Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].[O:6]1[CH:10]=[CH:9][C:8]([NH2:11])=[N:7]1>C(Cl)Cl>[Cl:1][CH2:2][C:3]([NH:11][C:8]1[CH:9]=[CH:10][O:6][N:7]=1)=[O:4]
Reactant: Nc1ccon1
Reactant: O=C(Cl)CCl
Solvent: ClCCl
Product: O=C(CCl)Nc1ccon1
Temperature: 0 °C
Reaction time: 2 h
Yield: 85.9 %

Procedure:
2-Chloroacetyl chloride (0.21 ml, 2.66 mmol) was dissolved in DCM (10 ml) and the solution was cooled to 0° C. with an ice-bath. Isoxazol-3-amine (0.41 ml, 5.58 mmol) was added dropwise and a white suspension was obtained. The mixture was stirred at room temperature for 2 hours, then the suspension was evaporated and the residue was purified by flash chromatography (ether/EtOAc=8/2 to 7/3) to obtain 2-chloro-N-(isoxazol-3-yl)acetamide (367 mg, 86% yield) as an off-white solid.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]([C:23]5[CH:28]=[CH:27][C:26]([CH2:29][OH:30])=[CH:25][CH:24]=5)[C:19]([CH3:22])=[CH:20][CH:21]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[C:31]1(C)C=CC(S(O)(=O)=O)=CC=1.CO>C1(C)C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]([C:23]5[CH:24]=[CH:25][C:26]([CH2:29][O:30][CH3:31])=[CH:27][CH:28]=5)[C:19]([CH3:22])=[CH:20][CH:21]=4)=[O:14])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)cc1-c1ccc(CO)cc1
Solvent: Cc1ccccc1
Solvent: CO
Product: COCc1ccc(-c2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2C)cc1
Yield: 23.1 %

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(4′-(hydroxymethyl)-6-methylbiphenyl-3-yl)cyclopropanecarboxamide (40 mg, 0.10 mmol), para-toluenesulfonic acid (24 mg, 0.13 mmol) and MeOH (53 μL, 1.3 mmol) were dissolved in toluene (2.0 mL) and irradiated in the microwave at 140° C. for 10 minutes. Volatiles were removed in vacuo and crude product was purified by reverse phase HPLC to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(4′-(methoxymethyl)-6-methylbiphenyl-3-yl)cyclopropanecarboxamide (9.6 mg, 23%). ESI-MS m/z calc. 415.5, found 416.5 (M+1)+; retention time 3.68 minutes.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([CH3:10])[N:3]=1.[NH:11]1[CH:15]=[CH:14][CH:13]=[N:12]1>O1CCCC1>[CH3:9][O:8][C:6]1[CH:5]=[C:4]([CH3:10])[N:3]=[C:2]([N:11]2[CH:15]=[CH:14][CH:13]=[N:12]2)[N:7]=1
Reactant: COc1cc(C)nc(Cl)n1
Reactant: c1cn[nH]c1
Solvent: C1CCOC1
Product: COc1cc(C)nc(-n2cccn2)n1
Yield: 54.2 %

Procedure:
In anhydrous tetrahydrofuran, 159 mg of 2-chloro-4-methoxy-6-methylpyrimidine was substituted with 68 mg of pyrazole. The reaction mixture was treated according to the procedure of Example 5 to yield 103 mg of 4-methoxy-6-methyl-2-(1-pyrazolyl)pyrimidine, and recrystallized from n-hexane to give a compound having a melting point of 52.5°-53° C.
Reaction SMILES: [NH2:1][C:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[CH:3]=1.[F:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[F:20])[CH:15]=O>>[F:11][C:12]1[CH:13]=[C:14]([CH:15]2[C:3]3[C:4](=[O:10])[CH2:5][C:6]([CH3:9])([CH3:8])[CH2:7][C:2]=3[NH:1][C:2]3[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[C:3]2=3)[CH:17]=[CH:18][C:19]=1[F:20]
Reactant: CC1(C)CC(=O)C=C(N)C1
Reactant: O=Cc1ccc(F)c(F)c1
Product: CC1(C)CC(=O)C2=C(C1)NC1=C(C(=O)CC(C)(C)C1)C2c1ccc(F)c(F)c1

