Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[N+:18]([O-])=O)[C:9]1=[O:21])[CH3:7])(=[O:3])[CH3:2].C(O)C.[Cl-].[NH4+].O>[Fe]>[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[NH2:18])[C:9]1=[O:21])[CH3:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@@H](C)n1ccc2c([N+](=O)[O-])cccc2c1=O
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(=O)OC[C@@H](C)n1ccc2c(N)cccc2c1=O
Temperature: 85 °C
Reaction time: 1 h
Yield: 98.6 %

Procedure:
A round bottom flask was charged with (R)-2-(5-nitro-1-oxoisoquinolin-2(1H)-yl)propyl acetate (24 g, 0.074 mol), ethanol (500 mL, 8 mol), and was heated at 85° C. Ammonium chloride (50 g, 0.9 mol) in water (150 mL, 8.3 mol) was added followed by iron (20 g, 0.3 mol) in two portions. The reaction was stirred for 1 hour and poured onto dichloromethane (200 mL) and extracted. the solvent was removed under reduced pressureunder reduced pressure to afford the desired product as red oil (19 g, 100%).
Reaction SMILES: [CH2:1]([NH:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N+:14]([O-:16])=[O:15])(=[O:7])=[O:6])[CH:2]=[CH2:3].[Br:17][CH2:18][CH2:19]Br>CN(C=O)C>[CH2:1]([N:4]([CH2:19][CH2:18][Br:17])[S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N+:14]([O-:16])=[O:15])(=[O:7])=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCNS(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: BrCCBr
Solvent: CN(C)C=O
Product: C=CCN(CCBr)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Yield: 48.7 %

Procedure:
N-Allyl-2-nitro-benzenesulfonamide (570 mg, 2.35 mmol) is dissolved in DMF (5 mL) and then CsCO3 (920 mg, 2.82 mmol) and 1,2-dibromoethane (884 mg, 4.71 mmol) is added. The mixture is then microwaved for 30 min at 150° C., then filtered and the solid washed with EtOAc (30 mL). The organic is washed with Brine (20 mL) and then dried over Na2SO4 and then concentrated to dryness. HPLC (CH3CN/H2O/0.1% TFA) provides N-Allyl-N-(2-bromo-ethyl)-2-nitro-benzenesulfonamide (400 mg, 48%). MS-ES [M+H]+=351.1.
Reaction SMILES: C([N:3]1[CH2:21][CH2:20][C@@:10]23[C:11]4[CH:12]=[C:13]([O:18][CH3:19])[CH:14]=[CH:15][C:16]=4[CH2:17][C@@H:4]1[C@@H:5]2[CH2:6][CH2:7][C:8](=[O:22])[CH2:9]3)#N.[ClH:23]>>[ClH:23].[CH3:19][O:18][C:13]1[CH:14]=[CH:15][C:16]2[CH2:17][C@H:4]3[NH:3][CH2:21][CH2:20][C@@:10]4([C:11]=2[CH:12]=1)[C@H:5]3[CH2:6][CH2:7][C:8](=[O:22])[CH2:9]4
Reactant: COc1ccc2c(c1)[C@]13CCN(C#N)[C@H](C2)[C@@H]1CCC(=O)C3
Agent: Cl
Product: COc1ccc2c(c1)[C@]13CCN[C@H](C2)[C@@H]1CCC(=O)C3

Procedure:
A suspension of 17-cyano-3-methoxymorphinan-6-one (6.9 g; prepared in Part B) in 200 ml of 2 N HCl was refluxed for 8 hours. The resulting solution was treated as in Example 1C to yield 5.2 g of crystalline product, mp 190°-200° C. An additional 0.9 g was obtained from the mother liquor. Total yield was 6.1 g (85%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:10]([O-:12])=[O:11])=[C:7]([CH:9]=1)[NH2:8].C(O)(C(F)(F)F)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:34][S:35][C:36]1[O:37][C:38]2[CH:44]=[C:43]([CH:45]=O)[CH:42]=[CH:41][C:39]=2[N:40]=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:10]([O-:12])=[O:11])=[C:7]([CH:9]=1)[NH:8][CH2:45][C:43]1[CH:42]=[CH:41][C:39]2[N:40]=[C:36]([S:35][CH3:34])[O:37][C:38]=2[CH:44]=1
Reactant: CSc1nc2ccc(C=O)cc2o1
Reactant: COc1ccc([N+](=O)[O-])c(N)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1ccc([N+](=O)[O-])c(NCc2ccc3nc(SC)oc3c2)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 102.6 %

