Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]([N:22]3[C:26](=[O:27])[C@@H:25]([CH2:28][C:29]([NH:31][O:32][CH2:33][CH2:34][O:35]C=C)=[O:30])[NH:24][C:23]3=[O:38])[C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>CO>[OH:35][CH2:34][CH2:33][O:32][NH:31][C:29](=[O:30])[CH2:28][C@@H:25]1[C:26](=[O:27])[N:22]([C@H:13]([C:11]2[NH:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=3)=[CH:9][N:10]=2)[C@H:14]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH3:15])[C:23](=[O:38])[NH:24]1
Reactant: C=COCCONC(=O)C[C@H]1NC(=O)N([C@H](c2ncc(-c3ccc(I)cc3)[nH]2)[C@@H](C)c2ccccc2)C1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Product: C[C@@H](c1ccccc1)[C@@H](c1ncc(-c2ccc(I)cc2)[nH]1)N1C(=O)N[C@H](CC(=O)NOCCO)C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 69.6 %

Procedure:
To a solution of 2-((R)-1-{(1S,2S)-1-[5-(4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-2,5-dioxo-imidazolidin-4-yl)-N-(2-vinyloxy-ethoxy)-acetamide (64 mg, 0.1 mmol) in methanol (3 mL) was added aqueous 1 N hydrochloric acid (3 mL). The mixture was stirred at room temperature for 3 hours. Saturated aqueous sodium carbonate solution (10 mL) was added and the reaction mixture was extracted with ethyl acetate (2×50 mL). The organic layers were successively washed with saturated aqueous sodium carbonate solution then brine, dried over sodium sulfate, filtered, concentrated and the residue purified by chromatography over silica gel gradient eluted from 100% methylene chloride up to 10% v/v methanol/methylene chloride during 30 minutes to give N-(2-hydroxy-ethoxy)-2-((R)-1-{(1S,2S)-1-[5-(4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-2,5-dioxo-imidazolidin-4-yl)-acetamide as a white solid (42 mg, 61%). LC-MS: calcd for C25H26IN5O5 [M+H+] 604. Found 604.
Reaction SMILES: C(C1CCNCC1)C1C=CC=CC=1.C([O:16][C:17](=[O:55])[C:18]([CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][CH:45]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:44][CH2:43]1)([NH:32]C(OC(C)(C)C)=O)[CH2:19][CH2:20][CH2:21][CH2:22][B:23]1[O:27]C(C)(C)C(C)(C)[O:24]1)C.[ClH:56]>O>[ClH:56].[ClH:56].[NH2:32][C:18]([CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][CH:45]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:44][CH2:43]1)([CH2:19][CH2:20][CH2:21][CH2:22][B:23]([OH:27])[OH:24])[C:17]([OH:55])=[O:16]
Reactant: CCOC(=O)C(CCCCB1OC(C)(C)C(C)(C)O1)(CCN1CCC(Cc2ccccc2)CC1)NC(=O)OC(C)(C)C
Agent: Cl
Agent: c1ccc(CC2CCNCC2)cc1
Solvent: O
Product: NC(CCCCB(O)O)(CCN1CCC(Cc2ccccc2)CC1)C(=O)O
Temperature: 25 °C