Procedure:
Reaction of 3-amino-5,5-dimethyl-2-cyclohexen-1-one with 3,4-difluorobenzaldehyde in an analogous manner to that described in Example 1 gave 9-(3,4-difluorophenyl)-3,4,6,7,9,10-hexahydro-3,3,6,6-tetramethyl-1,8(2H,5H)-acridinedione. Crystallization from absolute ethanol/water gave a pale yellow crystalline solid of melting point 270° C. (decomposition).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([S:12][C:13]2[CH:18]=[N:17][CH:16]=[CH:15][N:14]=2)=[CH:7][C:6]=1[CH3:19])=O.[NH2:20][C:21]([NH2:23])=[S:22]>CCO>[CH3:19][C:6]1[CH:7]=[C:8]([S:12][C:13]2[CH:18]=[N:17][CH:16]=[CH:15][N:14]=2)[CH:9]=[C:10]([CH3:11])[C:5]=1[C:3]1[N:20]=[C:21]([NH2:23])[S:22][CH:2]=1
Reactant: Cc1cc(Sc2cnccn2)cc(C)c1C(=O)CBr
Reactant: NC(N)=S
Solvent: CCO
Product: Cc1cc(Sc2cnccn2)cc(C)c1-c1csc(N)n1
Yield: 41.7 %

Procedure:
A mixture of 2-bromo-1-(2,6-dimethyl-4-(pyrazin-2-ylthio)phenyl)ethanone (11-4, 4.00 g, 11.9 mmol) and thiourea (902.9 mg, 11.9 mmol) in 95% EtOH (15 mL) was heated at reflux for 16 hr. The solution was concentrated and added with water (50 mL) and saturated aqueous Na2CO3 (10.0 mL). The resultant precipitate was filtered and recrystallized in toluene (30 mL). The solids were filtered and dried under vacuum to give 4-(2,6-dimethyl-4-(pyrazin-2-ylthio)phenyl)thiazol-2-amine (11-5, 1.56 g) as yellow solids in 42% yield: 1H NMR (500 MHz, CDCl3) δ 8.43 (s, 1 H), 8.36 (s, 1 H), 8.31 (s, 1 H), 7.47 (s, 2 H), 6.34 (s, 1 H), 2.24 (s, 6 H). ESI-MS: m/z 315.2 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[CH:9](=O)[CH2:10][CH3:11]>>[CH2:10]([C:11]1[S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=1)[CH3:9]
Reactant: CCC=O
Reactant: Nc1ccccc1S
Product: CCc1nc2ccccc2s1

Procedure:
The procedure of Example 1 was repeated, except that the reactants consisted of 37.5 g. of 2-aminothiophenol and 17.5 g. of propionaldehyde. The residue which remained after the removal of solvent was distilled in vacuo, chromatographed on a silica gel column with toluene as eluant, and redistilled at 94°-104°/0.3 mm. to give 2-ethylbenzothiazoline. The following elemental micro-analysis was obtained:
Reaction SMILES: [CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]4[C:17]([C:22]([OH:24])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=4)=[CH:12][CH:11]=3)[C:7]3[CH:25]=[C:26]([C:30]4[N:31]=[CH:32][N:33]([CH2:35][CH2:36][O:37]C)[CH:34]=4)[CH:27]=[C:28]([CH3:29])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1.B(Br)(Br)Br.O>C(Cl)Cl>[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]4[C:17]([C:22]([OH:24])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=4)=[CH:12][CH:11]=3)[C:7]3[CH:25]=[C:26]([C:30]4[N:31]=[CH:32][N:33]([CH2:35][CH2:36][OH:37])[CH:34]=4)[CH:27]=[C:28]([CH3:29])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1
Reactant: COCCn1cnc(-c2cc(C)c3nc(C4CC4)n(Cc4ccc(-c5ccccc5C(=O)O)cc4)c3c2)c1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: O
Product: Cc1cc(-c2cn(CCO)cn2)cc2c1nc(C1CC1)n2Cc1ccc(-c2ccccc2C(=O)O)cc1
Reaction time: 0.17 h

