Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[C:6]([NH:13][C:14]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=1)(OC(C)(C)C)=O.[C:21]([O:26][CH2:27][CH3:28])(=[O:25])C([O-])=O.Cl.[OH-].[Na+]>C1COCC1>[NH:13]1[C:14]2=[N:15][CH:16]=[CH:17][CH:18]=[C:19]2[CH:20]=[C:6]1[C:21]([O:26][CH2:27][CH3:28])=[O:25]
Reactant: CCOC(=O)C(=O)[O-]
Reactant: Cc1cccnc1NC(=O)OC(C)(C)C
Agent: Cl
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2cccnc2[nH]1
Temperature: 0 °C
Reaction time: 1 h
Yield: 39.4 %

Procedure:
30 ml of n-butyllithium are added, under nitrogen, at a temperature of less than 5° C., to 5 g of 2-(N-Boc)amino-3-methylpyridine in 100 ml of THF. After stirring for 1 hour at 0° C., the lithiated derivative thus formed is added to a solution of 7 g of ethyl oxalate in 50 ml of THF at −3° C. The reaction medium is allowed to return to RT and is then poured slowly into 25 ml of 6N HCl at 0° C., while maintaining the temperature below 100° C. This mixture is heated at 50° C. for 2 hours and the pH is then brought to 3 by addition of 1N NaOH. This mixture is extracted with Et2O and the organic phase is taken up in K2CO3 solution and then dried and evaporated to give 1.8 g of the expected compound in the form of white crystals: m.p.=162° C.
Reaction SMILES: S([O-])([O-])(=O)=O.[Na+].[Na+].[OH-].[K+].[CH2:10]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[N:28][NH2:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)[CH:11]=[CH2:12]>C(O)C.[Hg]=O>[CH2:10]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[N+:28]=[N-:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)[CH:11]=[CH2:12]
Reactant: C=CCOCc1ccc(C(=NN)c2ccccc2)cc1
Agent: O=S(=O)([O-])[O-]
Agent: O=[Hg]
Agent: [K+]
Solvent: CCO
Product: C=CCOCc1ccc(C(=[N+]=[N-])c2ccccc2)cc1
Reaction time: 2 h
Yield: 97.7 %

Procedure:
To a mixture of mercury (II) oxide (3.1 g, 14 mmol), sodium sulphate (2.4 g, 16 mmol) and sat potassium hydroxide in ethanol (3 ml) was added a solution of 10 (3.2 g, 12 mmol) in dry TIM (20 ml). The mixture was stirred in the dark for 2 h. then filtered through a celite pad. Concentration of the filtrate in vacuo yielded 11 (3.1 g, 100%) as a dark red oil; δH (CDCl3) 3.90-3.94 (m, 2H, OCH2CH═CH2), 4.38 (s, 2H, ArCH2O), 5.05-5.26 (m, 2H, OCH2CH═CH2), 5.74-5.94 (m, 1H, OCH2CH═CH2), 7.12-7.36 (m, 9H, Ar—H) ppm; δC 71.0, 71.6 (OCH2CH═CH2, ArCH2O), 117.0 (OCH2CH═CH2), 124.9, 125.0, 125.4, 128.5, 129.0 (Ar—C), 129.8, 130.1 (1-, 1′-C), 134.5 (OCH2CH═CH2), 135.6 (4-C) ppm; νmax (thin film) 3029, 2855, 2038, 1596, 1512, 1494, 1085 cm−1; m/z (Fr) 264 ([M]+, 70%), 252 (100%), 196 (35%); found (Fr) 264.1250, C17H16N2O requires 264.1263.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])([C:20](O)=[O:21])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].O.[OH-].[Na+]>O1CCCC1>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])([CH2:20][OH:21])[CH2:16][CH2:15]1)=[O:13])([CH3:9])([CH3:10])[CH3:8]
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CCN(C(=O)OC(C)(C)C)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)NC1(CO)CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 49.1 %