Procedure:
2-Amino-2-[2-(4-benzylpiperidin-1-yl)ethyl]-6-borono-hexanoic acid dihydrochloride is prepared in a manner analogous to that set forth in Example 16, except 4-benzylpiperidine is used as the amine in step 6. The final step is as follows: a solution of 2-[2-(4-benzylpiperidin-1-yl)ethyl]-2-tert-butoxycarbonylamino-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxa-borolan-2-yl)-hexanoic acid ethyl ester (95 mg) in 6 N hydrochloric acid (5 mL) was stirred at 95° C. overnight. After cooling to room temperature, the reaction mixture was transferred to a separatory funnel, diluted with deionized water (5 mL) and washed with dichloromethane (3×). The aqueous layer was frozen in liquid nitrogen and lyophilized to give the title compound as a colorless foam (42 mg); 1H NMR (D2O, 300 MHz) δ 7.24 (m, 2H), 7.13 (m, 3H), 3.42 (m, 2H), 3.18 (m, 1H), 3.00 (m, 1H), 2.78 (m, 2H), 2.44 (d, J=7.0 Hz, 2H), 2.16 (t, J=7.0 Hz, 2H), 1.76 (m, 5H), 1.24 (m, 5H), 1.09 (m, 1H) and 0.61 (t, J=7.0 Hz, 2H); MS (+CI): m/z for C20H33BN2O4: expected 376.3. found 377.2 (M+H)+, 359.2 (M+H−H2O)+.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:7]([I:10])=[CH:6][C:3]=1[CH:4]=[O:5].[C:11]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)#[N:12].C([O-])([O-])=O.[K+].[K+]>CN(C)C(=O)C>[CH:4]([C:3]1[CH:6]=[C:7]([I:10])[CH:8]=[CH:9][C:2]=1[O:19][C:16]1[CH:17]=[CH:18][C:13]([C:11]#[N:12])=[CH:14][CH:15]=1)=[O:5]
Reactant: O=Cc1cc(I)ccc1F
Reactant: N#Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: N#Cc1ccc(Oc2ccc(I)cc2C=O)cc1
Yield: 68 %

Procedure:
In a manner similar to the method described in Example 50a, 2-fluoro-5-iodobenzaldehyde (2 g, 8 mmol) (Aldrich) was reacted with 4-cyanophenol (1.43 g, 12 mmol) and K2CO3 in N,N-dimethylacetamide to give 4-(2-formyl-4-iodo-phenoxy)-benzonitrile as a light yellow solid (Yield 1.9 g, 70.4%).
Reaction SMILES: C(C([CH:9]=[CH:10][C:11]([C:17]#[N:18])=[C:12](O)[C:13]([OH:15])=[O:14])=C(O)C(O)=O)#N.[Cl:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23].C1(C)C=CC=CC=1>O>[C:17]([C:11]1[CH:10]=[CH:9][N:23]([C:22]2[CH:24]=[CH:25][CH:26]=[C:20]([Cl:19])[CH:21]=2)[C:12]=1[C:13]([OH:15])=[O:14])#[N:18]
Reactant: Nc1cccc(Cl)c1
Reactant: N#CC(C=CC(C#N)=C(O)C(=O)O)=C(O)C(=O)O
Solvent: Cc1ccccc1
Solvent: O
Product: N#Cc1ccn(-c2cccc(Cl)c2)c1C(=O)O