Procedure:
A solution of 500 mg (1.0 mMol) of 4'-[(2-cyclopropyl-4-methyl-6-(1-(2-methoxyethyl)-imidazol-4-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid and 1.5 g (6.0 mMol) of boron tribromide in 50 ml of methylene chloride is stirred for 16 hours at ambient temperature, then mixed with about 30 ml of water and stirred vigorously for another 10 minutes. This mixture is evaporated to dryness and the residue is refluxed in about 40 ml of ethanol for 10 minutes. The mixture is evaporated to dryness once more, the residue is dissolved in about 30 ml of 2N ammonia solution and this solution is adjusted to pH 5-6 with 2N acetic acid. The crude product precipitated is suction filtered and purified by column chromatography (80 g silica gel; eluant:methylene chloride/methanol=4:1).
Reaction SMILES: C=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:9]1[CH:14]=[C:13](Cl)[CH:12]=[C:11]([C:16]([O:18]O)=O)[CH:10]=1>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[CH:6]1[CH:5]=[CH:4][C:3]([C@H:2]2[O:18][C@@H:16]2[C:11]2[CH:12]=[CH:13][CH:14]=[CH:9][CH:10]=2)=[CH:8][CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=Cc1ccccc1
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Product: c1ccc([C@H]2O[C@@H]2c2ccccc2)cc1
Yield: 83 %

Procedure:
Reaction of styrene with Grubbs' second generation catalyst for 6 hours, followed by reaction of the subsequent product with 5 equivalents of site-isolated MCPBA for 14 hours gave trans-stilbene oxide in 83% yield. The 1H and 13C NMR spectra agreed with those reported in the literature. 1H NMR (CDCl3): 7.33-7.38 (m, 10H), 3.87 (s, 213C NMR (CDCl3): 62.81, 125.47, 128.29, 128.53, 137.07.
Reaction SMILES: C(O[C@@:5]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[F:25])([C@H:12]([S:14](Cl)(=[O:16])=[O:15])[CH3:13])[CH2:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1)(=O)C.[CH3:26][NH:27][CH3:28]>ClCCl>[CH3:26][N:27]([CH3:28])[S:14]([C:12](=[C:5]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[F:25])[CH2:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1)[CH3:13])(=[O:15])=[O:16]
Reactant: CNC
Reactant: CC(=O)O[C@@](Cn1cncn1)(c1ccc(F)cc1F)[C@@H](C)S(=O)(=O)Cl
Solvent: ClCCl
Product: CC(=C(Cn1cncn1)c1ccc(F)cc1F)S(=O)(=O)N(C)C
Reaction time: 0.17 h
Yield: 18.4 %

Procedure:
In dichloromethane (15 ml) was dissolved (2R,3R)-3-chlorosulfonyl-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butyl acetate (3.0 g). To the solution was added, under ice-cooling, dimethylamine (0.6 g). The reaction mixture was stirred for 10 minutes under ice-cooling, which was then concentrated. The concentrate was subjected to a silica gel chromatography (eluent: hexane/ethyl acetate=1/2→ethyl acetate) for purification to give, as the first eluate, N,N-dimethyl-3-(2,4-difluorophenyl)-4-(1H-1,2,4-triazol-1-yl)-2-butene-2-sulfonamide (isomer B, Compound 35, 0.48 g) as a pale yellow oily substance, and, as the second eluate, N,N-dimethyl-3-(2,4-difluorophenyl)-4-(1H-1,2,4-triazol-1-yl)-2-butene-2-sufonamide (isomer A, Compound 34, 0.80 g) as a pale yellow oily substance.
Reaction SMILES: [N:1]([C:4]1[C:9]([F:10])=[CH:8][N:7]=[CH:6][C:5]=1/[CH:11]=[N:12]/[C:13]1[C:18](Cl)=[CH:17][C:16]([N+:20]([O-:22])=[O:21])=[CH:15][C:14]=1[Cl:23])=[N+:2]=[N-:3].[NH2:24][C:25]1C(Cl)=CC([N+]([O-])=O)=CC=1C#N>>[N:1]([C:4]1[C:9]([F:10])=[CH:8][N:7]=[CH:6][C:5]=1/[CH:11]=[N:12]/[C:13]1[C:14]([Cl:23])=[CH:15][C:16]([N+:20]([O-:22])=[O:21])=[CH:17][C:18]=1[C:25]#[N:24])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=Nc1c(F)cncc1/C=N/c1c(Cl)cc([N+](=O)[O-])cc1Cl
Reactant: N#Cc1cc([N+](=O)[O-])cc(Cl)c1N
Product: N#Cc1cc([N+](=O)[O-])cc(Cl)c1/N=C/c1cncc(F)c1N=[N+]=[N-]
Temperature: 25 °C