Procedure:
To a solution of 5-methoxy-2-nitroaniline (500 mg, 2.99 mmol) and TFA (3.07 mL) in DCM (15 mL) at 5° C. was added NaBH(OAc)3 (1.9 g, 8.97 mmol). To the resulting mixture at 0° C. was added dropwise a solution of 2-(methylthio)benzo[d]oxazole-6-carbaldehyde (630 mg, 3.29 mmol) in DCM (10 mL) and. the mixture was stirred at 0° C. for 2 h. The reaction mixture was diluted with DCM and washed with H2O, aq NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give 5-methoxy-N-((2-(methylthio)benzo[d]oxazol-6-yl)methyl)-2-nitro aniline as a light brown solid (1.06 g, 100%). 1H NMR (300 MHz, DMSO-d6) δ 8.90 (t, 1H), 8.04 (d, J=8.7 Hz, 1H), 7.68 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.41 (d, J=7.5 Hz, 1H), 6.28-6.32 (m, 2H), 4.73 (d, J=6 Hz, 2H), 3.72 (s, 3H), 2.74 (s, 3H). LCMS (ESI) m/z 345 (M+H)+.
Reaction SMILES: [Br:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:6]=1[Cl:12])=[O:4].[Br:13][C:14]1[CH:19]=[CH:18][C:17]([S:20][CH2:21][CH:22]([OH:25])[CH2:23]O)=[CH:16][CH:15]=1.CC1C=CC(S(O)(=O)=O)=CC=1.C(O)CCC>O.C1C=CC=CC=1>[Br:1][CH2:2][C:3]1([C:5]2[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:6]=2[Cl:12])[O:25][CH:22]([CH2:21][S:20][C:17]2[CH:18]=[CH:19][C:14]([Br:13])=[CH:15][CH:16]=2)[CH2:23][O:4]1
Reactant: OCC(O)CSc1ccc(Br)cc1
Reactant: O=C(CBr)c1ccc(Cl)cc1Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: CCCCO
Solvent: O
Product: Clc1ccc(C2(CBr)OCC(CSc3ccc(Br)cc3)O2)c(Cl)c1

Procedure:
A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone, 15.8 parts of 3-(4-bromophenylthio)-1,2-propanediol, 3 parts of 4-methylbenzenesulfonic acid, 180 parts of butanol and 90 parts of benzene is stirred and refluxed for 12 hours with water-separator. The reaction mixture is evaporated and the residue is dissolved in trichloromethane. The solution is stirred with silica gel for 30 minutes. The latter is filtered off and the filtrate is evaporated, yielding A + B 2-(bromomethyl)-4-(4-bromophenylthiomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane as a residue.
Reaction SMILES: [Na].Cl[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([CH:9]=[CH:10][N:11]=2)[N:8]=1.[CH2:12]([OH:14])[CH3:13]>>[CH2:12]([O:14][C:3]1[CH:4]=[CH:5][C:6]2[N:7]([CH:9]=[CH:10][N:11]=2)[N:8]=1)[CH3:13]
Reactant: CCO
Reactant: Clc1ccc2nccn2n1
Agent: [Na]
Product: CCOc1ccc2nccn2n1

Procedure:
Sodium metal (0.55 g) is dissolved in 30 ml of ethanol and, to the solution, is added 3 g of 6-chloroimidazo[1,2-b]pyridazine and the mixture is heated under reflux for 3 hours. The solvent is then evaporated off under reduced pressure and the residue is dissolved in water and the mixture is extracted with methylene chloride. The extracts are combined, washed with saturated solution of sodium chloride and dried over MgSO4. The solvent is then evaporated to give 3.3 g of the title compound as colorless crystals.
Reaction SMILES: [C:1]1([O:7][C:8]2[CH:15]=[CH:14][C:11]([CH2:12][NH2:13])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC(OC1C=CC(F)=CC=1)=O.Cl[C:28]([O:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)=[O:29]>>[C:1]1([O:7][C:8]2[CH:15]=[CH:14][C:11]([CH2:12][NH:13][C:28](=[O:29])[O:30][C:31]3[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=3)=[CH:10][CH:9]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NCc1ccc(Oc2ccccc2)cc1
Reactant: COc1ccc(OC(=O)Cl)cc1
Agent: O=C(Cl)Oc1ccc(F)cc1
Product: COc1ccc(OC(=O)NCc2ccc(Oc3ccccc3)cc2)cc1