Procedure:
A mixture of 9.2 g of the diethyl ester of 3,6-dicyano-2,7-dihydroxy-2,4,6-octatrienedioic acid, 7.0 g of 3-chloroaniline and 75 ml of dry toluene was stirred at reflux for 3 hours, water of reaction being distilled from the mixture as it was formed. The resulting mixture was filtered and the solvent was evaporated under reduced pressure. The residue was dissolved in 35 ml of hot ethanol and the solution was chilled in a freezer. The resulting solid was filtered and dried under vacuum to give the ethyl ester of 3-cyano-1-(3-chlorophenyl)-1H-pyrrole-2-carboxylic acid (5A), m.p.: 113°-116° C.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][O:6][N:7]=[C:8]([C:24](=[O:26])[CH3:25])[C:9]([NH:11][CH:12]1[C:22](=[O:23])[N:14]2[C:15]([C:19]([OH:21])=[O:20])=[CH:16][CH2:17][S:18][C@H:13]12)=[O:10].[BrH:27].[NH+]1C=CC=CC=1.C(OCC)(=O)C>O1CCCC1.O>[CH3:5][O:6][N:7]=[C:8]([C:24](=[O:26])[CH2:25][Br:27])[C:9]([NH:11][CH:12]1[C:22](=[O:23])[N:14]2[C:15]([C:19]([OH:21])=[O:20])=[CH:16][CH2:17][S:18][C@H:13]12)=[O:10]
Reactant: CON=C(C(C)=O)C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12
Reactant: Br
Agent: [Al+3]
Agent: [Cl-]
Agent: c1cc[nH+]cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: CON=C(C(=O)CBr)C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Aluminum chloride (120 mg.) was added to a solution of 7-(2-methoxyimino-3-oxobutyramido)-3-cephem-4-carboxylic acid (syn isomer, 50 mg.) in dry tetrahydrofuran (10 ml.). Pridinium hydrobromide perbromide (50 mg.) was added to the solution, and stirred at room temperature for 20 minutes. Ethyl acetate (50 ml.) and water (10 ml.) were added to the resultant solution and the mixture was treated in a similar manner to that of the above Example 10-(8) to give 7-(2-methoxyimino-3-oxo-4-bromobutyramido)-3-cephem-4-carboxylic acid (syn isomer, 52.5 mg.)
Reaction SMILES: [CH2:1]([S:8][CH:9]([CH:34]=O)[CH2:10][NH:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][C:17]=2[N:23]([CH3:33])[S:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)(=[O:26])=[O:25])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:36]1[CH2:41][CH2:40][S:39][CH2:38][CH2:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl>[CH2:1]([S:8][CH:9]([CH2:34][N:36]1[CH2:41][CH2:40][S:39][CH2:38][CH2:37]1)[CH2:10][NH:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][C:17]=2[N:23]([CH3:33])[S:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)(=[O:26])=[O:25])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C1CSCCN1
Reactant: CN(c1cccc2cc(C(=O)NCC(C=O)SCc3ccccc3)[nH]c12)S(=O)(=O)c1ccccn1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCCl
Product: CN(c1cccc2cc(C(=O)NCC(CN3CCSCC3)SCc3ccccc3)[nH]c12)S(=O)(=O)c1ccccn1
Temperature: 25 °C
Reaction time: 15 h
Yield: 95 %

Procedure:
To a mixture of N-[2-(benzylthio)-3-oxopropyl]-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (0.60 g), thiomorpholine (0.21 mL) and 1,2-dichloroethane (25 mL) was added sodium triacetoxyborohydride (0.65 g), and the mixture was stirred at room temperature for 15 hr. The reaction solution was acidified with diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=35:65-55:45) to give the title compound (0.67 g, yield: 95%) as a colorless oil. MS: 596 (MH+).
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N+:12]([O-])=O)=[CH:4][C:3]=1[C:15]([NH:17][CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([CH2:31][CH3:32])([CH3:30])[CH3:29])=[CH:24][C:23]=1[C:33]([CH2:36][CH3:37])([CH3:35])[CH3:34])=[O:16].C(O)(=O)C>O>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH2:12])=[CH:4][C:3]=1[C:15]([NH:17][CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([CH2:31][CH3:32])([CH3:29])[CH3:30])=[CH:24][C:23]=1[C:33]([CH2:36][CH3:37])([CH3:35])[CH3:34])=[O:16]
Reactant: CCC(C)(C)c1ccc(OCCCNC(=O)c2cc([N+](=O)[O-])c3ccccc3c2O)c(C(C)(C)CC)c1
Solvent: CC(=O)O
Solvent: O
Product: CCC(C)(C)c1ccc(OCCCNC(=O)c2cc(N)c3ccccc3c2O)c(C(C)(C)CC)c1
Yield: 85 %