Procedure:
Following the procedure described for [1-(4-azido-5-fluoropyridin-3-yl)-meth-(E)-ylidene]-(2,6-dichloro-4-nitrophenyl)-amine (Example 99, Step 1), 2-amino-3-chloro-5-nitrobenzonitrile was stirred at room temperature to afford the title compound which was used without purification (6.07 g, quantitative yield). LCMS (Method C): RT=3.69 min, m/z: 318 [M+H+−N2].
Reaction SMILES: [N+:1]([C:4]1[CH:18]=[CH:17][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][S:12](=[O:16])(=[O:15])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)([O-])=O.C.O.NN>CO>[NH2:1][C:4]1[CH:18]=[CH:17][C:7]([CH2:8][N:9]2[CH2:10][CH2:11][S:12](=[O:16])(=[O:15])[CH2:13][CH2:14]2)=[CH:6][CH:5]=1
Reactant: O=[N+]([O-])c1ccc(CN2CCS(=O)(=O)CC2)cc1
Agent: NN
Solvent: O
Solvent: CO
Product: Nc1ccc(CN2CCS(=O)(=O)CC2)cc1
Reaction time: 4 h

Procedure:
4-(4-Nitro-benzyl)-thiomorpholine 1,1-dioxide (110 mg, 0.41 mmol) is dissolved in MeOH (7 mL). To this solution is added FeCl3.6H2O (−20 mg, 0.07 mmol) and active Charcoal (12 mg, 1.0 mmol). The suspension is heated to reflux. Hydrazine hydrate (0.5 mL) is added, and reflux is continued for 4 h until full conversion, the active Charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue (85 mg, 86%) is directly used in the next step.
Reaction SMILES: [C:1]1([S:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[NH:19][C:18](=[O:23])[CH2:17][CH2:16]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[OH:25]>O>[C:1]1([S:7]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[NH:19][C:18](=[O:23])[CH2:17][CH2:16]3)=[O:25])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CO
Reactant: O=C1CCc2cc(OCCCCSc3ccccc3)ccc2N1
Solvent: O
Product: O=C1CCc2cc(OCCCCS(=O)c3ccccc3)ccc2N1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
1.6 gm of 6-(4-phenylmercapto-butoxy)-3,4-dihydro-carbostyril were dissolved in 50 ml of methanol, and 0.9 gm of N-bromosuccininimide were added. After stirring for 15 hours at room temperature, the mixture was diluted with 500 ml of hot water (80° C.) and decanted from the initially oily precipitate which gradually crystallized. After recrystallization from xylene, white crystals with a melting point of 144° to 145° C. were obtained.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C@@:9]([NH:31][S@@:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH2:38]=[CH:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C@@:9]([NH:31][S@@:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:3][C:2]=1[CH:38]=[CH:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
Reactant: C=Cc1ccccc1
Reactant: CC(C)(C)[S@@](=O)N[C@@](Cc1ccccc1)(c1cc(F)cc(OC(F)(F)C(F)F)c1)c1ccc(F)c(Br)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Product: CC(C)(C)[S@@](=O)N[C@@](Cc1ccccc1)(c1cc(F)cc(OC(F)(F)C(F)F)c1)c1ccc(F)c(C=Cc2ccccc2)c1
Temperature: 85 °C
Yield: 23 %