Procedure:
The procedure is carried out in a manner similar to Example 4, replacing the 4-phenylbenzylamine with 4-phenyloxybenzylamine and the 4-fluorophenyl chloroformate with 4-methoxyphenyl chloroformate.
Reaction SMILES: [Br:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][CH:6]2O.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]=[CH:6]2
Reactant: OC1CCc2c1ccc(F)c2Br
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: Fc1ccc2c(c1Br)CC=C2
Temperature: 25 °C
Yield: 78.7 %

Procedure:
A solution of Example 25B (923 mg, 3.99 mmol) and TsOH (45.6 mg, 0.240 mmol) in toluene (20 mL) was heated to reflux for 2 hours. The mixture was cooled to ambient temperature and was then concentrated under reduced pressure. The residue was passed through a silica gel frit to provide the title compound (670 mg, 3.14 mmol, 79%). MS (DCI) m/z 231 (M+NH4)+.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][CH2:12][C:13]2[CH:14]=[C:15]([C:19]3[CH:20]=[C:21]([C:29]([CH3:33])([CH3:32])[C:30]#[N:31])[CH:22]=[C:23]4[C:28]=3[N:27]=[CH:26][CH:25]=[CH:24]4)[CH:16]=[CH:17][CH:18]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>>[C:30]([C:29]([CH3:33])([CH3:32])[C:21]1[CH:22]=[C:23]2[C:28](=[C:19]([C:15]3[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=3)[CH2:12][N:11]([C:8]3[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=3)[C:34](=[O:41])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:20]=1)[N:27]=[CH:26][CH:25]=[CH:24]2)#[N:31]
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)(C#N)c1cc(-c2cccc(CNc3ccc(S(C)(=O)=O)cc3)c2)c2ncccc2c1
Product: CC(C)(C#N)c1cc(-c2cccc(CN(C(=O)c3ccccc3)c3ccc(S(C)(=O)=O)cc3)c2)c2ncccc2c1

Procedure:
Prepared according to the procedure described in EXAMPLE 36 (Step 2 and 3) but using 2-(8-{3-[(4-methanesulfonyl-phenylamino)-methyl]-phenyl}-quinolin-6-yl)-2-methyl-propionitrile and benzoyl chloride as the starting materials.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH2:19])([CH3:4])([CH3:3])[CH3:2].C([O:25][C:26](=O)[CH2:27][C:28](=[O:41])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2[CH:36]=[N:37][CH:38]=[N:39][CH:40]=2)[CH:30]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]([F:17])([F:18])[F:16])=[CH:10][C:9]=1[NH:19][C:26](=[O:25])[CH2:27][C:28](=[O:41])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2[CH:40]=[N:39][CH:38]=[N:37][CH:36]=2)[CH:30]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-c2cncnc2)c1
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)c(C(F)(F)F)cc1N
Product: CC(C)(C)OC(=O)Nc1cc(Cl)c(C(F)(F)F)cc1NC(=O)CC(=O)c1cccc(-c2cncnc2)c1

Procedure:
The title compound was prepared from (2-amino-5-chloro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J19) (311 mg, 1.0 mmol) and 3-oxo-3-(3-pyrimidin-5-yl-phenyl)-propionic acid tert-butyl ester (Example K13) (298 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow oil (420 mg, 79%).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]=O)=[CH:8][C:7]([N+:13]([O-:15])=[O:14])=[CH:6][CH:5]=2.Cl.[NH2:17]O.C(OC(=O)C)(=O)C>C(O)=O.CN(C=O)C.O>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:11]#[N:17])=[CH:8][C:7]([N+:13]([O-:15])=[O:14])=[CH:6][CH:5]=2
Reactant: Cc1[nH]c2ccc([N+](=O)[O-])cc2c1C=O
Reactant: NO
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: Cc1[nH]c2ccc([N+](=O)[O-])cc2c1C#N
Reaction time: 1 h
Yield: 89.1 %