Procedure:
50 g of 1-hydroxy-4-nitro-N-[γ-(2,4-di-tert-amylphenoxy)propyl]-2-naphthamide was reduced using 50 g of reduced iron in 500 ml of a 90% acetic acid aqueous solution. The reaction mixture was poured into water and extracted with ethyl acetate. Then the ethyl acetate was removed by distillation and the residue was recrystallized from ligroin to obtain 40 g of the titled compound. The melting point was 132°-133° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:17][CH:16]=2)[N:12]=[C:11]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:30][CH:29]=2)[N:10]=1.I[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49].C(=O)([O-])[O-].[K+].[K+].CC(CC(C)=O)C>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].C(Cl)Cl>[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:19][CH:20]=2)[N:12]=[C:11]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)=[CH:30][CH:29]=2)[N:10]=1
Reactant: CCCCCCCCI
Reactant: Oc1ccc(-c2nc(-c3ccc(Oc4ccccc4)cc3)nc(-c3ccc(Oc4ccccc4)cc3)n2)c(O)c1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: CC(=O)CC(C)C
Solvent: ClCCl
Product: CCCCCCCCOc1ccc(-c2nc(-c3ccc(Oc4ccccc4)cc3)nc(-c3ccc(Oc4ccccc4)cc3)n2)c(O)c1
Temperature: 25 °C
Yield: 57.7 %

Procedure:
A mixture of 5 gm 2-(2,4-dihydroxyphenyl)-4,6-bis(4-phenoxyphenyl)-1,3,5-triazine, 2.5 gm 1-iodooctane, 6.6 gm anhydrous potassium carbonate, 0.5 gm Aliquat 336 and 25 ml MIBK was heated to reflux for 3 hr. The reaction mixture was cooled to room temperature, diluted with methylene chloride, filtered through Celite. The filtrate was concentrated under reduced pressure. The residue thus obtained was passed through a silica gel column. The material thus obtained was crystallized with acetone to give 3.5 gm of pure 2-(2-hydroxy-4-octyloxyphenyl)-4,6-bis(4-phenoxyphenyl)-1,3,5-triazine.
Reaction SMILES: [CH3:1][C:2]1[N:3]2[CH:9]=[N:8][CH:7]=[C:4]2[S:5][CH:6]=1.C([Li])CCC.[CH2:15]([Sn:19](Cl)([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:16][CH2:17][CH3:18]>C1COCC1.CCCCCC.[Cl-].[NH4+]>[CH2:24]([Sn:19]([CH2:15][CH2:16][CH2:17][CH3:18])([CH2:20][CH2:21][CH2:22][CH3:23])[C:6]1[S:5][C:4]2=[CH:7][N:8]=[CH:9][N:3]2[C:2]=1[CH3:1])[CH2:25][CH2:26][CH3:27]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: Cc1csc2cncn12
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1sc2cncn2c1C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 3-methylimidazo[5,1-b]thiazole (513.2 mg) in anhydrous THF (8 ml) was cooled to −78° C. under the atmosphere of argon, and a 1.6 N solution of n-butyl lithium in n-hexane (2.47 ml) was added dropwise. After the reaction was stirred at the same temperature for 1 hour, 1.06 ml of tri-n-butylstannyl chloride was added, and the mixture was further stirred at the same temperature for 1 hour and then for 30 minutes during which the mixture was allowed to be warmed to room temperature. The reaction mixture was diluted with 50 ml of a semi-saturated aqueous ammonium chloride solution, and extracted with 50 ml of diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was then removed under reduced pressure. The residue thus obtained was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 2-(tri-n-butylstannyl)-3-methylimidazo[5,1-b]thiazole in a yield of 1.44 g.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14].N1CCCCC1>C(O)C>[C:13]([C:15](=[CH:6][C:5]1[CH:8]=[CH:9][C:2]([F:1])=[CH:3][C:4]=1[N+:10]([O-:12])=[O:11])[C:16]([NH2:18])=[O:17])#[N:14]
Reactant: O=Cc1ccc(F)cc1[N+](=O)[O-]
Reactant: N#CCC(N)=O
Solvent: C1CCNCC1
Solvent: CCO
Product: N#CC(=Cc1ccc(F)cc1[N+](=O)[O-])C(N)=O
Temperature: 25 °C
Reaction time: 28 h