Procedure:
A 1M solution of lithium aluminium hydride in tetrahydrofuran (1.66 mL, 1.66 mmol) was added dropwise to a cooled (0° C.) solution of 4-tert-butoxycarbonylamino-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (400 mg, 1.1 mmol) in dry tetrahydrofuran (5 mL). The solution was stirred for 3 h at rt under nitrogen. Water (172 μL) and 10% sodium hydroxide aq (232 μL) were added and the mixture was stirred for 2 h. Further water (172 □L) was added and the mixture was filtered through a pad of celite and washed with diethyl ether. The crude product was purified by flash column chromatography on silica, eluting with 10% methanol in dichloromethane, to give 4-tert-butoxycarbonylamino-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (178 mg, 0.54 mmol, 49%). LC-MS (LCT2) m/z 353 [M+Na+], Rt 6.67 min.
Reaction SMILES: [C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:21]#[N:22])[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl.[NH2:24][OH:25].C(=O)([O-])[O-].[Na+].[Na+]>CCO.O>[OH:25][NH:24][C:21]([C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([NH:10][C@H:1]1[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:3][CH2:2]1)[CH:20]=[CH:19]2)=[NH:22]
Reactant: N#Cc1ccc2nc(N[C@@H]3CCc4ccccc43)ccc2c1
Reactant: NO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: N=C(NO)c1ccc2nc(N[C@@H]3CCc4ccccc43)ccc2c1
Yield: 87.9 %

Procedure:
A stirred suspension of 2-((R)-indan-1-ylamino)-quinoline-6-carbonitrile (143 mg, 0.5 mmol), hydroxylamine hydrochloride (129 mg, 1.86 mmol), sodium carbonate (106 mg, 1.0 mmol) in EtOH (2 ml) and water (2 ml) was heated under reflux conditions for 6 h, water (40 ml) was added, and the mixture was extracted with ethyl acetate (3×75 ml). The combined organic layers were washed with brine (20 ml), dried (MgSO4) and evaporated to yield the crude product as solid which was further purified by crystallization (dichloromethane/methanol/heptane) to yield N-hydroxy-2-((R)-indan-1-ylamino)-quinoline-6-carboxamidine as off-white solid (140 mg, 88%).
Reaction SMILES: [NH2:1][CH2:2][C:3]1([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:5][CH2:4]1.C(N(CC)CC)C.[Cl:21][C:22]1[N:31]=[C:30](Cl)[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([CH3:33])[CH:28]=2)[N:23]=1>O1CCCC1>[Cl:21][C:22]1[N:31]=[C:30]([NH:1][CH2:2][C:3]2([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[CH2:4][CH2:5]2)[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([CH3:33])[CH:28]=2)[N:23]=1
Reactant: CC(C)(C)OC(=O)NC1(CN)CC1
Reactant: Cc1ccc2nc(Cl)nc(Cl)c2c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1ccc2nc(Cl)nc(NCC3(NC(=O)OC(C)(C)C)CC3)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
To a solution of tert-butyl [1-(aminomethyl)cyclopropyl]carbamate (0.92 g, 4.9 mmol) in tetrahydrofuran (50 mL) was added triethylamine (1.3 mL, 9.4 mmol) followed by 2,4-dichloro-6-methylquinazoline (1.0 g, 4.7 mmol) in portions at room temperature. After being stirred at room temperature overnight, the resultant mixture was concentrated in vacuo to remove 20 mL of solvent and then stirred vigorously with water (200 mL). The formed solid was collected by filtration and washed with water and ether, then dried in vacuo to afford 1.5 g of the product as a white powder.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([N:14]1[CH2:18][CH:17]([CH2:19][S:20][C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:16]([CH2:40][OH:41])[CH2:15]1)(=[O:13])=[O:12].[H-].[Na+].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.O>CN(C=O)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([N:14]1[CH2:18][CH:17]([CH2:19][S:20][C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:16]([CH2:40][O:41][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:15]1)(=[O:13])=[O:12]
Reactant: O=S(=O)(c1ccc2ccccc2c1)N1CC(CO)C(CSC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=S(=O)(c1ccc2ccccc2c1)N1CC(COCc2ccccc2)C(CSC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Reaction time: 0.17 h
Yield: 60.6 %