Procedure:
2-methyl-5-nitro-1H-indole-3-carbaldehyde (375 mg, 1.84 mmol) and hydroxylamine hydrochloride (380 mg, 5.52 mmol) were suspended in formic acid (10 mL) and DMF (3 mL), and heated at 80° C. until the solution had turned dark orange (30 min). Quantitative conversion to the aldoxime intermediate was confirmed by LC/MS. 4 mL of acetic anhydride were added and heating was continued for 1 h. The reaction solution was diluted with cold water (20 mL), and the product extracted into EtOAc. The organic layer was washed with water (2×50 mL), brine (2×50 mL), dried over MgSO4, and filtered. The solvent was removed in vacuo to yield 2-methyl-5-nitro-1H-indole-3-carbonitrile as an ochre-colored solid (330 mg, 89% yield). Mass and purity were confirmed by LC/MS using an acetonitrile gradient with 0.035% TFA/water. Theoretical (M+H)+ m/z for C10H7N3O2=202.05; Found 202.2.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[S:11][C:12]1[S:13][C:14]2[CH:20]=[CH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17][C:15]=2[N:16]=1.[CH3:24][Si](C=[N+]=[N-])(C)C>CO.C1COCC1.CCCCCC>[CH3:24][O:22][C:21]([C:18]1[CH:19]=[CH:20][C:14]2[S:13][C:12]([S:11][C:3]3[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=3[Cl:1])=[N:16][C:15]=2[CH:17]=1)=[O:23]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=C(O)c1ccc2sc(Sc3ccc([N+](=O)[O-])cc3Cl)nc2c1
Solvent: C1CCOC1
Solvent: CO
Solvent: CCCCCC
Product: COC(=O)c1ccc2sc(Sc3ccc([N+](=O)[O-])cc3Cl)nc2c1
Reaction time: 18 h
Yield: 100 %

Procedure:
To a 0.25M solution of 2-(2-chloro-4-nitro-phenylsulfanyl)-benzothiazol-5-carboxylic acid (253), (1.38 g, 3.8 mmol) in 10% MeOH in THF was added a 2M solution of (trimethylsilyl)diazomethane in hexane, obtained from Aldrich, (2.1 mL, 4.18 mmol) and the resulting solution was allowed to stir for 18 hours. The crude reaction mixture was concentrated under vacuum to yield 1.4 g (100%) of ester 254 which was taken on without further purification.
Reaction SMILES: [OH-].[K+].[CH3:3]C1C=CC(S(N(N=O)C)(=O)=O)=CC=1.C(O)CO.CCOCC.[NH:26]1[C:30]2[CH:31]=[CH:32][C:33]([N:35]3[CH:39]([C:40]4[CH:45]=[C:44]([F:46])[C:43]([F:47])=[CH:42][C:41]=4[F:48])[C:38]([CH3:49])=[C:37]([OH:50])[C:36]3=[O:51])=[CH:34][C:29]=2[N:28]=[CH:27]1>CO>[NH:26]1[C:30]2[CH:31]=[CH:32][C:33]([N:35]3[CH:39]([C:40]4[CH:45]=[C:44]([F:46])[C:43]([F:47])=[CH:42][C:41]=4[F:48])[C:38]([CH3:49])=[C:37]([O:50][CH3:3])[C:36]3=[O:51])=[CH:34][C:29]=2[N:28]=[CH:27]1
Reactant: Cc1ccc(S(=O)(=O)N(C)N=O)cc1
Reactant: CC1=C(O)C(=O)N(c2ccc3[nH]cnc3c2)C1c1cc(F)c(F)cc1F
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: OCCO
Solvent: CO
Product: COC1=C(C)C(c2cc(F)c(F)cc2F)N(c2ccc3[nH]cnc3c2)C1=O