Procedure:
A mixture of 4-fluoro-2-nitrobenzaldehyde (8.70 g., 51.5 millimoles), 2-cyanoacetamide (4.7 g., 54.4 millimoles), piperidine (0.032 g., 0.37 millimole) and ethanol (80 ml.) is stirred at room temperature for 28 hours. The solid which formed is separated by filtration, washed with ethanol (45 ml.) and dried. Yield = 10 g. (83.5%) of the title acrylamide as light tan crystals. M.P. 278°-279° C.
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([C:13]=2[CH2:15][CH:16]=[O:17])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[CH3:18][Mg]I>CCOCC>[CH:11]1[C:12]2[C:7](=[CH:6][C:5]3[C:14]([C:13]=2[CH2:15][CH:16]([OH:17])[CH3:18])=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH:8]=[CH:9][CH:10]=1
Reactant: O=CCc1c2ccccc2cc2ccccc12
Reactant: C[Mg]I
Solvent: CCOCC
Product: CC(O)Cc1c2ccccc2cc2ccccc12
Yield: 88.9 %

Procedure:
9-anthrylacetaldehyde (1.1 g; 5 mmoles) was Soxhlet--extracted for a period of 6 hours in an ether solution (100 ml) of methylmagnesium iodide (30 mmoles; prepared from 0.72 g of magnesium). Work up as described above gave 1.05 g (89%) of 1-(9-anthryl)-2-propanol as pale yellow needle shaped crystals, mp 105°-107° C.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)Cl.[CH3:13][N:14]([CH3:18])[CH2:15][CH2:16][OH:17].[Na]>O>[C:1]([O:17][CH2:16][CH2:15][N:14]([CH3:18])[CH3:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CN(C)CCO
Agent: [Na]
Solvent: ClCCl
Solvent: O
Product: CN(C)CCOC(=O)c1ccccc1
Reaction time: 3.25 h
Yield: 61.6 %

Procedure:
A solution of 70.29 grams (0.50 mol) of benzoyl chloride in 500 milliters of methylene chloride was added to a solution of 44.57 grams (0.50 mol) of 2-dimethylaminoethanol, 20.0 grams (0.50 mol) of sodium hydroxideand 500 milliters of water over 15 minutes with rapid stirring. Stirring was continued for 3.25 hours after which the organic layer was separated, washed with water, dried over MgSO4 and concentrated. Distillation of the residue gave 59.5 grams of product; bp=102°-108° C./0.50 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:34][CH2:35][CH:36]1[CH2:38][CH2:37]1.C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:16]([CH2:17][C:18]([NH:34][CH2:35][CH:36]3[CH2:38][CH2:37]3)=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: O=C(O)Cn1c(-c2ccc(Cl)cc2)nc2cccnc21
Reactant: NCC1CC1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(Cn1c(-c2ccc(Cl)cc2)nc2cccnc21)NCC1CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 82.2 %

Procedure:
Under nitrogen bubbling, a mixture of 2-(4-chlorophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (4.0 g, 0.014 mole) and 1,1'-carbonyldiimidazole (2.27 g, 0.014 mole) in 150 ml of tetrahydrofuran was stirred at room temperature for 4 hours. Aminomethylcyclopropane hydrochloride (3.01 g, 0.028 mole) and triethylamine (2.83 g, 0.028 mole) were added and the reaction mixture was allowed to stir at room temperature overnight. The tetrahydrofuran was evaporated to dryness and the residue was treated with water. The solid was collected by filtration, washed with ater, and dried under high vacuum overnight. The solid was recrystallized from isopropyl alcohol with cooling. The crystalline precipitate was collected by filtration, washed with cold isopropyl alcohol and water, and dried under high vacuum at 60° C. overnight to give 3.92 g (82%) of crystals, mp 228°-229° C.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:3]=1[CH2:4][CH:5]1[CH2:9][CH2:8][N:7]([C:10]2([CH3:17])[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)[C:6]1=[O:18].CCN(CC)CC.[N+:31]([C:34]1[CH:42]=[CH:41][C:37]([C:38](Cl)=[O:39])=[CH:36][CH:35]=1)([O-:33])=[O:32]>C(Cl)Cl>[N+:31]([C:34]1[CH:35]=[CH:36][C:37]([C:38]([O:16][CH:13]2[CH2:14][CH2:15][C:10]([N:7]3[CH2:8][CH2:9][CH:5]([CH2:4][C:3]4[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:2]=4[Cl:1])[C:6]3=[O:18])([CH3:17])[CH2:11][CH2:12]2)=[O:39])=[CH:41][CH:42]=1)([O-:33])=[O:32]
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: CC1(N2CCC(Cc3ccc(Cl)cc3Cl)C2=O)CCC(O)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(N2CCC(Cc3ccc(Cl)cc3Cl)C2=O)CCC(OC(=O)c2ccc([N+](=O)[O-])cc2)CC1
Temperature: 0 °C
Yield: 147.4 %