Procedure:
To a solution of (3RS,4RS)-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanylmethyl-pyrrolidin-3-yl]-methanol (200 mg, 0.345 mmol) in DMF (2 ml) was added 60% NaH (15.2 mg, 0.379 mmol) at 0° C. and stirred for 10 min. Benzyl bromide (45 μl, 0.379 mmol) was added and stirred for 30 min at 0° C. and for 1 h at room temperature. Water was added and the mixture was extracted with dichloromethane. The organic phase was dried, filtered and evaporated. Flash chromatography (hexane/EtOAc 4:1=>1:1) gave 140 mg (61%) of (3RS,4RS)-1-(naphthalene-2-sulfonyl)-3-benzyloxymethyl-4-tritylsulfanylmethyl-pyrrolidine as a colorless foam, MS: 692 (M+Na)+.
Reaction SMILES: C([O:4][C@@H:5]1[C@H:9]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@@:8]([CH2:37][O:38][S:39]([C:42]2[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=2)(=[O:41])=[O:40])([CH2:18][O:19][Si:20]([C:33]([CH3:36])([CH3:35])[CH3:34])([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:7][C@H:6]1[N:49]1[C:66]2[N:65]=[CH:64][N:63]=[C:53]([NH:54][C:55](=[O:62])[C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[C:52]=2[N:51]=[CH:50]1)(=O)C.C(=O)([O-])[O-].[K+].[K+].Cl>CO>[CH2:11]([O:10][C@@H:9]1[C@@:8]([CH2:37][O:38][S:39]([C:42]2[CH:43]=[CH:44][C:45]([CH3:48])=[CH:46][CH:47]=2)(=[O:41])=[O:40])([CH2:18][O:19][Si:20]([C:33]([CH3:35])([CH3:34])[CH3:36])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[O:7][C@@H:6]([N:49]2[C:66]3[N:65]=[CH:64][N:63]=[C:53]([NH:54][C:55](=[O:62])[C:56]4[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=4)[C:52]=3[N:51]=[CH:50]2)[C@@H:5]1[OH:4])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CC(=O)O[C@H]1[C@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)O[C@@](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)(COS(=O)(=O)c2ccc(C)cc2)[C@H]1OCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: Cc1ccc(S(=O)(=O)OC[C@]2(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O[C@@H](n3cnc4c(NC(=O)c5ccccc5)ncnc43)[C@H](O)[C@@H]2OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 87.9 %

Procedure:
To a methyl alcohol solution (3.0 ml) of Compound 40 (167.9 mg, 0.182 mmol), potassium carbonate (15.0 mg, 0.109 mmol) was added at room temperature, and the mixture was stirred for 15 minute at room temperature. Concentrated hydrochloric acid was added to the reaction mixture to neutralize it, whereafter the system was extracted 3 times with methylene chloride. The organic phase was washed with a saturated sodium chloride solution, and then dried over sodium sulfate. The solvents were distilled off under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (CHCl3-MeOH, 30:1) to obtain a white powder, Compound 41 (140.5 mg, 0.160 mmol, 88%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:10]=1)[C:5]([OH:7])=O.C([O:21][C:22](=[O:38])[CH2:23][CH2:24][C:25]1[C:30]([CH3:31])=[CH:29][C:28]([C:32](=[NH:35])[NH:33]O)=[CH:27][C:26]=1[CH2:36][CH3:37])(C)(C)C>>[CH2:36]([C:26]1[CH:27]=[C:28]([C:32]2[N:33]=[C:5]([C:4]3[CH:8]=[C:9]([N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)[N:10]=[C:2]([CH3:1])[CH:3]=3)[O:7][N:35]=2)[CH:29]=[C:30]([CH3:31])[C:25]=1[CH2:24][CH2:23][C:22]([OH:38])=[O:21])[CH3:37]
Reactant: Cc1cc(C(=O)O)cc(N2CCOCC2)n1
Reactant: CCc1cc(C(=N)NO)cc(C)c1CCC(=O)OC(C)(C)C
Product: CCc1cc(-c2noc(-c3cc(C)nc(N4CCOCC4)c3)n2)cc(C)c1CCC(=O)O

