obtained is dissolved in a small amount of benzene and adsorbed on a silica gel column, which is then eluted with benzene: ethanol (50:1) to give 0.6 g. of crystals. The crystals are recrystallized from methanol-water (7:3) to give 0.25 g. of the desired product as colorless columns having a melting point of 125°-126° C. Yield 9.2%
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([NH2:10])[C:8]#[CH:9].F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21].[K+].[Br-]>CS(C)=O.O.C(N(CC)CC)C>[CH2:7]([NH:10][C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21])[C:8]#[CH:9]
Reactant: Cc1cc([N+](=O)[O-])ccc1F
Reactant: C#CCN
Agent: O=C([O-])[O-]
Agent: [Br-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: O
Product: C#CCNc1ccc([N+](=O)[O-])cc1C
Temperature: 50 °C

Procedure:
To a suspension of potassium carbonate (20.0 g) in DMSO (7 ml) was added triethylamine (3 ml) and 2-propyn-1-amine (7.10 g, 1.29×10-1 mole). 2-Fluoro-5-nitrotoluene (20.00 g, 1.29×10-1 mole) was added with stirring and the reaction mixture was heated at 50° C. for three days. The mixture was cooled, poured into excess water, and extracted with methylene chloride. The methylene chloride solution was dried over sodium sulfate, filtered and evaporated. The residue was chromotographed on a silica column, eluting with benzene, and recrystallized from benzene to afford yellow crystals; m.p. 121°-123° C. Yield: 15.02 g (61%). I.R. (KBr): 3344 (NH), 3226 (CH), 1580 and 1282 cm-1 (Ar-NO2).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21]([OH:23])=O)[CH:17]=2)[CH3:14])(=[O:12])=[O:11])=[C:5]([CH3:24])[CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[N:37]1([CH2:43][CH2:44][N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>ClCCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:24])[C:6]([S:10]([N:13]([CH3:14])[CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21]([N:40]3[CH2:39][CH2:38][N:37]([CH2:43][CH2:44][N:45]4[CH2:46][CH2:47][O:48][CH2:49][CH2:50]4)[CH2:42][CH2:41]3)=[O:23])[CH:17]=2)(=[O:11])=[O:12])=[C:7]([CH3:9])[CH:8]=1
Reactant: C1CN(CCN2CCOCC2)CCN1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)O)co2)c(C)c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)N3CCN(CCN4CCOCC4)CC3)co2)c(C)c1

Procedure:
The title compound was prepared according to general procedure AA using 5-({[(4-Methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)furan-3-carboxylic acid (63 mg, 0.18 mmol), CDI (58 mg, 0.36 mmol) and 4-[2-(piperazin-1-yl)ethyl]morpholine (60 mg, 0.30 mmol) in DCE (4.5 mL).
Reaction SMILES: [CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[CH2:18][CH2:19][C:20]([NH:22][C:23]1S[CH:25]=[CH:26][N:27]=1)=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N[C:29]1[CH:34]=CC=CN=1>>[CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[CH2:18][CH2:19][C:20]([NH:22][C:23]1[CH:34]=[CH:29][CH:25]=[CH:26][N:27]=1)=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(CCC1c2ccccc2C(=O)N1Cc1ccccc1)Nc1nccs1
Reactant: Nc1ccccn1
Product: O=C(CCC1c2ccccc2C(=O)N1Cc1ccccc1)Nc1ccccn1

Procedure:
The product from Example 1, Part E (200 mg, 0.68 mmol) and 2-aminopyridine (95 mg, 1.02 mmol) were converted to the title compound in a manner analogous to the method described in Example 2 (10 mg, 4%). 1H NMR (300 MHz, acetone-d6) δ 9.13 (br s, 1H), 8.02 (m, 2H), 7.63 (m, 2H), 7.48 (m, 3H), 7.20 (m, 5H), 6.91 (m, 1H), 5.13 (d, J=15 Hz, 1H), 4.48 (m, 1H), 4.24 (d, J=15 Hz, 1H), 2.35 (m, 2H), 1.84 (m, 2H). MS: m/z (MH+) 372.