Procedure:
The compound was synthesized starting from KOH (15 g, 267.8 mmol in water), diazald (20 g, 93.37 mmol 5 eq) ethylene glycol/Et2O (2/1 v/v, 140 mL), 1-(1H-benzo[d]imidazol-5-yl)-5-(2,4,5-trifluorophenyl)-3-hydroxy-4-methyl-1H-pyrrol-2(5H)-one (2 g, 5.57 mmol, 1 eq) and MeOH (50 mL); yield: 1.05 g (50.55%); MS m/z: 374.0 [M+H]+; 1H-NMR: (400 MHz, DMSO-D6) δ: 12.44 (s, 1H); 8.17 (s, 1H); 7.66 (s, 1H), 7.52-7.10 (m, 4H); 6.00 (s, 1H); 3.96 (s, 3H); 1.78 (s, 3H); HPLC (METHOD [A]): rt 12.37 min (98.7%)
Reaction SMILES: [CH3:1][O:2][CH:3]([O:13][CH3:14])[CH2:4][S:5][C:6]1[CH:7]=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=1.[N+:15]([C:18]1[CH:19]=[C:20]([N:24]=[C:25]=[O:26])[CH:21]=[CH:22][CH:23]=1)([O-:17])=[O:16].[N-]=C=O>C1C=CC=CC=1.C(N(CC)CC)C>[N+:15]([C:18]1[CH:19]=[C:20]([NH:24][C:25](=[O:26])[O:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([S:5][CH2:4][CH:3]([O:2][CH3:1])[O:13][CH3:14])[CH:7]=2)[CH:21]=[CH:22][CH:23]=1)([O-:17])=[O:16]
Reactant: O=C=Nc1cccc([N+](=O)[O-])c1
Reactant: COC(CSc1cccc(O)c1)OC
Agent: [N-]=C=O
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: COC(CSc1cccc(OC(=O)Nc2cccc([N+](=O)[O-])c2)c1)OC
Temperature: 25 °C
Reaction time: 6 h

Procedure:
3-(2,2-Dimethoxyethylthio)phenol (0.05 mole) dissolved in benzene (10 ml) is charged into a glass reaction flask equipped with a mechanical stirrer. 3-Nitrophenyl isocyanate (0.06 mole) and triethylamine (3 drops) are then added and the resulting mixture is stirred at room temperature for a period of about 6 hours. The mixture is then stripped of solvent and unreacted isocyanate to yield the desired product O-[3-(2,2-dimethoxyethylthio) phenyl] N-3-nitrophenylcarbamate as the residue.
Reaction SMILES: [OH:1][C@@H:2]1[C@H:6]([CH3:7])[NH:5][C:4](=O)[CH2:3]1.F[C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=1>>[OH:1][C@H:2]1[CH2:3][CH2:4][N:5]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[C@H:6]1[CH3:7]
Reactant: N#Cc1ccc(F)cc1
Reactant: C[C@@H]1NC(=O)C[C@@H]1O
Product: C[C@H]1[C@@H](O)CCN1c1ccc(C#N)cc1

Procedure:
Using (4S,5S)-4-hydroxy-5-methylpyrrolidin-2-one and 4-fluorobenzonitrile as starting materials, the title compound was obtained by the same manner as shown in Example 2 (reaction time 1 hr).
Reaction SMILES: C[C:2]1[CH:3]=[C:4]([N:9]2[C:18](/[CH:19]=[CH:20]/[C@H:21]3[O:26][C:25](=[O:27])[CH2:24][C@H:23]([OH:28])[CH2:22]3)=[C:17]([CH:29]([CH3:31])[CH3:30])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:32])[CH:5]=[C:6](C)[CH:7]=1.C(Cl)[Cl:34]>>[Cl:34][C:7]1[CH:2]=[CH:3][C:4]([N:9]2[C:18](/[CH:19]=[CH:20]/[C@H:21]3[O:26][CH:25]([OH:27])[CH2:24][C@H:23]([OH:28])[CH2:22]3)=[C:17]([CH:29]([CH3:30])[CH3:31])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:32])=[CH:5][CH:6]=1
Reactant: ClCCl
Reactant: Cc1cc(C)cc(-n2c(/C=C/[C@@H]3C[C@@H](O)CC(=O)O3)c(C(C)C)c3ccccc3c2=O)c1
Product: CC(C)c1c(/C=C/[C@@H]2C[C@@H](O)CC(O)O2)n(-c2ccc(Cl)cc2)c(=O)c2ccccc12