Procedure:
The title compound is prepared in analogy to Example 8 from 2-methyl-6-morpholin-4-yl-isonicotinic acid and 3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid tert-butyl ester; LC-MS: tR=0.98 min; [M+1]+=437.25.
Reaction SMILES: [Br:1][C:2]1[CH:27]=[CH:26][C:25]([O:28]C)=[CH:24][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([Cl:12])=[CH:10][N:9]=[C:8]([NH:13][C:14]2[CH:15]=[C:16]([CH2:20][CH2:21][CH2:22]O)[CH:17]=[CH:18][CH:19]=2)[N:7]=1.B(Br)(Br)[Br:31].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.C(=O)=O>[Br:1][C:2]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([Cl:12])=[CH:10][N:9]=[C:8]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][CH2:21][CH2:22][Br:31])[CH:15]=2)[N:7]=1
Reactant: COc1ccc(Br)c(CNc2nc(Nc3cccc(CCCO)c3)ncc2Cl)c1
Reactant: BrB(Br)Br
Agent: O=C([O-])[O-]
Agent: O=C=O
Agent: [Na+]
Solvent: ClCCl
Product: Oc1ccc(Br)c(CNc2nc(Nc3cccc(CCCBr)c3)ncc2Cl)c1
Temperature: 25 °C
Yield: 91 %

Procedure:
To a solution of 3-[3-({4-[(2-bromo-5-methoxybenzyl)amino]-5-chloropyrimidin-2-yl}amino)phenyl]propan-1-ol (3.0 g, 6.3 mmol) in methylene chloride (40 mL) was added slowly a solution of boron tribromide in methylene chloride (31 mL, 31 mmol, 1.0 M) at 0° C. The mixture was allowed to warm up to rt and stirred over the weekend. The resultant mixture was cooled in dry ice when Na2CO3 (saturated aqueous solution) was added. The mixture was filtered and the solid collected was triturated with EtOAc, followed by washing with cold water to give the desired product (3.0 grams, 91%) as an off-white powder. LCMS for C20H19Br2ClN4O (M+H)+: m/z=524.8, 526.8, 528.7.
Reaction SMILES: [Br:1][C:2]1[C:3]([N+:9]([O-])=O)=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[NH4+].[Cl-]>CCO.O.[Fe]>[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:4]([NH2:5])[C:3]=1[NH2:9]
Reactant: Nc1cccc(Br)c1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Nc1cccc(Br)c1N
Temperature: 25 °C
Yield: 98.8 %

Procedure:
A mixture of 3-bromo-2-nitroaniline (2 g, 9.2 mmol), Fe powder (1.54 g, 27.6 mmol) and NH4Cl (4.8 g, 52 mmol) in EtOH and H2O was stirred under reflux for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was diluted water extracted with ethyl acetate and the combined organic layers were dried and concentrated in vacuum to give the crude desired product (1.7 g, Yield 85%). This crude was used in the next step without further purification.
Reaction SMILES: C([Li])CCC.[Br:6][C:7]1[CH:19]=[CH:18][C:17]2[C:16]3[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=3)[C:10]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:9]=2[CH:8]=1.C[O:38]B(OC)OC.Cl>O1CCCC1>[Br:6][C:7]1[CH:19]=[CH:18][C:17]2[C:16]3[C:11](=[CH:12][C:13]([OH:38])=[CH:14][CH:15]=3)[C:10]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:9]=2[CH:8]=1
Reactant: CCCCCCCCC1(CCCCCCCC)c2cc(Br)ccc2-c2ccc(Br)cc21
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCCCCC1(CCCCCCCC)c2cc(O)ccc2-c2ccc(Br)cc21
Temperature: -70 °C
Reaction time: 1 h
Yield: 44.1 %