Procedure:
To a suspension of Pd(OAc)2 (9 mg, 0.04 mmol) and PPh3 (2 mg, 0.008 mmol) in DMF was added Bu4NBr (265 mg, 0.8 mmol), (R)—N—((S)-1-(3-bromo-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide, prepared as described in Procedure 62, (500 mg, 0.8 mmol), styrene (137 mg, 1.3 mmol) and K2CO3 (136 mg, 1.0 mmol). The reaction mixture was degassed and backfilled with argon several times. The reaction mixture was heated at 85° C. for 16 h. The reaction mixture was then poured into sat. NH4Cl and the aqueous phase was extracted with EtOAc. The combined organic portions were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO chromatography (12 g column, 0-30% EtOAc/hexane) to yield (R)—N—((R)-1-(4-fluoro-3-styrylphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide (119 mg, 23% yield). LCMS: RT=4.62 min [M+H] 632 (Phenomenex Luna C18, 50×4.6 mm, 10%-90% H2O/ACN with 0.1% TFA, 4 min gradient, flow rate 4 mL/min, monitoring at 220 nm).
Reaction SMILES: [CH3:1][S:2]([CH2:5][CH2:6][O:7][CH2:8][CH2:9][N:10]1[C:22]2[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:15]=[C:14]([NH2:23])[C:13]=2[N:12]=[C:11]1[CH3:24])(=[O:4])=[O:3].[H][H].[OH-].[Na+]>FC(F)(F)C(O)=O.O.[Pt]=O>[CH3:1][S:2]([CH2:5][CH2:6][O:7][CH2:8][CH2:9][N:10]1[C:22]2[C:21]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[N:15]=[C:14]([NH2:23])[C:13]=2[N:12]=[C:11]1[CH3:24])(=[O:3])=[O:4]
Reactant: [H][H]
Reactant: Cc1nc2c(N)nc3ccccc3c2n1CCOCCS(C)(=O)=O
Agent: O=[Pt]
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: Cc1nc2c(N)nc3c(c2n1CCOCCS(C)(=O)=O)CCCC3
Yield: 76.4 %

Procedure:
Solid platinum oxide (0.5) was added to a solution of 1-{2-[2-(methylsulfonyl)ethoxy]ethyl}-2-methyl-1H-imidazo[4,5-c]quinolin-4-amine (0.9 g, 2.6 mmol) in trifluoroacetic acid (7 mL) in a Parr vessel. The vessel was placed on a shaker and then pressurized with hydrogen to 50 psi (3.4×105 Pa). Hydrogen was added periodically to maintain the pressure. After 55 hours the reaction mixture was purged with nitrogen and then filtered through a layer of CELITE filter agent. The filter cake was washed with dichloromethane (˜200 mL). The filtrate was concentrated under reduced pressure to provide an oil. The oil was dissolved in water (50 mL). The pH of the solution was adjusted to pH 12 by the addition of aqueous 50% sodium hydroxide and then the solution was extracted with dichloromethane (2×100 mL). The combined extracts were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide crude product as a white foam. This material was recrystallized from ethyl acetate. The resulting off white plates were isolated by filtration, washed with ethyl acetate and dried under vacuum at 65° C. for 4 hours to provide 0.7 g of 1-{2-[2-(methylsulfonyl)ethoxy]ethyl}-2-methyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine, mp 173-175° C. 1H NMR (300 MHz, DMSO-d6) δ 5.65 (bs, 2H), 4.40 (t, J=5.0 Hz, 2H), 3.73 (t, J=5.6 Hz, 2H), 3.32 (t, J=5.6 Hz, 2H), 2.91 (m, 2H), 2.78 (s, 3H) 2.65 (m, 2H), 2.47 (s, 3H), 1.75 (m, 4H); MS (APCI) m/z 353 (M+
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([NH:23][C@H:24]3[CH2:28][CH2:27][CH2:26][C@H:25]3[C:29]([OH:31])=O)(=[O:22])=[O:21])=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:32][OH:33]>>[OH:33][NH:32][C:29]([C@@H:25]1[CH2:26][CH2:27][CH2:28][C@@H:24]1[NH:23][S:20]([C:17]1[CH:18]=[CH:19][C:14]([O:13][CH2:12][C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=[C:2]([CH3:1])[CH:11]=2)=[CH:15][CH:16]=1)(=[O:22])=[O:21])=[O:31]
Reactant: Cc1cc(COc2ccc(S(=O)(=O)N[C@H]3CCC[C@H]3C(=O)O)cc2)c2ccccc2n1
Reactant: NO
Product: Cc1cc(COc2ccc(S(=O)(=O)N[C@H]3CCC[C@H]3C(=O)NO)cc2)c2ccccc2n1
Yield: 69 %

Procedure:
According to the procedure of Example 10, Step 2, the reaction of 220.3 mg (0.5 mmol) of cis-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylic acid with hydroxylamine provided 156.1 mg of cis-N-hydroxy-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamide in 69% yield. MS: 456.1 (M+H)+
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH:5]([O:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[C:12](OC(=O)C)(=[O:14])[CH3:13]>>[CH3:1][CH:2]1[CH2:3][CH2:4][CH:5]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:14])[CH3:13])[CH2:6][CH2:7]1
Reactant: CC1CCC(OCCO)CC1
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OCCOC1CCC(C)CC1