Procedure:
(4R,6S)-(E)-6-(2-(2-(3,5-dimethylphenyl)-4-isopropyl-1-oxo-1,2-dihydroisoquinolin-3-yl)ethen-1-yl)-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one, m.p.181°-185° C. [α]D =+30.8° C. (CH2Cl2 at 22° C.) Found: C,75.1; H,6.84; N,3.18%. Required: C,75.2; H,6.77; N,3.25%. [NMR in CDCl3, 1.38-1.55 (1H,m), 1.48 (6H,d,J=8 Hz), 1.59-1.68 (1H,m), 2.17 (1H,d,J=4 Hz), 2.32 (6H,s), 2.53 (2H,m), 3.53 (1H,sept,J=8 Hz), 4.01 (1H,m), 5.09 (1H,m), 5.59 (1H,dd,J=16 Hz and J=5 Hz), 6.11 (1H,dd,J=16 Hz and J=1.5 Hz), 6.78 (2H,s), 7.00 (1H,s), 7.49 (1H,m), 7.68 (1H,m), 8.02 (1H,d,J=8 Hz), 8.49 (1H,m)];
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:21]=[CH:20][C:19]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:11]=3[CH:10]=2)O1.Br[C:40]1[CH:41]=[C:42]([C:47]2[O:48][C:49]([C:52]3[CH:57]=[CH:56][C:55]([O:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH3:66])=[CH:54][CH:53]=3)=[N:50][N:51]=2)[CH:43]=[C:44](Br)[CH:45]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[CH2:22]([C:12]1([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:13]2[CH:14]=[C:15]([C:40]3[CH:41]=[C:42]([C:47]4[O:48][C:49]([C:52]5[CH:57]=[CH:56][C:55]([O:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH3:66])=[CH:54][CH:53]=5)=[N:50][N:51]=4)[CH:43]=[C:44]([C:9]4[CH:21]=[CH:20][C:19]5[C:18]6[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=6)[C:12]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:11]=5[CH:10]=4)[CH:45]=3)[CH:16]=[CH:17][C:18]=2[C:19]2[C:11]1=[CH:10][CH:9]=[CH:21][CH:20]=2)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCOc1ccc(-c2nnc(-c3cc(Br)cc(Br)c3)o2)cc1
Reactant: CCCCCCCCC1(CCCCCCCC)c2ccccc2-c2ccc(B3OC(C)(C)C(C)(C)O3)cc21
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCCCCCCCOc1ccc(-c2nnc(-c3cc(-c4ccc5c(c4)C(CCCCCCCC)(CCCCCCCC)c4ccccc4-5)cc(-c4ccc5c(c4)C(CCCCCCCC)(CCCCCCCC)c4ccccc4-5)c3)o2)cc1
Temperature: 80 °C
Yield: 74.7 %

Procedure:
Into a flask was introduced 2.8 mL of toluene, 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9-dioctylfluorene (0.80 g, 1.5 mmol), 2-(3,5-dibromophenyl)-5-[4-(octyloxy)phenyl]-1,3,4-oxadiazole from Example 7 (0.375 g, 0.7 mmole), Aliqua™ 336 (0.15 g, 0.4 mmol) and 1.4 mL of aqueous 2M Na2CO3. This was N2 purged for 1 h. The flask was heated to about 80° C. and tetrakistriphenylphosphine palladium (0) (12 mg, 0.01 mmol) then added under a nitrogen purge. The content of the flask was refluxed for 21 hrs. The reaction flask was allowed to cool to RT and about 5 mL water added and the organic layer separated. The aqueous layer was extracted with 3×15 mL ether. The organic layers were combined and washed successively with saturated NaCl twice and then dried over MgSO4. Concentration gave an oil that was purified by flash chromatography (eluent: 10% ethyl acetate in hexane) and dried as an oil under vacuum for 30 minutes to give 0.59 grams of 2-[3,5-Bis-(9,9-dioctyl-9H-fluoren-2-yl)-phenyl]-5-(4-octyloxy-phenyl)-[1,3,4]oxadiazole.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([C:28]([NH2:30])=[O:29])[C:12]3[NH:13][C:14]4[C:19]([C:20]=3[CH:21]=2)=[CH:18][CH:17]=[C:16]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:15]=4)=[CH:5][C:4]=1[CH3:31])=O.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C1COCC1>C(Cl)Cl>[CH3:31][C:4]1[CH:5]=[C:6]([C:9]2[CH:10]=[C:11]([C:28]([NH2:30])=[O:29])[C:12]3[NH:13][C:14]4[C:19]([C:20]=3[CH:21]=2)=[CH:18][CH:17]=[C:16]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)[CH:15]=4)[CH:7]=[CH:8][C:3]=1[CH2:1][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1
Reactant: Cc1cc(-c2cc(C(N)=O)c3[nH]c4cc(N5CCOCC5)ccc4c3c2)ccc1C=O
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: Cc1cc(-c2cc(C(N)=O)c3[nH]c4cc(N5CCOCC5)ccc4c3c2)ccc1CN1CCOCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
3-(4-formyl-3-methylphenyl)-7-morpholino-9H-carbazole-1-carboxamide (20 mg, 0.034 mmol), morpholine (0.05 mL, 0.574 mmol), sodium triacetoxyborohydride (100 mg, 0.472 mmol) were mixed with THF (5 mL) and CH2Cl2 (2 mL) in a sealed microwave vial. The mixture was stirred for 3 hr at r.t. The mixture was concentrated and purified using preparative HPLC to give titled product. MS (ESI) m/z 485.25 (M+H)+. 1H NMR (DMSO-d6) δ ppm 11.10 (s, 1H), 8.44 (s, 1H), 8.28 (s, 1H), 8.13 (s, 1H), 8.04 (d, 1H, J=8.6), 7.67 (s, 1H), 7.62 (d, 1H, J=8.0), 7.47(s, 1H), 7.33 (d, 1H, J=7.6), 7.24 (s, 1H), 6.93 (dd, 1H, J=8.6, 1.9), 3.8 (t, 4H, J=4.7), 3.58 (bs, 4H), 3.49 (s, 2H). 3.19 (t, 4H, J=4.6), 2.45 (s, 3H), 2.4 (bs, 4H).
Reaction SMILES: [CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Si:25](OS(C(F)(F)F)(=O)=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].O>C(Cl)Cl>[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][C:12]([O:15][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])=[CH:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCC(OCc2ccccc2)CC1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)[Si](C)(C)OC1=CCC(OCc2ccccc2)CC1
Temperature: 25 °C