Procedure:
2.5M n-butyllithium in hexanes (20.0 cm3, 0.05 mol) was added dropwise to a solution of 2,7-dibromo-9,9-dioctylfluorene (20.0 g, 0.0364 mol) and tetrahydrofuran (300 cm3) maintaining a temperature of −70° C. After stirring for 1 h, trimethylborate (9.45 g, 0.09 mol) was added dropwise. After allowing the solution to reach RT, 20% hydrochloric acid (100 cm3) was added and the solution stirred for a further 1.5 h. The product was extracted into diethyl ether (2×100 cm3) and the combined extracts washed with water (2×100 cm3), dried (MgSO4) and concentrated to a pale yellow oil. Diethyl ether (200 cm3) and hydrogen peroxide (30%, 100 cm3) were added and the solution heated under gentle reflux for 2.5 h with vigorous stirring. The ether layer was separated off and the aqueous layer extracted into diethyl ether (3×50 cm3). The combined organic layers were washed with saturated sodium metabisulphite solution (2×100 cm3), dried (MgSO4), filtered and evaporated down under slightly reduced pressure to a pale yellow oil, which was purified by column chromatography [silica gel, dichloromethane:hexane:ethanol 50:50:1] and recrystallisation from hexane to yield a white crystalline solid (yield 7.80 g, 45%), GC: 99%, mpt 110° C.
Reaction SMILES: [O:1]=[C:2]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=3)[CH:8]=2)[NH:3]1.[CH2:27]([NH2:31])[CH2:28][CH2:29][CH3:30]>>[CH2:27]([NH:31][S:23]([C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[NH:3][C:2](=[O:1])[CH:11]=[C:10]3[C:12]([F:15])([F:14])[F:13])=[CH:18][CH:19]=1)(=[O:25])=[O:24])[CH2:28][CH2:29][CH3:30]
Reactant: O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1
Reactant: CCCCN
Product: CCCCNS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
Yield: 91.2 %

Procedure:
4-(2-oxo-4-trifluoromethyl-1,2-dihydroquinolin-6-ylmethyl)benzenesulfonyl chloride (Preparation 1, 26 mg, 65 μmol) was reacted with an excess of n-BuNH2 (190 mg, 2600 μmol) by the same procedure used for Example 1. After reaction, the solvents were evaporated off under reduced pressure & the residue partitioned between EtOAc (10 mL) & 2 M HCl (3 mL). The organic phase was washed with H2O (2 mL), 1 M NaOH (3 mL), & brine (2 mL), before being dried (MgSO4). Filtration & solvent evaporation furnished the title compound (26 mg, 84%): δH ((CD3)2SO)=0.75 (t, 3H), 1.20–1.35 (m, 4H), 2.65 (m, 2H), 4.15 (s, 2H), 6.95 (s, 1H), 7.35–7.55 (m, 5H), 7.70 (d, 2H); m/z (ES+)=480.2 [M+H+MeCN]+.
Reaction SMILES: CCN(C(C)C)C(C)C.[CH2:10]([O:17][N:18]1[C:24](=[O:25])[N:23]2[CH2:26][C@H:19]1[CH2:20][CH2:21][C@H:22]2[C:27]([NH:29][NH2:30])=[O:28])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C:31]([O:35][C:36]([NH:38][CH2:39][CH2:40][C:41](O)=[O:42])=[O:37])([CH3:34])([CH3:33])[CH3:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:10]([O:17][N:18]1[C:24](=[O:25])[N:23]2[CH2:26][C@H:19]1[CH2:20][CH2:21][C@H:22]2[C:27]([NH:29][NH:30][C:41](=[O:42])[CH2:40][CH2:39][NH:38][C:36](=[O:37])[O:35][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:28])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CC(C)(C)OC(=O)NCCC(=O)O
Reactant: NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NCCC(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 104.7 %