Procedure:
Dissolve 3-(2,4-dichlorobenzyl)-1-(4-hydroxy-1-methylcyclohexyl)pyrrolidin-2-one (0.50 g, 0.51 mmol) in DCM (100 mL) and cool the solution to 0° C. under N2. Add Et3N (0.71 g, 7.06 mmol) and 4-nitrobenzoyl chloride (0.52 g, 2.82 mmol) and stir the reaction overnight at room temperature. Add water (100 mL) and extract the aqueous with EtOAc (3×100 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 20-60% of EtOAc/Hexane) to give 0.38 g (54%) of the title compound as a white solid. 1H NMR (CDCl3) δ 8.25 (m, 2H), 8.16 (m, 2H), 7.38 (d, 1H), 7.20 (d, 1H), 7.16 (dd, 1H), 5.18 (m, 1H), 3.25 (m, 3H), 2.65 (m, 2H), 2.42 (m, 1H), 2.19 (m, 1H), 1.95 (m, 1H), 1.80 (m, 6H), 1.62 (m, 1H), 1.28 (s, 3H).
Reaction SMILES: [C:1]([N:8]([CH3:29])[CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][CH2:16][C:17]2[CH:18]=[C:19]([B:26]([OH:28])[OH:27])[CH:20]=[CH:21][C:22]=2[O:23][CH2:24][CH3:25])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.[Cl:37][C:38]1[C:39]2[CH:49]=[CH:48][CH:47]=[CH:46][C:40]=2[S:41][C:42]=1[C:43](Cl)=[O:44]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:1]([N:8]([CH3:29])[CH:9]1[CH2:10][CH2:11][CH:12]([N:15]([CH2:16][C:17]2[CH:18]=[C:19]([B:26]([OH:27])[OH:28])[CH:20]=[CH:21][C:22]=2[O:23][CH2:24][CH3:25])[C:43]([C:42]2[S:41][C:40]3[CH:46]=[CH:47][CH:48]=[CH:49][C:39]=3[C:38]=2[Cl:37])=[O:44])[CH2:13][CH2:14]1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]
Reactant: CCOc1ccc(B(O)O)cc1CNC1CCC(N(C)C(=O)OC(C)(C)C)CC1
Reactant: O=C(Cl)c1sc2ccccc2c1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOc1ccc(B(O)O)cc1CN(C(=O)c1sc2ccccc2c1Cl)C1CCC(N(C)C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of boronic acid 11 (700 mg, 1.72 mmol) in DCM (15 mL) at 0° C. is treated with triethylamine (0.48 mL, 3.45 mmol), followed by 3-chlorobenzo-[b]thiophene-2-carbonyl chloride (439 mg, 1.90 mmol) in one portion. After warming to RT, the solution is stirred 16 h. Analysis by LC/MS at this juncture confirmed the reaction is complete. Thus the reaction is diluted with aqueous NaHCO3 (20 mL) and extracted into EtOAc (3×25 mL). The combined EtOAc phases are dried (Na2SO4) and reduced in vacuo to afford the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9](CS([O-])(=O)=O)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[OH:17][C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][CH:9]([O:17][C:18]2[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=2)[CH2:10][CH2:11]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCC(CS(=O)(=O)[O-])CC1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)N1CCC(Oc2ccc(C=O)cc2)CC1
Temperature: 80 °C
Reaction time: 12 h
Yield: 63.2 %