Procedure:
5.65 Grams (0.04 moles) of 2-(4-methylcyclohexoxy)ethanol (prepared above), 0.8 gm of Amberlyst 15 and 100 ml. of acetic anhydride are charged to a 250 ml flask fitted with a magnetic stirrer and Friedrick condenser. The mixture is heated at reflux for 11/2hours, filtered, and acetic anhydride removed by evaporation. The mixture is distilled and 7.92 gms of 2-(4-methylcyclohexoxy)ethylacetate obtained. The structure of the 2-(4-methylcyclohexoxy)ethylacetate is confirmed by NMR. The 2-(4-methylcyclohexoxy)ethylacetate has an extremely pleasant natural, fruity, wine-like odor.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([O:9][CH3:10])[N:3]=1.[O:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH2:13][CH:12]1[CH2:20][NH2:21].C([O-])(O)=O.[Na+]>CCO.O>[Cl:8][C:6]1[N:5]=[C:4]([O:9][CH3:10])[N:3]=[C:2]([NH:21][CH2:20][CH:12]2[CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:11]2)[CH:7]=1
Reactant: NCC1Cc2ccccc2O1
Reactant: COc1nc(Cl)cc(Cl)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1nc(Cl)cc(NCC2Cc3ccccc3O2)n1
Yield: 74.5 %

Procedure:
A mixture of 4,6-dichloro-2-methoxy-pyrimidine (0.41 g, 2.3 mmol), C-(2,3-dihydro-benzofuran-2-yl)-methylamine (0.52 g, 3.47 mmol), and NaHCO3 (0.97 g, 12 mmol) in EtOH (7 mL) is heated to reflux for 3 h. The mixture is diluted with water (8 mL), filtered, washed (water). The solid is dissolved in EtOAc, dried (MgSO4), filtered, and concentrated in vacuo to afford (6-chloro-2-methoxy-pyrimidin-4-yl)-(2,3-dihydro-benzofuran-2-ylmethyl)-amine (0.5 g) as a solid. LCMS: RT=2.59 minutes; MS: 292 (M+H).
Reaction SMILES: C(Cl)CCl.[N+:5]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH3:18])[C:15]([OH:17])=O)=[CH:10][CH:9]=1)([O-:7])=[O:6].CCN(C(C)C)C(C)C.Cl.[N+:29]([C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)=[CH:34][CH:33]=1)([O-:31])=[O:30]>C(Cl)Cl.C(OCC)(=O)C>[N+:29]([C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][N:40]2[CH2:41][CH2:42][N:43]([C:15](=[O:17])[CH:14]([C:11]3[CH:10]=[CH:9][C:8]([N+:5]([O-:7])=[O:6])=[CH:13][CH:12]=3)[CH3:18])[CH2:44][CH2:45]2)=[CH:34][CH:33]=1)([O-:31])=[O:30]
Reactant: CC(C(=O)O)c1ccc([N+](=O)[O-])cc1
Reactant: O=[N+]([O-])c1ccc(CCN2CCNCC2)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: CC(C(=O)N1CCN(CCc2ccc([N+](=O)[O-])cc2)CC1)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 60.9 %