Procedure:
DIPEA (1.1 g, 8.3 mmol) was added to a 0° C. solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbohydrazide (1.0 g, 2.48 mmol) in DMF (10 mL). 3-((tert-Butoxycarbonyl)amino)propanoic acid (0.39 g, 2.07 mmol) and HATU (0.90 g, 2.48 mmol) were then added. The reaction mixture was stirred at 0° C. for 1 h and then was quenched with saturated sodium chloride (50 mL). The organic layer was separated and the aqueous layer was exacted with EtOAc (3×). The combined organic layer was washed with saturated sodium chloride (2×), dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography (gradient elution 10:1 to 2:1 hexanes/EtOAc) to afford tert-butyl (3-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-3-oxopropyl)carbamate (1.0 g, 87%). ESI-MS (EI+, m/z): 462 [M+H]+.
Reaction SMILES: C(OC=CC[S:8]C)(=O)C.CO.[C]=O.[C:14]([O:17][CH:18]([CH2:23][CH2:24][S:25][CH3:26])[C:19]([O:21][CH3:22])=O)(=[O:16])[CH3:15]>O1CCCC1.C1(C)C=CC=CC=1>[C:14]([O:17][CH:18]([CH2:23][CH2:24][S:25][CH3:26])[C:19]([O:21][CH3:22])=[S:8])(=[O:16])[CH3:15]
Reactant: COC(=O)C(CCSC)OC(C)=O
Reactant: CSCC=COC(C)=O
Agent: [C]=O
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Solvent: CO
Product: COC(=S)C(CCSC)OC(C)=O
Temperature: 100 °C

Procedure:
0.5 mmoles 1-acetoxy-3-methylthiopropene, (Z: E ratio 43:57), and 2.5 mmoles methanol were charged into a 71 cc stainless steel bomb equipped with a glass liner and a Teflon coated stir bar. No catalyst was added. Toluene was included as an internal standard. Five milliliters of tetrahydrofuran as a solvent were also included in the reaction system. The reaction mixture was charged under argon. The bomb was sealed and carbon monoxide at a pressure of 1000 psi (at room temperature) was charged to the bomb, and the bomb was heated to 100° C. and allowed to react for 44 hours with stirring. At the termination of the reaction, the reaction products were analyzed by gas chromatography and it was found that no 2-acetoxy-4-(methylthio)butanoic acid, methyl ester was produced, and that no 2-acetoxy-4-(methylthio)thiobutanoic acid, methyl ester was produced.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[C:15]2[N:16]([C:28]([CH:31]=O)=[CH:29][N:30]=2)[C:17]2[C:22]([N:23]=1)=[CH:21][C:20]([C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2.[BH4-].[Na+]>CO>[CH2:1]([NH:8][CH2:31][C:28]1[N:16]2[C:17]3[C:22]([N:23]=[C:14]([NH:13][CH2:12][CH2:11][CH2:10][OH:9])[C:15]2=[N:30][CH:29]=1)=[CH:21][C:20]([C:24]([F:26])([F:27])[F:25])=[CH:19][CH:18]=3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1cnc2c(NCCCO)nc3cc(C(F)(F)F)ccc3n12
Reactant: NCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: OCCCNc1nc2cc(C(F)(F)F)ccc2n2c(CNCc3ccccc3)cnc12
Temperature: 30 °C
Reaction time: 17 h

Procedure:
To a solution of the benzylamine (13 μL, 0.12 mmol) in methanol (400 μL) was added 4-[(3-hydroxypropyl)amino]-7-(trifluoromethyl)imidazo[1,2-a]quinoxaline-1-carbaldehyde (35 mg, 0.10 mmol). The reaction mixture was stirred at 30° C. for 17 h. After addition of NaBH4 (5 mg, 0.12 mmol), the mixture was stirred at 30° C. for 5 h. Then it was concentrated, diluted in ethyl acetate, washed with an aqueous saturated solution of ammonium chloride and extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered, concentrated in vacuo to give, after purification by preparative TLC (dichloromethane/methanol 9/1), the title compound (32 mg, 75%) as a colorless oil.
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6][CH3:7])=[O:5])#[N:2].[CH2:8]([C:15]1[C:16](=[O:26])[C:17]2[C:22]([C:23](=[O:25])[CH:24]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[NH2:2][C:1]1[O:25][C:23]2[C:22]3[C:17]([C:16]([OH:26])=[C:15]([CH2:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[C:24]=2[C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[CH:18][CH:19]=[CH:20][CH:21]=3
Reactant: COC(=O)CC#N
Reactant: O=C1C=C(Cc2ccccc2)C(=O)c2ccccc21
Product: COC(=O)c1c(N)oc2c1c(Cc1ccccc1)c(O)c1ccccc12