Procedure:
To a mixture of N-(ethoxycarbonyl)-piperidine-4-methanesulphonate (10 g) and 4-hydroxy benzaldehyde (5.8 g) in dry DMF (75 ml), K2CO3 (11 g) was added and the mixture was stirred at 80° C. for 12 h. At the end of this time, the reaction mixture was cooled, added water and extracted with EtOAc. The EtOAc extract was washed with 5% aqueous Na2CO3 solution followed by brine and dried over anhydrous sodium sulphate. The solvent was then removed by distillation under reduced pressure to give 7 g (63.6%) of the title compound as a semi solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][C:25]1[C:29](B(O)O)=[C:28]([CH3:33])[O:27][N:26]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:29]4[C:25]([CH3:24])=[N:26][O:27][C:28]=4[CH3:33])[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1noc(C)c1B(O)O
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Product: Cc1noc(C)c1-c1cc2c(cn1)OC(C1CCN(C(=O)OC(C)(C)C)CC1)C2

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 3,5-dimethyl-isoxazol-4-boronic acid following a procedure analogous to that described in Example 28. LC (method 7): tR=1.33 min; Mass spectrum (ESI+): m/z=400 [M+H]+.
Reaction SMILES: [CH3:1][NH:2][C:3]1[S:4][C:5]2[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][C:6]=2[N:7]=1.[CH:13]([C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=1)=O.[Sn](CCCC)(CCCC)(Cl)Cl.C1([SiH3])C=CC=CC=1>COCCOC>[CH3:1][NH:2][C:3]1[S:4][C:5]2[CH:11]=[CH:10][C:9]([NH:12][CH2:13][C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=3)=[CH:8][C:6]=2[N:7]=1
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: CNc1nc2cc(N)ccc2s1
Agent: CCCC[Sn](Cl)(Cl)CCCC
Agent: [SiH3]c1ccccc1
Solvent: COCCOC
Product: CNc1nc2cc(NCc3ccc(C(=O)O)cc3)ccc2s1
Yield: 91 %

Procedure:
A solution of aniline 456b (509 mg; 2.8 mmol); 4-formylbenzoic acid (426 mg; 2.8 mmol) and Bu2SnCl2 (198 mg; 0.65 mmol; 23% mol) in DME (14 mL) was stirred at room temperature for 3 min and treated with neat PhSiH3 (0.6 mL; 4.7 mmol; 1.7 mmol) and allowed to react for 18 h. After quenching the excess of silane with MeOH, the mixture was concentrated and purified by chromatographic column on silica gel (elution 5% MeOH in DCM) to give 729 mg (2.54 mmol; 91% yield) of acid 456c.
Reaction SMILES: [C:1]1([C:7]2[C:11]3[C:12](=[O:21])[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[C:19](=[O:20])[C:10]=3[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO>[C:7]([C:11]1[C:12](=[O:21])[C:13]2[C:18]([C:19](=[O:20])[C:10]=1[OH:9])=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[NH:8])[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1c2ccccc2C(=O)c2c(-c3ccccc3)noc21
Solvent: CO
Product: N=C(C1=C(O)C(=O)c2ccccc2C1=O)c1ccccc1
Yield: 62.5 %

Procedure:
A solution of 3-phenyl-4,9-dihydronaphtho-[2,3-d]isoxazole-4,9-dione (m.p. 133°-135°C, 500 mg) in methanol (400 ml) is irradiated by light of a low-pressure mercury lamp (35 W) at room temperature (20°-30°C) for 3 hours in argon atmosphere. After removal of methanol, the residue is extracted with chloroform. The extract is chromatographed on alumina. The chloroform insoluble residue is dissolved in a mixture of chloroform and methanol, and this solution is also chromatograped on alumina. The fractions containing the objective compound are combined, evaporated, and the residue is recrystallized from 70 % acetic acid to give 2-benzimidoyl-3-hydroxy-1,4-naphthoquinone (315 mg) as pale yellow scales, m.p. 258°14 259°C.