Procedure:
EDC (113 mg, 0.591 mmol) was added to a solution of 2-(4-nitrophenyl) propionic acid (92 mg, 0.473 mmol), Hunig's Base (0.083 ml, 0.473 mmol) and 1-[2-(4-Nitrophenyl)ethyl]piperazine hydrochloride (107 mg, 0.394 mmol) in 5 ml DCM and stirred at room temperature for 3 hours. The crude mixture was diluted with ethyl acetate and washed with saturated solution of NH4Cl, brine, dried over sodium sulfate, filtered and concentrated. Residue was purified by prep-TLC plate with 5% (NH4OH:MeOH 9:1) in DCM to yield 1-[2-(4-nitrophenyl)ethyl]-4-[2-(4-nitrophenyl)propanoyl]piperazine (100 mg, 0.24 mmol). 1H-NMR (500 MHz, DMSO) δ ppm 8.19 (d, J=9 Hz, 2H), 8.11 (d, J=9 Hz, 2H), 7.54 (d, J=9.Hz, 2H), 7.48 (d, J=9.Hz, 2H), 4.33 (q, 1H), 3.39-3.48 (m, 3H), 3.26-3.42 9 m, 2H), 2.82 (t, J=7.0 Hz, 2H), 2.5 (b, 1H), 2.35-2.40 (m, 2H), 2.26 (b, 1H), 2.0 (b, 1H), 1.30 (d, J=7 Hz, 3H).
Reaction SMILES: [CH2:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][N:5]=1)[CH2:2][CH3:3].[N+:14]([O-])([O-:16])=[O:15].[K+].[OH-].[NH4+]>S(=O)(=O)(O)O>[N+:14]([C:11]1[CH:12]=[C:13]2[C:8]([CH2:7][CH2:6][N:5]=[C:4]2[CH2:1][CH2:2][CH3:3])=[CH:9][CH:10]=1)([O-:16])=[O:15]
Reactant: CCCC1=NCCc2ccccc21
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Agent: [NH4+]
Product: CCCC1=NCCc2ccc([N+](=O)[O-])cc21
Temperature: 25 °C
Yield: 95.8 %

Procedure:
To a solution of 1-propyl-3,4-dihydroisoquinoline (7.4 g, 42 mmol) [E. Spath, F. Berger, and W. Kuntara, Chem. Ber., 1930, 63B, 134] in concentrated sulfuric acid (100 ml) at 0° C. was added in a single portion potassium nitrate (4.5 g, 45 mmol). The solution was allowed to slowly warm to ambient temperature overnight. The reaction mixture was poured onto ice and was basified with concentrated ammonium hydroxide. The resulting solid that formed in the cooled solution could not be filtered off satisfactorily. Hence, the reaction mixture was extracted twice with dichloromethane and the dried (magnesium sulfate) organic phases were concentrated in vacuo to give the intermediate 7-nitro-1-propyl-3,4-dihydroisoquinoline as an oil (8.78 g, 94%). This solid was taken up in methanol (200 ml), cooled to 0° C., and sodium borohydride (3.0 g) was added in portions over 0.5 h. After stirring for an additional 0.5 h, the reaction mixture was acidified to pH 5 using 6M hydrochloric acid. The solvent was concentrated at the rotoevaporator and the residue was partitioned between dichloromethane and dilute sodium hydroxide solution. The dried (magnesium sulfate) organic phase was concentrated to give the crude product as the free base. This was taken up in ethanol (200 ml) and hydrochloric acid in ethanol was added until acidic. The resulting solid which formed was collected to afford the title compound (5.60 g, 52%) as a pale yellow solid, m.p. 229-30.5° C. (dec.).
Reaction SMILES: COC1C=C(OC)C=CC=1C[O:6][N:7]1[C:12](=[O:13])[C:11]2[S:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:10]=2[NH:9][C:8]1=[O:21].[CH2:28](Cl)/[CH:29]=[CH:30]/[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>>[OH:6][N:7]1[C:12](=[O:13])[C:11]2[S:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:10]=2[N:9]([CH2:28][CH:29]=[CH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:8]1=[O:21]
Reactant: ClC/C=C/c1ccccc1
Reactant: COc1ccc(COn2c(=O)[nH]c3c(sc4ccccc43)c2=O)c(OC)c1
Product: O=c1c2sc3ccccc3c2n(CC=Cc2ccccc2)c(=O)n1O

Procedure:
Following general procedure B2 and D1, 3-(2,4-Dimethoxy-benzyloxy)-1H-benzo[4,5]thieno[3,2-d]pyrimidine-2,4-dione was alkylated with trans-cinnamyl chloride and subsequently deprotected to provide the title compound as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ 5.24 (s, 1H); 5.25 (s, 1H); 6.51-6.67 (m, 2H); 7.21 (dd, J=7 Hz, 1H); 7.28 (dd, J=8 Hz, 2H); 7.40 (d, J=7 Hz, 2H); 7.53 (dd, J=8 Hz, 1H); 7.61 (dd, J=8 Hz, 1H); 8.16 (d, J=8 Hz, 1H); 8.25 (d, J=8 Hz, 1H), 11.00 (br s, 1H); Ret. time=2.79 min., m/z=350.0.