Procedure:
The title compound was prepared by reaction of methyl cyanoacetate with 2-benzyl-1,4-naphthoquinone following the procedure outlined for example 1. Obtained as tan crystals (55%); m.p. 170°-171° C.; 1H NMR (CDCl3): 3.66(s, 3H), 4.05(s,2H), 5.07(s,2H), 7.17-7.53(m, 8H), 7.98(d, 1H), 8.10(d,1H); IR (nujol): 3309, 3479, 3566, 1725, 1604; Chemical ionization mass spectrum m/z (rel. intensity) 348 (M+H, 100); calculated for C21H17NO4C 72.61, H 4.93; measured C 72.79, H 4.68, N 4.00.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2CN(CCC)[CH2:12][N:11](C)[C:10]2=[N:19][N+:20]([O-:22])=[O:21])=[CH:4][N:3]=1.C(=O)([O-])O.[Na+].CO>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([NH:11][CH3:12])=[N:19][N+:20]([O-:22])=[O:21])=[CH:4][N:3]=1
Reactant: CCCN1CN(C)C(=N[N+](=O)[O-])N(Cc2ccc(Cl)nc2)C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CNC(=N[N+](=O)[O-])NCc1ccc(Cl)nc1
Temperature: 50 °C
Reaction time: 24 h

Procedure:
A mixture of 1.5 g of 1-(2-chloropyrid-5-ylmethyl)-2-nitroimino-3-methyl-5-n-propyl-1,3,5-triazacyclohexane, 0.5 g of solid sodium hydrogen carbonate, 20 ml of methanol and 10 ml of water is stirred for 24 hours at 50° C. The reaction mixture is concentrated by evaporation and the residue purified on silica gel with dichloromethane/methanol 95:5 as the eluant. This yields the title compound with a melting point of 149-151° C. (compound 2.2).
Reaction SMILES: [CH3:1][C:2]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:10][C:9]2[C:4](=[C:5]([Cl:16])[C:6]([Cl:15])=[C:7]([O:11]CC=C)[CH:8]=2)[C:3]1=[O:17].Cl.C(N(CC)[C:28]1[CH:33]=CC=C[CH:29]=1)C>>[CH3:1][C:2]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:10][C:9]2[C:4](=[C:5]([Cl:16])[C:6]([Cl:15])=[C:7]([OH:11])[C:8]=2[CH2:33][CH:28]=[CH2:29])[C:3]1=[O:17]
Reactant: C=CCOc1cc2c(c(Cl)c1Cl)C(=O)C(C)(c1ccccc1)C2
Reactant: CCN(CC)c1ccccc1
Agent: Cl
Product: C=CCc1c(O)c(Cl)c(Cl)c2c1CC(C)(c1ccccc1)C2=O

Procedure:
A mixture of 2-methyl-2-phenyl-5-allyloxy-6,7-dichloro-1-indanone (12.5 g., 0.036 mole) in N,N-diethylaniline (120 ml.) is refluxed for one and one-half hours then poured into excess cold dilute hydrochloric acid. The product is extracted into ether, washed with water and dried over anhydrous magnesium sulfate. Evaporation of the ether affords 2-methyl-2-phenyl-4-allyl-5-hydroxy-6,7-dichloro-1-indanone which melts at 125°C. after crystallization from butyl chloride.