Procedure:
To a stirred solution of 4-(benzyloxy)cyclohexanone (10 g, 49 mmol) and Hunig's base (17.1 mL, 98 mmol) in DCM (50 mL) was added TBSOTf (11.8 mL, 51.4 mmol) in DCM (50 mL) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature, and left to stir until the reaction was complete. The mixture was poured into water, and the organic layer was separated, dried, and concentrated. Purification by flash chromatography afforded the title compound. 1H NMR (600 MHz, CDCl3) δ 7.20-7.36 (m, 5H); 4.72 (br s, 1H); 4.55 (s, 2H); 3.60 (m, 1H); 1.72-2.38 (series of m, 6H); 0.90 (s, 9H); 0.10 (s, 6H).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.[F:10][C:11]1[N:26]=[CH:25][CH:24]=[CH:23][C:12]=1[C:13](NC1C=CC=CC=1C)=[O:14]>>[F:10][C:11]1[N:26]=[CH:25][CH:24]=[CH:23][C:12]=1[C:13]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([F:1])=[CH:3][C:4]=1[CH3:9])=[O:14]
Reactant: Cc1cc(F)ccc1N
Reactant: Cc1ccccc1NC(=O)c1cccnc1F
Product: Cc1cc(F)ccc1NC(=O)c1cccnc1F
Yield: 99 %

Procedure:
4-Fluoro-2-methylaniline (Aldrich, 0.18 mL, 1.6 mmol) was converted to the desired compound (0.098 g, 99%) in a manner similar to the preparation of 2-fluoro-N-o-tolylnicotinamide (Step A of Example 8). MS(ESI+) m/z 249 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:7])=[CH:4][C:3]=1[N+:16]([O-:18])=[O:17].[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1.[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH:1][C:2]2[CH:15]=[CH:14][C:5]([C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)=[O:7])=[CH:4][C:3]=2[N+:16]([O-:18])=[O:17])=[CH:23][CH:22]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Nc1ccc(C(=O)c2ccccc2)cc1[N+](=O)[O-]
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc(CNc2ccc(C(=O)c3ccccc3)cc2[N+](=O)[O-])cc1
Reaction time: 8 h
Yield: 59.2 %

Procedure:
To a solution of 2.20 g of 4-amino-3-nitrobenzophenone and 1.57 g of 4-methoxybenzyl chloride in 25 ml of N,N-dimethylformamide was added at room temperature 0.40 g of 60% dispersion of sodium hydride in mineral oil, and the mixture was stirred overnight. After addition of saturated ammonium chloride aqueous solution was completed, the reaction mixture diluted with ethyl acetate was washed with brine. Removal of the solvent under reduced pressure gave the crude product, which was chromatographed on silica gel. Elution with hexane-ethyl acetate (3:1) provided 1.95 g of 4-(4-methoxybenzylamino)-3-nitrobenzophenone.